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Nervous System Drugs

Autonomic Nervous System Drugs


Functions of ANS
The functioning of the organs of the human body is controlled by the endocrine system and the nervous system. The endocrine system is controlled by hormones that act as messengers. Circulating
hormones of the endocrine system exert a slowly developing and long lasting control compared to
the control exerted by the nervous system. The autonomic nervous system (ANS) controls involuntary body functions. The ANS is composed of two divisions, the sympathetic (adregenic) system and
the parasympathetic (cholinergic) system.
Nervous System

Central Nervous System (CNS)


Spinal cord and brain

Peripheral Nervous System (PNS)

Sensory somatic nervous System


12 pairs of cranial nerves
31 pairs of spinal nerves

Autonomic Nervous System (ANS)

Cholinergic

Adrenergic

Types of Neurons in ANS


Efferent neurons (motor neurons) deliver message from brain to organs
Afferent neurons Collects message from organs to the brain
Efferent neurons divided into the
Sympathetic (Adrenergic) nervous system
Parasympathetic (cholinergic) nervous system

Responsible for regulation of


Internal metabolic activity
Myocardium
Smooth muscle of the viscera
Glandular activity
Hormonal activity
Ensure that the body operates in optimum range

Afferent

Efferent


There are four types of adrenergic receptors. These are lpha-1 and lpha-2 and eta-1 and

eta-2. Alpha-receptors are located mainly in the blood vessels and pupils. eta-1 receptors
are in the heart and eta-2 receptors are mainly in the lungs, skeletal muscles and uterus.
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Sympathetic (adrenergic)
Originate in the thoracic and lumbar region
Post ganglionic nerve fibre very long
Preganglionic nerve fibre very short
Ganglia is near spinal cord
Neurotransmitters
Norepinephrine (NE)
Epinephrine (epi)
Dopamine (D)
ACh
Receptors:
Norepinephrine (NE) a1,a2, b1 (Not on b2)
Epinephrine (epi)a1, a2, b1, b2
DopamineD1 > b > a
ACh M1
Functions
Increase heart rate
Increase blood pressure
Increase blood flow to skeletal muscle and heart
Dilation of pupil and bronchioles
Adjust in response to stressful situation (trauma,
cold, fear, hypoglycemia, exercise)
Changes in emergencies (Fight or flight response)

Nervous System Drugs


Parasympathetic (Cholinergic)
Originate in sacral and cranial region
Post ganglionic nerve fibre very short
Preganglionic nerve fibre very long
Ganglia is near innervated organs
Neurotransmitters
ACh

Receptors
AChM1, M2, M3, M4 and M5

Functions
Maintains essential body functions
(Digestive, waste elimination).
Oppose or balance the action of
sympathetic.
Dominant over sympathetic in rest and
digest situation

Both the sympathetic and parasympathetic nerves innervate the same structures. Their actions are opposing
but not equal in scope.

Anatomic Distribution and Main Effects of Catecholamine Receptors


Receptor
1
1
2
2
1
1

Vessels
Brain (postsynaptic)

Site

Presynaptic
Membrane
Penis

1
2
1
2
2
2

Heart
Kidney
Juxtamedullary apparatus
Cerebral vessels
Bladder (including Longitudinal muscle)
Fat cells
Bronchial muscles
Vessels (Venules)
Pancreas

Liver, fat cells

D1, D2
D1, D2
D1
D1
D1
D2

Nigrostriatal pathway
Median eminence, anterior pituitary
Nucleus accumbens, limbic system
Renal and mesenteric vessels
Chemoreceptive trigger zone
Ganglia presynaptic membrane

Effect
Strong vasoconstriction
Neurotransmission
Contraction
Auto inhibition of norepinephrine
release
Ejaculation
Stimulation
Renin release
Dilation (?)
Relaxation
Lipolysis
Bronchodilation
Weak vasodilation
Relaxation
Insulin release
Gluconeogenesis,
Glycogenolysis,
Lipolysis
Motor coordination
Inhibition of prolactin release
Control of emotions
Dilation
Nausea
Auto inhibition of dopamine release

cAMP = cyclic adenosine monophosphate


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Effector Organ
Adipose

Sympathetic

Arterioles
Skin and mucosa
Skeletal Muscle
Bladder
Detrusor
Sphincter
Eye
Radial Muscle, iris
Sphincter muscle, iris
Ciliary muscle

Constriction (a1)
Usually relaxation (2, M)

Lipolysis (3)

Heart
Sinoatrial node
Atrioventricular node
Atria
Ventricles
Kidney
Lacrimal glands
Liver
Lung (bronchial muscle)
Male sex organs
Nasopharyngeal glands
Pancreas
Salivary Glands
Stomach & intestine
Motility
Sphincters
Secretion
Sweat glands
Uterus
Veins (systemic)
Spleen

Nervous System Drugs


Parasympathetic

Metabolise fatty acids

Some relaxation (M)


Some relaxation (M)

Relaxation (2)
Contraction (a1)

Contraction (M)
Relaxation (M)

Mydriasis (contraction, a1)

Accommodation
(Relaxation, 2)

Miosis (M)
Contraction for near
vision (M)

Heart rate (1)Chronotropic


Conduction (1)Dromotropic
Contractility (1)Inotropic

Heart rate (M)


Conduction (M)
Contractility (M)

?
Renin secretion (1)

Glycogen breakdown (2)


Relaxation (2)
Ejaculation (a2)
Insulin secretion (2)
Viscous secretion (a1)

Tear secretion (M)

Glycogen synthesis (M)


Contraction (M)
Erection (M)

Mucus secretion
Fluid secretion (M)
Marked water secretion
(M)

Decrease (2) Peristalisis


Contraction (a1)Spincter
-

Increase (M)
Relaxation (M)
Stimulation (M)

Secretion (M)
Contraction (a1) Relaxes detrusor
muscles
Relaxation (2)
Dilation (2)
Contraction (a1)

Secretion (M)
-

(a=alpha, =beta, M=cholinergic-muscarinic)

Abbrevation and Terminology


ANS
CNS
EPI
M
ACh
D
cAMP
NE

Automic Nervous System


Central Nervous System
Epinephrine
Cholinergic-muscarinic
Acetylcholine
Dopamine
Cyclic Adenosine Monophosphate
Norepinephrine

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Nervous System Drugs

Generic and Brand


Epinephrine

Epipen, Anapen

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Adrenergic Drugs

Adrenergic Drugs
(Sympathetic Drugs)

Ach

Adrenergic agonists
Alpha agonist

Alpha 1 agonist
Alpha 2 agonist

Beta agonist

Beta 1 agonist
Beta 2 agonist

Mixed alpha and beta agonist

Alpha1 antagonists (a1-blockers)

Adrenergic antagonists
Alpha antagonists
(a-blockers)

Beta antagonists
(b-blockers)

Alpha 2 antagonists (a2blockers)


Alpha 1 and 2 antagonist
Beta antagonists (b-blockers)
Non selective b-blockers
Cardioselective b-blockers
Partial alpha and beta blockers
Partial agonist and antagonist

a1agonists
a1 agonists

Pharmacological
actions

Therapeutic use

Epinephrine
(in blood)

Norepinephrine

Adrenergic
Receptor

Adrenergic
Receptor

Adrenergic agonist (Sympathomimetics)











Phenylephrine
Pseudoephridine
Methoxamine
Bronchodilation
Blood Pressure
Peripheral Resistance
Closure Sphincter bladder
Mydriasis
Vasoconstriction
Dimetapp Cold (Night time) extra strength contains
Phenylephrine + chlorpheniramine + acetaminophen
Dimetapp Daytime Cold extra strength contains
Pseudoephedrine + Acetaminophen

a2 agonist Centrally acting antihypertensive


a2agonists

Methyldopa
Clonidine
Guanabenz

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Mechanism

Therapeutic use
Common side effects

Adrenergic Drugs

Decrease Central adrenergic outflow


a2 receptors located on perineuronal membrane
a2 receptors have inhibitory action on epinephrine and NE
Increase alpha2 receptors increase inhibitory action on epi and NE
Blood Pressure
Release of insulin
NE
Bradycardia
Centrally acting antihypertensive
Hypertension with renal disease (no decrease blood flow to kidney)
Rebound hypertension clonidine

b-agonists pharmacological actions


b-agonists non selective
Mechanism

Therapeutic use

Contraindication

Dobutamine (b1>b2)
Isoproterenol (b1 = b2)
Tachycardia
Increase lipolysis
+ve Inotropic effect (increase force of contraction of heart)
Increase Cardiac output (CO)
Increase Heart rate (HR)
Bronchodilation
Dobutamine (Dobutrex) the treatment of adults with cardiac
decompensation due to depressed contractility resulting from
organic heart disease or following cardiac surgical procedures in
which parenteral therapy is necessary for inotropic support.
Tachycardia and ventricular fibrillation

Beta 2 agonist
Beta2 agonist

Mechanism

Therapeutic use
Short acting beta 2
agonist

Short acting beta 2 agonist


Albuterol (Salbutamol)
Terbutaline
Metaproterenol
Pirbuterol
Long acting beta2 agonist
Salmeterol
Formeterol
Bronchodilation
Vasodilation
Slightly decrease peripheral resistance
Increase muscle and liver glycogenolysis
Relax uterine muscles
Increase release of glucagon
Treat Asthma and COPD
Rapid onset of action and provide relief for 4 to 6 hours.
Indicated in symptomatic treatments, rescue agents, combat acute bronchoconstriction
Albuterol, terbutaline, pirbuterol has little alpha-1 and beta-1 effects.
Does not effect by COMT enzymes because these are activated by non
COMT (Catechol Amine O-Methyl Transferase)

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Long acting beta 2


agonist

Adrenergic Drugs

Inhalation route has less toxic side effects than systemic routes.
Have less tachycardia, hyperglycemia, and hypokalemia effects with
inhalations routes.
Short acting are best reserved for treatment of acute exacerbations and
prophylaxis of exercise induce asthma
Salmeterol has long duration of action, providing bronchodilation for at
least 12 hours, and slow onset of action.
Indicated in maintenance treatment in combination with corticosteroids
especially for nocturnal asthma, EIA, and COPD
Not indicated in acute asthmatic attacks

Mixed a and b agonist


Mixed a and b agonist
Norepinephrine
Major affects

Dopamine
Epinephrine
Norepinephrine
a1, a2, b1 agonist
Vasoconstriction
Cardiac contractility
Systolic Blood Pressure (SBP)
Diastolic Blood Pressure (DBP)
Peripheral Resistance (PR)
Reflex bradycardia
Vasoconstriction causes peripheral resistance
Baroreceptor reflex stimulates cardiac contractility

Epinephrine (Adrenaline)
Action
Cardiovascular

Respiratory

Hyperglycemia

1, 2 at higher doses and 1 and 2 at lower doses


At low doses beta effects vasodilation
At high doses alpha effects vasoconstriction predominates.
oxygen demand
the rate of contraction (+ve chronotropic effect, b1 action)
the contractility of myocardium (+ve inotropic effect, b1 action)
systolic (SBP) and slight decrease diastolic (DBP) reflex
bradycardia
Intense bronchodilator used for allergic and histamine induced
bronchoconstriction
Has significant hyperglycemic effect ( glycogenolysis),
Release of insulin.
Causes lipolysis
Acute asthma
Anaphylactic shock (Type1 hypersensitivity)
Glaucoma (2% epinephrine solution)
In local anesthesia (1:100,000) Due to vasoconstrictor

CNS Anxiety, fear, tension, headache, and tremor


Hemorrhage Elevation of BP may cause hemorrhage
Arrhythmias Can trigger arrhythmias in patient using digitoxin
Pulmonary edema Can cause pulmonary edema

Therapeutic use

Side effects

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Adrenergic Drugs

Dopamine (Inotropin)
Mechanism
Major affects

Act on D1, D2, D3, D4, D5, and Mixed a and b agonist
Has +ve inotropic and +ve chronotropic effects
Dilates renal arterioles by increasing blood flow to kidney
Dopamine is drug of choice for shock given by continuous infusion.

Same as adrenergic agonist


Metabolizes to homovanillic acid

Adrenergic Blockers
Adrenergic antagonists

Alpha-blockers
(Adrenergic blockers)

Nonselective
(1 and 2
blockade)

Selective (1
Doxazocin (1)
Terazocin (1)
Tamsulosin (1a)

Reversible
Phentolamine

Beta blockers

1 , 2 , &

blockade
Carvedelol
Labetelol

Neuronal blockers

Selective ( 1
blockade)
Esmolol
Metoprolol
Atenolol
Acebutolol

Irreversible
Phenoxybenzamine

Nonselective
(1and 2
blockade)
Propanolol
Pindalol
Nadolol
Timolol
Levobutalol

a1-antagonists
a1-antagonists

Mechanism

Therapeutics use

Prazosin
Terazosin
Doxazosin
Tamsulosin ( 1A)
Alfuzosin ( 1A)
BP orthostatic hypotension
Total Peripheral Resistance
No Reflex tachycardia
Vasodilations
First dose effect (syncope) Fainting
Miosis
Antihypertensive
Symptomatic Benign Prostate Hyperplasia

Side effects

Postural (Orthostatic) hypotension


Headache, drowsiness, palpitation

Comments

Starting dose for doxazocin 1mg once daily and titrate slowly
Tamsulosin has no postural hypotension
Tamsulosin is a selective 1A receptor blocker

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Adrenergic Drugs

a2-antagonist
Yohimbine
Pharmacological
actions
Therapeutic use
Side effects
Contraindications
Mirtazepine

Yocon and odan


Blocks presynaptic a2
HR
BP
For impotency treatment
Postural hypotension
Renal and hepatic diseases
Cardiovascular disease

Used as antidepressant

a1 & a2 antagonists
a1 & a2 antagonist
Phentolamine
(Reversible)

Therapeutic use

Phenoxybenzamine
(Irreversible)

Pheochromocytoma

Competitive, short acting agent


a blockade
BP
Total Peripheral Resistance
Reflex tachycardia.

Used occasionally in patients to BP


Pheochromocytoma
Non-competitive long acting blocker
NE release is enhanced due to blockade of presynaptic a receptorscauses excessive response.
Used occasionally in patients to BP



Type of adrenal gland cancer


Can cause uncontrolled blood pressure
Can cause uncontrolled tachycardia
Increase heart rate and palpitation

b-blockers
Mixed b1 and b2antagonists (non
selective)
Mechanism

b1 antagonists
(cardioselective or
selective)

Propranolol
ProPiNaTionaLe
Pindolol
Nadolol
Timolol
Levobutolol
Reduce intra ocular pressure Decrease secretion of aqueous humor
Bradycardia
Bronchoconstriction (Bronchospasm)

Esmolol
Metoprolol
Acebutolol
Atenolol

Selective EMAA

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Mechanism
Mixed and
-antagonists
Mechanism
Partial agonist and
antagonist
Mechanism
ISA: Intrinsic
Sympathomimetic
Activity:

Adrenergic Drugs

Vasoconstriction
No bronchoconstriction
Labetalol: acts 1, 1 and 2 receptor (Non-ISA/alpha)
Carvedilol: acts 1, 1 and 2 receptors (Non-ISA/alpha)
Produce vasodilation BP
Peripheral vasoconstriction
Does not alter serum lipid levels
Acebutolol
Pindolol
Oxprenolol
Intrinsic sympathomimetic activity (ISA)
Minimized disturbances of lipid and carbohydrate metabolism.
The partial agonist stimulates the beta-receptors to which they
are bound; yet inhibit stimulation by the more potent endogenous
catecholamines, epinephrine and norepinephrine.

Summary of the side effects of adrenergic Drugs


(Sympathetic drugs)
Adrenergic agonists
Alpha agonist

1 agonist
Phenylephrine
Pseudoephridine


Beta agonist

2 agonist
Clonidine
Methyl dopa
1 agonist
2 agonist

Tremors
Palpitations
Hyperglycemia
Tachycardia

1 antagonists (a1-blockers)
Doxazocin
Prazocin
Terazocin
Tamsulosin
2 antagonists (a2-blockers)

Orthostatic hypotension
Tachycardia (No reflex tachycardia)
Vertigo
Sexual dysfunction
First dose effects (syncope)
Hypotension

Orthostatic hypotension
Reflex tachycardia
CNS insomnia, fatigue,
hallucinations, impotency (libido)
CVSDecrease HDL and increase
TG, bradycardia, orthostatic
hypotension

Mixed and agonist


Adrenergic
antagonists
Alpha antagonists
(a-blockers)

Beta antagonists
(b-blockers)

Increase BP
Inrease TPR
Vasoconstriction
Mydriasis
Decrease lipolysis
Decrease insulin secretions
Sexual dysfunction

1 and 2 antagonist

Non selective b-blockers


Propranolol
Pindolol
Nadolol
Levobutalol
Timolol

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Adrenergic Drugs

Cardioselective b-blockers
Esmolol
Metaprolol
Atenolol
Acebutalol
Partial alpha and beta blockers
Carvedilol
Labetelol
Partial agonist and antagonist
Acebutalol
Pindolol
Oxyprenolol

Adrenergic Drugs Tips




























Drugs that have +ve inotropic and +ve chronotropic effect is: dopamine.
Inotropic is: force of contraction (+ve increase in force of contraction)
Chronotropic is: heart rate (+ve increase in heart rate)
Drugs that have +ve inotropic and ve chronotropics is: Digoxin
Drugs that have +ve inotropic are: ACE Inhibitors.
Epinephrine is used for: Anophylactic reaction or hypersensitive reactions.
Epinephrine is: 1, 2, 1 and 2 agonist
Xylometazoline action is on alpha-adrenergic receptors.
Salbutamol is 2 agonist
Summary of 2 agonist:
2 agonist drugs have no anti-inflammatory effect and act as branchodilators
SABA always used as prn and tolerance can occur with regular use and also mask the symptoms
of inflammation.
SABA has additive effect with anticholinergic drugs (Ipratropium)
LABA always used as daily dose.
LABA has same effect as SABA but long duration of action.
LABA has synergistic effect with corticosteroids. (Products available: Fluticosone + Salmeterol
= Advair)
SABA and LABA are branchodilators.
Beta-blockers are drug of choice for uncomplicated hypertension in patient age under 65 years
old.
Beta-blockers are used cautiously in: Asthma, CHF, Diabetes and sever peripheral vascular
diseases.
Diabetic patient taking beta-blockers monitor? Blood sugar levels
Digoxin, non-DHP CCB may cause additive Bradycardia with beta blockers.
-blockers are drug of choice for orthostatic hypotension.
What adrenergic blockers are useful in treating Tachycardia? blockers (Propranolol)
The longest acting beta-blockers is? Nadolol
Example of irreversible and noncompetitive 1 and 2 blocker is Phenoxybenzamine
Examples of drugs that reverse effect of epinephrine associated vasocontriction 1 blockers.
Examples of sympathomimetic that should be avoided in Glaucoma Phenylephrine,
pseudoephridines.

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Adrenergic Drugs

Abbrevation and Terminology


NE
CNS
CO
HR
COPD
EIA
SBP
DBP
PR
TPR
BPH
IOP
BP
EMAA
ISA
HDL
ACE
SABA
LABA
CHF
DHP
CCB

Norepinephrine
Central Nervous System
Cardiac Output
Heart Rate
Catechol Amine O-Methyl Transferase
Exercise Induce Asthma
Systolic Blood Pressure
Diastolic Blood Pressure
Peripheral Resistance
Total Peripheral Resistance
Benign Prostate Hyperplasia
Intra Ocular Pressure
Blood Pressure
Esmalot, Metopralol, Acebutalot, Atenalol
Intrinsic Sympathomimetic Activity
High density Lipoperteins
Angiotism Converting Enzymes
Short Acting 2 Agonist
Long Acting 2 Agonist
Congestive Heart Failure
Dihydropyridine
Calcium Channel Blockers

Generic and Brand


Xylometazoline
Fluticasonet + Salmeterol

Otrivin
Advair

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Cholinergic Drugs

Cholinergic Drugs
(Parasympathetic Drugs)
Cholinergic
agonists
Direct
cholinergic
agonist
Acetylcholine
agonists
Pilocarpine
Cevimeline
Choline
estere
Bethanechol
Carbachol

Classification of Choliinergic Agonist

Indirect
cholinergic
agonists
Antiacetylcholinesterases

Quarternary
alcohols
Edrophonium
Tacrine
Donepezil

Carbamate
Physostigmone
Neostigmine
Demecarium
Pyridostigmine

Organophosphate
Echothiophate
Malathion
Parathion
Sarin
Soman

Acetylcholine is not reuptaken, it is terminted by enzyme Acetylcholine esterase. This enzyme


hydrolyse Acetylcholine into choline and acetate. This Acetylcholine esterase only found in synaspe.
Choline can be recycled but not ACh
Muscuranic innervation
Hearts have too kiond of tissue, muscle tissue such as atrial tissue and ventricle tissue also
specialized cells called Nodal cells. Node cells are highly innervated by parasympathetic system.
There is no innervations of the parasympathetic system in ventricle and purkinje fibre.
Only sympathetic system can innervate the blood vessels.(Smooth muscle)
Blood vessels (endothelium) - Muscuranic Receptors present
This endothelium Muscuranic receptor stimulation result in NO release.
This endothelium derived NO release.
This endothelium derived NO diffuses into smooth muscle and mediates relaxation of smooth
muscle by cAMP
So the only true Muscuranic agonist have the above action.
Nicotinic receptors (NN, NM)
NN Adrenal medulla, autonomic ganglia
NM Neuromuscular junction
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Cholinergic Drugs

Direct acting muscuranic agonist recluse (Braolyeardia)


The heart rate directly affectin on M3 receptors. Also their effect on endothelial blood vessel release
NO, which dialte, the smooth blood vessels. This will cause reflux Tachycardia.
Atropine overdose
Atropine is lipid soluble only physostigmine can enter CNS, so it will be used as Atropine antidote.
Summary of Cholinergic receptors effects:
Muscarinic
Receptor
Effect
Eye sphincter muscle M3
Contraction- causes miosis
Heart SA node
M2
Decrease HR (-ve chronotropy)-vagal arrest
AV node
M2
Decrease conduction velocity (-ve dromotrophy)
Lung- branchioles
M3
Branchospasm
Glands
M3
Increase secretions
GI tract
M3
Stomach-increase motility causes cramps
Intestine-increase motility causes diarrhea
Blood vessels
M3
Vasodilation but no innervation (to stimulate for action)
Nicotinic
N
Adrenal medulla
N
Increase secretion of epi and norepinephrine
Ganglia
Neuromuscular
Stimulation causes muscle hyperactivity
junction
Choline

Side Effects
Cholinergic drugs
Myopic accommodation
Bradycardia
Salivation
Lacrimation
Flushing
Diarrhea
Hypotension
Tremors

Choline

Anticholinergic
Hyper optic
accommodation and
increased intraocular
pressure
Tachycardia
Dry mouth
Blurred vision and
mydriasis
Constipation
Urinary retention
Dizziness and
drowsiness

Acetylcholine
CoA

Acetylcholine

Synaptic
vesicle
Presynaptic
receptor

Choline
Acetylcholine
Acetate

INTRACELLULAR
RESPONSE

Direct acting cholinergic drugs


Direct acting
Cholinergics

Acetylcholine
Pilocarpine
Bethanechol
Carbachol
Methacholine

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Pharmacological
actions

Cholinergic Drugs

Heart rate
Cardiac output
Blood pressure
saliva secretion
Miosis

Bethanecol: used clinically for its therapeutic effects in postoperative atony of the bowel, for abdominal
distention and urinary retention. Other drugs in this group are pilocarpine and carbachol, used in the
eye to treat glaucoma.
Urinary retention is the inability to empty the bladder. It can be due to a number of conditions such
as old age, prolonged surgery, tumours, distended bladder without voiding for long periods, exposure
to cold or anemia.
Glaucoma is disease of the eye characterized by increased intraocular pressure resulting in damage
to the optic nerve and the retina. It can lead to blindness if left untreated.
Pilocarpine is a cholinergic agent most often used to treat glaucoma since it produces a reduction in
intraocular pressure.
Side effects: cramps, diarrhea, and increased gastric acid. May cause bradycardia, flushing and a
fall in blood pressure, bronchoconstriction-causing difficulty in breathing, sweating and salivation.
If you look at the chart that showed the effects of the parasympathetic system, you should not be
surprised to see the side effects mimic the action of the parasympathetic system.

Indirect acting cholinergic drugs


Indirect acting cholinergic drugs further categorized as indirect acting reversible or
anticholinesterases and indirect irreversible or organophosphates.
Pharmacological
action
Indirect
irreversible or
organophosphates
Indirect actingreversible or
anticholinesterases

Miosis
Effects on muscarinic and nicotinic receptors.
Effects on NMJ and brain
Wide range of actions
Insecticides
Parathion
Malathion
Echothiophate
Physostigmine
Neostigmine
Pyridostigmine
Edrophonium
Donepezil
Tacrine

Neostagmine is used to treat myasthenia gravis. This disease is a disorder of skeletal (voluntary
striated) muscle due to excessive cholinesterase or lack of acetylcholine. It is characterized by
increasing fatigue and muscle weakness; some cases are mild, some are severe. Death usually
occurs due to respiratory depression.
Side effects: diarrhea, cramps, increased salivation, increased bronchial secretions, miosis, sweating
and muscle cramps.
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Cholinergic Drugs

Muscarinic antagonists
Anticholinergic
drugs

Pharmacological
actions

Anticholinergic
side effects

Atropine
Muscarinic antagonist
Ipratropium
Scopolamine
Benztropine
Tertiary amines
Quarternary amine
Tropicamide
Atropine
Ipratropium
Glycopyrrolate
Scopalamine
Tiotropium
Trihexyphenidyl
in salivation cause
dry mouth (xerostomia)
intestinal secretion Constipation
Increase HR Tachycardia
Mydriasis Pupil dilatation
Relaxation of detrussor muscle Urinary retention
Blurred vision
Dry mouth
Blurred vision
Tachycardia
Constipation
Urinary retention

Nicotinic Blockers (Ganglionic blockers)


Nicotine: Depolarizes ganglia, resulting first in stimulation and followed by paralysis of all ganglia,
increase in BP, HR, inceased peristalsis, and secretion.
a-Bungarotoxin
a -Bungarotoxin is a postsynaptic neurotoxin found in the venom of the Braided Krait snake
(Bungarus Multictus). Like other neurotoxins it blocks neuromuscular transmission.
-Bungarotoxin ( Bgtx) is a toxin known to interact with muscle nicotinic receptors and with some
neuronal nicotinic receptors.

NMJ blockers
These agents are used for surgical patients to relax the muscles during surgery. .
Pharmacological actions:
Blocks the cholinergic transmission between motor nerve and nicotinic receptors.
Antagonizes (non depolarizing type) and agonist (polarizing) the effect of acetycholine.
Classified as two categories of NMJ blockers:
Depolarizing: Succinylcholine
Depolarizing drug attaches to nicotinic receptors and act like acetylcholine to depolarize the
junction.
Causes opening of sodium channel associated with nicotinic receptors, which results in
depolarization of receptors.
Non-depolarizing:
Prevents the binding of acetylcholine.
Inhibits muscular contraction
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Cholinergic Drugs

Antagonist for non depolarizing agents are: neostigmine, edrophoniuum (cholinesterase


inhibitors)
At higher doses, these (non depolarizing) drugs block the ion channels of end plate and
reduced the ability of antagonists.
Indicated in anesthesia during surgery to relax skeletal muscles.
Side effects: Decrease the BP, paralysis of diaphragm
Depolarizing NMJ Blockers
Depolarizing Non Succinylcholine
competitive
Mechanism
Blocks the cholinergic transmission between motor nerve and nicotinic
receptors.
Antagonizes (non depolarizing type) effect of acetylcholine.
Therapeutic use
Clinically used in surgery to produce complete muscle relaxation.
Non-depolarizing NMJ Blockers
Non Depolarizing - Atracurium
competitive
Tubocurarine
Doxacurium
Pancuronium
Vecuronium
Mivacurium
Mechanism
Prevents the binding of acetylcholine
Inhibits muscular contraction.
At higher doses, these (non depolarizing) drugs block the ion channels
of end plate and reduced the ability of antagonists
Therapeutic uses
Indicated in anesthesia during surgery to relax skeletal muscles.
Side effects
Decrease BP
Paralysis of diaphragm
Antagonist for non Neostigmine, edrophonium (cholinesterase inhibitors)
depolarizing agents

Abbrevation and Terminology


SA
AV
PR
a -BgTx
ACh
NMJ
BP
HR

Generic and Brand


Pilocarpine
Atropine
Ipratropium
Scopolamine
Benztropine

Sinoatrial Node
Atroventricular Node
Peripheral Resistance
a -Bungarotoxin
Acetyl Choline
Neuro Muscular Junction
Blood Pressure
Heart Rate

IsotoCarpine
Atreza, AtroPen, Atropine Care, Atropisol
Atrovent, Atrovent HFA
Isopto Hyoscine, Maldemar, Scopace
Cogentin

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Tropicamide
Glycopyrrolate
Trihexyphenidyl
Atracurium
Tubocurarine
Doxacurium
Pancuronium
Vecuronium
Mivacurium
Succinylcholine
Physostigmine
Neostigmine
Pyridostigmine
Edrophonium
Donepezil
Tacrine
Malathion
Echothiophate
Neostigmine
Edrophonium

Cholinergic Drugs

Mydriacyl
Robinul, Robinul Forte
Artane
Tracrium
Tubarine. Metubine. Jex
Nuromax
Pavulon
Norcuron
Mivacron
Anectine, Quelicin, Sucostrin
Mestinon, Regonol
Prostigmin
Pyridostigmine
Enlon, Reversol, Tensilon
Aricept, Aricept ODT
Cognex
Ovide
Phospholine Iodide
Prostigmin
Enlon, Reversol, Tensilon

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Blood Pressure

Diuretics

Antihypertensive drugs

Antihypertensive Drugs
= Cardiac Output (CO)

Beta
Blockers

Calcium
Channel
Blockers

X Total Peripheral Resistance (TPR)

Alpha1
Blocker

Alpha2
agonists

ACE inhibitors

Angiotensin
antagonist

AT1 Receptor
Blocker

Blood Pressure is caused by Cardiac Contraction




Systole (contraction)


o
When the heart beats (systole) the pressure in the arteries leaving the heart

rises to about 120 mm Hg.


Diastole (relaxation)


o
Between beats (diastole) the arterial pressure drops to about 80 mm Hg


o
The 80 mm Hg DBP keeps the blood flowing between beats


Blood pressure is reported as SBP over DBP


o
Example: 120/80


Optimal BP is 120/80


Normal BP is 130/85


High normal BP is 130-139/85-89


Grade 1 (mild hypertension) 140-159/90-99


Grade 2 (moderate hypertension) 160-179/100-109


Grade 3 (severe hypertension) >180/>110


Isolate systolic hypertension >140 / <90


Diabetic or renal impairment >130/>80
Laplaces Law
Laplaces law describes how tension in the vessel wall increases with transmural pressure.
According to Laplaces law, the PRESSURE GRADIENT ACROSS THE VESSEL WALL is given
by: tiwhere Pout and Pin are the pressures outside and inside the vessel, respectively. T is the vessel
wall tension, and r is the vessel radius. If the vessel wall is completely flattened against a smooth
sensor surface (r), the measured pressure will be equal to the intra-luminal blood pressure
(DP0).
Systemic Blood Pressure Depends Upon
1-Cardiac Output and Resistance to Flow (TPR): CO = HR X SV
2-Kidney provide long term control of BP
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Antihypertensive drugs

By altering blood volume: Sympathetic stimulation releases the enzyme renin. Angiotensinogen and
angiotensin I & angiotensin II.
Angiotensin II is the bodies most potent circulating vasoconstrictor causing increases BP.
Angiotensin II stimulates aldosterone (ADH) secretion leading to increase kidney sodium reabsorption
and increase in blood volume, which contributes to increase in BP.
Systemic blood pressure depends upon cardiac output and resistance to flow








The more blood pumped into the arteries


the higher the pressure
Renin
Pressure also goes up if there is more

resistance to flow- this occurs when large
numbers of arterioles constrict
The body changes both CO and resistance
to adjust blood pressure, the higher the
blood pressure the more work the heart

must do to pump blood.

Angiotensin I
ACE
Angiotensin II

PR

BP

Aldosterone

Na/H2O retension

Blood
Volume

b-blockers
Beta-blockers are used to treat hypertension and angina. These drugs act by slowing the heartbeat,
which results in lowered blood pressure since blood pressure is affected by the heart rate and
peripheral resistance. Because of its action on the lining of arteries, propranolol is also used to treat
migraines.

Nonselective (
& 2)
1




Propranolol
Pindolol
Nadolol
Timolol
Levobutolol

Vasoconstriction
Reduce intra
ocular pressure
(IOP) =
secretion of
aqueous humor
Bradycardia

Cardioselective
( 1 only)




Esmolol
Metoprolol
Acebutolol
Atenolol
Bisoprolol
Betoxalol

Beta & Alpha


blockers

Partial agonist &


antagonist

Labetalol
Carvedilol

Acebutolol
Pindolol
Oxprenolol

Alpha receptors
Produce
vasodilatation =
BP
Beta blocker
cause Peripheral
vasoconstriction
Does not alter
serum lipid
levels

Intrinsic
sympathomimetic
activity (ISA)
Minimized
disturbances
of lipid and
carbohydrate
metabolism

Beta Blockers
Beta & Alpha
blockers
Partial agonist

& antagonist
CardioSelective

(b 1 only)
Nonselective (b1
& b2)

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Mixed b1 and b2antagonists (non
selective)

Mechanism

b1 antagonists
(cardioselective)

Mechanism
Mixed a and
b-antagonists
Mechanism
Partial agonist and
antagonist
Mechanism
ISA: Intrinsic
Sympathomimetic
Activity:

Side effects

Antihypertensive drugs

Propranolol
ProPiNaTionaLe
Pindolol
Nadolol
Timolol
Levobutolol
Reduce intra ocular pressure Decrease
secretion of aqueous humor
Bradycardia
Bronchoconstriction (Bronchospasm)
Esmolol
EMAA Selective
Metoprolol
Acebutolol
Atenolol
Vasoconstriction
No bronchoconstriction
Labetalol
Carvedilol
Produce vasodilation BP
Peripheral vasoconstriction
Does not alter serum lipid levels
Acebutolol
Pindolol
Oxprenolol
Intrinsic sympathomimetic activity
Minimized disturbances of lipid and
carbohydrate metabolism.
The partial agonist stimulates the betareceptors to which they are bound; yet
inhibit stimulation by the more potent
endogenous catecholamines, epinephrine and
norepinephrine.
The result of opposing actions is a muchdiminished effect on cardiac rate and cardiac
output.
Compared to b-blocker without ISA.

Slowed heartbeat (bradycardia), profound low


blood pressure (orthostatic hypotension), dizziness,
depression, drowsiness and some stomach upset and
hypoglycemia. Because of the effect of eta-blocker
on the eta-receptor of smooth muscle, the lining of
the bronchioles may be affected. These drugs can
aggravate asthma, breathing difficulty or shortness
of breath in some sensitive patients. These drugs
should not be given to asthma patients unless no
other class of drug can be used. However, esmalol,
acebutol, atenolol, bisoprolol, betaxolol and
metoprolol are selective -blockers and generally,
have less or no bronchospasm side effects. The
selective -blockers may be given to lower doses to
patients sensitive to these drugs if no other class of
medication can be used.

1 receptors

blood

CO
HR
Force

receptors

peripheral
vasodilation

Mechanism of action of beta-blockers


Effect of B receptor
on heart

Cardiac output

Renin

Preripheral
resistant

Angiotensin II

BP

Aldosterones
Na, H2O levels

Blood volume
Cardiac output

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Contraindications

Antihypertensive drugs
Beta-blockers therapeutic uses:

Bradycardia
Propranolol
Heart blockage
Asthma and bronchospasm (avoid non selective)
Peripheral vascular diseases such as Raynauds
phenomenon and intermittent claudication except
carvedilol and labetelol can be tried.
Timolol
Caution in congestive heart failure.
Left ventricular dysfunction
Drug and food interactions

Pindolol

Used for hypertension, angina,


post MI, migraine, essential
tremor, performance anxiety,
Hyperthyroidism (acutethyroid storm)

Used for hypertension, post


MI, migraine. Chronic
treatment of Open angle
glaucoma

Used for hypertension

Metaprolol
Cardioselective, used for
Propranolol is best absorbed with food but
hypertension, angina
consistency is the most important factor
Metoprolol is best taken with meals
Atenolol
Cardioselective, used for
These drugs should be taken at about same

hypertension
time every day
Esmolol
Cardioselective used for
Beta blocekers that have Ist pass metabolism;
hypertension, tachycardias
propranolol, timolol
Beta blocekers that have no biotransformation; Acebutolol Cardioselective, used for
hypertension, angina
atenolol
Beta blocekers that have blockadeeffect:
Decrease in contractility of heart and decrease
labetalol, carvedilol
in oxygen consumption
Beta blocekers that act as membrane stabilizer;
propranolol

-receptors

Indication

Contraindication
Side Effects

1-antagonist

2-agonist

Orthostatic hypotension
Tachycardia
Vertigo
Sexual dysfunction

Decrease lipolysis
Decrease insulin secretion
Sexual dysfunction

Hypertension
Benign Prostatic Hypertrophy
(BPH or enlarged prostate)
DOC for pheochromacytoma
hypertension

Hypertension
Treat withdrawal
symptoms in recovering
drug and alcohol abusers
(Clonidine)

Alpha-blockers are the drug of choice in


In addition to being used for hypertension, terazosin, doxazosin, tamsulosin and alfuzosin which are
chemically related to prozasin are often used to treat benign prostatic hypertrophy (BPH), the medical
term for enlarged prostate. These drugs cause the muscles of the bladder neck and prostate to relax,
thereby making it easier for patients to urinate. As Antihypertensives, they help control pressure by
relaxing blood vessels and permitting them to expand.
1 antagonists
Doxazosin mesylate
Prazosin hydrochloride
Terazosin hydrochloride dehydrate
Alfuzosin
Tamsulosin
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Antihypertensive drugs

pheochromacytoma hypertension.
Pharmacological actions of 1 anatagonist:
BP
Total Peripheral Resistance (TPR)
No Reflex tachycardia
Vasodilations
First dose effect (syncope)
Miosis
Side effects: Orthostatic hypotension, Tachycardia (No reflex tachycardia), Vertigo, Sexual dysfunction
to avoid the first dose effect of hypotension and occasional syncope, the starting doses should be small
and given at bedtime.

a2 agonist Centrally acting antihypertensive


2 agonist used to treat hypertension are centrally acting agents, which act directly in the brain to
change the signals send to the heart and blood vessels. These drugs are not commonly used, as it is
difficult to achieve the proper dose with these agents. They are generally reserved for people who
fail to respond to other therapies.
Other uses have been found for clonidine. Clonidine is sometimes used to treat withdrawal
symptoms in recovering drug and alcohol abusers.
a2 agonists
cAMP

Methyldopa
Clonidine
Guanabenz

ATP

Pharmacological actions 2 agonist:


Decrease Central adrenergic outflow
2 receptors have inhibitory action on epinephrine and NE
Increase 2 receptors increase inhibitory action on epi and NE
Blood Pressure
insulin secretions
NE
Norepinephrine
Bradycardia
Side effects: Decrease lipolysis, Decrease insulin secretions, Sexual dysfunction

Methyldopa (Aldomet)
Mechanism
Therapeutic use

a2 agonists
Inhibit norepinephrine release
Inhibit insulin release
Indicated in moderate to sever hypertension
Produced active metabolite (Methyl dopa Alpha methyl
norepinephrine)
Methyl dopa is prodrug
Drug of choice for hypertension in pregnancy.

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Side effects

Antihypertensive drugs

Cardiovascular Bradycardia, orthostatic hypotension


Blood related Hemolytic anemia, thrombocytopenia
Bone marrow depression
GI Dry mouth, nausea, diarrhea

Clonidine (Cataprex)
Chemistry
Clonidine contain imidazoline ring.
Therapeutic use Used in non complicated hypertension to lower BP.
Indicated in opioids and benzodiazepine withdrawal symptoms (CNS
symptom)
Side effects
CVS bradycardia orthostatic hypotension, severe rebound hypertension
CNS drowsiness, dizziness, agitation
Dosage
Precautions
Counselling

Transdermal patch
Pruritus and rash at the site of transdermal
Patch (TT1 (release 0.1 mg/24 h), TT2 (0.2 mg 24/h). TT3 (0.3 mg/24 h)
Dont discontinue abruptly, reduce dose over 2-3 days to reduce sever
hypertension
Dont miss any pill, Dont stop suddenly
Causes drowsiness
Need gradual withdrawal

Classification of Diuretics
Thiazide
Diuretics

Loop
Diuretics

K-sparing
diuretics

Carbonic acid
Inhibitor

Osmotic
diuretic

Chlorothiazide
Hydrochlorothiazide
Chlothalidone

Furosemide
Ethacrynic acid
Bemetanide

Spirolactone
Triamterene
Amiloride

Acetazolamide

Mannitol

Diuretics
Often called water-pills, diuretics increase urine production,
Reducing the body of sodium and water, thereby reducing the volume of blood that the heart
must pump, and in this manner decreasing blood pressure.
Side effects: stomach upset, frequent urination, potassium depletion, and dizziness.
Potassium blood levels should be monitored.
Foods rich in potassium may be ingested (eaten) daily. These are potatoes, bananas, cantaloupe,
and citrusfruit.
If potassium levels are very low, potassium chloride or potassium oral liquids may be used.
Mechanism of hypokalemia induced by CA inhibitors, loops and thiazide diuretics: Because of
upstream blockade of NaCl reabsorption there is Na+ consequently there is reuptake of Na+.
+ve charge in the cell. The increase +ve charge then pushes out K+ into the lumen.
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Antihypertensive drugs

Thiazide Diuretics
Thiazides

Pharmacological
actions

Therapeutic uses

Side effects

Thiazide Diuretic Mechanism


Hydrochlorothiazide
Chlorthiazide
Na and H2O retention
Thiazide diuretics
Indapamide
Metolazone
Blood Volume
H2O, Na, Cl, K, excretions
( levels in body), retain Calcium
May cause alkaline urinary pH by
Cardiac output
Peripheral resistant
effecting on carbonic anhydrase
Metabolic alkalosis (Hypochloremic
B.P.
alkalosis)
BP in both the supine and standing
position, except in elderly
Counteract Na/H2O retention caused
by other antihypertensives such as
hydralazine and -blockers
Especially useful in elderly and African populations and with chronic renal
diseases.
Not effective in patient renal clearance less than 50ml/min
Not preferable in diabetic and hyperlipidemic patient
Hypokalemia, hypomagnesia, hyponatremia, Hypercalcemia,
hyperuricemia, Hyperglycemia, Metabolic alkalosis, Photosensitivity
rashes, acute pancreatitis Libido, difficulty with erection and ejaculation
(long term).

Loop Diuretics
Loop
Mechanism

Therapeutic use
Side effects

Furosemide, Ethacrynic Acid,


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Bumetanide, Torsemide
Loop Diuretics
Increase H2O, Na, Cl, K and Ca
excretions (decrease levels in body)
Increase Ca2+ ion excretion
(Loops Lose Calcium)
Na+
No change in urinary pH; Metabolic
K+
Cl+
alkalosis (Hypochloremic alkalosis)
Act in the thick ascending loop of Henle
and inhibit the sodium/potassium
Inhibit the Na+K+2Cl- channel in the thick ascending loop
dichloride co-transport system. Potent
agent can excrete up to 25% of filtered
Na+. No ions come into the cell therefore
the sodium pump and Na/Cl symport do not work.
DOC in renal disease (CrCl is less than 50ml/min), Acute pulmonary edema,
Hypercalcemia.
OH DANG!
Ototoxicity
Hypokalemia
Dehydration
Allergy (sulfa), except ethacrinic acid

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Antihypertensive drugs

Nephritis (intestinal)
Gout arthritis
Sequence of ototoxicity (etharynic acid>furosemide>bumetanide)
Do not use

If patient has renal stones


If patient has gout do not use loop and thiazides

Ethacrynic Acid Does not contain sulfonamide functional group no sulfa allergy

Potassium sparing
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Amiloride (Midamor)
Potassium sparing diuretics
Triamterene (Dyrenium)
Spironolactone (Aldactone)
The K+ STAys
Na+
Spironolactone
H+ K+
Triamterene
blue color urine
Amiloride
Inhibit Na+ reabsorption and K+, H+ excretion in
Act in the early collecting duct to
distal convoluted tubule and net results is
descreased Na+ reabsortion and K+, H+ excretion
inhibit the electrogenic reabsorption
of Na+ by blocking the Na channels
and hence the exchange of sodium for potassium.
After administration: Na+, Cl- elimination, K+, Ca++ (amiloride).
Increase Na, H2O, HCO3 excretion (decrease levels in body)
Decrease K+, H+ excretion
Alkaline urinary pH Increase excretion of HCO3
Spironolactone (Aldactone): competitive inhibits aldosterone at minor
Aldocorticoid receptors. Decreases potassium excretion.
Amiloride and triamterene
Act directly on late distal tubule and collecting duct. They disrupt
sodium exchange with Potassium and hydrogen by blocking sodium
channel
Decrease in the driving force for secretion of potassium and hydrogen.
Used in nephrogenic diabetic insipidus

Potassium sparing


Mechanism

Aldosterone
antagonist
Non aldosterone
antagonist

Amiloride, spironolactone and trianterene act as competitive antagonists of aldosterone in the


kidney. Because they are weak diuretics when given alone, they are often used in combination
with hydrochlorthiazide, as in Aldactazide, Apo-Triazide, Apo-Amilzide.
A side effect may be hyperkalemia, an increase in potassium levels, so that potassium
supplements are usually not taken with these drugs. If they are needed, the dose of potassium is
frequently administered three times a week instead of daily.

Osmotic Diuretics
Osmotic
Mechanism

Mannitol, and Urea


Increase excretion of H2O, Na, Cl and HCO3 (decrease levels in body)
Increase alkaline urinary pHIncrease excretion of HCO3
Increase tubular osmolarity Increase urine flow

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Antihypertensive drugs

Carbonic anhydrase Inhibitors





Acetazolamide
Increase excretion of H2O, Na, K, and HCO3 (Decrease levels in body)
Increase alkaline pH Inc. exc-HCO3
Cause metabolic acidosis

Type of diuretic

Ca

Mg

Na

Uric acid

Blood sugar

Lipids

Metabolic Disturbances

Thiazide

Hypokalemic metabolic alkalosis

Loop

Hypokalemic metabolic alkalosis

K-sparing

Hyperchloremic
metabolic acidosis (CO2)
Intracellular alkalosis

CAI

Heperchloremic metabolic
acidosis

Osmotic

Serum Electrolyte of Diuretics


In general, the opposite findings of serum electrolytes are seen in urine

Diuretics Tips





Diuretics that cause metabolic alkalosis:


Diuretics that cuase intracellular alkalosis:
Diuretics that act on distal convoluted tuble:
Diuretic that cause metabolic acidosis:
Diuretics that have greater vasodilation effect:
Hyperlipidemia NOT generally siginificant at low doses, (<25mg/d), at higher doses what type
lipid increases:
Patient taking Hydrochlorothiazide should be monitored:

ACE Inhibitors
Angiotensin II is a substance produced in the body that causes the blood vessels to constrict (become
smaller in diameter). ACE inhibitors inhibit Angiotensin II formation. These drugs represent a
major advance in hypertensive treatment and have most displaced digoxin as the drug of choice in
congestive heart failure. ACE inhibitors are used to treat hypertension and congestive heart failure.
ACE inhibitors also tend to protect the kidneys of diabetics from developing renal failure when used
in the early stages of diabetic nephropathy.
Side effects: profound low pressure, taste abnormalities, dry cough, blood cell abnormalities, and
kidney problems. They are contraindicated in pregnancy. A persistent dry cough may necessitate
discontinuing the drug. Use of potassium supplements and ACE inhibitors increase the risk of
hyperkalemia.
ACE Inhibitors
Captopril, Benazepril, Cilazapril, Enalapril,
Fosinopril, Lisinopril, Perindopril, Quinapril,
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Ramipril, Trandolapril
Pharmacological actions

Antihypertensive drugs

Liver
Angiotensinogen

sympathetic output
Bloodstream
Vasodilation of smooth muscles
Renin
levels of bradykinincauses dry cough
Angiotensin I
and vasodilation
retention of Na and H2O
Angiotensin
converting
Above combined effect produce in preload
enzyme
Kidney
Lung
and after load
Angiotensin II
cardiac output (CO).
Dilation of venous blood vessels leads to
Vasoconstriction
decrease in cardiac preload by venous
Aldosterone secretion
capacitance.
ADH secretion
Arterial dilator reduces systemic arteriolar
Thirst
resistance and after load.
Angiotensin II Formation
Lower BP by reducing peripheral vascular
resistance with reflexly increasing cardiac output rate.
By reducing circulating angiotensin II levels ACE the secretion of aldosterone, resulting
retention of Na and H2O.
Little change in HR, or GFR.
Therapeutic use




1ST LINE: Heart Failure


Diabetes nephropathy
Angiotensinogen
(alpha globulin in blood)
Post MI
Uncomplicated hypertension,
Renin
and pre-hypertensive patient
(kidney)
LVH (Left ventricular
Angiotensin II
Heart failure)
Angiotensin I
Prior CVA/TIA (Cardiovascular
Attacks/ Transient Ischemic attacks)
& in renal disease
ACE I
Dry cough (5-15%)
Hypotension
Hyperkalemia
Renal insufficiencies
Angioedema (rare)
Reversible neutropenia
Proteinuria (presence of protein in urine)
Fatigue

Sympathetic action
Vasodilation

BP

Bradykinin

Side effects

Contra
Indications:

Pregnancy (absolute): Can produce hypotension in the fetus leading renal failure
and death, skull hypoplasia and death.
Documented angioedema-secondary angioedema,
Bilateral renal artery stenosis.
Captopril should be taken one hour before meals.
High fat meals may reduce absorption of Accupril
Food does not effect the other drugs in this class

Na & H2O levels

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Tips

Antihypertensive drugs

ACE Inhibitors Side effects (CAPTOPRIL)


Cough
Angioedema
Proteinuria
Taste changes (Dysgeusia)
HypOtension
Pregnancy contraindication (fetal renal damage)
Rash
Increased renin
Lower angiotensin II

ARB Inhibitors
These drugs are used to control high blood pressure and appear to have the same benefits as ACE
inhibitors, without producing the common side effect (experienced by as many as 30% of patients)
of a dry cough. These drugs block the effects of Angiotensin II, a naturally occurring substance that
causes blood vessels to narrow (constrict). When these drugs are administered, blood vessels dilate,
thereby lowering blood pressure and decreasing the workload of the heart.
Mechanism: Angiotensin binds to its own receptors, AT-1 receptors are found on vascular muscle and
in the adrenals. Stimulation leads to vasoconstriction and release of aldosterone in the adrenal gland.
ARB Inhibitors
Losartan
Candesartan
Valsartan
Irbesartan
Telmisartan
Side effects
Less dry cough (cough associated with ACE inhibitors does appear with these drugs),
Bradykinin causes vasodilation of arterioles and venules results TPR.Less Dry cough
Dizziness,
Hypotension/syncope
Renal dysfunction. (Reversible renal failure)
Hyperkalemia
Angioedema
Contraindications
Pregnancy (Renal fetal toxicity),
Bilateral renal artery stenosis (stenosis = abnormal narrowing of passage or opening, such blood
vessels or heart valve.

Vasodilators
Preload: Volume

of blood that fills the ventricle during diastole.


After load: The pressure that must overcome for the heart to pump blood into the arterial system.
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Antihypertensive drugs

Vasodilators cause the smooth muscle in


Vasodilators
blood vessels to relax. Relaxed or dilated
blood vessels allow more blood to flow
through, causing a reduction in blood
pressure by decreasing peripheral resistance.
Indirect Vasodilators:
Direct Vasodilators:
As vasodilators work, the blood vessels
ACE inhibitors
Hydralazine
become dilated causing a drop in pressure
Calcium
channel blockers
Sodium Nitroprusside
because there is less blood volume to fill
Minoxidil
the vessel. The body can compensate for
this by retaining enough fluid to fill the
blood vessel sufficiently to raise the blood pressure again.
Hydralazine and minoxidil are direct vasolidators not usually used a sole therapy for high blood
pressure, as their effect is usually short-lived when administered alone. Minoxidil is available in
tablets and also as a topical lotion for treatment of male-pattern baldness).
Pharmacological action
Vasodilators reduce excessive preload and after load.
Elevated after load causes the heart to work harder to pump blood into arterial system.
Dilation of venous blood vessels leads to decrease in cardiac preload by increasing venous
capacitance.
In arteries dilators reduce systemic arteriole resistance and decrease after load.

Minoxidil (Rogaine)
Mechanism
Therapeutic use
Side effects

For alopecia

A prodrug, which must be conjugated with a sulfate to form the active


drug.
Minoxidil is potent renal vasodilator and stimulator of renin release.
Hypertension and alopecia treatment
Salt and water retention (use a diuretic)
Reflex tachycardia
Pulmonary hypertension
Blurred vision
Hypertrichosis - topical solution is now marketed for baldness.
Each mL of clear, colorless to slightly yellow solution contains:
minoxidil 20mg (2%), in alcohol (63%), propylene glycol (20%) and
water.
For external use only. Store at controlled room temperature (15to
30C).
Hypertrichosis (excessive hair growth) occurs continued treatment over
4 weeks

Emergencey use drugs


Hydralazine (Apresoline)
Mechanism
Therapeutic use

Acts directly relaxing arteriolar smooth muscle. Orthostatic hypotension is


not a problem.
Indicated in pregnancy induced hypertension (PIH)

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Side effects

Antihypertensive drugs

Salt and water retention, which may lead to CHF (use a diuretic).
Hematologic-neutropenia,
Leucopenia,
Agranulocytosis,
Muscle cramps,
Orthostatic hypotension
Tachycardia
Lupus like syndrome (Systemic Lupus Erythromatus)

Diazoxide (Hyperstat)
Mechanism
Therapeutic use
Side effects

Dilates arterial smooth muscle.


Used IV for the treatment of hypertensive emergencies
Salt and water retention
Hyperglycemia ( release of insulin)
Hypertrichosis

Sodium Nitroprusside
Mechanism
Therapeutic use
Side effects

Thiocyanate
toxicity

Dilates both resistance and capacitance vessels,


Nitroprusside when come in contact with red blood cells (RBC) produces
nitric oxide (NO), which then stimulates guanylate cyclase.
DOC for hypertensive crisis
Short term-excessive vasodilatation and hypotension. Long termaccumulation of cyanide and thiocyanate (24-hours).
Concomitant administration of sodium thiosulfate decrease cyanide
accumulation by changing into thiocyanate.
Nausea, disorientation and toxic psychoses

Antihypertensive Drugs Tips











Targeted isolated systolic BP should be


Hypertension with diabetes DOC is
Hypertension with renal disease DOC is
Hypertension + pheochromacytoma which antihypertensive should be avoided
Isolated systolic Hypertension which drugs should not use
Cardioselective beta-blockers are
What percent of patients diagnosed with high blood pressure have essential hypertension?
Name the cation most prevalent in the extracellular fluid of the body.
Why is bedtime the best time to dose terazosin?
What is the recommended sodium intake for a patient diagnosed with hypertension?

Summary of b - blockers
Pharmacological actions
b1 = decrease heart rate
b2 = bronchoconstriction
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Antihypertensive drugs

Peripheral vasoconstriction (Increase TPR)b2


Na/water retention
glycogenolysis (glycogen glucose)
glucagon secretions
Blocks the effect of isoproterenol

Antihypertensives Lowers blood pressure through reducing the PR or CO.


Diuretics
Create a negative sodium balance, reduce blood volume, and decrease vasoconstriction.
Peripheral sympatholytics
Blocks postganglionic adrenergic receptors, limiting release of neurotransmitters from
adrenergic receptors, or depleting intraneuronal catecholamine storage sites.
Central a2-sympathomimetics
Cause negative sympathetic outflow and lowering peripheral resistance.
Calcium channel blockers
Block voltage-gated calcium channels causes lower vascular resistance and blood pressure.
ACE inhibitors
Decrease Sodium retention by blocking the conversion of inactive Angiotensin I to
Angiotensin II.
Angiotensin II-receptor antagonist
Produced vasodilation and causes loss of salt and water thus decreasing the plasma volume, and
myogenic activity.
Vasodilators
Relaxes arterioles and veins, membrane hyperpolarization, decrease atrial resistance.

Abbrevation and Terminology


TPR
DBP
SBP
BP
CHF
CO
ADH
BPH
ACE
HR
ISA
EMAA
NE
DHP
NDHP
GFJ
CA
GFR
ARB
NO
RBC
PIH
SV
LVH
CVA

Total Peripheral Resistance


Diastolic Blood Pressure
Systolic Blood Pressure
Blood Pressure
Congestive Heart Failure
Cardiac Output
Antidiuretic Hormone
Benign Prostate Hyperplasia
Angiotensin-converting enzyme.
Heart Rate
Intrinsic Sympathomimetic Activity
Esmalot, Metopralol, Acebutalot, Atenalol
Norepinephrine
Dihydropyridine
Non Dihydropyridine
Grape Fruit Juice
Calcium
Glomerular Filtration Rate.
Angiotensin Receptor Blocker
Nitric Oxide
Red Blood Cells
Pregnancy induced hypertension
Stroke Volume
Left Ventricular Heart Failure
Cardiovascular attacks

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Antihypertensive drugs

Generic and Brand


Diltiazem
Minoxidil
Diazoxide
Hydralazine
Hydrochlorothiazide
Chlorthiazide
Indapamide
Metolazone
Mannitol
Acetazolamide
Amiloride
Triamterene
Spironolactone
Captopril
Benazepril
Cilazapril
Enalapril
Fosinopril
Lisinopril
Perindopril
Quinapril
Ramipril
Trandolapril
Losartan
Candesartan
Valsartan
Irbesartan
Telmisartan
Alfuzosin
Tamsulosin
Methyldopa
Propranolol
Pindolol
Nadolol
Timolol
Levobutolol
Esmolol
Metoprolol
Acebutolol
Atenolol
Bisoprolol
Betoxalol
Labetalol
Carvedilol
Oxprenolol
Clonidine
Guanabenz
Felodipine
Nicardipine
Furosemide
Ethacrynic Acid
Bumetanide
Torsemide

Cardizem, Dilacor, Tiazac


Loniten, Rogaine
Hyperstat, Proglycem
Apresoline
HydroDIURIL
Hygroton
Lozide
Mykrox, Zaroxolyn
Osmitrol
Dazamide or Diamox
Midamor
Dyrenium
Aldactone
Capoten
Lotensin
Inhibace
Vasotec
Monopril
Zestril, Prinivil
Coversyl
Accupril
Altace
Mavik
Cozaar
Atacand
Diovan
Avapro
Micardis
Xatral
Flomax
Aldpmet
Inderal, Inderal LA, InnoPran XL, Pronol
Visken, Betapindo,Calvisken,Decreten,Durapindol
Corgard
Betimol, Blocadren, Istalol, Timoptic
Betgan
Brevibloc
Lopressor, Toprol XL
Sectral
Tenormin
Bisoprolol Fumarate
Labetalol, Normodyne, Trandate
Coreg CR, Coreg
Oxprenolol
Catapres, Catapres-TTS, Duraclon, Duraclon
Wytensin
Renedil / Plendil
Cardene
Delone, Furosemide, Lasix
Edecrin
Bumex
Demadex

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Antihypertensive drugs

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Antihyperlipidemics Drugs

Antihyperlipedemic Drugs
Classification of Antihyperlipidemic Drugs

HMG-CoA
reductase
inhibitors
Lovastatin
Simvastatin
Pravastatin
Fluvastatin
Atorvastatin
Cervastatin

Nicotinic
acid

Bile acid
sequeste-rants

Fibric acid
derivatives

Niacin

Cholestyramine
Cholestipol

Cholesterol
Absorption
inhibitors
Ezetimibe
Ezetrol

Effects of Antihyperlipidemics on Lipoproteins


Drug class
Bile acid sequesterants
Nicotinic acid
HMG-CoA reductase inhibitors
Fibric acid derivatives

LDL

HDL

VLDL-TG

(TG)

Reference: Therapeutic Choices, 4th ed. page 242

Statins
Statins
Mechanism
Therapeutic use
Contraindicated
Side Effects

Drug interactions

Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin


HMG CoA reductase inhibitors (HMG = 3-hydroxy, 3-methyl glutaric acid)
Decrease LDL receptors (18 55%)
Lower cholesterol synthesis (cholesterol pills)
In pregnancy and breast-feeding, children or teenagers.
GI side effects GI upset, diarrhea, nausea and vomiting
Rhabdomyolysis (myopathy) disintegration and dissociation of muscles
Rhabdomyolysis is common in renal insufficiency patients.
Medication such as cyclosporine, itraconazole, erythromycin
(macrolide), gemfibrozil, niacin, fibrates and grapefruit juice increase
rhabdomyolysis, due to inhibition of CYP 34A enzyme, which is
essential for metabolism of statins Niacin

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Monitor

Antihyperlipidemics Drugs

LFT (Liver Function Test): Abnormalities in liver functionEvaluate


liver function and measure serum transaminases
CPK (creatinin phospho kinase) or CK
Fluvastatin, Lovastatin and Simvastatin should be taking at nighttime.
Rest other drugs anytime of the day

FLS

Known Metabolizing
Enzyme(s)
Grapefruit juice
Take
Food

Statin
Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin
CYP3A4
CYP2C9
CYP3A4 Not Known CYP2C9 CYP3A4
Avoid
With or
without

At night
With or
after

Avoid
At night
With or
after

With or
without

With or
without

Avoid
At night
With or without

FLS = Take at bed time (night)


ALS = Avoid Grapefruit juice (Because grape fruit juice inhibit CYP 3A4)

Antihyperlipidimocs/Dyslipidimics/Antihypercholesteremia

Cholesterol

D
O
F

I
n
t
e
s
t
i
n
e

Bile acid
Liver

Resins

Prevent
reabsorption
of bile acids

VLDL
Liver
Adipose
TG
Free VLDL Tissue
Fatty
Acids
sue
Ti s

Insoluble complex excreted into feces

Blood
circulation

TG-chylomicron

LDL

LDL

Metabolism of Plasma lipoproteins

Niacin (Nicotinic acid)


Mechanism

Therapeutic use
Side Effects

Niacin also known as vitamin B3


Mechanism: participation in tissue respiration oxidation reduction
reactions, which decreases hepatic LDL and VLDL production
Inhibits tubular secretion of uric acid, causes gout or hyperuricemia
Antihyperlipidemics
TG reduction 20 50% (Higher dosage)
HDL increase 15 35% (Greatest HDL raising effect)
Intense cutaneous flushing accompanied by uncomfortable feeling warm
and pruritic
Hyperglycemia
Hyperuricemia
GI distress
Hepatotoxicity

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Management

No-flush prep

Antihyperlipidemics Drugs

Administration of aspirin prior to taking niacin decrease flush.


Take with food
Tolerance develops in 1 2 weeks
Higher dose 2g/day may produce hepatic damage
Contains Inositol + Niacin

Bezafibrate
Fenofibrate
Gemfibrozil
Decrease TG levels
Increase HDL levels (moderately)
Decrease LDL levels
Inhibit cholesterol synthesis
Fibric acid derivatives
Treatment of choice in hypertriglyceridemia + diabetic patients.
HDL increase 10 20%
TG decrease 20 50% (Effective for TG)
Mild GI disturbances.
Lithiasis: because these drug increase bilary cholesterol excretion
predispose gallstone formation.
Sever hepatic and renal dysfunction, potentiates warfarin activity.
Preexisting gall bladder disease.
Liver Function test
Creatinin Kinase
Complete Blood Count
Renal function test
At 3, 6 and 12 mo, and yearly
Combination with Statins may lead to rhabdomyolysis

Fibrates
Fibrates
Mechanism

Therapeutic use
Side Effects
Contraindication

Monitoring

Drug interactions

Resins
Resins
Mechanism

Therapeutic use

Cholestyramine
Colestipol
Prevents absorption of cholesterol.
Anion-exchange resins bind with the enzymes in intestine and inhibit
the synthesis of cholesterol. Bile acids are synthesized from cholesterol.
Decrease LDL 15 30%
Increase HDL 3 10%
No change or increase in TG (disadvantage)
Drug of choice in pregnancy
Cholestyramine also relieves pruritis caused by accumulation of bile
acids in patients with biliary obstruction in cholestasis

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Side Effects
Drug-Drug
interactions

Antihyperlipidemics Drugs

Decrease absorption of ADEK fat-soluble vitamins.


High doses of folic acid and ascorbic acid absorption is reduced.
Most common GI problem: constipation.
These drug interfere with intestinal absorption of many drugs
(tetracycline, Phenobarbital, warfarin, pravastatin, fluvastatin, aspirin,
and thiazide diuretics)

Ezetimibe (Zetia)
Mechanism
Therapeutic use
Side Effects

Advantage

Selectively inhibit the intestinal absorption of cholesterol and related


phytosterol.
Used in combination with statins (increasing dose of statins only
does not decrease LDL levels, hence combination Ezetimibe is
recommended).
GI effects: Abdominal cramps,
Liver problems
Sexual dysfunction
Weight loss
Does not affects fat soluble vitamins
Low potential for drug interactions

Antihyperlipidemic Drugs Tips
















Goal of antihyperlipidemic therapy is


FLS = only taken at night (at bedtime), for maximum effect.
Pravastatin and rosuvastatin have no drug interactions
Statins increase risk of arrhythmias at night
HMG Co A inhibitors are mainly metabolized by
HMG Co A inhibitors side effect rhabdomyolysis patient may notice by
Which antihyperlipedemic have no effect or increase triglyceride levels
Which antihyperlipidemics have equal proportion effect on LDL, HDL and TG
Resins act what part of GI
Hydrochlorothiazide effect on lipids include
ACE inhibitors effect on lipids include
CCB effects on lipids
Lovastatin is given with food because
DOC for cholesterol in DM patients
Normal levels of lipids: LDL = <2.2 mmol/L; HDL = >0.9 mmol/L; TG = <3.6 mmol/L; Total
cholesterol = 5mmol/L

Abbrevation and Terminology


VLDL
LDL
HDL

Very Low-Density Lipoprotein


Low-density Lipoprotein
High-Density Lipoprotein

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TG
CBC
HMG
LFT
CPK or CK
ADEK
DM
HMG

Antihyperlipidemics Drugs

Complete Blood Count


3-hydroxy, 3-methyl glutaric acid
Liver Function Test
Creatinin Kinase
Vitamin A, D, E and K
Diabees Mellitue
3- Hydroxy, 3- Methylglutaric acid

Generic and Brand


Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin
Simvastatin
Bezafibrate
Fenofibrate
Gemfibrozil
Cholestyramine
Colestipol
Ezetimibe

Lipitor
Lescol
Mevacor
Pravachol
Crestor
Zocor
Bezalip
Lipidil
Lopid
Questran
Colestid
Zetia

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Antihyperlipidemics Drugs

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Coronary Artery Disease

Coronary Artery Diseases


Types of angina
Stable angina

Unstable angina Exercise-induced Chronic angina

Prinzmetal angina
Or
Vasospastic angina

Nocturnal Angina

Coronary artery Diseases


The most common complications associated with Coronary artery disease include: Angina pectoris,
Myocardial infarction, post Myocardial infarction,and Ischemic stroke. Insufficient supply of oxygen
to heart can lead to Ischemic conditions.

Myocardial ischemia is usually caused by coronary vessel atherosclerosis (High LDL


and high cholesterol is the most common risk factor). As the vessel lumen narrows blood
flow is reduced.

Other causes that limit coronary blood flow include: Arterial thrombi and Spasm

Angina Pectoris
Angina are those symptoms of myocardial ischemia that occur when myocardial oxygen availability
is insufficient to meet myocardial oxygen demand.
These symptoms include:

Chest discomfort often described as heaviness, pressure, and squeezing. The sensation is
localized typically in the sternal region.

Symptoms often last one to five minutes. Angina can radiate to the left shoulder, to both arms
(ulnar surfaces of the forearm and hand), and can radiate to the neck, jaw, teeth, epigastrium and
back.

Types of angina
Angina Pectoris

Severe chest pain because of inadequate coronary blood flow to supply


oxygen demand.
Which is usually aggravated by exertion or stress and relieved by
nitroglycerine.
The most common form of IHD.

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Types of angina
pectoris

Stable angina or
classical

Unstable
angina/resting/
Crescendo

Nocturnal
angina (angina
decubitus)
Prinzmetal
angina
(vasospastic or
variant angina)

Coronary Artery Disease

Stable angina/ Classic angina (most common-90%)


Unstable angina
Exercise induced angina
Exertion angina
Chronic angina
Prinzmetal angina
Nocturnal angina
Mostly secondary to atherosclerosis (high LDL)
Due to obstruction in coronary arteries
More predictable
Precipitated by exertion or emotional stress or by heavy meal.
Relieved by rest or using nitroglycerines
The most serious one (worsening pain)
Thrombosis in a branch
Caused by formation atherosclerotic (disease of arteries, in fatty plaques
develop in inner wall), occurs at rest
ACE inhibitors are used as single treatment
Decreased response to rest and nitroglycerine
This angina occurs in the recumbent position and is not specifically related
to either rest or exertion
Nitroglycerine may relieve the paroxysmal nocturnal dyspnea
Coronary artery spasm that reduces blood flow precipitates this angina.
Secondary to coronary artery spasm
Usually occurs at rest (pain may disrupt sleep)
Calcium channel blockers are most effective
Drugs Used In Angina Pectoris

Vasodilators
Nitrates

Cardiac depressants

Calcium blockers, and ACE inhibitors


Nifedipine, Verapamil, Diltiazem

Short duration
Inhaled amyl nitrite
Sublingual
Nitroglycerine
Isosorbide dinitrite

Intermediate
Oral regular or sustainedrelease Nitroglycerine
Isosorbide dinitrite

-blockers
Proponolol
Long duration
Transdermal
Ntiroglycerine patch

Treatment of angina
The following beta-blockers are used in treatment of angina:
Beta-blockers with Selective Intrinsic Sympathomimetic Activity (ISA):
Acebutolol hydrochloride Beta-blockers with Non-ISA: Atenolol
and Metoprolol tartrate can be used.
Beta-blockers with Nonselective, ISA: Pindolol
Beta-blockers with Nonselective, Non-ISA: Nadolol, Propranolol hydrochloride,
Timolol maleate
Calcium Channel Blockers are used in treatment of angina:
Amlodipine besylate, Diltiazem hydrochloride, Nifedipine, Verapamil hydrochloride
The following Coronary Vasodilators, Nitrates are used in treatment of angina:
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Coronary Artery Disease

Nitroglycerin, Isosorbide dinitrate, Isosorbide-5-mononitrate.


Nitrates
Nitrites
Nitric oxide (NO)
Vascular smooth
muscle relaxation

cGMP

Dephosphorylation of
myosin light chain

Nitrates
Organic nitrates act primarily by vasodilation (especially venodilation), which reduces
myocardial preload and therefore myocardial oxygen demand.
Nitrates also promote redistribution of blood flow to relative ischemic areas.
Mechanism

Side effects

Storage
Conditions

Drug
interactions
Dosage forms

Vascular smooth muscle relaxation


Two major effects
Dilation of the large veins (resulting of pooling blood in veins this
reduces preload and decrease work of heart.
Dilates coronary vasculature, providing increased blood supply to the heart
muscles.
The Most common side effect is headache.
Higher doses: Postural hypotension, facial flushing and tachycardia.
Tolerancedevelops rapidly.
This can be overcome by using nitrate free period and restore sensitivity
to drug.
Amber color, glass and metal capped
Dispense in original container
Discard cotton present on tablets in bottle.
Drug expires after 6 months from the day bottle open.
Light sensitive, hygroscopic.
Cause hypotension with Sildenafil , Tadanafil, Verdanafil.
Additive hypotension effect
Nitroglycerine SL Acute
Nitroglycerine Pump Acute
Nitroglycerine Patch Maintenance

Nitrites
Therapeutic use
Side effects

DOC for hypertensive crisis


Cyanide toxicity (releases CN)
Sodium thiosulfite is an antidote
(Cyanide (Intermediate) + Sodium thiosulfite Sodium thiocyanate
(water soluble)
Photosensitive

Ca2+ channel Blockers


These agents are used to treat hypertension and are effective in treating angina as well. All muscles,
including the smooth muscle of the blood vessels, require calcium in order to contract. If the
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Coronary Artery Disease

calcium-channel blocking agents block the entrance of calcium into the muscle, the muscle will not
contract. This will allow themuscle to relax and subsequently reduce the blood pressure. Other
therapeutic uses: angina, migraine, antiarrhythmic.
Non
dihydropyridines

Diltiazem hydrochloride
Verapamil hydrochloride

Mechanism

Verapamil is similar to Beta blockers in effect


Verapamil can cause bradycardia
The effect on Heart is graded from higher to lower: verapamil >
diltiazem > nifedipine
Verapamil avoid using in CHF (cause ve inotropic effect) and
constipation
Dihydropyridine
Nifedipine
Felodipine
Amlodipine
Nicardipine
Nifedipine is similar to Nitrate in effect (Peripheral decrease afterload,
dihydropyridine can cause tachycardia.
Dihydropyridines Relax and dilating arteries. The effect on vascular smooth
muscles is high with dihydropyridine: nifedipine > diltiazem > verapamil
Comparison of dihydropyridine and Non-dihydropyridine
DHP

NDHP

Cause Reflex tachycardia


Cause Bradycardia
No heart blockade
Cause Heart blockade
Peripheral vasodilation
Myocardial vasodilation
Amlodipine long half-life
Negative (-ve) inotropic
(Only amlodipine does not cause
effect (worsening CHF)
reflex tachycardia)
Can be used in asthma
Avoid CYP3A4 Inhibitors/Inducers (GFJ)

Diltiazem
Veropamil
Av conducting
decrease
Coronary Dilatation

Side effects: flushing, profound low blood pressure, swelling of legs and feet, constipation and
stomach upset. If edema (swelling) of the legs and feet occur, a diuretic may be added to the
regimen.

Nifedipine (Adalat)
Mechanism
Therapeutic use
Side Effects

A calcium blocker which interfere with conduction of signals in the


muscles of the heart and vessels.
Given regularly to prevent Angina attacks.
Reduce high blood pressure and is often helpful in improving
circulation to the limbs in disorders such as Raynauds disease.
Blood pressure will fall too low and sometimes causes heart rhythm.
Tachycardia, flushing, headache, dizziness, Orthostatic hypotension,
and edema

Amlodipine (Norvasc)
Mechanism

A calcium blocker which interfere with conduction of signals in the


muscles of the heart and vessels.

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Therapeutic use
Side Effects

Coronary Artery Disease

Angina and Chest pain


Can be safely used by asthmatic and non-insulin-dependent
diabetic.
Blood pressure may fall too low
Sometime may cause mild to moderate leg and ankle swelling

Diltiazem (Cardizem)
Mechanism
Therapeutic use
Side Effects

A calcium channel blocker that interfere with the conduction of


signals in the muscles of the heart and blood vessels.
Angina
Longer acting formulations are used to treat high blood pressure
Usually well tolerated, occasional hypotension or orthostatic
hypotension, flushing, arrhythmia, and bradycardia. Use with
caution in patient with CHF

Myocardial Infarction (Heart attack)


Mechanism
Drug of Choice
for Acute coronary
syndrome

ASA

Post MI

Myocardial ischemia is usually caused by coronary vessel


atherosclerosis. As the vessel lumen narrows blood flow is reduced
Acute MI b-blockers, ACE, CCB,
Prophylaxis (prevention) ASA (60-81 mg/day), Nitroglycerine
Severe chest pain Morphine
AnticoagulantsHeparins, LMWH,
Warfarin
AntiplateletsAspirin, clopidogrel,
ticlopidine
Coronary arteries
A = Analgesics
Zone 1: Necrosis
A = Antipyretics
Zone 2: Injury
A = Antiinflammatory
Zone 3: Ischemia
A = Antiplatelets (60-81 mg/day)
Myocardial infarction(MI)
Aspirin decrease morbidity and mortality
No CCB
Thrombolytic used for coronary perfusion, eg: streptokinase
Also Glycoprotein IIB, IIIA inhibitors such Tirofiban can be used

STEMI treatment: ASA, Beta-blockers, Nitrates, CCB, Thrombolytics


NSTEMI treatment: ASA, Beta-blockers, Nitrates, Heparin

Coronary Artery Disease Tips









Nitroglycerine spray storage and administration


Nitroglycerine SL storage condition require
Light sensitive
Nitrates should be avoid taking with
What is active moiety of nitrates
Nitroglycerine is chemically classified as
Nitroglycerine + seldanafil can cause hypotension and this due to nitroglycerine and seldanafil.
The most common side effect of nitroglycerine is headache; therefore nitroglycerine should be

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Coronary Artery Disease

taken while sitting position.


Nitroglycerine patch can cause tolerance, to avoid tolerance use nitrate free period.
What drugs effective in MI prevention and treatment
What drugs should be avoided in MI
Severe chest pain associated with MI treated by
STEMI
NSTEMI
At what dose ASA act as Antiplatelet
ASA act as irreversible Antiplatelet drug
Nitrates Increase nitrites Increase Nitric oxide (NO) vascular smooth muscle relaxation

Abbrevation and Terminology


LDL
IHD
SL
CN
CCB
MI
ACE
ASA
STEMI
NSTEMI

Low-density Lipoprotein

Angiotensin-Converting Enzyme
Acetyl Saliaylate
ST-Segment Elevation MI
non-ST-Segment Elevation MI

Generic and Brand


Verdanafil
Sildenafil
Tadanafil
Nitroprusside

Levitra
Viagra
Cialis
Nitropress

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Coronary Artery Disease

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Coronary Artery Disease

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Congestive Heart Failure

Congestive Heart Failure (CHF)


Drugs Used to treat Congestive Heart Failure
Vasodilators

Positive inotropic drugs

Cardioic
glycosides
Digoxin
Digitoxin
Quabain

-agonists,
Dobutamine
PDE inhibitors
Amrinone

ACE inhibitors
Captopril
Enalapril
Lisinopril

Nitrates,
Nitroprusside,
Hydralazine,
PDE inhibitors
Milrinone

Congestive heart failure is characterized by reduced cardiac output so that the heart is not able to
pump sufficient oxygenated blood strongly enough to reach the tissues. The heart beat is weak and
rapid and the heart muscles may hypertrophy (grow larger) to compensate for reduced cardiac output.
Atrial fibrillation occurs when the atria beat rapidly and out of sequence.
Cardiac Heart failure due to:
Increased sympathetic activity
Fluid retention (edema)
Decrease in heart muscle contractility
Due to negative (-ve) inotropic effect
Due to +ve chronotropic effects
Left systolic dysfunction
Left sided failure (systolic failure)
This is the most common type of heart failure, Often due to hypertension. Due left ventricular
(systolic) dysfunction leads to pulmonary edema; Symptoms: SOB (Dyspnea), Wheezing. Can be
treated by ACE I, and beta blockers (rarely in chronic), only carvedilol (1, 2 and 1).
The Most common etiology of left sided heart failure is:
Due to impaired pumping ability of the heart
Usually occurs in Left ventricular ejection fraction
May be present without CHF
Ejection fraction is lower than 35%, it is Left ventricular dysfunction (systolic failure)
Right Sided Heart failure (diastolic failure)
Due to chronic lung disease, Diastolic filling is impaired this can leads to peripheral edema.
Symptoms: edema in veins, legs, bowel. Diuretics or Dihydropyridine CCBs treats right-sided
heart failure.
Ejection fraction is greater than 45%, it is Right ventricular dysfunction (Diastolic failure)

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PP
B

CO

Congestive Heart Failure


Renin
&
Angiotensin II

Renal Blood Flow

CHF
Aldosterone

Venous
Pressure
Capillary
Filtration

Na/H2O retension

EDEMA

The Treatment of Congestive Heart Failure (CHF)


The treatment of congestive heart failure may include: diurectics to reduce the back-up of fluids
in the lungs an the rest of the body; vasodilators that decrease vacular resistance and help improve
circulation through the heart; ACE inhibitors to improve cardiac function an y may slow the
progression of CHF and Angiotensin II AT1 receptor antagonists.

Cardiac glycosides
Mechanism

Positive Inotropic
effect
Negative
chronotropic effect
Vagomimetic effect
Side effects

Digoxin, digitoxin, Ouaban


Cardiac glycoside increase myocardial contractility ad efficiency
Improve systemic circulations
Improve renal perfusion
Reduce edema
Inhibit the membrane bound Na+/K+ activated ATPase
Increase intracellular sodium concentration
Reduce calcium transport form cell
Facilitate calcium entry via voltage gated membrane channel
Increased vagal tone of the (SA) node
Reduced CNS sympathetic out flow
Systemic arteriolar and venous constriction
Increased vagal tone of the sinoatrial (SA) node.
Early stages of toxicity:
GI: Anorexia, nausea & vomiting and diarrhea
CNS: Headache, visual disturbances (green and yellow vision) Confusion,
neuralgia, delirium

Digoxin (Lanoxin)
Digoxin

Bioavailability

Therapeutic use

Digoxin is the most widely used


cardiac glycoside
Dont confuse with digoxin with
doxepin, Desoxyn, or digitoxin.
75% bioavailability, 20-40% protein
bound
T1/2 = 40 hr
Urinary excretion
CHF, Atrial fibrillation, protects ventricles

[K]i

Inhibits (slows)
Na/K ATPase

K
Na/K
ATPase

Na
[Na]i
Na/Ca
X-ch

Na Reduced Na
gradient slows
Ca removal

Ca
Digoxin Mechanism of Action

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Side effects

Congestive Heart Failure

1st sign: GI effects: Nausea, vomiting,


diarrhea, Blurry yellow vision,
scotoma.
CVS Arrhythmias, ventricular
tachycardia
CNS visual disturbances
(blurred vision)
Patient should understand the
importance of follow up laboratory
test for this medication;
Pulse
ECG
Adjust the dose with renal failure
patients
Do not take extra dose if dose missed.
Use same brand consistently.
Avoid high dose sodium medications
Do not take with high fiber food; fiber
diet may reduce digoxin absorption.

Monitor

Counselling

Increased force of contraction

Increased ejection of blood

Decreases and systolic volume

Decreases wall tension

Improves Oxygenation

Digoxin mechanism of action


Electrolyte rearrangement
(Mechanism)

Increased Vagal tone


(Mechanism)

Inotropy
(Desired)

Tachyarrhythmias
(Side effect)

Bradyarrhythmias
(Side effect)

Ca i
Heart Rate
(Desired)

Digitalis toxicity
Digitalis
toxicity

Predisposing
factors

Toxicities of digoxin
increased by renal failure
(decrease excretion)
Hypokalemia, or
hyperkalemia (potentiates
drug effect)
Hypothyroidism, hypoxia,
renal failure and myocarditis
also predisposing factors for
digitalis toxicities.

Drugs that cause digitalis toxicity


Drugs that digoxin
levels
Amidorne
Verapamil
Erythromycin
Tetracyclin
Quinidine

Drugs that K+
levels
Thiazides
Loop diuretics
Corticosteroids

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Digitalis
toxicity
Management

Antidote

Digitalis toxicity: Reduced


potassium levels
Digitalis toxicity can be
managed by: discontinue
digoxin, monitor blood
potassium levels. Sever
tachycardia may require
the use of FAB antibodies.
Which bind to inactive
digoxin
Digifab

Congestive Heart Failure


Comparison of digoxin and digitoxin
Digoxin
Digoxin has advantage
of a relatively short
half-life, which allows
better treatment of
toxic reactions.

Digitoxin
Binds strongly to
proteins extravascular
space, resulting in
large volume of
distribution.

Rapid onset of action.

Slow onset of action

Digoxin eliminated
largely unchanged in
urine

Extensively
metabolized by liver
before it excrete in
feces.

CHF Tips






Left ventricular heart failure cause


Right ventricular heart failure cause
DOC for CHF
Digoxin pharmacological action include
Comparison of digoxin and digitoxin, which is short acting and why
Digoxin antidote
Signs of digoxin toxicity

Abbrevation and Terminology


CHF
ACE
CCB
CNS
SA
ECG
CVS

Congestive Heart Failure


Angiotensin-Converting Enzyme
Calcium Channel Blocker
Central Nervous System
Sinoatrial
Electrocardiograph
Cardiovascular System

Generic and Brand


Amidorne
Verapamil
Erythromycin
Tetracyclin
Quinidine
Digoxin
Digitoxin
Ouaban

Calan, Calan SR, Covera-HS, Isoptin,Isoptin


Emtet, Panmycin, Sumycin, Sumycin
Quin-Tab, Quinadure, Quinaglute, Quinidex
Lanoxin
Crystodigin

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Antiarrhythmic Drugs

Anti Arrhythmic Drugs


Antiarrhythmic Drugs Classification

Class II
-blockers
Esmolol
(Propranolol)
Timolol
Atenolol
Metoprolol
Nadolol

Class I
Ia-Na+ channel
blockers
Quinidine
Procainamide
Disopyramide
Amiodarone
Ib: Lidocaine
Mexiletine
Tocainide
Ic: Flecainide
ropafenone

1a
1b
1c
II
III
IV

Arrhythmias

Class III
K+ channel
inhibitors
Amiodarone
(Cordarone)
Bretylium
Dofetilide
Sotolol

Na+ channel blocker


Na+ channel blocker
Na+ channel blocker
Beta blockers
K+ channel blockers
Ca2+ channel

Class IV
Ca 2+ channel
blockers
Verapamil
Diltiazem
Nifedipine
(Procardia, Adalat)

Miscellaneous
Adenosine
Magnesium

Slows phase 0 depolarization


Shortens phase 3 repolarization
Significantly slow phase 0 depolarization
Decrease phase 4 depolarization
Prolong phase 3 repolarization
Shortens action potential

Arrhythmias develop because of abnormal impulse generation, propagation or both.


Cardiac arrhythmias are related to abnormal electrical activity within the heart resulting in either
altered rhythm or impulse conduction.
Dysrhythmiadisturbed heart rhythm
Arrhythmia absence of rhythm
Bradycardia - a heart rate that is lower than normal (<60 beats/min).
Tachycardia - a heart rate that is higher than normal (> 100 beats/min).
Paroxysmal - an arrhythmia that suddenly begins and ends (may occur with fever)
Sinus bradycardia - low sinus rate <60 beats/min (between the pacemaker and atria).
Sinus tachycardia - high sinus rate of 100-180 beats/min as occurs during exercise or other
conditions that lead to increased SA nodal firing rate.
Atrial flutter - sinus rate of 250-350 beats/min.
Sick sinus syndrome - a disturbance of SA nodal function that results in a markedly variable
rhythm (cycles of bradycardia and tachycardia).
Atrial tachycardia - a series of 3 or more consecutive atrial premature beats occurring at a
frequency >100/min; usually due to abnormal focus within the atria and paroxysmal in nature.
This type of rhythm includes paroxysmal atrial tachycardia (PAT).
Atrial fibrillation uncoordinated atrial depolarizations.
Junctional escape rhythm - SA node suppression can result in AV node-generated rhythm of 4060 beats/min (not preceded by p-wave).
AV nodal blocks - a conduction block within the AV node (or occasionally in the bundle of His)
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Antiarrhythmic Drugs

that impairs impulse conduction from the atria to the ventricles.


Types of pacemakers
Natural (main) pacemaker of heart
SA node
Latent pacemaker of heart
AV node
Bundles of His
Purkinje fibers
Pulse direction: SA node AV node His Purkinje fibers
Supraventricular arrhythmias (SVA)arrhythmias develops above the bundles of His
Ventricular arrhythmias (VA)-->develops below the bundle of His
Types of arrhythmias
Supraventricular (atrial) SVA
Premature atrial contraction
Atrial flutter
Atrial fibrillation
Paroxysmal supraventricular tachycardia (PSVT)
Sinus tachycardia
Sinus bradycardia
Ventricular arrhythmias (VA)
Premature Ventricular Contraction (PVC)
Ventricular tachycardia (VT)
Ventricular fibrillation (VF)

Heart blockade:
The electrical impulses are partially or fully blocked between the atria and the ventricles. The SA
node in the right atrium fires at the normal rate, but the rate at which the ventricles contract (pulse
rate) depends on how many impulses get through to the ventricles.
Three types:
1st degree ---blockage of pulsation
2nd degree ----blockage of pulsation
3rd degree---complete heart block
First-degree heart block means there is a slight delay in each impulse going from the atria to the
ventricles. But, each impulse does get through and the heart rate is normal.
Second-degree heart block means that some impulses from the atria are not conducted through to
the ventricles. The rate that the ventricles contract can then be slow.
Third degree or complete heart block means that no impulses are conducted through. The
ventricles then contract at their own intrinsic rate of about 20-40 beats per minute. So, you have a
very slow pulse.
Myocardial Action Potential Curve
Myocardial action potential curve reflects action potential, which describe electrical activity of five
phases.
This occurs in atrial and ventricular myocytes and Purkinje fibers

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Antiarrhythmic Drugs

Phase 0: Rapid Depolarization: Na+ enters the cell


All Class Ia drugs
Phase 1: Early rapid repolarization: K+ leaves the cell
Phase 2: Plateau: Ca2+ enters the cell
Phase 3: Final rapid repolarization: K+ pumped out
of the cell
Phase 4: Slow depolarization: K+ inside the cell and
Na+, Ca2+ out side the cell
Phase 1 to starting phase 3 is Absolute refractor
Period or Effective refractory period The cell
cannot respond to any stimuli
During Phase 3 is relative refractory period The
cell ability to respond stimuli increases or cell can
respond to strong stimuli

Myocardial action potential curve

Torsade de pointes
A problem in one of the ion channels can prolong the Q-T interval. A prolonged Q-T interval can
increase risk for a type of arrhythmia called torsade de pointes. When torsade de pointes occurs,
heart cannot pump enough oxygen-rich blood to the rest of body, especially your brain. Torsade de
pointes can also lead to ventricular fibrillation, a dangerous form of arrhythmia that causes rapid,
uncoordinated contractions in the muscle fibers of the ventricles. With ventricular fibrillation, the
heart cannot pump oxygen-rich blood to the rest of the body, which can lead to death.
Drugs and diseases that can lead to QT-prolongation
Phenothiazines and haloperidol antipsychotics
Type III antiarrhythmic drugs
In patients with hepatic failure.
Electrocardiograph Wave Forms
The electrical activity occurred during depolarization and
repolarization transmitted through electrodes attached to
the body and transformed by an electrocardiograph (ECG)
in to series of waveforms;
P WAVE: indicated atrial depolarization
PR INTERVAL: indicates the spread of the impulse from the atria through Purkenje fibres.
QRS complex: indicates ventricular depolarization
ST segment: indicates phase 2 of the action potential- the absolute refractory period.
T wave: shows phase 3 of the action potential-ventricular repolarization.
Q-T interval mechanical contraction of the ventricles (Torse de pointes)
U wave caused by hypokalemia

Arrhythmias Treatment
Class I
Class Ia

Quinidine decrease 50% digoxin, SE:Torsades de pointes


Procainamide SE:Torsades de pointes
Disopyramide SE:Torsades de pointes

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Class Ia

Therapeutic use
Class Ib

Therapeutic use
Class Ic

Therapeutic use
Class II
Beta blockers

Therapeutic use
Class III
K+ channel
blockers

Class IV
Ca2+ channel
blockers
Therapeutic use
Digoxin

Therapeutic use

Antiarrhythmic Drugs

Pharmacological action;
Slow the phase 0 (slow entry of Sodium ion)
Prolong re-polarization
Prolong effective refractory period
Indicated to treat SVT, VT
Lidocaine
Tocainamide
Mexiletine
Pharmacological action:
Minimal effect on Phase 0 Slow phase III repolarization (decrease K
pump out)
Indicated to treat VT, VA
iv Lidocaine: used to treat cardioversion related arrhythmias
Encainide,
Propafenone decrease 25-50% digoxin
Flecainide
Pharmacological action:
Very effective on slowing phase 0 depolarization
Little effect on repolarization
Indicated to treat VA
Propranolol
Atenolol
Timolol
Pharmacological action:
Competitively block catecholamine induced stimulation of Beta
receptor thereby
Suppress phase IV depolarization
Indicated to treat AT, SVT, VT, VA
Amiodarone blue skin, photosensitivity, photophobia
Bretylium
Sotalol
Prolong Phase III repolarization (Prolong QT interval)Torose de
pointes
Indicated to treat VA
Verapamil
Diltiazem
Nifedipine
Pharmacological action: Shortens action potential
Indicated to treat SVA, VA
Pharmacological action: Effects vagotonic response (vegomimetic)
thereby increases AV nodal refractoriness.
It is contraindicated in ventricular fibrillation.
Ventricular tachycardia may result from digitalis toxicities
Indicated to treat SVA (atrial arrhythmias) only
Contraindicated in ventricular arrhythmias

Quinidine (Quinaglute)
Mechanism

Binds to sodium activated channels


Inhibits ectopic arrhythmias, VA

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Antiarrhythmic Drugs

Therapeutic use

Drug-Drug

interaction



Side Effects

Counselling

Atrial, AV junctional, and ventricular tachycardia.


Maintain sinus rhythm after direct atrial flutter or fibrillation.
Antihypertensive, Anticoagulant Quinidine may increase the effects of
these
drugs.
Phenobarbital and Phenytoin reduce the effect of quinidine
Digoxin-Quinidine increases the effects of digoxin (decrease 50% digoxin
dose).
SA and AV block or asystole, nausea, vomiting, diarrhea (cinchonism-large
doses-blurred vision, tinnitus, headache, disorientation and psychosis. Torsos
De pointes (VA)
Toxic levelinduce ventricular tachycardia.
Increases steady state concentration of digoxin by displacing PPB
Report tinnitus, blurred vision immediately
Avoid concurrent use of aluminum containing antacids
Keep out of reach of children
Administer after meal to minimize gastric distress
Dont crush tablets because drug irritates mucosa.

Procainamide (Pronestyl)
Mechanism
Side Effects

Binds to sodium activated channels


Chronic use: lupus like syndrome (25-30%), toxic levelsasystole or
induction of VA.
GI intolerance is less than quinidine.
CNS- depression, hallucinations and psychosis.

Amiodarone (Cordarone)
Therapeutic use

Side effects (4P)

Counseling

Amiodarone is structurally related to thyroxine, and it contains iodine.


1. DOC antiarrhythmic & recommended in more severe LVD & if CI with / BB
2. IV Amiodarone effec-tive in terminating VT, more so in preventing
recurrence
3. Most effective for thx in electrical storm
4. Usually used as an empiric therapy
Respiratory: Pulmonary, including intererstitial pneumonitis; Respiratory
muscle impairment
GI: nausea, anorexia, constipation; hepatitis and cirrhosis;
Hypothyroidism; hyperthyroidism; Amiodarone inhibit peripheral conversion
of T4 to T3
Blue skin color (pigmentation), corneal deposits, hepatic toxicity, optic neuritis,
erectile dysfunction, photophobia
Avoid exposure to sunlight, use sunscreen
Avoid grapefruit juice

Digoxin (Lanoxin)
Therapeutic use
Contraindicated

Atrial arrhythmias
Ventricular fibrillation and hypokalimic patients

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Counseling

Antiarrhythmic Drugs

May be taken with or without food


Meals w/ bran fiber, antacids may reduce amt of drug absorbed
Store between15-25 C in a tight container and protect from light

Antiarrhythmic drugs Tips








What phases of action potential curve have no effect of stimuli


Relative refractory period is
Phase I action potential is 40 (+ve) due to
What drug cause QT prolongation (torse des pointes)
Digoxin is contraindicated in what type of arrhthmias
Patient taking digoxin, the prescription is expired what will you do?
Amiodorone side effects are: Photosensitive reactions, skin pigmentation, Blurred vision.
Pulmonary toxicity, Pneumonitis.

Abbrevation and Terminology


SVA
PSVT
VA
VT
SVT
SA
AV
PVC
ECG
PPB
LVD
BB

Supra Ventricular Arihythmias


Paroxysmal SupraVentricular Tachycardia
Ventricular Arihythmias
Ventricular Tachycardic
Supraventricular tachycardia
Premature ventricular contraction
Electrocardiograph
Beta Blocker

Generic and Brand


Amiodarone
Digoxin
Procainamide
Disopyramide
Encainide
Ropafenone
Digoxina
Quinidine
Procainamide
Flecainide

Cordarone
Lanoxin
Procaine SR
Norpace CR
Enkaid
Rhythmol
Lanoxin
Quinaglute, Quinidex
Pronestyl, Procan, Procanbid
Tambocor

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Anticoagulants

Anticoagulants
Anticoagulants

Antithrombin III

Mucopolysaccharide

Vitamin K
analogue

Protein C

Endogenous
Anticoagulant
LMWH

Warfarin
Heparin

Intrinsic Pathway
Damaged surface

Extrinsic Pathway

Kininogen,Kallikrein
Xll

Trauma

Xlla

Xl a

Xl
lX

Prothrombin (ll)

Tissue factor

Va

Trauma

Xa

Final
Common
Pathway

Vll

Vlla

lXa
Vllla

Thrombin (lla)

Fibrinogen (l)

Fibrin (la)
Xllla

Cross-linked
fibrin clot

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Anticoagulants

Heparin
Mechanism

Therapeutic use
Drug-Drug
interaction
Side Effects
Contraindications
Monitoring

Advantage

Binds to the antithrombin III (also known as heparin cofactor) to cause a


rapid anticoagulation effect.
Heparin catalyzes the factor (thrombin activation factor) 2a, 9a, 10a,
11a, 12a, and 13a.
Major antithrombotic drug for DVT and pulmonary embolism. To
prevent postoperative venous thrombosis in-patient undergoing surgery.
Maximum effect occurs within minutes
Do not take ASA, which may increase the anticoagulant effect of this
drug and the risk of bleeding in the intestines or joints.
Hypersensitivity reaction (chills, fever, urticaria etc),
Bleeding
Heparin induce Thrombocytopenia
Heparin Anticoagulation Mechanism
Alcoholics
Bleeding disorders
Without Heparin
With Heparin
clotting factors
Active clotting factors
Brain, eye, spinal chord surgeries. Active
IIa, IXa, Xa, XIa, XIIa, XIIIa IIa, IXa, Xa, XIa, XIIa, XIIIa
Periodic blood and liver test
will be required
Anti-thrombin III
Rapid Anti Thrombin III
Slow
& Heparin
aPTT (activated Partial
Thromboplastin Time)
after 6 hours of initiating heparin.
Inactive factors
Inactive
Heparin Assay
Can be used in pregnancy
2,9,10,11,12,13

Low Molecular Weight Heparin (LMWH)


LMWH
(Low Molecular
Weight Heparin)
Mechanism
Therapeutic
Monitoring
Side effects

Enoxaparin
Dalteparin
Tinzaparin
Ardeparin
LMWH are not interchangeable with heparin in their actions and
use. Because these highly acidic. These administered parenterally as
sodium salt. Because poorly absorbed from GI tract.
The prevention of DVT or PE
Does not change Prothrombin Levels
Act longer and do not require close blood monitoring as Heparin does
Hypersensitivity reaction (chills, fever, urticaria etc),
Bleeding
Heparin induce Thrombocytopenia
Osteoporosis

Warfarin (Coumadin)
Mechanism

Vitamin K antagonist producing


their anticoagulant effect
by interfering with cyclic
interconversion of vitamin K and it
2,3-epoxide (vitamin K epoxide).
Inhibition of K-dependent proteins
or clotting factors (prothrombin or
factors 2, 7, 9 and 10)

War farin
Vitamin K epoxide reductase
Polypeptides Vitamin K
O

CO2
HOOC
NH2
Precursor of clotting Factors
II, VII, IX, X

VitaminK epoxide
O
HOOC

COONH2

Active Clotting Factors


II, VII, IX, X

Warfarin effects in 8-12 hours Vitamin K takes 24 hours to be effective

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Therapeutic

Drug-Drug
interactions

Side Effects
Monitoring

Antidote

Anticoagulant used to prevent


blood clots, mainly in areas where
blood flow is slowest, particularly
in the leg and pelvic veins.
A wide variety of drugs, such
as ASA, barbiturates, oral
contraceptives, cimetidine,
diuretics, certain laxatives, certain
depressants, and certain antibiotics
interact with warfarin, either by
increasing or decreasing the anti
clotting effect.
Bleeding, Purple toe syndrome,
Skin necrosis
PT (Prothrombin Time) ratio and
INR (International Normalized
Ratio) are performed daily upon
starting warfarin.
Oral anticoagulant therapy Warfarin
INR should be between 2 - 3
Vitamin K

Anticoagulants

ASA & NSAID


Acute alcohol
Cotrimoxazole

Metronidazole
Phenylbutazone

Warfarin

INR

Due to decrease
synthesis of clotting
factor
Cefamindole
Cefaprazone
Cefatetan
Cefametazole

Due to additive
effects
Heparin
LMWH

Thrombolytic
agents

Comparison of heparin and warfarin


Heparin
Warfarin
Source:
Natural
Synthetic
Route

Parenteral

Oral (recently IV)

Mech

Enhances the
serum protease
antithrombin
III results in
inactivation of
fators IIa, IXa, Xa,
XIa, XIIa, XIIIa
Protamin sulfate

Inhibits the hepatic


synthesis of vit K
dependent factors
II, VII, IX, X

Antidote
Site of
action

In vitro, In vivo

Vitamin K,
phytanadione
In vivo only (liver)

Onset of
Faster (minutes)
Slower (6-8 hours)
action
Pregnancy Yes
NO (Terotogenic)
Protamine sulfate: Works by acid base neutralization

INR
Warfarin

Chronic
alcohol
Barbiturates
Rifampin
Vitamin K

Dark green
Vegetables

Anticoagulant Practice Tips







Heparin antidote
Patient taking heparin monitored for
Heparin action include
What is the safest anticoagulant in pregnancy
What are the factors heparin inhibits
Monitor warfarin through

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Anticoagulants

What do you monitor in LMWH


Vitamin K supplements and green vegetable effect on INR by
Increase in INR can increase risk of
Heparin antidote action is due to
If patient taking warfarin and INR is 4 5, what is appropriate recommendation
ASA interact with warfarin by
Warfarin act on what factors
Patient after 2 days, air flight, reports pain on his legs. His medical history includes, DVT and
currently using warfarin
Recurrance of Heparin induced Thrombocytopenia syndrome can be prevented by using

Abbrevation and Terminology


DVT
ASA
LMWH
PE
PT
INR
TIA
STEMI
MI
aPTT
NSAID

Deep Vein Thrombosis


Acetyl Saliaylate
Low Molecular Weight Heparin
Pulmonary Embolism
Prothrombin Time
International Normalized Ratio
Transient Ischemic attack
ST-Segment Elevation MI
Myocardial Infarction
activated Partial Thromboplastin Time
Nonsteroidal Anti-Inflammatory Drug

Generic and Brand


Digoxin
Heparin
Warfarin

Digitek, Lanoxicaps, Lanoxin


Hemochron, Hep-Lock, Hep-Lock U/P, Heparin, HepFlush-10,
Coumadin, Jantoven

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Antiplatelet Drugs

10

Antiplatelet Drugs
Antiplatelet Drugs

ASA

Dipyridamole

Ticlopidine
&
Clopidogrel

Glycoprotein
inhibitors
Eptifibatide
Tirrofiban

Prostaglandin
analogs
Epoprostenol

Platelets, of the elements of blood cells, tend to clump together. The following drugs interfere with
the coagulation by inhibiting platelet aggregation. Heart attacks and strokes occur when a blood
clot that forms in a narrowed portion of an artery blood flow and cuts off the supply of oxygen and
nutrients to the tissue that lies beyond the site of the clot.
ASA (Salicylates)
Clopidogrel
Ticlopidine
Theonopyridine
Dipyridamole
Dipiperdino-dinitro pyrimidine
Fab fragments of human monoclonal antibody to the Glycoproteine (GPIIb/IIIa) receptors
(Abciximab, tirofiban, eptifibatide).

Ticlopidine (Ticlid)
Mechanism
Therapeutic use
Side effects
Contraindications

Storage conditions

Dosage

Antiplatelet (to prevent blood clot)


Reduce thrombotic risk in-patient who cannot use aspirin.
Hemorrhagic: complications such as bruising or ecchymosis, epistaxis
Presence or history of hematopoietic disorders (such as neutropenia,
thrombocytopenia or agranulocytosis);
Hemorrhagic diathesis or presence of hemostatic disorder;
Conditions associated with active bleeding, such as bleeding peptic ulcer
or intracranial bleeding; severe liver dysfunction.
Store at room temperature. Dispense in light-resistant containers. Blister
packs should not be exposed to light
The recommended dose is 250mg twice daily with food.

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Food and drug
interactions

Antiplatelet Drugs

Ticlopidine should be taken with meals to minimize GI intolerance.

Clopidogrel (Plavix)
Mechanism
Therapeutic use
Side Effects
Drug-Drug
interaction
Contraindication
Monitoring

An antiplatelet drugs that is used to prevent blood clots from forming.


It reduces the tendency of platelet to stick together when blood flow
disrupted.
Drug of choice for Transient Ischemic attacks (TIA), and stroke.
Bruising and nosebleeds
Increase the effects of ASA in platelets, as will the risk of GI bleeding
when Clopidogrel is taken with ASA and other NSAIDs.
Not recommended with infants and children
Bleeding

Antiplatelet summary
Drug of choice in STEMI
Patient cannot take aspirin due stomach ulcers for MI prophylaxis, what is an alternate drug
of choice
If patient is allergic to aspirin what is alternate drug
Drug of choice for transient Ischemic attack (TIA)
What is the effect of aspirin on warfarin
What dose of aspirin act as Antiplatelet

Abbrevation and Terminology


ASA
TIA
NSAID

Acetyl Saliaylate
Transient Ischemic attack
Nonsteroidal Anti-Inflammatory Drug

Generic and Brand


Ticlopidine
Clopidogrel

Ticlid
Plavix

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Thrombolytic Drugs

11

Thrombolytic Drugs
Thrombolytic Drugs

Streptok inase
(Strepto protein from
Group C-B-hemplytic
steptococci bacteria

tissue
plasminogen
activator tPA
Clot selective
Mechanism




Therapeutic

Side Effects

Anistreptase (Aminase)
Prodrug of streptokinase

Uro k inase
(Abbokinase)

t-pa
(tissue type
plasminogen activator)
Alteplase (activase)
Directly degrade
Reteplase (Retevase)
fibrin and
very high affinity to
fibrinogen
plasminogen, bound to
thrombus

Alteplase
Reteplase
Tenecteplase
Streptokinase
VIIa
Blood
Urokinase
IX
X
Anistreplase
Xa
X
Prothrombin (II)
Thrombin IIa
Facilitate conversion of
plasminogen to plasmin that
Thrombolytics:
XII
Streptokinase
subsequently hydrolyzes fibrin
Urokinase
to dissolve clots
Alteplase
Fibrinogen
Recombinant DNA derivatives
Catalyzation
of tissue plasminogen activator
(tPA).
Plasminogen
Plasmin Fibrin (Soluble)
They contain 527 and 355 amino
XIIa
acids of natural tPA.
Fibrin degradation product
Fibrin (insoluble)
tPA catalyzes the conversion of
Site of injury
plasminogen to plasmin.
Acute MI and acute massive
pulmonary embolism (PE), DVT
Hypersensitivity reactions
Internal GI bleeding, retroperitoneal
bleeding, superficial bleeding at catheter injection site.
Nausea and vomiting

Streptokinase (Streptase)
Mechanism

An enzyme produce by streptococcus bacteria.


Dissolve the fibrin of blood clots, especially those in the arteries of the
heart and lungs.

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Therapeutic use
Drug-Drug
interactions
Side Effects

Monitoring

Thrombolytic Drugs

Acute coronary syndrome


Deep vein thrombosis (DVT), Pulmonary Embolism (PE)
There is an increase bleeding when anticoagulants are taken at the same
time as streptokinase.
Can produce allergic reactions (urticaria) Give antihistamine before
starting the treatment.
Excessive bleeding
Branchospasm
Angioneurotic edema
Headache
Dont give second streptokinase within 6 months of the First treatment.

Urokinase (Abbokinase)
Mechanism
Therapeutic use
Side effects

Two-chain serine protease obtained from cultured human kidney cell.


Coronary artery thrombosis, Pulmonary embolism.
Allergic reactions may lead to bronchospasm and skin rash

Anistreplase (Eminase)
Mechanism
Therapeutic use

APSAC (Anisoylated plasminogen streptokinase activator complex)


It is a complex of human lys-plasminogen and streptokinase with anisoyl group
blocking catalyst site.
Acute MI, coronary artery emboli lysis

Thrombolytics Tips
t-PAs are
DOC for ST segment elevation myocardial infarction (STEMI)
Embolus

Abbrevation and Terminology


APSAC
DVT

Anisoylated plasminogen streptokinase activator complex


Deep Vein Thrombosis

Generic and Brand


Streptokinase
Urokinase
Anistreplase

Streptase
Abbokinase
Eminase

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Antidepressants

12

Antidepressants
Classification of Antidepressants

Monoamine Oxidase (MAO)


Inhibitors
Irreversible MAO
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Isocarboxazid
Clorgyline
Reversible MAOI (RIMA)
Moclobemide

Amine reuptake
inhibitors drugs

Non-selective
5HT, NE, D

5HT, NE

Dual action

Tricyclics (TCAs)

SNRI
Venlafaxine

Tertiary amine type (5HT<NE)


Amitriptyline
Imipramine
Secondary amine type
(5HT =NE)
Desipramine
Nortriptyline

a2 receptor inhibitors

Mirtazapine (SARI)

5HT only
Selective serotonin
Reuptake inhibitors (SSRIs)
Fluoxetine (Prozac)
Fluvoxamine
Paroxetine
Sertraline
Citalopram
e-citalopram

sNDRI
Bupropion

Abbreviations: 5HT = 5-hydroxy tryptamine (Serotonin), NE = Norepinephrine,


SNRI = Serotonin Norepinephrine Reuptake Inhibitors, NDRI = Norepinephrine Dopamine Reuptake
Inhibitor; RIMAs = reversible inhibitors of monoamine oxidase, TCA = Tricyclic Antidepressants
Signs of depression include: sadness, tearfulness, dejection, self-criticism, loss of ability to experience
pleasure, loss of appetite, inability to sleep and loss of libido. Antidepressant drugs work by altering
the concentration of neurotransmitters (chemicals) in the brain. It is believed that depression is caused
when the levels of serotonin and norepinephrine, two neurtotransmitters in the brain, are deficient, but
it is not understood which one is more responsible for depression. The drugs act by causing build up
of one or both of the neurotransmitters in the synapse, (the gap between two nerves) or by increasing
the nerve cells sensitivity to the neurotransmitters.
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Antidepressants

Classes of antidepressant drugs include: tricyclic compounds (TCAs), monoamine oxidase inhibitors
(MAOIs), selective serotonin re-uptake inhibitors (SSRIs) and reversible inhibitors of monoamine
oxidase (RIMAs).

Selective Serotonin Reuptake Inhibitors (SSRI)


The SSRIs are selective in blocking the reabsorption of serotonin by nerve cells by acting at the
5-HT receptors, and therefore, increasing the amount of serotonin available in the brain. This class
of antidepressants has fewer side effects than MAOIs or TCAs. They are also used for bulimia,
obsessive-compulsive disorder and panic attacks.
SSRI

Mechanism
Metabolic enzymes

Therapeutic use
Side effects

Advantage

Serotonergic
syndrome
(Contraindications)
Discontinued
syndrome

Citalopram (Celexa)
E-citalopram
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline (Zoloft)
Selective serotonin reuptake inhibitors:Increase serotonin levels
Most common metabolizing enzymes
SSRI inhibit CYP 2D6
CYP3A4
CYP 1A9
Antidepressant
Antianxiety
Sexual dysfunction (orgasmic delay)Alprostadil may be helpful
GI Nausea (Most common)
Headache
Insomnia
Nervousness
Fatigue

1st line treatment for major depression


No Weight gain (no change in weight)
No cardiovascular side effects
Greater tolerability and ease of dosing
No hypotension
Serotonergic syndrome may occur if the SSRI are combined with MAO
Inhibitors, SSRI and TCA.
Do not combine with SSRI
Do not combine with TCA
FINISH
Flu like syndrome
Insomnia
Nausea
Imbalance
Sensory disturbances
Hyper activity

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Tips

Antidepressants

Most anorexicFluoxetine
Most nauseating Fluvoxamine
Most weight gain Mirtazapine
Citalopram SE: Somnolence
All SSRIs have common SE: Nausea
Antidepressants with Less sexual dysfunction Bupropion,
Mirtazapine, moclobemide
Onset of action
It normally takes 2-4 weeks for antidepressant to have an effect.
Wash out period
Two SSRIs or SSRI with TCA or MAOI should not combine
If switch from one SSRI to other (SSRI, TCA or MAOI), waiting period
required (washout period)
All SSRIs have washout period for 2 weeks, Except: Fluoxetine (require
5 weeks)
Tramadol
Meperidine
Amphetamine
Dopamine
Cocaine
Methyldopa
MAO Inhibitors
Dextromethorphan
SSRI
Caffeine
TCA
Lithium
SSRI
MAO Inhibitors
TCAs
St.John wort

Serotonergic symptoms
Hyperpyrexia (Fever)
Agitation
Hypotension
Tremors / Shivering
Seizure
Coma, and death

Tricyclic Antidepressants
TCA

Amitriptyline, Clomipramine Desipramine Doxepin Imipramine ,


Maprotiline, Nortriptyline Trimipramine

Secondary amine type


(NE = 5HT)
Tertiary amine type
NE > 5HT

Mechanism

Dibenzocycloheptadiene (eg: Nortriptyline)


Dibenzapine (eg; Desipramine)
Dibenzapine (eg: Imipramine)
Dibenzocycloheptadiene (eg: Amitriptyline)
More anticholinergic side effects than secondary amine
NE and 5HT Reuptake inhibitor

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Therapeutic use

Side effects

Contraindications
Overdose symptoms

Overdose treatment
Tips

Antidepressants

Antidepressant
Neuropathy painAmitriptyline
Enuresis in children (Bedwetting) Imipramine
Anxiety disorder (OCD)
CVD effects Orthostatic Hypotension, Tachycardia (AV blockade)
Weight Gain
Sexual Dysfunction
Confusion/Delirium
Bone marrow depression
Mania with manic depressive illnesses
Anticholinergic side effects
Constipation
Blurred vision
Urinary retention
Dry mouth
MAO inhibitors, SSRI
Nausea
Constipation
Confusion
Sleepiness
Palpitation
Dizziness
Dry mouth
Blurred vision
Fever
Contact physician immediatelyif any such symptoms appears.
Activated charcoal
Less hypotensive TCA
Nortriptyline (Aventyl)
Most Anticholinergic and
sedative TCAAmitriptyline
(Elavil)
Least sedative of TCA
Nortriptyline
Less anticholinergic TCANortriptyline
Take medication daily
Antidepressants must be taken for two to four weeks for a noticeable
effect
Continue to take medication even if you are feeling better
Do not stop taking the antidepressant without checking with the
physician

Monoamino oxidase Inhibitors


The monoamine oxidase inhibitors (MAOIs) were the first class of compounds used to treat
depression. Patients, taking these drugs, must monitor their diet for tyramine, an amino acid
present in many foods that are fermented, aged or smoked. There are a number of foods containing
tyramine and some drugs must be avoided. Monoamine oxidase is an enzyme, which inactivates the
neurotransmitters, epinephrine, norepinephrine and dopamine. These drugs inhibit the destruction
of these brain chemicals, which leads to increased concentrations of these neurotransmitters, which
may account for their antidepressant activity.
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MAO Inhibitors
Mechanism

Therapeutic use
Side effects

Drug interactions
Can cause
Serotonergic
syndrome

Serotonergic
syndrome

Hypertensive
crisis
Food to avoid

Antidepressants

Phenelzine Tranylcypromine, Isocarboxazid


Inhibit both MAOA and MAOB.:Blocks deamination in brain biogenic
amines
Clorgyline MAOA selective
Selegiline MAOB selective (used as antiparkinson drug)
Antidepressant, Anti anxiety, Narcolepsy
CVS affects Orthostatic Hypotension, Tachycardia, Arrhythmias, and
Stroke.
CNS effects Sleep disturbances, CNS stimulations
Weight Gain
Sexual Dysfunction
Anticholinergic less than TCA
Avoid concomitant use of:
Meperidine
Amphetamine
SSRI
TCA
Dopamine
Cocaine
Methyldopa
Dextromethorphan
Caffeine
Pseudoephridine
Lithium
Serotonin syndrome symptoms includes:
Hyperpyrexia
Agitation
Neuromuscular pains
Hypotension
Coma, and death
Caused by combination of MAOIs with SSRI or TCAs or narcotics
(meperidine).
Use washout period for 2 weeks before administering SSRI.
Inhibitions of MAOI in brain causes catalyze oxidative deamination of toxic
substances such as tyramine.
Tyramine is present in foods such as fermented food cheese, wine etc.
Aged cheese (cheddar, blue and Swiss), yogurt, smoked meats, wine, liquor,
yeast, raisins, chocolate, dry salami, pepperoni, sausage, bananas, figs, tea and
coffee.
Drugs: Sympathomimectis, ephedrine, pseudoephridine.

Reversible Inhibitors of Monoamine Oxidase (RIMAs)


Moclobemide are short acting, reversible inhibitors of monoamine oxidase, the enzyme which
inactivates the neurotransmitters, epinephrine, norepinephrine and dopamine. This drug inhibits the
destruction of these brain chemicals, which leads to increased concentration of these neurotransmitters,
which may account for the antidepressant activity of moclobemide. Short acting, reversible inhibitor
of monoamine oxidase, the enzyme which inactivates the epinephrine, norepinephrine, and dopamine
Side effects: headache, abdominal fullness, GI upset, dry mouth, and sedation.

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Antidepressants

Dual action antidepressants


Dual action

Bupropion

Venlafaxine

Mirtazapine

Bupropion
Venlafaxine
Mirtazapine
Trazodone and Nefazadone
Serotonin (very little), Dopamine and Norepinephrine reuptake inhibitor
(sNDRI)
SE: Stimulant affect (tachycardia, agitation), aggravation of psychosis,
aggravation of seizure (Reduce seizure threshold)
Also used for smoking cessation (Zyban)
1st line treatment for Major depression
Least sexual dysfunction and weight gain
Inhibits Serotonin and Norepinephrine, Some degree of dopamine reuptake
inhibitor (SNRI)
Stimulant affect Anxiety, agitation, headache, insomnia
At higher dose 225 mg / day, it has cardiovascular side effects, such as dose
dependent hypertension.
At lower dose (75 and 150mg) it acts on 5HT only, higher dose (225mg)
5HT ,NE and Dopamine.
Alpha2 antagonist and potent 5HT2 receptor antagonist
Increases release of norepinephrine and serotonins.
Side effects: Increase appetite, Sedation
Increase serum cholesterol levels

Lithium (Lithobid)
Therapeutic use

Pharmacokinetics

Therapeutic levels
Dose
Side effects

Mood stabilizer drug of choice to treat manic depressions


Used prophylactically in treating manic-depressive patient and to treat
manic episodes.
Bipolar depression (disorder)
Steady state reached in 5 days
Poor therapeutic window
Renal excretion










Acute mania: 1.0 to 1.5 mEq/liter


Maintenance bipolar disorder: 0.6 to 1.2 mEq/liter
Increasing dose 300 mg/day raises level 0.2 mEq/liter
Start: 300 mg PO bid, effective dose: 900 to 1800 mg per day divided
bid
Tremor
Polydipsia
Hypothermia or hyperthermia
Weight gain and weight loss
Nausea or Vomiting
Diarrhea
Hypothyroidism and hyperthyroidism

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Toxic symptoms
(Over 1.5 mEq/L)

Monitoring
Drug interactions

Antidepressants

Cerebellar Signs or symptoms


Drowsiness
In coordination
Dizziness
Blurred vision
Confusion
Seizures
Fluid retention
Change in heart rate or rhythm
Lithium serum levels
Renal Function tests
Thyroid Function Tests
Diuretics, NSAIDs, ACE Inhibitors

Antidepressant Tips






























SSRI onset of action is


Fluoxetine washout period
Buprapion, trazadone and mirtazepine have least sexual dysfunction
Depression with sexual dysfunction
Depression with insomnia
Depression with diabetes
Take SSRI in the morning
Take TCAs in evening or bedtime
Higher dose of venlafaxine (225mg/day) have effect on
Patient on antidepressants and shows with dilated pupil, may be due to
TCA onset of action is
A substance found commonly in fermented foods which can be toxic when MAO inhibitors
are used
MAO is classified as
SSRI inhibit cytochrome CYP2D6
Mirtazepine may cause higher weight gain
Avoid cheese with
Milk + MAOI
St. John wort have antidepressant effect
Serotonergic symptoms
DOC in Bipolar disorders and manic depression -->
Normal blood levels of lithium in adult is 1.5 mEq/L
Lithium concentration varies with Na+ ions
Li+ conc. increases with decrease Na+
Li+ conc. decreases with Increase in Na+
ACEI decrease Na+
NSAID decrease Na+ renal perfusion is less
Thiazides deplete Na+
Fluoxetine (SSRI) increase Li+ toxicity
Renal dysfunction
Dehydration
Lithium toxicity symptoms -->

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Antidepressants

Abbrevation and Terminology


MAO
SARI
SSRI
D
NE
SNRI
NDRI
RIMA
TCA
OCD
CVD
GAD
5HT

Generic and Brand


Citalopram
E-citalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Amitriptyline
Clomipramine
Desipramine
Doxepin
Imipramine
Maprotiline
Nortriptyline
Trimipramine
Phenelzine
Tranylcypromine
Isocarboxazid
Bupropion
Venlafaxine
Mirtazapine
Trazodone
Nefazadone
Lithium

Monoamine Oxidase
Selective serotonin reuptake inhibitor
Dopamine
Norepinephrine
Serotonin Norepinephrine Reuptake Inhibitors
Norepinephrine Dopamine Reuptake Inhibitor
Reversible Inhibitors of Monoamine oxidase
Tricyclic Antidepressants
Obsessive-Compulsive Disorder
Cardiovascular Disease
General Anxiety Disorde
5-hydroxy tryptamine (Serotonin)

Celexa
Proxac
Luvox
Paxil
Zoloft
Anafranil
Norpramin
Sinequan
Tofranil
Aventyl
Surmontil
Nardil
Parnate
Wellbutrin SR
Effexor
Remeron
Desyrel
Lithobid

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Sedatives, hypnotics and Anxiolytics

13

Sedatives, Hypnotics and


Anxiolytics
Classification of Sedative-Hypnotic Drugs
Barbiturates

Benzodiazepines


Long action
Diazepam
Fluorazepam
Clorazepate

Intermediat
Alprazolam
Lorazepam
Temazepam
Estazolam

Short acting
Oxazepam
Triazolam
Midazolam
Ultra-short
action
Thiopental

Non-benzodiazepines
Zaleplon
Zopiclone
Zolpidem
Other anxiolytics:
Buspirone, Hydroxyzine

Intermediate
Amobarbital
Secobarbital
Pentobarbital

Long action
Phenobarbital

Sedatives (anxiolytic agents): Reduce anxiety with little effect on motor or mental functions.
Hypnotics: Produce drowsiness and reduce onset of sleep.
Insomnia disturbed or fragmented sleep, often associated with physical or emotional illness
Anxiolytic a drug that decreases anxiety

Sedatives
Benzodiazepines

Aldehyde
derivative

Antihistamine

Barbiturates

Others sedatives

Cyclopyrolones

Pyrazolopyrimidines

Hypnotic &
Sedatives

Benzodiazepines

Short acting
Midazolam
Estazolam
Triazolam (Halcion)

Intermediate acting
Alprazolam (Xanax)
Lorazepam (Ativan)
Oxazepam (generics)
Temazepam (Restoril)
Nitrazepam

Long acting
Diazepam (generics)
Flurazepam (Dalmane)
Clonazepam,
Chlordiazepoxide

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Sedatives, hypnotics and Anxiolytics

Benzodiazepines
Benzodiazepine are minor tranquilizers are used to treat insomnia and anxiety. The following are
terms that are used to describe some conditions dealing with anxiety or sleep disorders. Anxiolytic a
drug that decreases anxiety: insomnia disturbed or fragmented sleep, often associated with physical
or emotional illness: sedative a drug which causes drowsiness but not sleep, reduces anxiety and
irritability; hypnotic a drug which will produce sleep. Sometimes a larger dose of a sedative will
cause a hypnotic action.
Mechanism

Benzodiazepine receptors BZ1 and BZ2 are found in brain


BZ1 and BZ2 are parallel to GABA receptors

Benzodiazepine
therapeutic actions

Sedative and hypnotic


action

Anticonvulsant action
Muscle relaxant action
Dependence

Withdrawal symptoms
Benzodiazepine antidote

Reduce anxiety
Insomnia; Sedative and hypnotic action
Anticonvulsant action
Muscle relaxant action
Flurazepam (no rebound insomnia)
Quazepam (No rebound insomnia)
Temazepam
Triazolam used for insomnia often rebound insomnia
Alprazolam (used in treatment of panic disorders)
Clonazepam (useful in treating absence seizures)
Diazepamstatus epilepticus
Diazepammuscle spasm, muscle degenerative disease
Physical and psychological dependence (at high doses)
Withdrawal symptoms upon abrupt discontinuation
Long acting withdrawal symptoms occurs after number of days
Short acting benzodiazepine associated with immediate withdrawal
symptoms if it is stopped abruptly.
Confusion, anxiety, agitation, restlessness, insomnia, and tension.
Rapid development of tolerance and withdrawl symptoms occurs
with short acting.
Flumazenil

Other sedatives
Mechanism
Therapeutic use
Zaleplon

Zopiclone, Zaleplon, Zolpidem


Not a benzodiazepine, Acts on subset of benzodiazepine receptors
Insomnia
Act on benzodiazepine receptors
No anticonvulsant and muscle relaxant activity
Short half life 1 hours
Headache most common
Reduce sleep latency, used in initial treatment

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Zopiclone

Sedatives, hypnotics and Anxiolytics

Act on subset benzodiazepine receptors


No anticonvulsant and muscle relaxant activity
Short half life 5 hours
Bitter metallic taste
Bad breath
Confusion most common in elderly
Do not accumulate, may cause less withdrawal effects and less rebound
insomnia:
Less tolerance
Minimal additive effect with alcohol
Acts on subset of benzodiazepine receptors.
It is not a benzodiazepine
It is has no anticonvulsant properties
It does not have muscle relaxing properties

Zolpidem

Zolpidem (Ambien)
Mechanism

Therapeutic use
Advantages

Side effects

Acts on subset of benzodiazepine receptors.


It is not a benzodiazepine
It is has no anticonvulsant properties
It does not have muscle relaxing properties
Indicated in treatment of insomnia
Show no withdrawal effect
No tolerance with prolong use
Minimal rebound insomnia
Rapid onset of action
Elimination half life is 3hours
NIGHTmares
Dizziness Agitation
GI upset
Headache
DayTime drowsiness (hangover effect)

Barbiturates
Barbiturates

Ultra-short action
Thiopental

Short acting
Amobarbital
Secobarbital
Pentobarbital

Long action
Phenobarbital

Barbiturates are used much less commonly than before. They are effective only for a few weeks
since they alter the length of time spent in R.E.M. sleep. They should only be used for short-term
therapy as sedative or hypnotics.
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Barbiturates

Mechanism

Metabolic Enzymes
Therapeutic use
Withdrawal
symptoms

Poisoning
Poisoning
management
Barbiturates
antagonist

Sedatives, hypnotics and Anxiolytics

Phenobarbitals (Luminal, Solfoton) Long acting


Amobarbital (Amytal) short acting
Butabarbital (Butisol) short acting
Pentobarbital (Nembutal) short acting
Secobarbital (Seconal) short acting
Thiopental (Pentothal) shortest acting (acts within second)
Primidone active drug is phenobarbital (metabolite)
Two side chains in position 5 are essential for sedative hypnotic activity
Long acting have a phenyl and a ethyl group in position 5
1-Interfere with Na and K transport across membrane.
2-Potentiate GABAA action on Cl- entry
3- Do not bind to BZ1 and BZ2 receptors
Sedation (calming effect, reduce excitement)
Respiratory depression
Barbiturates induce CYP450 in liver, reduces the effect of several drugs
that depends on CYP450.
Anesthesia
Anti seizure
Anxiety
Addiction potential
Abrupt withdrawal of barbiturates may cause:
Tremors
Anxiety
Weakness
Restlessness
Nausea
Vomiting
Seizures
Delirium
Cardiac arrest
Withdrawal symptoms are more severe than opioids, can cause death.
Severe depression of respiration
Cardiovascular depression
Shock like condition shallow and infrequent breathing
Artificial respiration
Purging stomach content
Hemodialysis
Alkalinization of urine for phenobarbital
Aminophylline

Miscellaneous
Non-barbiturate
sedatives
Chloralhydrate
Antihistamine

Chloralhydrate
Alcohol
Antihistamine
Buspirone
Tri chlorinated derivative of acetaldehyde
Doxylamine and other antihistamine are used as OTC treatment of sleep
disorders

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Hydroxyzine
Mechanism
Therapeutic use
Advantages
Buspirone

Ethanol

Sedatives, hypnotics and Anxiolytics

H1 antihistamine with antiemetic activity


Antihistamine, Antiemetic, Anxiety, Sedation prior to dental procedure,
Insomnia
Low tendency of habituation thus it is useful for anxiety in-patient who a
history of drug abuses.
Buspirone acts on 5HT1a receptors and D2 receptors causes minimal
sedation, least addiction liability.
Disadvantage: slow onset of action
Advantage: Less interference with motor functions (helpful in elderly)
Ethanol Acetaldyhyde acetate or acitic acid
Ethanol is metabolized in liver, first to acetaldehyde by alcohol
dehydrogenase and acetate by aldehyde dehydrogenase.
Ethanol has sedative and antianxiety effect.

Sedative and Hypnotics Tips












Long acting benzodiazepine include


Intermediate acting
Short acting
Alcohol withdrawal symptom delirium is treated by
Benzodiazepine has high tolerance and addiction potential.
If few pills of benzodiazepine fall down, what you do?
Least addiction potential
Least hangover hypnotic
Zaleplon and zopiclone act
Valerian is used for
Ginko biloba is used for

Anxiolytics
Azaspirodecanedione
Derivatives
Benzodiazepines

Various Anxiolytics

Buspirone hydrochloride










Types of Anxiety Disorders



Anxiety disorder

Alprazolam
Bromazepam
Chlordiazepoxide hydrochloride
Clorazepate dipotassium
Diazepam
Lorazepam
Oxazepam
Hydroxyzine hydrochloride Antihistamine
Paroxetine SSRI
Trifluoperazine hydrochloride Antipsychotics
Venlafaxine antidepressant

Drug of choice (DOC)

Alternate

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Sedatives, hypnotics and Anxiolytics

Panic Disorder (PD)

Benzodiazepines (BDZs)
Alprazolam 0.25mg TID or QID or
clonazepam 0.25 to 0.5mg BID

Panic Disorder with


Agoraphobia (PDA)

Cognitive Behavior Therapy (CBT)

Social Phobia (Social


Anxiety Disorder (SAD)stage fear or public speaking
fear

Low-dose propranolol (10mg) taken


30 minutes before the event.

MAOIs can be used;


moclobemide (in
antidepressant doses)

Obsessive-Compulsive
Disorder (OCD)
Post-traumatic Stress
Disorder (PTSD)

Clomipramine

SSRIs

Paroxetine is the only agent


specifically approved for treatment
of PTSD in Canada
All SSRIs

Citalopram

Generalized Anxiety
Disorder (GAD)
Attention Deficit
Hyperactivity Disorder
(ADHD)

(SSRIs) fluoxetine,
fluvoxamine, paroxetine,
sertraline and citalopram

Methylphenidate (Ritalin (IR) or


Concerta (XL) dexamphetamine
are each effective in over 80% of
accurately diagnosed ADHD

Abbrevation and Terminology


GABA
BZ
5HT
OTC
CBT
SSRI
TCA
PTSD
OCD
GAD
SAD
PD
ADHD

Gamma-Aminobutyric Acid
Benzodiazepine
5-hydroxy tryptamine (Serotonin)
Over The Counter
Cognitive Behavior Therapy
Selective Serotonin Reuptake Inhibitor
Tricyclic Antidepressants
Post-traumatic Stress Disorder
Obsessive Compulsive Disorder
Generalized Anxiety Disorder
Social Anxiety Disorder
Panic Disorder
Attention Deficit Hyperactivity Disorder

Generic and Brand


Zolpidem
Phenobarbitals
Amobarbital
Butabarbital
Pentobarbital
Secobarbital
Thiopental
Primidone

Ambien
Luminal, Solfoton
Amytal
Butisol
Nembutal
Seconal
Pentothal
Myidone, Mysoline

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CNS Stimulants

14

CNS stimulants


These drugs have a stimulating effect on the CNS. As a side effect, they decrease appetite and for
many years were used as appetite suppressants. Addiction and abuse were side effects of taking these
drugs. Furthermore, they are known as uppers and people hooked on them needed downers to
be able to sleep, causing more problems. Today, they are used mainly to treat hyperkinetic children
(attention deficit syndrome) where the child is unable to concentrate. It would seem that the drugs
would soup up the patient, but the opposite occurs.
These drugs are also used to treat narcolepsy, a condition where the patient lapses into momentary
sleep while sitting. This may occur as many as 20 times a day and is dangerous if it were to happen
while the patient is driving or operating machinery.
CNS Stimulants

Psychomotor:
Methylxanthines
Cocaine
Nicotine
Amphetamines
Methylphenidate

Psychomimetic:
Phencyclidine
Lysergic acid diethylamide
Tetrahydrocannabinol

Psychomtor Stimulants
Mechanism

Cocaine
Amphetamines
Dexamphetamine

Methylxanthines

Excitement
Euphoria
Decrease feeling of fatigue
Increase motor activity
Ester type Local anesthetic
Blockade of voltage sodium ion activated channel
Side effects Anxiety, depression, seizures, cardiac arrhythmias.
Therapeutic use: Attention Deficit Hyperactivity Disorder (ADHD)
Psychological and physical dependency addiction potential
Development of tolerance to euphoric and anorectic effects of chronic use.
Less tolerant to convulsions and toxic CNS effect
Amphetamine are classified as controlled drugs
Theophylline tea
Caffeine coffee
Theobromine cocoa

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CNS Stimulants

Psychomimetic stimulants
Mechanism
Hallucinogens

Bring changes in thought patterns


Mood pattern
Little effect on brainstem and spinal cord
Phencyclidine (PCP)
Lysergic acid diethylamide (LSD)
Tetrahydrocannabinol (THC) or dronabinol (marijuana)

CNS stimulants Tips


Theophylline is chemically related to
All CNS stimulants have addiction potential
In ADHD treatment it is important to emphasize non-pharmacological recommendations such
as taking breakfast every day and good sleep in night, counsel parents and teachers.
Hallucinogens are

Abbrevation and Terminology


ADHD
PCP
LSD
THC
CNS

Attention Deficit Hyperactivity Disorder


Phencyclidine
Lysergic acid diethylamide
Tetrahydrocannabinol
Central Nervous System

Generic and Brand


Amphetamines
Methylphenidate

Adderall, Vyvanse, and Dexedrine


Ritalin

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Antipsychotics Drugs

15

Anti Psychotic Drugs


The following antipsychotic agents are classed as major tranquilizers and are used to help people
with schizophrenia and other psychoses (major mental disorders).
Antipsychotics
Atypical
Clozapine
Risperidone
Olanzapine
Quetiapine

Sertindol
Phenotiazines:
Chlorpromazine
Fluphenazine
Thioridazine

Thioxanthenes:
*Chlorprothixene
*Thiothixene

Butyrophenones
*Haloperidol
*Droperidol

Typical

Diphenylbutyrylpiperidine
*Pimozide

Dibenzoxazepine
* Loxapine

Dihydroidolon
* Molindone

The schizophrenic individual is out of touch with reality, hallucinates, hears voices and exhibits
bizarre behaviour. These symptoms are only one aspect of schizophrenia. Other symptoms are:
social withdrawal, and an inability to communicate or to concentrate.
Schizophrenia Symptoms (Psychosis)
Positive Symptoms
Reality distortions
Delusions persecution
Grandiosity
Thought broadcasting
Thought insertion
Loose associations
Gestures
Mind-reading
Being controlled

Hallucinations
Auditory (most common)
Olfactory
Somatic
Visual

Negative Symptoms

Disorganizations
Disorganized speech
Incoherent speech
Tangentiality
Loose association

Blunted affect
Lack of expressed emotion
Poor eye contact and inattentiveness
Reduced spontaneity

Disorganized behavior
Agitation
Hostility
Assaultiveness
Uncooperativeness
Inappropriate sexual/social behavior
Inappropriate dress
Catatonia

Alogia
Lack of spontaneity of conversation
poor ability to concentrate
Avolation /apathy
Lack of interest in activities
No motivation, social withdrawal
Poor hygiene
Anhedonia
Loss of pleasure
Few recreational activates
Attentional impairment
Lack of ability to concentrate on tasks or
conversation

Antipsychotics

Muscarinic
receptor

receptors

Dopamine

Serotonin
receptor

H 1 receptors

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Antipsychotics Drugs

Antipsychotics

1st generation

Chlorpromazine
Prochlorpromazine
Haloperidol
Droperidol
Flupenthixol
Fluphenazine
Thioridazine

2 nd generation

Clozapine (Clozaril)
Olanzapine
Risperidone
Quetiapine

Zuclopenthixol

1st Generation antipsychotics


Mechanism

Therapeutic use

Block dopamine receptors in Cortical and limbic areas of brain


D1, D5 activates adenylyl cyclase
D2, D3, D4 Inhibit adenylyl cyclase
1st generation antipsychotics mainly bind to D2
Blockade in dopamine at basal ganglia leads to side effects such as
Parkinsonism (Extrapyramidal side effects)
Antipsychotics

Side effects

Extrapyramidal Symptoms (EPS) Parkinsonism


Sexual Dysfunction
Anticholinergic Side effects
Tardive Diskinesia
Sedation
Advantage
Low weight gain
Disadvantage
High EPS
High sexual dysfunction,
High anticholinergic side effects
Parkinsons
T = Tremor
Symptoms
R = Rigidity
A = Akithisia
P = Postural instability
Extrapyramidal symptoms:

Parkinsons like symptoms (Tremors)

Akthisia (motor restlessness)

Tardive Dyskinesia (inappropriate postures of neck, trunk and limbs)

2nd Generation Antipsychotics


Mechanism

Atypical or 2nd generation inhibit serotonin (5HT) receptors and dopamine


receptor
Some examples:
Clozapine 5HT2, D1 and D2, D4, muscarinic, and alpha adrenergic rceptors
Risperidone Blocks 5HT2 greater than D2 receptors
Quetiapine Least effect on dopamine

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Antipsychotics Drugs

Therapeutic use

Antipsychotics

Side effects

EPS
Sexual Dysfunction
Anticholinergic Side effects
Tardive Diskinesia
Sedation
High weight gain
Low EPS
Low sexual dysfunction
Low anticholinergic side effects
High weight gain

Advantage
Disadvantage

Comparison of antipsychotic drug side effects:


Typical (1st generation)
High sedation
Low weight gain
High Tardive Dyskinesis
High Anticholinergic SE
High Sexual Dysfuntion
High EPS

Atypical (2nd generation)


Low sedation (respiradone)
High weight gain (clozapine)
Low Tardive Dyskinesia clozapine
Low Anticholinergic side effects
Low SD (quitiepine)
Low EPS

Antipsychotics Tips














1st generation 4 8 weeks no response, change to 2nd generation.


Severe case of psychosis (schizophrenia) or bipolar disorder-->
For 2 episode, continue for 2 5 yrs
2nd gen (clozapine, olanzapine) increase risk of lipids and diabetes, EXCEPT: Respiridone
Least extra pyramidal symptoms
Highest EPS
Patient experiencing hallucination
Patient experiencing social withdrawal
2nd generation covers
Schizophrenia is characterized by
Metoclopramide
Chlorpromazine
Tardive dyskinesia is caused by
TD symptoms
For resistance schizophrenia DOC

1st gen (haloperidol, loxapine, chlorpromazine, thioridazine) is effective in positive schizophrenic


symptoms. However, 2nd gen (clozapine, risperidone, olanzapine, quetiapine) covers negative
schizophrenic symptoms. Olanzapine, not effective for the treatment of resistance, and resperidon
works for negative and positive symptoms.
Orthostatic hypotension is SE of --> 2nd Generation antipsychotics (can cause additive effects with
other antihypertensive drugs)

Abbrevation and Terminology


EPS
Extrapyramidal Symptoms
5HT
5-hydroxy tryptamine (Serotonin)
Extra pyramidal side effects (EPS): Tardive dyskinesia, (inappropriate posture of neck, limbs and
trunk), Parkinson symptoms.
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Antipsychotics Drugs

Generic and Brand


Chlorpromazine
Prochlorpromazine
Haloperidol
Droperidol
Flupenthixol
Fluphenazine
Thioridazine
Trifluoperazine
Zuclopenthixol
Clozapine
Olanzapine
Risperidone
Quetiapine

Largactil
Compazine
Haldol, Serenace
Droleptan, Thalamonal
Depixol, Fluanxol
Modecate, Moditen, Motipress, Motival
Melleril
Stelazine, Porstelin
Clopixol
Clozaril
Zyprexa, Zyprexa Zydis
Risperdal, Risperdal Consta, Risperdal M-Tab
Seroquel XR, Seroquel

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Epilepsy

16

Epilepsy
Antiseizure drugs

Reduces NMDA
Receptor activation

Felbamate

Affect GABA
receptors

Reduce Na+ conductance


in hyperactive neurons

Reduce Ca2+
current through
T-channels

Phenobarbital
Ethosuximide

Carbamazepine
Diazepam

Phenytoin
Vigabatrin
Fosphenytoin
Topiramate

Lamotrigine
Tiagabine
Primidone
Gabapentine
Valproate
Valproic acid

Seizure: Abnormal electrical discharge from local areas and spread around the brain adjacent areas.
Condition like hypoxia, uremia, bacterial meningitis, genetic predisposition and drugs such as
cocaine, penicillin G, anticholinergics can produce seizure. Withdrawal from chronic use of alcohol,
barbiturates, benzodiazepines and most anti seizure medication can also lead to seizures.
Epilepsy: Epilepsy is a disorder of the brain characterized by recurrent and spontaneous seizures which
are self-limiting. Which usually recur unpredictably.
Convulsions: Involuntary contractions (abrupt) of voluntary muscles.
Seizures (Epilepsy) are characterized as: Partial and Generalized seizures.
Partial Most common (80%)
Comments
Simple partial
Seizures begin locally
Consciousness not impaired
With motor symptoms Jerking, lip smacking,
chewing motions
With autonomic symptomsSweating, pupil dilation,
With behavioral symptoms

Drug of choice
Drug of choice
1st
Carbamazepine
2nd Phenytoin
3rd Primidone
4th Gabapentin

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Complex partial

Generalized seizures
Absence seizures
(Petit mal)
Myoclonic seizures
Tonic-clonic seizure
(grand mal)

Status epilepticus

Epilepsy

Seizure begin locally


With conscious impairment
Begin as simple
With or without automatism (automatism: picking
at cloths is common may follow visual, auditory
hallucinations)

Drug of choice:
1st Carbamazepine
2nd Phenytoin
3rd Phenobarbital
4th Valproic acid

True absence seizures (Petit mal)10 - 30 seconds, causes alteration of


consciousness, starts with occasional blinking (Nystagmus)
Avoid Phenytoin and carbamazepine use in absence seizure
Involuntary jerking of facial, limb, trunk muscles
Clonic seizures
Sustained muscle contraction altering with relaxation
Tonic seizuresMuscle stiffening
Sudden loss of Consciousness, become rigid, falls to the ground, last
about 1 minute.
In some cases no regain of brief consciousness between attacksDOC is iv
diazepam.

Seizure Type

1st Choice

Generalized
Tonic-clonic
(Grand-mal)

Absence
(petit-mal)
Myclonic and Atonic
Partial (simple or complex) with
or without 2 generalization

Alternative therapy

Carbamazepine
Phenytoin
Valproic Acid
Ethosuximide
Valproic Acid
Valproic Acid
Carbamazepine
Phenytoin

Clobazam
Lamotrigine
Levetirecetam
Topiramitrate
- Same as above-Same as aboveGabapentin
Oxcarbazepine
Phenobarbital
Primidone
Valproic Acid
Vigabatrin

Carbamazepine (Tegretol)
Mechanism
Therapeutic use
Side effects

Management

By blocking Na channels reduces abnormal impulses in brain


Partial seizures
Tonic clonic seizures
Treat trigeminal neuralgia
Rash, liver enzymes, neutropenia, aplastic anemia
Chronic: drowsiness, vertigo (The sensation of dizziness and a confused,
disoriented state of mind).
Aplastic anemia
Stevens Johnson syndrome (skin hypersensitivity reactions)
Acute intoxication: Coma, hyperirritability, convulsions and respiratory
depression
Start low and increase gradually
CR may be better tolerated, improve compliance
May upset stomach, if so take with food or milk

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Epilepsy

Phenytoin (Dilantin)
Phenytoin decreases the sodium content of nerve in the brain and thereby decreases the
hyperexcitability of the cells that are involved in initiating seizures.
Mechanism

Stabilizes neuronal membranes to depolarization by decreasing flux of


Na+ ions into neurons in the resting state or during repolarization.
Therapeutic use
Partial seizures
Tonic clonic seizures
Status epilepticus caused by recurrent tonic clonic seizures
NOT effective for absence (Petit-Mal) seizures.
Side effects
Skin rash
Gingival hyperplasia
Encephalopathy
Blood dyscrasias
Nystagmus
Hirsutism
Birth defects cleft palate
Pharmacokinetics
Oral absorption is slow
Chronic administration is always oral
Metabolized by hydroxylation in liver.
At low doses half-life is 24 hours.
As dose increase hydroxylation becomes saturated, and can produce large in
increase plasma concentration, resulting in drug-induced toxicity.
Folic acid accelerates metabolism of phenytoin
Dosages
Chewable tablets, Capsules, Suspension, i.v.
Phenytoin metabolism is inhibited by:
Sulfonamide

Isoniazid
Chloramphenicol
Dicumarol
Phenytoin metabolism is stimulated by:
Carbamazepine

Phenobarbital (Luminal)
Primidone
Mechanism
Therapeutic use

Side Effects

Advantage
Disadvantage

Metabolite of phenobarbital
Increase seizure threshold by decreasing postsynaptic excitation by
stimulating postsynaptic GABA-A receptor inhibitor response as CNS
depressant.
Epilepsy
Sleeping and sedative drug
When combined with other drugs it is used in anxiety associated with
menopausal symptoms
Unwanted sedation
Skin rash (Phenobarbital)
Depression
Libido (Primidone)
Long t1/2
Metabolism inhibited by Valproic acid

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Tips

Epilepsy

Declining use because of side effects

Clobazam (Frisium)
Mechanism
Therapeutic use
Side effects
Management

Dose

Produce CNS effects by interacting with macromolecular protein complex in


the neuronal membrane, which includes gamma aminobutyric acid (GABA)
receptors, high-affinity benzodiazepine receptors and chloride channels.
Anticonvulsant
Useful as add on for patients nearly seizure free.
Ataxia
CNS: Insomnia, depression, dizziness, drowsiness, Lightheadedness
Tolerance to therapeutic effects.
Advantage: Very safe, rapid onset
Disadvantage: Tolerance (initially, good response then no control for
seizures)
-not recommended for use in patients with major depressive disorder or
psychosis in which anxiety is not a prominent feature.
Abrupt withdrawal may lead to symptoms such as anxiety, insomnia,
psychomotor agitation, GI discomfort.
5-15mg/day

Ethosuximide (Zarontin)
Mechanism
Therapeutic use
Side effects
Management

Inhibit Na+ and K+ adenosine triphosphate system (Na+, K+ ATPase)


Anticonvulsant
GI: nausea, anorexia, vomiting,
CNS: drowsiness
Advantage: Few drug interaction
Disadvantage: For absence seizure only, No protection for generalized tonicclonic

Gabapentin (Neurontin)
Mechanism
Therapeutic use
Side effects
Advantage:

Disadvantage
Tips

Blocks Na+ currents.


Analog of GABA,Gabapentin is structurally related to the neurotransmitter
GABA receptors, it is not metabolized to GABA or to GABA agonists,
Partial seizures, DOC in trigeminal neuralgia
When initiating therapy CNS: somnolence, Sedation, Fatigue, Dizziness and
Ataxia
Safe, well tolerated,
Not metabolized,
Can be used in liver failure,
No interaction with oral contraceptives
Not for generalized seizure
Administration with aluminum/ magnesium antacid may
Bioavailability
Very expensive at high doses, best used as add on drug

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Epilepsy

Lamotrigine (Lamictal)
Mechanism
Therapeutic use
Side effects
Advantage:
Disadvantage:
Comment:

Inhibit glutamate and aspartate release and blocks sodium channels and
prevents repetitive firing
Anticonvulsant
Rash,
CNS: Somnolence, dizziness, insomnia
Broad spectrum, no enzyme induction, some patients more alert
Metabolism inhibited by valproic acid.
Only available in oral form
Very expensive at high doses

Topiramate (Topamax)
Side Effects
Management
Advantage
Disadvantage:

Cognitive dysfunction, Headache, Kidney stones


Weight loss
Limit use
Broad spectrum, safe, few drug interaction, Weight loss
efficacy of OCS, expensive

Valproic Acid
Valproic acid and divalproex are related chemicals. Divalproex is a mixture of valproic acid
and sodium valproate. In the body they are metabolized to separate compounds, and both exert
anticonvulsant effects.
Mechanism
Reduces the propagation of abnormal electrical charge in the brain. It may
enhance GABA action at inhibitory synapses
Therapeutic use
Side Effects

Monitoring

Most effective in treatment of myoclonic seizures


GI: Nausea, Weight gain (Increase appetite)
Tremor
Hair loss (alopecia)
Blood dyscrasias
Hepatoxicity
Edema
Menstrual irregularities
Teratogenicity
Photosensitivity
Steven Johnsons syndrome
Pregnancy Neural tube defects
Liver function test (LFT), Complete blood count (CBC)
Advantages: Low incidence of rash No interactions with oral contraceptives
Disadvantage: high drug interaction (but do not reduce OCs efficacy)
Comment: Drug of Choice for patients with mixed generalized seizures,
absence, myoclonus, tonic seizure)
Not for partial seizure

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Epilepsy

Vigabatrin (Sabril)
Side Effects

Advantage
Disadvantages

Low incidence of psychosis


Depression
Visual problems
Comment: Limited use because of visual defects
Well tolerated, few drug interactions, does not cause skin, blood, liver
adverse effect
May worsen absence seizures, myoclonus
Expensive when using high doses

Antiepileptic drugs Tips























Carbamazepine interferes with thyroid function test


Phenobarbital and phenytoin stimulates -->
Carbamazepine is DOC for -->
DOC for status epilepticus is -->
Avoid phenytoin in -->
Phenytoin have -->
Gingival hyperplacia associated with phenytoin is treated by mouth hygiene and
chlorohexidine mouth wash.
Chlorhexidine is used for -->.
Carbamazepine, phenytoin, clonazepam -->
Gabapentin and valproic acid, lamotrigine have no interaction with oral contraceptives
Topiramate cause
Gabapentin has least
Phenytoin available as -->.
Carbamazepine available as -->
Clobazam has high
Gabapentin and lamotrigine
Xerostomia
Sialorrhea
Vigabatrin + carbamazepine
A patient is on phenytoin but now dose is increased, when is the appropriate time to measure
steady state
Phenytoin blood levels monitored for
List the monitoring parameters for phenytoin.

Abbrevation and Terminology


CR
GABA
CBC
LFT
OC

Gamma-Aminobutyric Acid
Complete Blood Count
Liver Function Test

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Epilepsy

Generic and Brand


Carbamazepine
Phenytoin
Phenobarbital
Libido
Clobazam
Ethosuximide
Gabapentin
Lamotrigine
Topiramate
Vigabatrin

Tegretol, Carbatrol, Epitol


Dilantin
Luminal
Primidone
Frisium, Urbanol
Zarontin
Gabarone, Neurontin
Lamictal
Topamax
Sabril

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Epilepsy

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17

Dementia
Definitions:
Dementia is a declined in mental ability that usually progresses slowly, in which memory, thinking,
judgment, and ability to pay attention and learn is impaired, and personality may deteriorate.
Delerium is a potentially reversible condition that usually comes so sudden. The person has diminished
ability to pay attention and often confused, disoriented, and unable to think clearly.

Alzheimers Disease
A progressive form of dementia. Alzheimers disease is a progressive, relentless
loss of mental function, characterized by degeneration of brain tissue, including loss of nerve cells and
the development of senile plaques and neurofibrillary tangles.
Alzheimers disease:

Alzheimer disease occurs due to in Acetylcholine (ACh). It is very rare among people younger than
60. It becomes more common with increasing age. It affects only about 1% of people aged 60 to 64,
but up to 30% of those older than 85.
Treatment: Acetylcholine agonist: Donepezil , Rivastigmine, Tacrine, Galanthamine
These drugs may improve cognitive function temporarily, but they do not slow the progression of
the disease.
Drugs for Alzheimers Disease

Reversible
Acetylcholinesterase inhibitor

Nonselective

Physostigmine
Tacrine
Galanthamine

Selective

Donepezil

Rivastigmine
(relatively selective

Donepezil (Aricept)
Mechanism

Acetylcholinesterase inhibitor

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Side effects
Dosage
Advantage
Drug and Drug
Interactions
Monitor

Dementia

GI effects Nausea, vomiting, Diarrhea


CNS effects Fatigue / insomnia, Headache
Other effects Muscle cramps, Anorexia, Difficulty in passing urine
Daily one dose in the morning or evening
Initial: 5mg/day Target: 10mg/day Adjust dose after 4 wk
Daily one dose
Toxicity may be by inhibitors of CYP2D6 or CYP3A4 (e.g.,
paroxetine, erythromycin, prednisone, grapefruit juice, nefazodone)
Effectiveness may be by inducers of CYP2D6 or CYP3A4 (e.g.,
carbamazepine, phenytoin, rifampin)
Periodic checks may be performed to see benefit of drug

Rivastigmine (Exelon)
Mechanism
Side effects

Therapeutic use
Dosage

Selective Acetylcholinesterase inhibitor


Weight loss due to reduced appetite
Nausea, abdominal pain
Depression, agitation, confusion
Drowsiness, dizziness
Weakness, trembling
Sweating, malaise
Convulsions (rare)
Effective in Lewy body dementia
Treatment of Lewy body dementia. Avoid antipsychotics
Acute pain such as dysmenorrhea (painful periods)
For rivastigmine, the initial dose is 1.5 mg PO BID, and can be doubled
to 3.0 mg PO BID after 30 days, which is the minimum effective dose.

Galanthamine
Mechanism
Therapeutic use
Side effects
Dosage

Effective in Alzheimers and vascular dementia


Nausea, vomiting, abdominal pain, diarrhea, indigestion, decreased appetite
and weight loss, headache, dizziness, tiredness, sleepiness or sleeplessness,
confusion, runny nose, urinary tract infection, falls
16- 32 mg bid

Dementia Tips







DOC for Alzheimers is -->


Alzheimers occurs due to-->
Donepezil and rivastigmine and galatamine all have anorexia SE.
Delirium is
Amnesia is
What are risk factors for Alzheimers disease
Levy body dementia -->
Galantamine is classified as

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Abbrevation and Terminology


ACh
PO

Acetylcholine

Generic and Brand


Donepezil
Rivastigmine
Tacrine
Galanthamine

Aricept
Exelon
Razadyne, Reminyl, Memeron

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Dementia

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Anti-Parkinsons Drugs

18

Anti-Parkinsons Drugs
Drugs to treat Parkinsons Disease

DA
precursor


L-dopa

Peripheral
dopa
decarboxylase
inhibitor

DA
agonist

MAO B
inhibitor

Anticholinergic

Selegiline

Benztropine

Pramipexole
Ropinirole

Anti-viral
drug

Carbidopa

Combination
Sinemet

COMT
inhibitors

Entacapone Amantadine

Ergots
Bromocriptine
Pergolide

Wearing off effects: After 3-4 years of treatment, drug loose its efficacy.
Parkinsons is a condition, which is characterized by muscle tremors at rest, muscle weakness,
emotionless facial expressions, increased sweating and salivation, disturbances of motion and
increased postural balance difficulty. These patients have a deficiency of the neurotransmitter,
dopamine, allowing acetylcholine to dominate.

Mechanism

Parkinson disease associated with () Decrease of dopamine in the nigrostriatal


dopaminergic system, this results in increased acetylcholine levels and upsets the
DA/Ach balance.
Increase in dopamine and acetylcholine ratio
Symptoms
TRAP
Tremor
Rigidity
Akinesia/Bradykinesia
Postural instability
Primary PD
Onset is generally after age 40
The pigmented neurons of the substantia nigra, locus caeruleus, and other brain
stem dopaminergic cell groups are lost.
Secondary PD Cause with drugs (antipsychotic drugs or reserpine), or exogenous toxins
Co-administration of an anticholinergic drug (eg, benztropine 0.2 to 2 mg po tid) or
amantadine (100 mg po bid) may reduce the resulting symptoms.

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Anti-Parkinsons Drugs

Anti-Parkinsons drugs action


Gut

Brain

Peripheral tissues
3-O-Methyldopa

3-O-Methyldopa
Tolcapone

Tolcapone

Striatal neuron
Ldopa

Levodopa

Ldopa

Carbidopa

Dopamine

Dopamine
Pergolide and other agonists

D1 and D2
receptors

Dopamine

Selegiline
Dihydroxyphenylacetic
Acid (DOPAC) + H2O2

Dyskinesias: Involuntary, nonrepetitive, occasionally stereotypical movements affecting distal,


proximal, and axial musculature in varying combinations. Most dyskinesias are due to basal ganglia
disorders.
Extrapyramidal symptoms:
Parkinsons like symptoms (TRAP)
Akthisia (motor restlessness)
Tardive Dyskinesia (inappropriate postures of neck, trunk and limbs)
Chorea is brief, purposeless involuntary movements of the distal extremities and face, which may
merge imperceptibly into purposeful or semipurposeful acts that mask the involuntary motion.
Athetosis is writhing movements, often with alternating postures of the proximal limbs that blend
continuously into a flowing stream of movement.
Huntingtons Disease
(Huntingtons Chorea; Chronic Progressive Chorea; Hereditary Chorea)
Parkinsons Disease
Anti-Parkinsons Drugs
Drugs used to treat Parkinsonism are anticholinergics (benztropine, trihexyphenidyl) and dopaminergics
(levodopa, pergolide, pramipexole and ropinirole) drugs and an irreversible inhibitor of the enzyme
monoamine oxidase (selegiline).
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Anti-Parkinsons Drugs

Levodopa preparations



Levodopa/carbidopa (sinemet IR): Immidiat release tablets


Levodopa/carbidopa (sinemet CR): controlled release tablets
Levodopa/benserazide
Levodopa (L-dopa)/carbidopa - the single most effective anti-Parkinson drug; it is changed
into dopamine in the brain.

Side effects: Nausea, vomiting, orthostatic hypotension, dyskinesia, hallucinations, confusion


Long term use of L-dopa/carbidopa therapy can produce: mydriasis & precipitation of glaucoma,
melanoma
High protein content meals interfere with transport of levodopa into CNS.
Levodopa should be taken on an empty stomach, typically 45min before a meal
Pyridoxin(SE) <-- Levodopa MAO-I(cause hypertensive crisis)
The most common side effects of LEVODOPA are nausea, hypotension, and hallucinations.
Domperidone (motilium) is useful for managing nausea and hypotension.
After 3-5 years of levodopa therapy, patients begin to develop motor fluctuations (wearing off, onoff) and dyskinesias. The exact cause of these late side effects is uncertain. Several strategies can be
tried in an attempt to manage motor fluctuations.
Adverse Effect
on-off (sudden
freezing unrelated to
time and dose
wearing off

Dyskinesias
Psychosis, confusion,
agitation, hallucinations,
delusions
Orthostatic hypotension

Nausea and vomiting

Management Strategies
Add a dopamine agonist
Switch to Sinemet CR
Administer levodopa more frequently
Switch to Sinemet CR
Add or increase dose of a dopamine agonist
Switch to a different dopamine agonist
Decrease dose of levodopa or dopamine agonist
Switch to a different dopamine agonist
Decrease dose of levodopa or dopamine agonist
Discontinue anticholinergic drugs, amantadine, selegiline
Can be caused by anti-parkinsonian medications, other medications
and by Parkinsons disease itself. A lying and standing blood pressure
should be checked at each visit
Decrease dose of levodopa or dopamine agonist, increase gradually
Add salt to diet
Add domperidine or fludrocortisone
Take levodopa with food
Increase dose of levodopa or dopamine agonist gradually over several
weeks

Benztropine (Benztropine)
Therapeutic use

Direct acting D2 agonist, antimuscarinic with some DA reuptake inhibitor

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Side effects
Contraindications
Counseling

Anti-Parkinsons Drugs

Anticholinergic side effects, avoid in elderly, aggravation of glaucoma,


memory impairment. Drowsiness, Dizziness, dyskinesia, hallucinations and
confusion.
Pregnancy, Inhibits the lactation, should not be used in breast-feeding
mothers. Hypertension.
Take drug with food, snacks, milk to reduce GI side effects

Antiviral Agent
Indicated in drug induced PD because levodopa will reverse the beneficial effect of the drug.
Side effects: edema of ankles.

Amantadine (Symmetrel)
Therapeutic use
Drug-Drug interaction
Side Effects

Antiviral agent with antiparkinsonian properties.


Indicated in drug induced PD because levodopa will reverse the
beneficial effect of the drug and also indicated for prevention and
treatment of Influenza A viral infections.
Amantadine may add to the effects of anticholinergic drugs.
Anticholinergic side effects
Hallucinations
Edema of feet & ankles

Entracapone (Comtan)
Mechanism
Side Effects

COMT inhibitor (Catecholamine O-Methyl transferase)


Dyskinesia, sleep disorders, hallucinations, nausea, diarrhea, anorexia

Bromocriptine (Parlodel)
Mechanism
Therapeutic use

Drug-Drug
interaction

Contraindication

Direct acting D2 agonist. Inhibiting the secretion of the hormone


prolactin from pituitary gland.
Relieving symptoms of parkinsonism
Treatment of conditions associated with prolactin production such as
Female infertility and Male infertility and impotence.
Treat benign breast condition and some menstrual disorder.
Antipsychotics oppose the action of Bromocriptine and increase the risk
of parkinsonism.
Using Bromocriptine with Ephedrine, Pseudoephedrine, and
phenothiazines, Erythromycin and other macrolide antibiotics may lead
to severe adverse effects.
Pregnancy, hypertension

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Side Effects

Anti-Parkinsons Drugs

Drowsiness, Dizziness, dyskinesia, hallucinations and confusion


Pleural fibrosis (do chest X-ray before initiating)
Erythromelalgia (painful red swelling of the legs)
Used for the treatment of neuroleptic malignant syndrome and is
approved for hyperprolactinemia.
Inhibits the lactation, should not be used in breast-feeding mothers.
Take drug with food, snacks, milk to reduce GI side effects

Pergolide (Permax)
Mechanism
Therapeutic use

Direct acting D2 agonist, efficacious and longer effective than


bromocriptine.
Used with L-dopa when L-dopa not active alone

Pramipexole (Mirapex)
Mechanism
Therapeutic use
Side Effects

Monitoring

Stimulates dopamine in the brain


Helps relieve signs and symptoms of Parkinsons disease.
Dizziness
Insomnia
Lightheadedness
Rarely it can cause hallucinations or dyskinesia.
Sudden onset of sleep
Regular monitoring of your parkinsonian symptoms, and report any
changes to the physician.

Selegline (deprenyl)
Selective inhibitor of MAOB at low doses. Indicated in early stages of PD and as an adjunct to
levodopa in patients who exhibit deterioration in their response.
SE: insomnia, confusion, hallucinations, anorexia, diarrhea, increase dyskinesia,

Anti Parkinsons drugs Tips












PD is due to decrease in Dopamine


Levodopa does penetrate into brain
Dopamine does not penetrate into brain
Carbidopa does not penetrate into brain
Dyskinesia
Metochlopramide an antinauseating drug should be avoided in PD patient
All antipsychotic required caution in PD
Levodopa/carbidopa is DOC in PD
Selegline is a selective MAO- type B inhibitor
Akinesia Characterized by difficulty in initiating movement
Bradykinesia --> slowness in performing common voluntary movement, including, standing,
walking, eating, writing, and talking.
Over treatment of Parkinsonism drugs can result into Psychotic symptoms

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Anti-Parkinsons Drugs

Abbrevation and Terminology


COMT
DA
TRAP
PD
MAO

Catecholamine O-Methyl transferase


Tartrate Resistent Acid Phosphatase
Monoamine Oxidase

Generic and Brand


Domperidone
Tolcapone
Benztropine
Amantadine
Entracapone
Bromocriptine
Pergolide
Pramipexole
Selegline

Motilium
Tasmar
Benztropine
Symmetrel
Comtan
Parlodel
Permax
Mirapex
Deprenyl

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Anesthetics

19

Anesthetics
Local Anesthetics classification

Amides Type

Esters Type
Long duration
Tetracaine
Medium Duration
Cocaine

Short duration
Procaine

Long duration
Bupivacaine
Ropivacaine

Surface-active
Benzocaine
Cocaine

Medium duration
Lidocaine

Inhibit sensory nerves that carry stimuli to CNS


Block nerve fiber conduction
Blockade is reversible must continue administration of the drug for effects to continue
Ester local anesthetics: produce PABA as metabolic product
Amide local anesthetics: Metabolized by liver
Most local anesthetic solutions contain the vasoconstrictor epinephrine
Epinephrine used (1:100000) in local anesthetics as vasoconstrictor
o Epinephrine in local anesthetic helps:
To prolong the duration of action
Reduce systemic absorption thereby decrease systemic toxicity
General Anesthetics

Intravenous

Inhaled

Gas
Nitrous oxide
Ether (diethyl ether)

Volatile liquid
Halothane
Enflurane
Isoflurane

Barbiturate
Thiopental

Miscellaneous
Propofol

Dissociative
Ketamine

Benzodiazepines
Midazolam

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Anesthetics

Inhaled anesthetic are used to provide general surgical anesthesia


Intravenous are indicated to induce drowsiness and provide relaxation before the induction of
inhalational general anesthetics
The minimum alveolar concentration (MAC) is the alveolar anesthetic concentration at one
atmosphere (760 mm Hg) preventing movement in 50% of patients exposed to noxious stimuli.
Halothane (Fluothane) is used in pediatric anesthesia; it is infrequently used in adults.
Isoflurane (Forane), enflurane (Ethrane), sevoflurane (Sevorane, Ultane) anddesflurane (Suprane) are
frequently used in adults.
Enflurane is used as an inhalational agent for adults; but is not widely used for pediatric cases.
Isoflurane may be the most widely used inhalational agent.
Sequence of MAC
Nitrous oxide > Ether > Enflurane >Isoflurane > Halothane
Nitrous Oxide: With a MAC value of 105%, nitrous oxide, by itself is not suitable or safe as a sole
anesthetic agent. Nitrous oxide is an effective analgesic
Effective: Nitrous oxide in combination with: Thiopental for induction, a skeletal muscle relaxant and
hyperventilation to reduce CO2.
Use as an adjunct to other inhalational agents allows reduction in their dosage.
Ketamine
Short acting non-barbiturate anesthetic induces a dissociated state in which the patient appears
awake but is unconscious and does not feel pain.
Causes sedation, immobility, amnesia, and nightmares, and uses hypertension and increases cardiac
output-avoid use in stroke and High BP patients.
Mainly used for short procedures
Propofol
Sedative or hypnotic
Used in induction and maintenance of anesthesia
Fast onset (40 seconds of administration)
Poor analgesic
Fentanyl
Narcotic
Available as transdermal patch (Duragesic), and good analgesic property

Anesthetic Tips








Ester type of local anesthetic metabolize to Para Amino Benzoic acid


Epinephrine is a
Epinephrine helps
Local anesthetic do not produce
Benzocaine topical anesthetic is used for
Ester type local anesthetic include
Procainamide
Lidocaine is used for
Thiopental is classified as

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Anesthetics

Malignant hyperthermia associated with


General anesthetic safe in children

Abbrevation and Terminology


MAC
CNS
PABA

Minimum Alveolar Concentration


Central Nervous System
Para Amino Benzoic acid

Generic and Brand


Halothane
Isoflurane
Enflurane
Sevoflurane
Desflurane

Fluothane
Forane
Ethrane
Sevorane, Ultane
Suprane

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Anesthetics

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Opioids

20

Opioids
Opioid Analgesics Classification
Mixed agonist antagonist
Pentazocine
Nalbuphine

Agonists

Strong
Morphine
Heroin
Meperidine
Methadone
Other agents
Fentanyl
Levorphanol

Moderate
Codeine
Oxycodone
Hydrocodone

Antagonists
Naloxone
Naltrexone

Weak
Propoxyphene

Opioids are used for moderate to severe pain of trauma, post-surgical pain, pain associated with myocardial infarction and pain of terminal illness. Physical and psychological dependence (addiction)
can occur when opiates are administered for some time. When tolerance develops, the patient requires increasing amounts of drug to treat pain. All opioids are habit forming, however, titrated doses
tolerate pain, the risk of addiction is slight.
Opioid receptors and neurotransmitters
Functions
Analgesia-Supraspinal
Analgesia- Spinal

Receptors
Mu (m)/delta (d)
+
+

Respiratory depression
Sedation
Euphoria
Dysphoria
Physical dependence and tolerance
Constipation

++
++
+
+
+

Kappa (k)
+
+
+
+
+
+

Opiate
Receptors
Mu (m)
Kappa (k)
Delta (d)

Neurotransmitters
b-Endorphin
Dynorphin
Enkephalins

Distribution of opioid receptors


Opioid receptors
Effects
Brainstem
Respiration
Cough
Nausea
Vomiting
Maintenance of blood pressure
Papillary diameter
Control of stomach secretions
Medial Thalamus
Deep pain
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Spinal cord

Opioids

At substantia gelatinosa Receipt and integration of incoming sensory


information
Neuroendocrine secretions
(The highest concentration of opioid receptors located in amygdale)
Influence emotional behavior
Inhibit Ca 2+ dependent release of excitations
Inhibit pro inflammatory substances from nerve ending.
These may contribute to inflammatory effect of opioid
Response or sensitivity to painful stimuli

Hypothalamus
Limbic system
Periphery
Immune cells
Opioid Analgesics
Therapeutic use

Side Effects

Overdose

Drug-Drug
interactions
Addiction potential

All opioids

Analgesia- Best for dull aching type of pain. Increase tolerance or


reaction to pain.
Sedation -Drowsiness, inability to concentrate, short term memory loss
Cough -Direct suppression of cough center in brain. Not used for this
effect because of addictive ability
GI tract: constipation Emesis& nausea:
Decrease respiration- hypoxic.
Pinpoint pupil - Due to increase in cholinergic activity.
Urinary retention
Urticaria
Bronchoconstriction
Hypotension
Not used when treating head trauma, because of increase pCO2 due to
decrease respiration causes cerebral vasodilation
Three characteristic symptoms: pinpoint pupil, decrease respiration, coma
Absolute contraindication: MAOI to meperidine
Other opioids relative contraindication
Sedative and hypnotics increase respirator depression
TCA and antipsychoticsincrease sedation
Morphine
Meperidine
Methadone
Fentanyl
Codeine
Propoxyphene
Addiction potential concern in cancer chemotherapy
7 10 days use in surgery no addiction
Increase dose increments and decrease dose in increments
Do not change frequency but may increase dose (if choice between
frequency and increase dose)

Opioid analgesic therapeutic effects


Morphine
Hydrocodone
Codeine

For chronic use


Cannot be glucuronidase at 6-position. Used in renal failure
Codeine derivative, used for pain cough suppression
More addictive than codeine.
Used for cough suppression and mild to moderate pain.
Analgesia does not increase with dose (ceiling effect).
Additive effect with ASA and acetaminophen

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Oxycodone

Meperidine

Pentazocin

Methadone

Butorphanol
Nalbuphine
Naloxone
Naltrexone
Nalmefene

Opioids

Codeine derivative, used for pain cough suppression.


More addictive than codeine.
Oral form, long half-life
Used for suppressing opioid withdrawal symptoms
Less emetic effect
Milder withdrawal symptoms.
Used during labor. Anticholinergic effect. No miosis, Tachycardia (IV),
Toxic doses may cause CNS stimulation
Normeperidine (metabolite) - hallucinations and convulsions
Constipation and urinary retention less than for morphine.
May precipitate (trigger) withdrawal symptoms when given instead of
morphine. Oral and IM dosing.
Same as pentazocine.
Used for chronic pain only (intranasal, refract headache)
Same as for pentazocine.
Low respiratory depression. Little euphoria (excited state of mind).
Analgesia during labor.
Full antagonist. IV only because first pass effect is 98%.
Short half-life.
Partial antagonist, Long half-life. Is given orally.
Treat alcoholics decrease craving.
Injectable blocker. Longer half life than naloxone

Opioids Tips























Dyspnea is
Avoid opioids in head trauma patients
Morphine active metabolite
Analgesic activity of morphine
Codeine is metabolized by
Patient taking Tylenol # 3 + hydromorphone
Methadone is used for
Morphine over dose symptoms
Which opioids has highest addiction potential
In Angina pain what opioids is used
Drugs used to treat opioids withdrawal symptoms
Opioid antagonist
A patient developed seizure after initiating opioids therapy, which opioids would be
responsible
Opioids least used in
Pinpoint pupil is opioids
Patient on methadone and has already missed dose for three consecutive days, what is
appropriate suggestion
Avoid opioids with MAOI
Opioid induced constipation treated by
Enkephalins are
A patient is on opioids, having constipation, started taking psyllium laxatives but no
improvement, you advise him
How to apply fentanyl transdermal patch
Allergic to morphine can use
What is the antidote for an OxyContin overdose?
Name the antagonist of choice for an opiod overdose.

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Opioids

Least respiratory depression Meperidine


If allergic to morphine Meperidine and Fentanyl can be used
Higly fat soluble opioids Fentanyl
Preferred opioids in labor meperidine
Sequence of addiction/abuse liability: Morphine = Meperidine = Methadone = Fentanyl >
codeine > Propoxyphene

Abbrevation and Terminology


MAOI

Monoamine Oxidase Inhibitor

Generic and Brand


Pentazocine
Nalbuphine
Naloxone
Naltrexone
Meperidine
Methadone
Fentanyl
Levorphanol
Oxycodone
Hydrocodone
Propoxyphene
Naltrexone

Talwin, Talwin NX
Nubain
Narcan, Narcan Neonatal
Depade, ReVia, Vivitrol
Demerol, Meperitab
Diskets, Dolophine, Methadose
Actiq, Duragesic, Fentora, Sublimaze
Levo-Dromoran
Endocodone, Eth-OxyDose, OxyContin OxyFast,
Hycodan, Hydromet, Hydropane, Mycodone, Tussigon
Darvon, Darvon-N 100, Darvon-N,
Depade, ReVia, Vivitrol

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21

Non-Steroidal Anti-inflammatory Drugs

Analgesics
Acetic acid
derivatives
(including
indole
derivatives)

Fenamates

COX-2
inhibitors

Napthylalkanoes

Celecoxib
Meloxicam
Valdecoxib

Floctafenine
Mefenamic acid

Diclofenac potassium
Diclofenac sodium
Etodolac
Indomethacin
Ketorolac tromethamine
Sulindac
Tolmetin sodium

Salicylic acid
derivatives

Oxicams

Nabumetone

Acetaminophen

Propionic acid
Derivatives

Meloxicam
Piroxicam
Tenoxicam

Acetylsalicylic acid (ASA)


Diflunisal
Choline Magnesium
trisalicylate
Choline Salicylate
Triethanolamine salicylate

Fenoprofen Calcium
Flurbiprofen
Ibuprofen
Ketoprofen
Naproxen sodium
Oxaprozin
Tiaprofenic acid

Summary of NSAIDs induced ulcers


Risk Factors for
Development of
Upper GI side effects
with NSAID

Age > 65
Anticoagulants or oral glucocorticoids
History of peptic ulcer disease
History of upper GI conditions
Comorbid medical conditions
Misoprostol
PGE1 analog
Increases bicarbonate secretions
Increase mucus secretions
Proton pump inhibitor (Omeprazole,lansoprazole)

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Recommendation

ASA
Salicylate allergies

Non-Steroidal Anti-inflammatory Drugs

Proton pump inhibitors elevate pH 4


Acts as an antacids
Prevents and treat NSAID induced ulcers
Sucralfate
Mucus protective agents
Aluminum hydroxide and sulphate sucrose (disaccharide)
Should be avoided with antacids
Taken empty stomach
Products like misoprostol (Cytotec) act as protectant and are
prescribed with NSAIDs to prevent gastric ulcers.
Sucralfate (Sulcrate) ranitidine (Zantac) and proton pump
inhibitors, such as omeprazole (Losec), are sometimes often
administered at the same time as NSAIDS to prevent ulcers.
Reyes syndrome in children with chickenpox and flu (primarily ASA)
If allergy with one NSAIDs avoid all other NSAIDs use

Acetylsalicylic Acid
Mechanism

In low doses inhibits platelet COX production of thromboxane A2


preventing platelet aggregation.
Cox permanently inhibited for life of the platelet.
Platelet life 7-10 days.
Antiinflammatory
Analgesic
Antipyretic
Antiplatelet
Prevent blood clot
Prophylactic treatment of MI to prevent infarction and stroke.
Treatment for transient ischemic attacks to reduce stroke and
vascular deaths.

Therapeutic use

Ibuprofen (Advil, Motrin)


Ibuprofen
Mechanism
Therapeutic use

Side Effects
Drug-drug
interaction

Advil, Motrin, Novo-Profen, Apo-ibuprofen, Nu-ibuprofen


A NSAID which reduces pain, stiffness, and inflammation
Treat for symptoms of:
Osteoarthritis
Rheumatoid arthritis
Acute Gout attacks
Relief of mild to moderate:
Headache
Menstrual and dental pain
Pain resulting from soft tissue injuries
Pain that may follow an operation
Heartburn and indigestion
Black or bloodstained feces (should be reported without delay)
Nausea and vomiting, rash, breathlessness, ringing of ears (rare
Ibuprofen interacts with ASA, NSAIDs, oral anticoagulants and
corticosteroids will increase the risk of bleeding and peptic ulcer.

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Contraindication
Monitoring

Non-Steroidal Anti-inflammatory Drugs

Not usually prescribed to pregnant women


Avoid alcohol (it may increase risk of stomach disorders)

Butalbital
Therapeutic use
Side Effects
Management

Analgesic
Dependence
Additive sedation with other CNS depressants (e.g. alcohol)

Naproxen
Therapeutic use

Side Effects
Management

NSAID to reduce pain, stiffness, and inflammation.


Relieves symptoms of rheumatoid arthritis, ankylosing spondylitis, and
osteoarthritis.
Acute attacks of gout
GI upset
Increase risk in bleeding
Use on only 2 days/wk for headache, for symptomatic treatment only, less
risk of rebound than with other analgesics; useful in premenstrual attacks

Ketoprofen
Mechanism

NSAID

Therapeutic use

Side Effects

Nausea and vomiting


Abdominal pain
Heartburn

Drug-drug
interaction

NSAIDs and ASA will increase the risk of bleeding with Ketoprofen
Lithium, digoxin, and methotrexate may raise blood levels with
Ketoprofen.
Alcohol may increase risk of stomach disorders
Quinolone antibiotics may increase the risk of seizures

Contraindication

Relieves pain and reduces inflammatory and stiffness in:


Rheumatoid arthritis
Osteoarthritis
Ankylosing spondylitis

Diclofenac
Mechanism
Therapeutic use

Analgesic similar to acetaminophen


Relieves mild to moderate headache
Menstrual pain
Pain following surgery
Acute attacks of gout
Relieves pain and stiffness associated w/ rheumatoid arthritis and
osteoarthritis (when given regularly)

Side Effects

GI disorders

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Drug-Drug
interaction
Contraindication
Monitoring

Non-Steroidal Anti-inflammatory Drugs

It interacts with NSAIDs, oral anticoagulants, and corticosteroids, risk


of bleeding and ulcer may increase
Cyclosporin with Diclofenac may increase the risk of kidney problems
Not usually prescribed in the last month of pregnancy as it may
increase the risk of affecting babys heart and promote prolong labour.
There is an increase risk of bleeding from peptic ulcers and in bowel
with prolonged use.

Piroxicam
Therapeutic use
Side Effects
Drug-drug
interaction

Contraindication
Monitoring

Gives relief to the symptoms of Osteoarthritis, Rheumatoid arthritis,


acute attacks of gout, alkylosing spondylitis.
Stomach ulcer
Nausea, dizziness, swollen feet, rash, wheezing
Increase the risk of bleeding and or peptic ulcer with NSAIDs,
corticosteroids, and oral anticoagulant drugs.
Piroxicam may raise the blood levels into undesirable extent with
Lithium, digoxin, and methotrexate.
Piroxicam may reduce the beneficial effects of antihypertensive and
diuretic drugs.
Piroxicam may increase the risk of convultion side effect of
Ciprofloxacin, norfloxacin, and ofloxacin
Not recommended to pregnant, infants and children.
Alcohol may increase the risk of stomach disorders
Periodic blood count and liver function test
Rash, wheezing, black or bloodstained feces, bruising or bleeding

NSAIDs Tips


















Analgesic action of acetaminophen is due to


If allergic to aspirin
Rye syndrome with
Life span of platelet
Sulfaslazine metabolism occurs in
Acetaminophen least used in
Antiplatelet action of aspirin at what dose
Symptoms of salicylism is treated by
Misoprostol is
Misoprostol chemically classified as
Salicylism generally occurs at what dose
Mercaptopurine is produced by
ASA and acetaminophen interchangeable for
All NSAIDs common complication is
Aspirin toxicity
In alcoholic patient if acetaminophen given in multigrams, which substance is decreased
Acetaminophen antidote
Acetaminophen metabolized by
What are pharmacological action of COXII selective -->

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Non-Steroidal Anti-inflammatory Drugs

Which salicylate cause folic acid deficiency -->


What is mechanism of N-acetylcysteine -->
DOC for aspirin induced asthma -->
Which NSAID has most effect on kindney (Crcl) -->
The primary active component of sulfasalazing
What if kind of reaction ASA undergoes in stomach
Toxicity of ASA in child will be worse than in adults because
Rye syndrome
Which is the strongest endogenous pain producer
Salicylate toxicity excessive respiration is due to
Diclofenac eye drops causes
Ketorolac is used to treat
PGE2 analog
PGF2a analog
PGE1 analog
PGI2
TxA2

Abbrevation and Terminology


NSAIDS
PGE
ASA
COX
MI

Nonsteroidal Anti-Inflammatory Drugs


Prostaglandin
Acetyl Saliaylate
Cycloxygenase
Myocardial Infarction

Antipyretic: a drug to reduce fever.


An analgesic: a drug used to relieve pain.
Antiinflammatory: Drugs that reduce redness and swelling.

Generic and Brand

Misoprostol
Sucralfate
Ranitidine
Omeprazole
Ibuprofen
Butalbital
Naproxen
Ketoprofen
Diclofenac
Piroxicam

Cytotec
Sulcrate
Zantac
Losec
Advil, Motrin
Fiorinal with ASA +codein
Naprosyn, Anaprox, Novo-Naprox
Apo-Keto, Noveo-Keto, Orudis SR
Volraren, Cataflam, Solaraze
Apo-Piroxicam, Feldene, Novo-Pirocam

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Non-Steroidal Anti-inflammatory Drugs

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Autocoids

22

Autocoids
Autocoids (Local hormones): Chemical mediators that the body releases as a response to pathogens
or noxious substances. Produced in the body and has profound pharmacological effects.
Classification of autocoids
Amines type Histamine, Serotonins
No real clinical application in the treatment of diseases however antihistamines are of great
importance.
Endogenous Peptides
Prostaglandins, Prostacyclin, Thromboxane, Leukotrienes, bradykinins
Site of production for endogenous peptides are GIT, kidneys, lungs, pancreas and uterus.



Prostaglandins pain sensation, development of inflammation, edema


Thromboxane aggregation of platelets
Prostacyclin inhibition of platelet aggregation
Leukotrienes inflammation, chemotactic properties (pull substances to them),
branchoconstriction.

Histamines
Histamine H1-receptor blockers

Particularly
Diphenhydramine,
promethazine

Anti
Cholinergic
(muscarinic)
receptor

Particularly
promethazine

Alpha
Adrenergic
receptor

Dopamine
receptor

Particularly
cyproheptadine

Serotonin
receptor

All H1- antihistamines

Histamine H1
receptor

Histamine H2
receptor

Histamines have three receptors H1, H2 and H3


H1 Receptor Functions
H1- typical allergic and anaphylactic response to histamines.
Bronchoconstriction
Vasodilation
Increase capillary permeability
Spasmodic contractions of gastrointestinal smooth muscle (GI)
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Autocoids

H1 antihistamine pharmacological actions (Drugs action)


Blocks histamine effect on:
Allergic symptoms
Seasonal rhinitis
Conjunctivitis
Rhinoviral infections (common cold)
Urticaria
Comments
Usually lipid soluble
Similar in terms of absorption and distribution
Good absorption after oral administration distribution with peak plasma concentration of 1 2 hours
Allows some to go to the blood-brain-barrier especially structural resemblance to histamine

H1 Antihistamine Chemical classification
ETHYLENE DIAMINES: Pyrilamine, Tripelennamine
ALKYLAMINES: Brompheniramine, Chlorpheniramine, Acrivastine.
ETHANOLAMINES: Diphenhydramine, dimenhydrinate, doxylamine
PIPERAZINES: Meclizine, Cyclizine, Hydroxyzine, Cetirizine
PHENOTHIAZINE: Promethazine
DIBENZOCYCLOHEPTENES: Cycloheptadienes
PTHALAZINONE: Azelastine
PIPERIDINE: Terfenadine, Astemizole, Levocabastine, Loratadine, Fexofenadine.
H2 antihistamines
H2-Receptors Mediated Functions
H2-receptors responses to histamine such as: Increased secretion of gastric acid, Increase pepsin and
Intrinsic factor (Castles factor).
H2 receptor antagonist competitively block H2 receptors thus blocking the effect of histamines on
gastric secretions
H2 antagonist: Ranitidine, Cimetidine, Famotidine, Nizatidine

Serotonin (5-Hydroxy tryptamine 5HT)


Serotonin

5HT1a

Agonist
Buspirone
(BuSpar)

5-HT1b/1d

Agonist
Triptans
Sumatriptan
Rizatriptan
Zolmitriptan
Naratriptan

5-HT2

5HT3

Ergotamine (DHE)
Antagonist of 5-HT2a
Atypical antipsychotic
Olanzapine, clozapine,
and risperidone

5HT4

Antagonist
Ondansetron
Alosetron
Fabesetron
Ramosetron

Agonist
Cisapride

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Autocoids

Tryptophan (amino acid) 5-hydroxy tryptophan Serotonin (Neurotransmitter)


Conversion of tryptophan to serotonin takes place in two reaction, first hydroxylation and
decarboxylation catalyzed by tryptophan hydroxylase and L-amino acid decarboxylase
respectively. Serotonin contain indole ring.
Serotonin group has several subtypes of receptors:
5HT2Vasoconstriction, platelet aggregation
5HT3Nausea / vomiting
5HT4 Release of acetyl choline in the enteric region.
5HT1, 5HT2, and 5HT3Anxiety, depression, aggression, impulsive and appetite
5HT1DAuto receptors inhibit presynaptic activity in both serotonergic and adrenergic neurons
in the CNS.

Serotonin Agonist
5HT1D/1B receptor agonist
TRIPTANS (all are indole derivatives)
Sumatriptan
Rizatriptan
Naratriptan
Zolmitriptan
Almotriptan
Frovatriptan
5HT1D receptor agonist side effects: Feeling of warmth, dizziness, tightness or heaviness in the chest,
rarely patient may experience chest pain.
5HT4 agonist
Cisapride (a benzamide)
Tagaseride (indole derivative)
Ergotamine-serotonin partial agonist: Ergot alkaloids have agonist and antagonist properties

Serotonin Antagonist
5HT3 receptor antagonist
Ondansetron (indole derivatives),
Granisetron (benzimidazole derivative)
Ergot alkaloids and derivatives with antagonist/partial agonist activity include:
Ergonovine
Dihydroergotamine (DHE)
Methysergide
Bromocriptine
Ondansetron side effects: Constipation, headache, dizziness and Granisetron--diarrhea

Prostaglandin
Prostaglandin chemical classification
Prostaglandin has been classified based presence and absence of keto or hydroxyl groups
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Autocoids

at 9 and 11. Subscripts relate to the number of double bond present in aliphatic chains
Platelet aggregation, Relax bronchial and GI smooth muscles, Relax smooth muscles, Inhibit gastric
acid secretion, Pain, Edema, Inflammation
Prostaglandin analogs

PGF2

PGI2

Latanoprost

Epoprostenol

Thromboxane A2

Branchial &
Branchial &
Branchial &
smooth
smooth
smooth
muscle
muscle
muscle
dilatation
constriction
dilatation
Pharmacological actions of prostaglandins

Blood vessels
dilatation

Platelet
aggregation

PGE2

PGE1

Misoprostol
Alprastadil

Dinoprostone

TxA2

Inhibit
aggregation

Corticosteroids

Receptors
PGI2

Actions
Vasodilation
Decrease platelets aggregation
Maintaining renal blood flow

PGE1

Protects gastric mucose


Inhibiton acid secretion
Stimulation of mucus secretion

Leukotrienes

Lipoxygenase
Arachinodic acid

Membrane
phospholoipids

NSAID, Aspirin, COX-II


Phospholipase A2

PGE2
Pyrogen elevate PGE2

Contraction of uterus

PGF2

Bronchoconstriction
Contraction of uterus

PGD2

Vasodialtion
Inhibition of platelets aggregation

TXA2

Increase Platelets aggregation


Vasoconstriction

Prostaglandins G

Hydroperoxidase
PGH2

Dipyridamole

Prostacyclin (PGI2)

PGE2 & PGF2

Thromboxane A

Platelet aggregation
Vascular tone

Uterine tone

Paltelet aggrega

Vascular tone

Vascular tone

Bronchial tone

PGE Analogs

Cyclooxygenase

Uterine tone

Bronchial tone

PGE1 analogs
Misoprostol (Cytotec): is used for prevention of NSAID induced GI ulcers.
Chemically it is ecosonides
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Autocoids

Combination products: Naproxen + Misoprostol, Diclophenac + Misoprostol (Arthrotec)


Alprostadil
In adults for the treatment of impotence
Alprostadil (Caverject, Prostin VR pediatrics) is used treating impotence due to erectile dysfunction.
Alprostadil (Prostin VR pediatric) is used for temporary maintenance of a patent ductus arteriosus
when awaiting corrective surgery for congenital heart defects.
PGE2 analogs
Dinoprost, Dinoprostone
Dinoprostone derovatives Abortificient
Dinoprostone (Prostin E2, Prepidil, Cervidil) are used for their abortifacient effects and to induce
cervical ripening in pregnancy.
PGF2a analogs
PGF2a analogs are selective Prostanoid FP receptor, inhibitors that reduce IOP, and increase outflow
of aqueous humor.
Latanoprost (Xalatan) (Used topically to lower intra ocular pressure in OAG)
Travoprost (Travatan) topical ophthalmic drug
Bimatoprost (Lumigan) topical ophthalmic drug
Unoprostone (Rescula) topical ophthalmic drug
Carboprost (Hemabate) abortificient (withdrawn)
Precautions: Opthalmic solutions have been reported to cause changes to pigmentated tissue.
The changes include the increased pigmentation and and growth of eyelashes and increased
pigmentation of iris and periorbital tissue (eyelid). The increased pigmentation is permanent.
Latanoprost (Xalatan)
Store unopened bottle under refrigeration. Protect from light. Once opended store botte in cool
place (refrigerate if possible) for upto 6 weeks.
Bimatoprost (Lumigan)
Store at room temperature, no refirigeration necessary
PGI analogs (Prostacylcin)
Epoprostenol (Prostcyclin, Flolan):
Used in the treatment of emergency pulmonary hypertension.
Prostaglandin analogs

Leukotrienes
Physiological functions
LTC and LTD antagonists

Play important role in numerous
physiological functions.

Slow reacting substance of anaphylaxis.

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Heart Negative inotropic, Smooth muscles


chemotaxis (Chemotaxis = movement of cell in
response to the chemical gradient)

GI tract Neutrophil chemotaxis

Autocoids

Pulmonary (major) Bronchoconstriction,


increase permeability, and increase mucus secretion.

Blood Chemotactic agent for neutrophils,


eosinophils, and modify lymphocyte proliferation
and differentiation.

Two important leukotrienes antagonists


LTC4 and LTD4
Leukotriene antagonist: (LTC4 and LTD4)
e.g. Zafirlukast (Accolate) and montelukast (Singulair)Peptid mimetic structure. Indicated in
prophylaxis of asthma.
Zafirlukast (Accolate)
Therapeutic use: For the prophylaxis and chronic treatment of asthma in adults and children
12years of age and older. Side effects include: GI upset, liver dysfunction.
Take empty stomach to enhance it absorption





Montelukast (Singulair)
Similar profile to that of Zafirlukast.
Can be used in children over 2-year age
Montelukast may be taken without regard of food.
Available as chewable tablet (once daily in the evening).
Administer granules directly into mouth or mix with teaspoon of cold or room temperature
applesauce, carrot, rice or ice cream.
Do not take aspirin or NSAIDs while on this medication.

Abbrevation and Terminology


5HT
DHE
PGF
FP
LTC
LTD
PGI
OAG
IOP

5-hydroxy tryptamine (Serotonin)


Dihydroergotamine

Generic and Brand


Misoprostol
Alprostadil
Dinoprostone

Cytotec
Caverject, Prostin VR pediatrics
Prostin E2, Prepidil, Cervidil

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Latanoprost
Travoprost
Bimatoprost
Unoprostone
Carboprost
Epoprostenol
Zafirlukast
Montelukast

Autocoids

Xalatan
Travatan
Lumigan
Rescula
Hemabate
Prostcyclin, Flolan
Accolate
Singulair

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Autocoids

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Insulin and Anitdiabetic Drugs

23

Insulin and Antidiabetic Drugs

There are two types of diabetes mellitis, Type I and Type II. For Type I diabetes, patients need insulin
injections. Type I diabetes is known as insulin dependent diabetes mellitis (IDDM). It usually begins
in young people under 40 and of normal weight. Onset is sudden and severe; ketones are found in the
blood and urine.
Types of Insulin

Ultra rapid

Rapid

Intermediate

Long-acting

Ultralente
Protamine
Zinc

Insulin lispro
Glargine

Types of insulin are categorized by their onset of action, and these relative positions hold true for
their effectiveness and their duration of action as well.
NPH
Lente

Regular
Semilente

Oral Diabetic drugs


Insulin
Secretagogues

Sulfonylureas

1 Generation
Tolbutamide
Tolazamide
Chlorpropamide
st

Nonsulfonylurea insulin
secretagogue
Meglitinides
Repaglinide
Neglitinide
Biguanide
Metformin

2 Generation
Glyburide
Glipizide
Glimepiride
nd

-glucosidase
inhibitor
*Acarbose
Thiazolidinedione
*Pioglitazone
*Rosiglitazone

Type I and Type II Diabetes Mellitus (DM)


Insulin
Duration
Humalog (H) (lispro)
synthetic

Very short
(fastest)
iv form

Onset
(hours)

Peak
(hours)

5-10
min

30-40
min

Usual Effective
Duration of Action
(hours)
2-3 h

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Regular (R)
(suitable for iv dose). Both
human and animal source
NPH (N) Isophane
Amorphous precipitate of
insulin w/ zinc ion acetate
buffer
Ultralente
Zinc suspension crystals
in acetate buffer contain
large particles that are slow
dissolve


Rapid (short)
-1 h
Subcutaneous
Or iv (in emergencies)
Intermediate
2-4 h
Semilente (30%)

1-3 h

5-7 (dose-dependent;
may be longer)

6-10 h

14-18 h
not suitable for iv
dose

Long
(70%)
Slowest onset of
action but Longest
hypoglycemic effect.

18-28 h

Type I and Type II Diabetes Mellitus (DM)


DM
Type I Insulin dependent DM
(IDDM)
5 10%
Juvenile onset
Destruction of b-cells in pancreas
No production of insulin Associated
with treatment is by Diet and
insulin.
Ketoacidosis occurs
Treatment

Insulin and Anitdiabetic Drugs

Insulin

Oral
hypoglycemics

4-5 h

Type II Non-insulin dependent DM


(NIDDM)
>90%
Adult onset (40 yrs)
Milder form
Very strong genetic predisposition
Inability of beta cells to produce adequate
insulin and doesnt meet the bodys
requirements.
Mainly due insulin resistance
Diet
Oral hypoglycemics
Oral hypoglycemics + insulin
Sulfonyl ureas Stimulate insulin
secretions
Meglitimides Stimulate insulin
secretions
Biguanides Inhibit gluconeogenesis in
liver, increase glucose uptake in cell.
Thiozolidinediones Increase insulin
sensitivity (decrease resistance) increase
glucose uptake in cell.
Alpha glucosidase inhibitorsInhibit
glucosidase in GI tract.
Intestinal lipase inhibitors Orlistat

Diagnosis (Diabetic)
1-Symptoms
2-Random Blood sugar levels > 14.0 mmol/L
3-Fasting Blood sugar levels > 11.1mmol/L
4-Post prandial BSL > 14.0 mmol/L
5-Glycosylated hemoglobin (HbA1c) > 7%
Normal Blood sugar levels (BSL)
Fasting BSL 5-6 mmol/L
Random BSL 11.1 mmol/L
Post prandial 14.0 mmol/L
HbA1C is 4 - 6%
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Insulin and Anitdiabetic Drugs

Measures past three months Blood sugar levels


Used to determine antidiabetic drugs compliance of pathient
Insulin Combinations
Insulin storage conditions
Should be stored in refrigerator
Can be stored at room temperature 28 days (1 month)
Do not shake vigorously
If you notice turbidity or vapors or precipitation, do not use, discard it

Oral antidibetics
Hypglycemic drugs: Sulfonylureas, Meglitinides
Antihyperglycemics: Biguanides, Thizolinediones
Medication

Mechanism

Side effects

Contraindications

Sulfonylureas
Glyburide (DiaBeta)
Chlorpropamide
(Diabinese)
Gliclazide

Stimulate release of
endogenous insulin

Hypoglycemia
Nausea
GI discomfort
Weight gain

Meglitinides
Repaglinide (Gluconorm)

Stimulate release of
endogenous insulin
(rapid-acting, better
post-prandial glucose control): Must
take before meals,
because
Decrease postprandial glucose levels.
1-Reduce gluconeogenesis,
2-increase glucose
utilization

Hypoglycemia, especially if taken empty


stomach
(Less frequent than
with sulfonylureas)
Weight gain

Hepatic or renal
Impairment
Chlorpropamide not a good
choice in elderly (long half
life)
Not used in Type 1 DM
Pregnancy
It is important to Avoid
alcohol, it can cause disulfiram type reactions.
Hypersensitivity
Diabetic Ketoacidosis
(DKA)
Not indicated in type I diabetes
Contraindicated Pregnancy

Biguanides
Metformin (Glucophage)

Lactic acidosis, in
hepatic and renal disease patients
GI discomfort Anorexia, nausea, diarrhea, metallic taste
Due to anorexia
caused by metformin
this drugs used for
weight loss.

Hepatic or renal
Impairment
Alcoholism
Advanced age
Previous lactic acidosis
DOC in obese
Therapeutic uses also include: To treat Infertility
For weight loss

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Thiazolidinediones
Rosiglitazone
(Avandia)
Pioglitazone
(Actos)

Glucosidase
Inhibitors
Acarbose
(Prandase)


1-Increase peripheral
insulin sensitivity,
2-Reduce gluconeogenesis

Decrease the absorption of carbohydrates


(thus decreasing
postprandial rise of
glucose)

Insulin and Anitdiabetic Drugs


Increased HDL, Increase LDL and Pioglitazone (decrease
TG),
Weight gain,
Hepatotoxicity,
Anemia
Fluid retention

Flatulence
Abdominal
Cramping, nausea
Diarrhea.
Decrease metformin
bioavailability.

Liver disease,
Congestive heart failure
(CHF)
Gender selective Resume
ovulation in previously anovulatory women (example:
polycystic ovarian syndrome). Increase chances
of pregnancy, if insufficient
contraception not used.
May be taken with or without food
Hypersensitivity,
DKA,
Inflammatory Bowel
Disease (IBD)
Pregnancy & Lactation,
Liver cirrhosis
With first bite of meal.
Skip the dose if you skip
meals.

Intestinal lipase inhibitor


Orlistat (Xenical)

Intestinal lipase inhibitor


120 mg TID with
meals

Diarrhea
Steatorrhea (Fatty
stools)
Abdominal discomfort
Oily leakage

May interfere with abdominal absorption of fat soluble


vitamin ADEK

Chlorpropamide (Diabinese)
Mechanism
Therapeutic use

Contraindications

Side Effects

Increased insulin release from beta cells of the pancreas


To control hyperglycemia in glyburide-responsive DM of stable,
mild, nonketosis prone, maturity onset or adult type which cannot be
controlled solely by proper dietary management, exercise and weight
reduction or when insulin therapy is not appropriate.
Patients during stress conditions such as severe infection, trauma or
surgery.
Patients with liver disease or renal impairment; or frank jaundice.
Chlorpropamide not a good choice in elderly (long half life)
Hypoglycemia, GI discomfort: Nausea

Repaglinide (Gluconorm)
Mechanism
Therapeutic use

Stimulate release of endogeneous insulin (rapid-acting, better postprandial glucose control)

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Contraindications
Side Effects

Insulin and Anitdiabetic Drugs

Hypersensitivity
Diabetic Ketoacidosis (DKA)
Hypoglycemia(less frequent than with sulfonylureas)

Gliclazide (Diamicron)
Mechanism
Therapeutic use
Side Effects
Drug-drug
interaction
Contraindication
Monitoring

Stimulates the production and secretion of insulin from the islet cells of
pancreas.
Treat adult (maturity-onset) diabetes mellitus
Faintness and confusion
Weakness and tremor
Sweating, constipation and diarrhea
Corticosteroids, estrogens, diuretics, rifampin, other drugs may reduce
the effect of gliclazide.
Alcohol
Not recommended to pregnant, lactating mothers, and children.
Regular testing of sugar levels in the blood and urine is required.
Periodic assessment of the eyes, heart, and kidneys may also be
advised.

Meglitimides ( Repaglinide, Natelinide)


Mechanism
Contraindication
Side effects
Drug-Drug
interactions

Stimulates the release of insulin


Type I and pregnancy
Hypoglycemia if meal not taken
Repaglinide has weight gain side effect
-Clearance inhibited by ketoconazole, miconazole, and erythromycin
-Enhance clearance with barbiturates, rifampin, and carbamazepine

Metformin (Glucophage)
Mechanism
Therapeutic use
Side Effects

Contraindication
Drug-Drug
interactions

Does not stimulate secretion of insulin like sulfonyl ureas. Rather decreases
hepatic glucose output by inhibition of gluconeogenesis.
Reduces LDL, VLDL, cholesterol levels
To control hyperglycemia
For the treatment of obese diabetic patients.
No weight gain side effect.
Preferred in obese patients
Lactic acidosis (in hepatic or renal failure patient), metallic taste, N, D and
anorexia
Contraindicated in renal and hepatic impairments.
During pregnancy
Patient with history of Lactic acidosis, irrespective or precipitating factors
Alcohol potentiates effects, avoid alcohol
Potentiates other oral hypoglycemics

Rosiglitazone (Avandia)
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Mechanism
Therapeutic Effects

Insulin and Anitdiabetic Drugs

Increasing insulin sensitivity in type 2 DM. It improves sensitivity


to insulin in muscle and adipose tissue and inhibits hepatic
gluconeogenesis.
As monotherapy, in patients not controlled by diet and exercise alone.
To reduce insulin resistance and lower elevated blood glucose in patients
with type II DM.

Pioglitazone (Actos)
Mechanism

Therapeutic use
Contraindications
Side Effects
Drug-Drug
interactions

A Thiazolinidinedione antidiabetic agent that depends on the presence of


insulin for its mechanism of action.
Decreases insulin resistance in the periphery and liver.
Improves glycemic control while reducing circulating insulin levels.
Increasing insulin sensitivity in type 2 diabetes. It improves sensitivity to
insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis
Serious hepatic impairment, acute heart failure.
Weight gain, fluid retention, hemodilution, varying effects on lipids:
increase HDL, Increase LDL, Pioglitazone decrease TG
Increase the risk of pregnancy, recommend adequate contraception not
used.
Resume ovulation in previously anovulatory (polycystic ovarian
syndrome).
TZDs potentiates other hypoglycemic
Combination: rosiglitazone + metformin (avandia)

Acarbose (Prandase)
Mechanism
Therapeutic
use
Drug-Drug
interaction

Dose
Side Effects
Monitoring

Inhibits alpha glucosidase in intestinal border thus decrease absorption of


starch and disaccharides.
For type II DM in combination with other antidiabetic drugs.
May decrease metformin bioavailability
Potentiates other oral hypoglycemic effects
Diuretics, cortecosteroid, estrogen, oral contraceptives, phenytoin, and
sympathomimetics drugs may increase blood glucose level and effect diabetic
control
50 -100 mg TID with each meal start low and go slow.
Flatulence, diarrhea, abdominal pain, cramps, nausea
Regular testing of after meal blood sugar level.
In combination oral hypoglycemic therapy always use agents from different
class of oral hypoglycemics.

Orlistat (Xenical)
Mechanism
Therapeutic use
Drug-Drug
interaction
Dose
Side Effects

Blocks the action of stomach and pancreatic enzymes (lipases) that digest fats,
so fats and other fat soluble vitamins ADEK are not absorb in the body but pass
through and excreted in the feces.
Reduces fats stores and produce weight loss.
Orlistat increases blood levels and toxicity of pravastatin
120-360mg daily
Diarrhea, abdominal discomfort, oily leakage

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Insulin and Anitdiabetic Drugs

Antidiabetic drugs Tips












Acarbose mechanism
Orlistat mechanism
Difference between glyburide and glimepride
Antidiabetic drugs taken before or after meals
Insulin works on cell wall
The antidiabetic drug side effect of anorexia
Anticholesterol DOC in diabetic patient
Metformin monitoring
Which antidiabetic drugs are not used in type I DM
What antidiabetic drug of choice in pregnancy
If patient has admitted in surgical ward and her blood glucose levels high, what is drug of
choice
Which of the available forms of insulin should be used IV to correct excessive preprandial
glucose concentrations?
BMI = weight in Kg/ (height in m)2

Abbrevation and Terminology


IDDM
NPH
NIDDM
BSL
DKA
HDL
LDL
TG
ADEK
VLDL

Insulin Dependent Diabetes Mellitis


Non Insulin Dependent DM
Blood Sugar Levels
Diabetic Ketoacidosis
High Density Lipoprotein
Low Density Lipoprotein
Triglyarides
Fat Soluble Vitamins
Very Low Density Iipoprotein

Generic and Brand


Sulfonylureas
Glyburide
Chlorpropamide
Repaglinide
Rosiglitazone
Pioglitazone
Acarbose
Orlistat
Chlorpropamide
Gliclazide
Natelinide
Metformin

DiaBeta
Diabinese
Gluconorm
Avandia
Actos
Prandase
Xenical
Orinase, Diabinese, Insulase
Diamicron
Starlix
Glucophage

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Insulin and Anitdiabetic Drugs

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Thyroids Disorders

24

Thyroid disorders
Drugs Used In Thyroid Disease

Hypothyroids

Thyroxine (T4)
Dessicated thyroid
hormone.
Synthroid
Thioamides:
Methimazole
Propylthiouracil

Symptoms

Treatment

Monitoring

Pregnancy

Hyperthyroids

Triidothyronine (T3)
Iodide
Lugol solution:
(KI+I)

131

Ipodate

Hypothyroidism
Sensitivity to cold
Constipation
Bradycardia
Weight gain
Dry flaky skin
Coarse hair
Slowed speech
Puffy face, hands, feet
Hearing loss
Decreased libido
Slow return of deep tendon
reflexes
If untreated myxedema and coma
will develop
Thyroxin (T4)
Triiodothyronine (T3)

Hyperthyroidism
Intolerance to heat
Diarrhea
Tachycardia
Weight loss
Nervousness
Heart palpitation
More common in pregnancy

Most sensitive test is:


Serum TSH assay (increase)
Decreased free T4
Decreased free T3

Serum TSH assay (decrease)


Increase Free T3
Increase T4

Thioamides
Methimazole
Propylthiouracil
Iodide
Radioactive iodide

PTU is drug of choice

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Thyroids Disorders

Levothyroxine (Eltroxin, Synthroid)


Mechanism
Therapeutic use
Side effects

Drug-drug
interaction

Over dose
Monitoring

Food and drug


interactions

A major hormone of thyroid gland


Goiter, thyroid cancer
Rare side effects such as
Anxiety
Diarrhea
Weight loss
Sweating
Insomnia
Muscle cramps
Antiepileptic, Cholestyramine, and sucralfate may reduce the absorption of
Levothyroxine.
Levothyroxine may increase the effects of warfarin
Glycemic control may decline with initiation of L-T4 , potentially
necessment of antihyperglycemic Agents.
Symptoms of hyperthyroidism if over-treated; possible exacerbation of
angina.
Periodic tests of thyroid function
Monitor TSH levels to adjust initial dosage after 6-8 weeks then as
required or annually adrenal insufficiency may adrenal insufficiency may
have to be increased during pregnancy to maintain TSH in desired range;
check TSH each trimester and 4-6 wk after any dosage adjustment.
May decrease absorption of levothyroxine by: Iron salts, Cholestyramine
Colestipol Sucralfate

Drugs used to treat Hyperthyroidism

Methimazole (Tapazole)
Thioamides
Mechanism

Pharmacokinetics

Similarities between
Carbimazole and
Methimazole

Do not prevent the uptake of I by the gland they inhibit the synthesis of
T3 and T4 by inhibiting the iodination of tyrosine in the thyroglobulin
Blocks the coupling of the iodo thyroxine
Inhibits the conversion of T4 to T3
Therefore thyroid hormone synthesis is decreased.
Obvious effects are very slow since it takes 3-4 weeks before the
hormone levels show a decrease
Well absorbed,
Slow excretion
t1/2 is 6 hours
Both drugs accumulate in the plasma
Both cross the placental barrier and can accumulate in the thyroid gland
of the fetus

Propylthiouracil (Propyl-Thyracil)
Mechanism
Therapeutic use

Manage the overactive thyroid gland


Hyperthyroidism
DOC in pregnancy

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Side Effects

Thyroids Disorders

Disadvantage
Contraindication

Monitoring

Periodic tests of thyroid function, and blood cell counts.

Pharmacokinetics

Reduction in white blood cells leading to the risk of infection


Nausea and vomiting,
Joint pain, headache,
Rash and itching,
Jaundice, fever
Propylthiouracil rapid absorption after oral administration
Peak serum levels seen after 1 hour
t1/2 is only 2 hours
Extensive first pass metabolism
Excreted by the kidneys as glucuronide (inactive)
Preferred in pregnancy for it does not cross the placental barrier
Strongly protein bound
Secreted in breast milk less than methimazole
More agranulocytosis seen than that of Methimazole
Prescribed with caution in pregnant mothers. There is risk of goiter and
hypothyroidism in the newborn infant if too high dose is used. Reduce
dose to infant and children.

Jaundice
Sore throat and fever

Thyroid drugs Tips















Calcitonin is stimulated by
TSH is secreted from
In treatment of hypothyroidism with T4 have effect on
Hypothyroidism is monitored by
DOC in pregnancy for hyperthyroidism
Hypothyroidism symptoms
Hyperthyroidism is
Hypothyroidism is
T4 metabolized to T3 by deiodinase enzyme
Discontinue antithyroid if patient notice even a single rash
Sweating is symptom of
Lugol solution is?
Lugol solution can stain.
Why is it beneficial to add propranolol to a drug regimen of a patient diagnosed with
hyperthyroidism?

Abbrevation and Terminology


TSH
HRT

Thyroid Stimulant Hormone


Hormone Receptor

Generic and Brand


Methimazole
Propylthiouracil
Levothyroxine

Tapazole
Propyl-Thyracil
Drug of Choice

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Thyroids Disorders

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Gonadal Hormone and Gonadal Antagonist

25

Gonadal Hormones And


Antagonists
Gonadal Hormones And Antagonists
Ovary
Estrogen
Ethinyl estradiol
Mestranol (prodrug)

Testes
Progesterone
Norethidrone
Norgestrel
Norethynodrel
Norgestimate
Desogestrel

Testosterone

Anti-testosterone drugs

Included in this category are: androgens (male sex hormones), estrogens (female sex hormones) and
progestins. These chemicals are needed for the development, maintenance and function of the sexual
organs and are necessary for normal pregnancy to occur, be maintained and for birth
Clinical Uses for Various Estrogen Preparations

Palliative treatment of
advanced prostate cancer
Diethylstilbestrol

Estrogen

Conjugated estrogens
Estradiol
Estradiol transdermal

Estrogens are female sex hormones that are used primarily to decrease bone loss and to treat the
symptoms of menopause. Estrogen is used to reduce or prevent osteoporosis in susceptible women.
Estrogens decrease the frequency and severity of hot flashes as well as the dryness in the vagina that
many post-menopausal women experience.
Estradiol Exist in body in equilibrium with estrone
Estriol
Estrone
Ethinyl estradiol 17 alpha estradiol
Mestranol
Quinestrol used for estrogen replacement therapy (HRT)
Diethylstilbestrol Non steroidal synthetic estrogen (stilbene derivatives)

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Gonadal Hormone and Gonadal Antagonist

Therapeutic use

Estrogen is component of all brands of oral contraceptive pills.


Estrogen is used to reduce or prevent osteoporosis in susceptible women.
(Both senile and post menopausal)
Estrogen is componenent of Diane 25 & 35 and Alese oral contraceptive that
are used for the treatment of acne.
HRT To treat menopause symptoms Vasomotor symptoms, vaginal
atropy, psychological disorders
To treat prostate cancer.
To treat Primary hypogonadism

Side effects

GI Nausea and vomiting are the most common, weight gain, diarrhea
CNSHeadache, Breast tenderness
CV Edema, Hypertension, stroke, MI, Increased risk of thromboembolic
diseases

Contraindicated in

Prolonged used of unopposed estrogens (estrogen given without


progesterone) in postmenstrual women increases the risk of endometrial
cancer.
Deep vein thrombosis or (thromboembolic diseases)
Vaginal bleeding
Breast cancer

Antiestrogens
Mechanism
Therapeutic use

Tamoxifen
Clomiphene
Inhibit or modify the action of estrogen
These drugs are non-steroidal antiestrogenic compounds equally effective in
oral or injection.
Tamoxifen Breast cancer
ClomipheneFertility drugs

Tamoxifen
Mechanism
Indication
Side effects

Tamoxifen competes for binding to the estrogen receptors thereby


inhibits the action of estrogen.
Tamoxifen is indicated in advanced breast cancer in postmenopausal
women.
Hot flashes
Nausea, vomiting Least nauseating anticancer drugs
Vaginal bleeding
Menstrual irregularities
Risk of endometrial cancer

Clomiphene (Clomid)
Mechanism

Clomiphene Interferes with negative feedback of estrogen on


hypothalamus and pituitary thereby increases the secretion of
gonadotropin releasing hormone (GnRH) and causes stimulation of
ovulation.

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Therapeutic use
Contraindication
Side effects

Gonadal Hormone and Gonadal Antagonist

Clomiphene is used to treat infertility associated with anovulatory


cycles.
Not effective in women whose ovulatory disfunction is due to pituitary
or ovarian failure.
Dose related
Ovarian enlargement
Vasomotor flushes
Visual disturbances

Selective Estrogen Receptor Modulator (SERM)


Raloxifene
Reduces bone resorption thereby decrease bone turnover
Exhibit estrogen like (agonist) effect on bones and lipid metabolism
Exhibit estrogen antagonist action on uterine and breast tissues.
Therapeutic use: Prevention of osteoporosis.

Progestins
Progestins are female sex hormones that may be used with estrogens in oral contraceptive pills,
hormone replacement therapy, and treat menstrual irregularities, and as cancer treatment.
Classification of progestins
Two types of progestins
17-alpha hydroxyprogesterone
A. Medroxyprogesterone acetate
B. Megestrol aceta
17-alpha ethinylandrogens (more potent)
A. Norethindrone
B. Norethynodrel
Commonly used in OCs
Potent oral activity
More lipid soluble
Less first pass metabolism
Mechanism Progestins are produced in males from testes.
Adrenal cortex produced progestins in males and females.
Progestins in females promote the development of a secretor endometrium that
can accommodate implantation of newly formed embryo.
The high level of progestins produced in second half of menstrual cycle inhibits
the production of gonadotropins and thereby further ovulation.
Therapeutic Major clinical use in contraception, generally used with estrogen.
use
Not widely used as alone because of its rapid metabolism results in low
bioavailability.
Progestins are indicated in uterine bleeding, dysmenorrhea, suppression of
postpartum lactone, and endometrium cancer.
Endometriosis
Side Effects Edema
Depression
Menstrual irregularities (breakthrough bleeding, amenorrhea)
Androgen like progestins can increase LDL and HDL ratio cholesterol, weight
gain and edema,
Hirsutism, and acne can cause thrombophlebitis (inflammation of wall of vein)
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Gonadal Hormone and Gonadal Antagonist

Antiprogestins- Mifepristone (RU-486)


Mechanism

Therapeutic use

Side Effects

Progestin antagonist with partial agonist activity


Mifepristone also has anti glucocorticoid property.
Causes abortion if administered in early pregnancy (85%)due to interference
with progestins and decrease in production of hCG (human Chorionic
Gonadotropin)
Abortifacient: Administration of mifepristone used as contraceptive
given once a month when progestin levels are high (Prostaglandin E1 and
misoprostol orally after single dose of mifepristone effectively terminates
the gestation.
Uterine bleeding, and possibility of incomplete abortion

Androgens
Testosterone is the androgen that leads to the development of male secondary sexual characteristics
and maintains the male reproductive system.
Androgens are used to treat delayed puberty in males who do not develop normal testicular function.
They are also used illegally by athletes to build muscle mass. They are very dangerous when used for
this as they may lead to aggressive behaviour, and may cause liver and/or brain tumours and death.
Androgens

Danazol
Nandrolone
Stanozolol
Fluoxymesterone

Mechanism

Testosterone is commonly prescribed in the treatment of female breast


cancer, androgen deficiency, and for stimulation of growth, weight gain,
and red blood cell production. Commonly known as anabolic steroids
because they promote muscle growth. They are also commonly used to
help patients recover from a surgery and cancer treatment that resulted in
damage to muscle tissue.
Used in males with inadequate androgen secretion
Anabolic steroids can be used in sever burns, for speedy recovery from
surgery.
Indicated in conjunction with other hormones in pituitary dwarfism.
Non approved uses: Androgenic steroids in increase of lean body mass,
muscle strength, aggressiveness in body builders and athletes
Danazol indicated in endometriosis (ectopic growth of the endometrium)
Androgens orally ineffective
In males: priapism (continuous erection), impotency, gynecomastia.
In females; masculinization, acne, hirsutism, deepening of voice,
menstrual irregularities.
Contra indicated in pregnancy.
Increase LDL, decrease HDL levels, increase Coronary Artery Disease
(CAD), fluid retention (edema)

Therapeutic use

Side effects

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Gonadal Hormone and Gonadal Antagonist

Antiandrogens- Finasteride

Mechanism

Therapeutic use
Side effects

Dose
Contraindication

Finasteride
Dutasteride
Flutamide
Cyproterone acetate
Inhibit the synthesis of androgen.
Finasteride: steroid like drug approved for BPH treatment.
Finasteride: inhibits the 5-alpha reductase: Competitive and specific
inhibitor of type II 5-alpha reductase
Indicated in BPH, and to treat men who have lost scalp hair.
Decrease libido.
Sexual dysfunction
Breast tenderness
Hirsutism
Hypersensitive reactions like rashes, pruritic, swelling face and lips
Testicular pain
5mg for BPH treatment
1mg daily for 3 months for hair growth in men
Not indicated in woman and children. Woman should not handle or
break tablet when they are pregnant.
Finasteride may cause external genitalia abnormalities in male fetus.

Endocrine disorders Tips























ACTH is secreted by
Example of antiandrogenic drug
What partial antiestrogen cause hot flushes
Metformin + glyburide may cause
Increase in cortisone cause (Hypercorticoids)
Decrease in cortisone cause (Hypocorticoids)
Glutathione is
Diabetic Ketoacedosis (DKA) mainly occurs in
During ovulation increase of
Corpus luteum is stimulated by
Purpose of frequent glucose level monitoring
What steroidal hormone structure have phenolic ring
Decrease in cortisone cause
Aldosterone secreted from
Cortisone is secreted form
Hoshimoto disease
Example of antithyroid drugs
Fineseride (Proscar), Dutasteride (Avodant) is
Vitamin D3 acts as
Myxedema is malfunction of
The effect of vasopressing on kidney
Deficiency (absence) of Antidiuretic Hormone (ADH) or vasopressin cause Diabetes Insipidus
(DI)
Glutathione protects
The endocrine gland plays important rule in calcium metabolism
The major factor that controls Na excretion in kidney
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Gonadal Hormone and Gonadal Antagonist

The effect of the antidiuretic hormone is to


In post menopausal therapy which drugs have risk of endometrial cancer
The substance naturally occurs in body called
Thyroid is NOT a part of
Oral contraceptives completely contraindicated in
Insulin has pharmacodynamic effect on
Oxytosin is secreted from
Oxytosin is used
Glucogon cause
Calcium reabsorption of distal convoluted tubule due to
Normal Cholesterol =

Abbrevation and Terminology


HRT
ADH
GnRH
HDL
LDL
BPH
ACTH
DKA

Hormone Replacement Therapy


Antidiuretic Hormone
Gonadotropin-Releasing Hormone
High-Density Lipoprotein
Low-density Lipoprotein
Benign Prostate Hyperplacia
Adrenocorticotropic Hormone
Diabetic Ketoacedosis

Generic and Brand


Tamoxifen
Clomiphene
Mifepristone
Danazol
Nandrolone
Stanozolol
Fluoxymesterone
Dutasteride
Flutamide
Cyproterone acetate
Dutasteride

Nolvadex, Soltamox
Clomid
Mifeprex
Danocrine
Durabolin, Kabolin
Winstrol
Halotestin, Android-F, Ora-Testryl.
Avodart
Eulexin
Diane
Avodant

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Adrenal Corticosteroids

26

Adrenal Corticosteroids

The adrenal hormones, or corticosteroids, are drugs with powerful anti-inflammatory effects. These
are used for replacement therapy in conditions such as, Addisons disease, a condition of adrenal
insufficiency. In replacement therapy, the adverse effects are minimal since hormones are being
replaced and are not added to those already in the body.
Corticosteroids are used for their anti-inflammatory, anti-allergic and anti-stress effects. Prednisone
is used as replacement therapy and also for its anti-inflammatory effects in many conditions, such as
arthritis, allergies and asthma.

Glucocorticoids
Classification
Short acting (8-12 hour)
Intermediate acting (18-36
hours)
Long acting (1-3 days)
Mechanism

Side Effects

Drug and Food interactions

Hydrocortisone
Cortisone
Prednisone
Prednisolone
Methylprednisolone
Triamcilone
Betamethasone
Dexamethasone
Paramethasone
Promote normal intermediately metabolism
Increase resistant to stress
Alter blood cell levels in plasma
Anti-inflammatory action by inhibiting IgE
High doses stimulate gastric acid and pepsin production and may
cause peptic ulcers.
Chronic use causes sever bone loss (Due to decrease in calcium)
and myopathy leads to weakness
Concentration of topical Glucocorticoids depends on site of use
on the body.
Take with food
Should not be stopped suddenly, taper off or gradually decrease
dose.
Diabetic drugs glyburide, chlorpropamide, glipizide,
tolbutamide, and tolzamide.
Can rise blood sugar noticeably
Monitor blood sugar levels

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Therapeutic use

Side effects

Adrenal
Corticosteroid

Corticosteroid
biosynthesis
inhibitors
Mechanism



Indications
of Adrenal
corticosteroids

Adrenal Corticosteroids

To treat severe allergic reaction


To treat chronic ulcerative colitis
To treat nephrotic syndrome and renal diseases
Topical agent to treat diaper rash and dermatitis
Topical agents for ophthalmic disorders
To treat rheumatic carditis
To treat severe arthritis
To treat acute and chronic adrenal deficiencies
To treat Nausea and vomiting associated with cancer
chemotherapy
GI peptic ulcer, hemorrhage, acute pancreatitis, ulcerative
esophagitis
CNS headache, Increased IOP, muscle weakness, euphoria
and dysphoria
Hormonal Weight gain, osteoporosis, hyperglycemia
(Diabetes), flushing of face and neck, cushingoid (moon face
and buffalo hump) and increase risk of infections.
CV edema and hypertension
Skin thinning

Cortisone
Hydrocortisone
Betamethasone
Beclomethasone
Prednisolone
Prednisone
Triamcilone
Methylprednisolone
Ketoconazole
Spironolactone
Mifepristone
Metyrapone
Aminoglutethimide
For anti-inflammatory corticoids: Glucocorticoids effects on the distribution,
concentration, and function of leukocytes. These include decrease in
concentration of lymphocytes T and B cells) and increase in concentration of
neutrophils.
Decrease basophils, eosinophils and monocytes, and inhibition of the ability
of leukocyte and macrophages to responds mitogen and antigen.
The above Inhibitory response also results in reduce the amount of histamine
release from basophils to inhibit kinins.
Indications of adrenal corticosteroids
Addisons disease (caused by dysfunction of adrenal cortex)hydrocortisone.
Cushing syndrome (caused by hypersecretion of glucocorticoids that is due
to excess secretion of corticotropin by anterior pituitary to adrenal tumor.
dexamethasone test is used in diagnosis.
Congenital adrenal hyperplasia (CAH)results from enzyme defects
administration of sufficient corticosteroids.
Indicated in inflammatory symptoms of rheumatoid arthritis, osteoarthritis,
skin condition. Redness, swelling, heat, and tenderness that commonly treated
by adrenal corticoids
Indicated in treatment of allergies.

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Adrenal Corticosteroids

Formulations

Systemic:
IM Cortisone, triamcinolone, desoxycorticosterone
IV and IM Dexamethasone, hydrocortisone, methylprednisolone,
prednisolone.
Inhaled Aerosol Beclomethasone, flunisolide, fluticasone, triamcinolone
Topical Hydrocortisone, beclomethasone, dexamethasone, triamcinolone,
Oral: All corticosteroids can be administered orally.
Long term use Osteoporosis --> is due negative calcium balance
Side effects
Increase risk of infection due to impaired wound healing and immunosuppression
associated with Diabetes due to hyperglycemia SE
oral steroids
Increased appetite can cause weight gain

Hypertension is due to increase water retention (Edema)
Peptic ulcers
Euphoria
Psychosis
Immunosuppression due to suppression of IgE.

Adrenocorticoids Tips



Increase in cortisone cause -->


Decrease corticosteroids cause -->
What is steroid sparing drug -->
Aldosterone are secreted from -->

Abbrevation and Terminology


CNS
IOP

Cental Nervous System


Intra Ocular Pressure

Generic and Brand


Cortisone
Hydrocortisone
Betamethasone
Beclomethasone
Prednisolone
Prednisone
Triamcilone
Methylprednisolone
Ketoconazole
Spironolactone
Mifepristone
Metyrapone
Aminoglutethimide

Cortone
A-hydroCort, Ala-Cort, Ala-Scalpt, Anu-Med HC
Diprosone, Diprolene
Beclovent, Beconase AQ, Beconase, Qvar , Vancenase
AK-Pred, Bubbli-Pred, Econopred, Econopred Plus
Deltasone, Predone, Sterapred, Sterapred DS
A-Methapred, Cortimed, Depmedalone, Depo-Medrol, Medralone
Extina, Kuric, Nizoral Shampoo, Nizoral, Nizoral A-D, Xolegel
Aldactone, Spirono
Mifeprex
Metopirone
Aminoglutethimide

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Adrenal Corticosteroids

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Oral Contraceptives

27

Oral Contraceptives

Oral contraceptives (birth control pills) are combinations of estrogen and progestins.
The combination preparations may be monophasic, biphasic or triphasic. They contain various
estrogens and progestins. Some common ones are listed:
Drugs that Causes Of
OC Failure

Contraindications

Precautions

Starting Hormonal
Contraceptives

Alcohol -excessive chronic,


Antibiotics (ampicillin, cotrimoxazole, griseofulvin, metronidazole,
nitrofurantoin, neomycin, penicillin, rifabutin, rifampin &
tetracycline),
Anticonvulsants (carbamazepine, ethosuximide, oxcarbazepine,
phenobarbital, phenytoin, primidone & topiramate dose),
Antivirals (nelfinavir & ritonavir), modafinil, red clover & St. Johns
wort.
Active thromboembolic disease
Undiagnosed vaginal bleeding
Acute or chronic obstructive liver disease
Known or suspected breast cancer
Known or suspected pregnancy
Hypertension - may use OCs if hypertension controlled
CVD, hyperlipidemia- OCs with new progestins preferred because of
more favorable lipid profile
Diabetes - low dose OCs unlikely to affect glucose control but
estrogen may complicate vascular disease
Epilepsy - some anticonvulsants OCs efficacy due to metabolism;
may require use of OCs with >35ug EE
Hepatitis, cirrhosis - avoid OCs if active disease; may use if liver
enzymes have returned to normal
Gallbladder disease - may be exacerbated by OCs
Migraine - avoid OCs if classic, complex, age 35 (stroke)
Inflammatory bowel disease - active diarrhea may reduce absorption
and efficacy of OCs and require backup method
Systemic lupus erythematosus - avoid OCs as estrogens can
complicate vascular disease
Smoking women over age 35 - if light smoker (<15cigs/day) or on
nicotine patch, can use 20 mg EE product but risk of DVT.
Starting Combined OCs:
Most effective if started Day 1 of menstrual period can be started any
day up to Day 6
To avoid weekend periods, start on 1st Sunday after period begins
If started after Day 5 use backup method for first 7 -10 days as
ovulation may not be suppressed
Starting Progestin-only Pill (POP):
Start on Day 1 of menstrual period and daily thereafter
Use backup method for first month

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Starting Hormonal
Contraceptives

Oral Contraceptives

Starting Depo-Provera: im
Should be injected during the first 5 days of menstrual cycle rule out
pregnancy
Repeat injection q12 weeks - effective for up to 14 wks

Side Effects & Their


Management

Breakthrough bleeding - most common in 1st 3 months ; if persists


beyond 3-6mon check for other causes (eg. chlamydia). Change to
OC with estrogen/progestin depending on when BTB occurs in the
cycle; may also be related to poor compliance, smoking, DIs
Breast tenderness - if persists beyond 1st 3months rule out pathologic
causes; change to OC with estrogen/progestin
Weight gain - may appetite in 1st month but overall weight gain is
minimal with low dose OCs & within normal limits for age-related
gain; may be cyclical due to Na & H20 retention
Nausea - often subsides within 3 months; take at hs with food or change
to lower estrogen content
Headache - tension headaches unaffected but hormone related or
vascular migraines may ; if precipitated or exacerbated by OCs
should avoid their use
Acne - sometimes worsens initially but usually improves in the long
term; change to androgenic OC or use topical therapy
Chloasma - irreversible and idiosyncratic; exacerbated by sunlight so
use sunscreen and reduce exposure; estrogen dose
Miss pills
Miss one pill: Take as soon as you remember and take usual pill next
day. This means that you might take two pills in a day.
Miss two pills in a row:
First two weeks: Take two pills the day you remember and two pills
next day. Then take one pill until you finish pack.
Use back up method of birth control, if you have sex in next seven
days of missing pill.
Third week: Safely dispose remained pills and start new pack same day.
(If youre on Sunday start schedule continue one pill until Sunday).
You may not have periods this month.
If you miss two periods in a row call doctor.
Plan B (Levonorgestrel Progestin only
0.75mg per dose)
Very efective within 24hrs and can be used upto 5 days unprotected
Or Minipill
inter course.
Or Morning after pill
Schedule 2 (Pharmacist intervention)
or
Contains 2 pills (use 2nd pill after 12 hours of 1st pill)
Emergency
To treat Nausea and vomiting associated with this pill can be treated
contraception
by Gravol (dimenhydrinate)
Side effects plan B
Nausea (23.1%), Vomiting (5%), Dizziness, fatigue

Abbrevation and Terminology


OC
DVT
BTB

Oral Contraceptive
Deep Veinthrombosis
Break Through Bleeding

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Oral Contraceptives

Generic and Brand


Levonorgestrel, Ethinyl Estradiol
Ethinyl Estradiol, Norethindrone

Alesse
Brevicon
Demulen
Diane-35
Ortho-Cept
Marvelon
Ortho
Min-Ovral
Triphasil
Synphasic

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Oral Contraceptives

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Osteoarthritis

28

Osteoarthritis
Osteoarthritis

Nonsteroidal Antiinflammatory Drugs


Topical
Diclofenac sodium
(pennsaid)

Pain Therapy,
Topical

Synovial Fluid
Replacement

Corticosteroids

Capsaicin
Methyl salicylate
Menthol
Triethanolamine
salicylate

Hylan G-F 20
Hyaluronic acid sodium
Sodium hyaluronate

Betamethasone valerate
Cortisone acetate
Dexamethasone
Dexamethasone sodium
phosphate
Methyl prednisolone
acetate
Prednisolone
Triamcinolone
Triamcinolone diacetate

Glucocorticoids
Antigen

Viscous supplements
Intraarticular injections

NSAIDs

Activation of
macrophages

Prostaglandins
Methotrexate

Activation
of T cells

IL-2

TNF

Activation of
B cells

Induction
of cytotoxic
T cells

Production of
autoimmune
antibodies

Cytokines

Joint
inflammation
Synoviocyte
proliferation,
Bone and
cartilage
destruction

IgRF
complex
es

Diclofenac (Voltaren)
Therapeutic use

Side Effects

Relieves mild to moderate headache


Menstrual pain
Pain following surgery
Acute attacks of gout
Relieves pain and stiffness associated w/ rheumatoid arthritis and
osteoarthritis (when given regularly)
GI disorders

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Drug-Drug
interaction
Contraindication
Monitoring

Osteoarthritis

It interacts with NSAIDs, oral anticoagulants, and corticosteroids, risk of


bleeding and ulcer may increase
Cyclosporin with diclofenac may increase the risk of kidney problems
Not usually prescribed in the last month of pregnancy as it may increase the
risk of affecting babys heart and promote prolong labour.
There is an increase risk of bleeding from peptic ulcers and in bowel with
prolonged use.

Osteoarthritis Tips













Allergic to aspirin
Aspirin use in children with flu symptoms can cause
Peptobismol (Bismuth subsalicylate) can cause Rye syndrome in childrem.
Ibuprofen is safe in children under 12 years (No Rye syndrome)
Misprostol is
Azotemia
Topical pain relievers
Hylorunan injections (synovial fluid replacement) act as viscous supplement given
Misoprostol is
What type of exercise in osteoarthitis
Acetaminophen is least used in
Risk factors for renal toxicity associated with NSAIDs and COX II inhibitors include .
Counseling of Capscicin
Corticosteroids are used primarily for their action as

Symptoms
Stiffness
Localized
Pain
Inflammation
Risk factor

Osteoarthritis
Morning or after inactivity (last 30
min)
Limited affected joints.
Worsens With Activity Or
After Prolong Use, (weight bearing
activity)
Uncommon
>65 years
Degenerative joint disease caused
by breakdown of the cartilage b/w
bones, degradation of articular
cartilage in synovial joints

Rheumatoid Arthritis
In the morning (last 1 hour)
Not localized
Worsens with prolong inactivity. (Usually
improves with activity).
Common
Autoimmune inflammatory condition
Chronic systemic
Symmetrical synovitis affecting similar
joints bilateral.

Abbrevation and Terminology


COX
OA

Cylco Oxygenase
Osteoarthritis Tips

Diclofenac

Cataflam, Solaraze

Generic and Brand

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Desease Modifying Antirheumatic Drugs

29

Disease Modifying Antirheumatic


Drugs
Disease Modifying Antirheumatic Drugs (DMARDs)

DMARDS

Cytotoxics

Gold preparations

Azathioprine
Methotrexate
sodium Gold
Standards for
treatment of RA

Aurothioglucose
Sodium
aurothioglucose

Other DMARDs
Cyclosporine
Hydroxychloroquine
sulfateSE: Corneal &
retinal deposition
Leflunomide C/I in
pregnancy
Penicillamine
Sulfasalazine C/I: ASA
& Sulfa allergy

Biological response
modifiers
Adalimumab
Anakinra
Etanercept
Infliximab

A chronic inflammatory disease with frequent acute attacks. The immune system is involved in
attacking the joints and surrounding structures such as muscle tendons and most other connective
tissue. There is inflammation of the synovial membrane.
Biological
Response Modifiers
Infliximab

Etanercept
Infliximab

Infliximab (Remicade)
Etanercept (Embrel)
Anakinra (Kineret)
Binds to the Tumor Necrosis Factor (TNFa)
Inhibit interleukin-1 (IL-1), a key mediator of inflammatory NF
synovitis as well as bone and cartilage destruction.
Improve the sign and symptom of active RA
Must be given with Methotrexate to prevent formation of antibodies.
Binds to the Tumor Necrosis Factor (TNF alpha and beta)
Given SC twice weekly
Side effects: Most common: Respiratory tract infections
Given every 8 week by iv
Most common SE is Respiratory tract infections (Pneumonitis)
Storage: Refrigerator (2 8oC)
Do not freeze

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Desease Modifying Antirheumatic Drugs

Methotrexate (Rheumatrex)
Mechanism
Therapeutic use

Side effects

Dose

Monitoring

Folic acid antagonist


Treat Rheumatoid arthritis
An anticancer drug, and used together with other anticancer drugs in the
treatment of Leukemia, Lymphoma, and solid cancers such as Breast,
bladder, head, and neck.
Treat uncontrolled psoriasis until less potent drug can be re-introduced.
Nausea, diarrhea
Flu-like aches
Oral ulcers (mouth ulcer): Treated by folic acid or folinic supplements.
Bone marrow and liver toxicity
Immunosuppression
Hepatotoxicity
Renal failure
Leukopenia
Abnormal LFT
Pulmonary toxicities in children
Susceptible to Infections (P. carinii)
Starting 7.5 15 mg po Q wk. Increase by 2.5 5 mg Q 2 - 4 wk.
Maximum 25 mg/ wk
Maintenance dose: 7.5 20 mg po, sc or IM Q wk (single dose if
tolerated or divided in 2 or 3 doses Q 12 h)
Effectiveness seen after 2- 6 weeks
Administer; PO, IM, SC
If GI upset occurs: 2.5 mg start (12 h after) 2.5 mg (12 h after) 2.5
mg
Methotrexate weekly doses 20-25 mg (orally or parenteral) for at least
three months.
Concurrent use of folic acid reduces oral ulcers side effect.
Alcohol restriction may minimize hepatotoxicity.
Regular monitoring is mandatory:
Baseline hepatitis B and C serology
Chest X-ray
CBC
LFTs
Creatinin Q 1-2 months

Azathioprine (Imuran)
Refractory RA
Metabolism
Therapeutic use
Side effects

Azathioprine is cleaved in vivo to mercaptopurine


Drug interaction with allopurinol (indicated in gouty arthritis), decrease
one third dose of azathioprine
Hematologic Leukopenia and/or thrombocytopenia and rarely as
agranulocytosis
GI effects Nausea and vomiting
Hepatic: Hepatotoxicity

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Contraindications

Desease Modifying Antirheumatic Drugs

Pregnancy
Children
Patients with rheumatoid arthritis previously treated with alkylating
agents (cyclophosphamide, chlorambucil, melphalan or others) may
have a prohibitive risk of neoplasia if treated with azathioprine.

Hydroxychloroquine (Plaquenil)
Therapeutic use
Side Effects

Overdose
management

Treat Rheumatoid arthritis, Malaria


Retinopathy Irreversible retinal damage (but is rare. In its early form, it
appears reversible upon discontinuation of the drug)
Skin rashes
GI disturbances
For management of a suspected drug overdose, CPhA recommends that you
contact your regional Poison Control Centre

Sulfasalazine (Azulfidine)
Mechanism

Therapeutic use
Side effects

Dose
Pharmacokinetics
Contraindications

Allergies

A chemical combination of sulfonamide and salicylate (5-ASA)


Sulfasalazine is a relatively weak inhibitor of the cyclo-oxygenase
enzyme, but a potent inhibitor of15-prostaglandin dehydrogenase
(PGDH), which is the main metabolic pathway for the prostaglandins
Second line therapy in ulcerative colitis (UC)
Blood Dyscrasias: aplastic anemia, agranulocytosis, purpura,
thrombocytopenia and hypoprothrombinemia, pancytopenia, macrocytosis
Hypersensitivity: erythema multiforme (Stevens-Johnson syndrome)
Skin: facial edema,
Gastrointestinal: hepatitis, pancreatitis
Nervous System: smell and taste disorders
PO or rectally
About 20% of sulfasalazine is absorbed in the small intestine after oral
administration
In patients with hypersensitivity to component of the product,
sulfonamides, or salicylates. In patients in whom acute asthmatic attacks,
urticaria, rhinitis or other allergic manifestations are precipitated by
ASA or other nonsteroidal anti-inflammatory agents. Fatal anaphylactic
reactions have occurred in such individuals.
In patients with intestinal and urinary obstructions.
In patients with porphyria, as these drugs have been reported to precipitate
an acute attack.
Infants under 2 year age
If allergic to the following drug avoid sulfasalazine
ASA
Furosemide
Thiazide diuretics
Carbonic anhydrase inhibitors,
Sulfonamides sulfapyridine

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Counselling

Desease Modifying Antirheumatic Drugs

Discolors urine and May color skin orange yellow.


May permanently stain soft lenses
Take drug after meals to reduce GI distress and to facilitate passage into
intestine.

Leflunomide (Arava)
Mechanism
Therapeutic use
Side Effects

Monitoring

Isoxazole immunomodulator, inhibits dihydro orate dehydrogenase.


Washout

It reduces pain and inflammation and slow progression of structural damage

Diarrhea, Nausea
Weight Loss
Flu like syndrome
Skin rash
Alopecia
Hypokalemia
Male patient have possible male mediated fetal toxicity. Reliable
contraception during treatment should be guaranteed.
Pregnancy must be avoided if either partner receiving leflunomide.
Leflunomide should be administered to patients only under careful
medical supervision.
For men having received leflunomide and wishing to have children.
Plasma levels of active metabolite should be less than 0.02 mg/L
Using Cholestyramine resin

Cyclosporine (Neoral)
Cyclosporin PO
Therapeutic use
Side effects

Precautions

Drug interactions
(Cyclosporin is
metabolized by
CYP3A4)

Neoral or Sandimmune I.V


3-10 mg/Kg/day for RA
Kidney transplantation
Organ transplantation rejection
Psoriasis/Rheumatoid Arthritis/Nephrotic Syndrome
Renal Very common: renal dysfunction
Cardiovascular Very common: hypertension (particularly in heart
transplant patients)
Nervous System Very common: tremor, headache
Metabolic Very common: hyperlipidemia
NSAID therapy should be discontinued where possible. As nonsteroidal
anti-inflammatory drugs alone can have an adverse effect on renal
function, addition of these drugs to Neoral or Sandimmune I.V. therapy
or an increase in their dosage should be accompanied by particular close
monitoring of renal function.
Drugs that increase cyclosporin serum concentration:
Ketoconazole
Fluconazole, Itraconazole
Macrolide antibiotics (mainly erythromycin and clarithromycin)
Corticosteroids, Oral contraceptives
Norethisterone or danazol
Calcium channel blockers: Diltiazem, Verapamil, Nicardipine
Metoclopramide

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Desease Modifying Antirheumatic Drugs

Drug interactions
(Cyclosporin is
metabolized by
CYP3A4)

Drugs that decrease cyclosporin serum concentration


Phenytoin or phenobarbital, Rifampin i.v. Sulfadimine i.v. and trimethoprim
i.v. Nafcillin, Carbamazepine, Octreotide, Barbiturates, Metamizole,
Probucol, Orlistat, Hypericum perforatum (St. Johns wort), Troglitazone

Food and drug


interaction

Grapefruit juice should be avoided

Minocycline (Minocin)
Minocycline
Therapeutic use

Side Effects

Contraindication

Drug and food


interactions

Broad spectrum antibiotic


Rheumathoid arthritis
Acne
Chlamydia (lymphogranuloma, Psittacosis)
Rickettsia (Rocky mountain spotted fever)
Mycoplasma pneumonia
Lyme disease
Less phototoxicity than tetracycline
CNS Vestibular problems: dizziness, nausea, vomiting
GI effects anorexia, nausea, vomiting, diarrhea, stomatitis, glossitis,
enterocolitis, pancreatitis, pruritus ani, constipation
Skin maculopapular and erythematous rashes, SJS
Pregnancy, children under 13 yrs, breast-feeding.
Newborns, Infants and Children: The use of tetracyclines, including
minocycline, during tooth development in last half of pregnancy.
Teeth and Bone: Dental staining (yellow-gray-brown) in infants of patient
who have last half term of pregnancy
Antacids containing aluminum, calcium or magnesium and oral iron
preparations impair absorption and should not be given to patients taking
oral minocycline.

D-penicillamine (Cuprimine)
Mechanism
Therapeutic use

Side Effects
Non Wilson disease
patients

Chelating agent
Wilsons disease (excess copper)
Chronic lead poisoning
Active Rheumatoid arthritis
For refractory RA, if other drugs fail.
Urticaria, Pruritis, Rashes, Bone marrow depression,
Thrombocytopenia, Leucopenia, Tinnitus, Proteinuria
Diarrhea (17%)
5-10 mg of copper can administered as 5-10 drops of Copper sulphate
solutions in fruit juice twice daily (do not use in Wilson disease patients).
Penicillamine should be given empty stomach. (increase absorption)

Gold sodium thiomalate


Therapeutic use

Treat Rheumatoid arthritis

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Desease Modifying Antirheumatic Drugs

Side Effects

Most common
Skin rashes
Proteinuria (after IM admin.)
Nitritoid reaction (low blood pressure and syncope after injections)
Pruritis (pruriginous), dermatitis
Angioedema
Thrombocytopenia
Aplastic anemia
Diarrhea
Stomatitis
Proteinuria

Post dose reactions

Arthralgias, flushing, hypotension

Rheumathoid arthritis Tips
















Drug of choice (DOC) in RA is DMARDs (Methotrexate)


Which DMARD cannot be given for life
Infliximab mechanism
Infliximab storage conditions
ASA antipyretic mechanism due to
ASA toxicity
Nutropin is
Methotrexate used for
Mucositis (Stomatitis) is Side effects of
Patient taking methotrexate, to prevent bucal ulcer, should recommend
Shorter onset of action in DMARDs -->e
Osteoporosis associated with the use of which of OA drug -->
Which DMARDs require ophthalmic examination monitoring-->
Mucositis is side effect of
Pannus means

Abbrevation and Terminology


DMARD
RA
ASA
TNF
LFT
CBC
UC
NSAID
SJS
OA

Disease Modifying Antirheumatic Drugs


Rheumathoid Arthritis
Acetyl Saliaylate
Tumor necrosis factor
Liver Funtion Test
Complete Blood Count
Ulceralive Colitis
Nonsteroidal Anti-Inflammatory Drug
Steven Johnson Syndrome
Ostreoarthitis

Generic and Brand


Leflunomide
Cyclosporine
Minocycline
D-penicillamine
Infliximab
Etanercept
Anakinra

Arava
Neoral
Cleeravue-M, Dynacin, Minocin, Myrac
Cuprimine
Remicade
Embrel
Kineret

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Gout and Hyperuricemia

30

Gout and Hyperuricemia


Hyperuricemia
Therapy

Gout attack therapy

Antimitotics and
anti-inflammatory
action

Colchicine

Corticosteroids

Nonsteroidal
Anti-inflammatory
Drugs (NSAIDs)

UricosuricsIncrease
excretion of uric acid

Xanthine oxidase
inhibitors prevents
conversion of purine to
uric acid

Indomethacin Highest antiinflammatory NSAID


Phenylbutazone
Sulindac

Dexamethasone
Dexamethasone sodium phosphate
Hydrocortisone sodium succinate
Methylprednisolone acetate
Prednisone
Triamcinolone

Probenecid Take with full glass of


H2O
Sulfinpyrazone Take with full
glass of H2O

Allopurinol Take
with full glass of H2O

Basics of Gout arthritis


Gout is a disease in which monosodium urate monohydrate (MSU) crystal deposit in joints, soft
tissues such as cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium tubules.
Gout arthritis involves 4 Stages

Asymptomatic hyperuricemia
Acute gouty attacks
Intercritical gout
Tophaceous gout
Asymptomatic hyperuricemia
Normal serum urate levels:
Woman 360 mmol/L
Men 420 mmol/L
More common in: Men over 40 year of age
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Gout and Hyperuricemia

Hereditary metabolic disease that is a form of acute arthritis and is marked by inflammation of the
joints.
Gout is associated with increased body stores of uric acid.
Acute attacks involve joint inflammation caused by precipitation of uric acid crystals.
Hyperuricemia
Urate crystal in joints inflammatory response
Acute gout arthritis
Abrupt onset of excruciating pain and inflammation of joint during the night or early morning.
Patient cannot tolerate even light pressure such as a bed sheet on the affected joint.
Attacks often resolve spontaneously over 3- 10 days. 1st line treatment is NSAIDs
For sever pain Intra-articular injection of corticosteroid. (especially in patient with polyarticular
gout)
Colchicine It relieves pain within 24 hours in 90% patients if treated within few hours of attacks.
Side effects: GI abdominal pain, cramps, diarrhea, N and V
Rarely Neuropathy, myopathy, bone marrow suppression

Intercritical gout: Most patient have second attack within 6 24 months.
Chronic tophaceous gout: May occur after 12 year of first attack.

Colchicine
Mechanism

Colchicine is as selective inhibitor of microtubule assembly, reduced


leukocyte migration and phagocytosis: the drug may also reduce
production of leukotriene B4.
Because it reacts with tubulin and interferes with microtubule
assembly, this is general mitotic poison. Tubulin is necessary for
normal cell division, motility and much other process: therefore,
colchicine has systemic side effects if used in excess

Therapeutic use

Used only for Gout, can be used as IV


Antiinflammatory action only
No analgesic effect, No uricosuric effect

Side effects

Diarrhea, nausea, and abdominal pain.


Chronic use can produce hemorrhagic gastroenteritis, hematuria,
alopecia, agranulocytosis and peripheral neuropathy

Drug-Drug
interactions

Taking cyclosporine with colchicine may lead to adverse effects on the


kidneys.

Indomethacin (Indocin)
Mechanism

Potent NSAIDs such as indomethacin also effective (but not as


selective) in inhibiting the inflammation of acute gouty arthritis.
NSAIDs acts through prostaglandin formation and through inhibition
of crystal phagocytosis by macrophage

Therapeutic use
Side effects

Use to treat gout arthritis


Indomethacin may cause renal damage or bone marrow depression.

Probenecid (Benemid)
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Mechanism

Therapeutic use
Side effects
Counselling

Gout and Hyperuricemia

Uric acid is both actively secreted and actively reabsorbed in the


kidney. Probenecid partially inhibits both the active secretion and the
active reabsorption.
Uricosuric agents are weak acids that compete with uric acid, in the S2
segment of the proximal renal tubule, for reabsorption by weak acid
mechanism
Gout
Before using probenecid check to see that the patient is not a high
excreter of uric acid, otherwise the use of drug may precipitate uric
acid crystals in the kidney
Take plenty of water

Sulfinpyrazone (Anturane)
Mechanism

Therapeutic use
Side effects
Counselling

Sulfinpyrazone partially inhibits both the active secretion and the active
reabsorption
Inhibits platelet aggregation
Gout arthritis
Urate crystal formation
Take plenty of water

Allopurinol (Zyloprim)
Mechanism
Metabolism
Therapeutic
use
Side effects

Drug-Drug
interactions
Counselling

Allopurinol is a suicide inhibitor of


xanthine oxidase (XO)
Purine uric acid
Allopurinol oxypurinol
Reduce uric acid pool

Ribose - 5 - P + ATP

5 - Phosphoribosyl - 1 - Pyrophoshate (PRPP) + Glutamine

Inosinic Acid

Inosine

Hypoxanthine

Hypersensitivity rashes
Peripheral neuritis and necrotizing
vasculitis
GI intolerance, diarrhea
Xanthine oxidase
In condition with large purine turnover xanthine

Xanthine
stone formation may occur
Alkalinize the urine to increase solubility
Xanthine oxidase

With 6-mercaptopurine (but not thioguanine)


Uric Acid
Must decrease by 2/3 if used with allopurinol.
Xanthine oxidase is main biotransforming enzyme for 6-mercaptopurine.
Example of 6-mercaptopurines is azathioprine, an anticancer drug
Take plenty of water

Gout arthritis Practice Tips






Not used in acute gout attack


Purine structure present in
Take plenty of fluids (water) with
Colchicine act as
The end product of purine metabolism

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Gout and Hyperuricemia

Sulfinpyrazone is used as
A uricosuric drug is one that
Colchicine is mainly used for

Abbrevation and Terminology


XO

xanthine oxidase

Generic and Brand


Colchicine
Indomethacin
Probenecid
Sulfinpyrazone
Allopurinol

Indocin
Benemid, Probalan
Anturane
Zyloprim

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Osteoporosis

31

Osteoporosis
Osteoporosis Treatment

Selected Estrogen
Receptor Modulators
(SERMs)

Calcium Supplements

Anti parathyroid
Hormones

Calcium carbonate
Calcium gluconate

Calcitonin

Benzothiophene

Bisphosphonates
Parathyroid hormones

Alendronate
Etidronate
Risedronate

Raloxifene
hydrochloride

Teriparatide


Non Modifiable
Age > 65 y
Vertebral compression fractures
Postmenopausal woman (not on estrogen
therapy)
Premature menopause (<45 years)
Gender (Female)
Family history
Thin and small boned (overweight is NOT a
risk factor)
Hypogonadism
Race: Caucasians, Asians
Hyperparathyroidism
Hypocalcemia
Ingested
Ca2+

(
(
(
(

)
)
)
)

Fecal
Ca2+

Modifiable
Low calcium intake (<1000 mg
elemental calcium per day)
Inadequate sun exposure.
Cigarette smoking
Excessive Alcohol intake
Caffeine containing beverages.
Sedentary life style
Excessive heparin therapy
Oral Corticosteroid therapy

1,25-Dihydroxycholecalciferol

(+)
Absorption

Secretion

ECF
Ca2+

Bone formation
Bone resorption
(-)

Filtration

(+)

Reabsorption Calcitonin

(+)

PTH,
1,25-Dihydroxycholecalciferol

PTH

Urinary Ca2+ excretion

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Osteoporosis

Calcium and Vitamin


D supplements

Calcium carbonate (40% Elemental calcium) Provides most


calcium, usually require requires an acidic environment for absorption.
Tricalcium phosphate (Calcium phosphate, tribasic) 39%
Calcium chloride 27%
Calcium citrate (21%) good choice for seniors
Calcium lactate (13%)
Calcium gluconate (9.3%) least elemental calcium
Dose of Calcium
4 8 Year: 800mg/day
9 18 year 1300 mg/day
Perimenopausal woman: Not less than 1000mg/day
Men 18 50 year 1000mg/day
Men over 50 year 1500mg/day
Pregnant and lactating woman > 18 year: 1000mg/day

Dose of Vitamin D

Men and woman over 50 year: 800 IU (20mcg) day


Men and woman under 50 year: 400IU (10mcg) day
Active Vitamin D is Vitamin D3 (Cholicalceferal)

Bisphosphonates
Bisphosphonates

Alendronate (Fosamax) = Increase bone mass, and reduce Non


Vertebral fracture or decrease vertebral fractures)
Etidronate (Didronel) = Decrease vertebral fractures only
Risedronate (Actonel)
Fosavance (Alendronate + Vitamin D 2800 IU)

Mechanism

Decrease bone resorption via several mechanisms


Inhibition of the osteoclastic proton pumps necessary for dissolution of
hydroxyapatite.
Decrease osteoclastic formation or activation.
Increase osteoclastic apoptosis (cell death)Decrease resorption
Bisphosphonates act as a potent, specific inhibitor of osteoclast
mediated bone death.
Bisphosphonates are synthetic analog of pyrophosphate that bind to the
hydroxyapatite that found in bone.

Therapeutic use

Side Effects

Diarrhea, Nausea, Altered taste, Abdominal pain, Night time leg


cramps,
Esophageal ulcers
Osteomalacia (etidronate only) (osteomalacia = softening of bones due
to vitamin D deficiency

Osteoporosis Prevention
Treatment of post menopause bone loss
Treatment of osteoporosis
Treatment of Glucocorticoid induced osteoporosis
Pagets disease = Excessive activity of osteoclasts.
Metastatic bone cancer
Bisphosphonates have decreased rate of bone fracture in osteoporosis
and Pagets disease patients
Bisphosphonates have anti resorptive activity.
Risedronate has highest anti resorptive activity and than alendronate.
Etidronate has lowest anti resorptive activity

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Dose

Alendronate
Counseling

Osteoporosis

Alendronate (Fosamax) available in a once weekly 70mg tablet


Available dosage forms: 5 mg, 10mg, 35 mg, 40 mg, 70 mg
Prevention of osteoporosis in postmenopausal women once 5 mg
daily
Treatment of osteoporosis in women 10 mg once daily or 70 mg tablet
once weekly
Treatment and prevention of glucocorticoid induced osteoporosis in
men and women5 mg once daily
Treatment of osteoporosis in men one 10 mg tablet once daily or 70 mg
once a week.
Risedronate (Actonel) = Available dosage forms: 5 mg, 35 mg,
Take first thing in the morning empty stomach
Take with plenty of water
Do not lie down for 30-45 min after medications (stay upright)
Calcium supplements should be separated by 2hours before or after

Raloxifene (Evista)
Mechanism

Selective Estrogen Receptor Modulator (SERM)


Estrogen like action on bone and lipid metabolism
Estrogen antagonist action in breast and endometrium

Therapeutic use

Prevents postmenopausal bone loss, increases bone density


approximately 3%, decrease vertebral fractures
Has estrogenic and antiestrogenic activity
It does not have effect on endometrium like tamoxifen and estrogen,
therefore may not predispose uterine cancer.
Lower cholesterol and LDL but no effect on HDL and TG.
For prevention of osteoporosis in postmenopausal

Side Effects

Increase risk of Deep vein thrombosis (DVT)


Avoid in who are pregnant and planning to become pregnant.
Aggravate hot flushes
Coadministration of cholestyramine reduces absorption up to 60%. Do
not take together.

Calcitonin salmon
Calcitonin is a hormone secreted from thyroid gland
Calcitonin hormone helps bone formation by transporting Ca from blood to bones
Mechanism: Directly effect on osteoclast and decrease bone resorption through direct effect.
Two products are available
Miacalcin
200 IU/day intranasally
Common SE is nasal irritation
Calcimar, caltine
50 100 IU sc/day or Q 2nd day or 5days/wk
Not approved for osteoporosis

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Osteoporosis

Osteoporosis Tips








Bone remodeling occurs, when which is present


Osteoporosis is caused by
Risk factors of osteoporosis
Androgen deficiency cause
What is NOT risk factor of osteroporosis
Recommended daily allowance of vitamin D is
Elderly may absorb calcium poorly due to
Calcium supplement in elderly
Paget Disease

Abbrevation and Terminology


SERM
LDL
HDL
TG
DVT

Selective Estrogen Receptor Modulator


Low Density Lipoprotein
High Density Lipoprotein
Deep Vein Thrombosis

Generic and Brand


Raloxifene
Alendronate
Etidronate
Risedronate
Fosavance

Evista
Fosamax
Didronel
Actonel
Alendronate

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Asthma and COPD

32

Asthma and COPD


Bronchodilators

b2-adrenergic
agonist

Anti-inflammatory drugs

Methyl
xanthene

Aerosol
corticosteroids

Mast cell
stabilizers

Theophylline
Cromolyn sodium
Aminophyllinne

Nedocromil

Muscarinic
Fluticasone

antagonist
Beclamethasone

Ipratropium

Tiotropium (Spiriva)

Leukoteine antagonists

Leukotriene
receptors
antagonist

Zafirlukast
Montelukast

Inhibitory
of 5-lipo
oxygenase
enzyme
Zileuton

Short acting
Long acting
Albuterol (salbutamol)
Formeterol
Isoproterenol
Salmeterol
Isoetharine
Metaproterenol
Terbutaline
Asthma Triggers (factors that increase risk of asthma)
Triggers
Early asthmatic response- Symptoms only (i.e., bronchoconstriction)

Cold air

Exercise

Emotional stress
Late asthmatic response- Worsening asthma
Allergens (Pollens, cockroach, molds, animal dandur)

Respiratory viruses

Occupational chemicals

Drugs ASA, NSAIDs

Food additives sulfites, tartrazine

Air pollution (including cigarette smoke)
GERD

Sinusitis

Treatment for chronic asthma


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Asthma and COPD

Beta2 agonist drugs


Beta2 Agonist

Mechanism

Therapeutic use
Short acting beta 2 agonist:
Albuterol, terbutaline,
pirbuterol

Long acting beta 2 agonist:


Salmeterol

SE

Short acting beta2 agonist (SABA)


Albuterol (Salbutamol)
Terbutaline
Metaproterenol
Pirbuterol
Long acting beta2 agonist (LABA)
Salmeterol
Formoterol (short acting 1- 3 min and long duration 12 hours)
Bronchodilation
Vasodilatation
Slightly decrease peripheral resistance
Increase muscle and liver glycogenolysis
Relax uterine muscles
Increase release of glucagon
Treat Asthma
Rapid onset of action and provide relief for 4 to 6 hours.
Indicated in symptomatic treatments, rescue agents, combat
acute bronchoconstriction
Albuterol, terbutaline, pirbuterol has little alpha-1 and beta -1
effects.
Does not effect by COMT enzymes because these are activated
by non COMT
Inhalation route has less toxic side effects than systemic routes.
Have less tachycardia, hyperglycemia, and hypokalemia effects
with inhalations routes.
Short acting are best reserved for treatment of acute
exacerbations and prophylaxis of exercise induce asthma (EIA)
Salmeterol has long duration of action, providing bronchodilation
for at least 12 hours, and slow onset of action.
Indicated in maintenance treatment in combination with
corticosteroids especially for nocturnal asthma, EIA, and COPD
Not indicated in acute asthmatic attacks
Tremors (shaking) due to effect on beta2 receptors of muscles
Cardiovascular SE (tachycardia, palpitation) due to effect on
Beta 1 receptors

Salbutamol (Ventolin)
Mechanism
Therapeutic use
Side effects
Recommendation
Contraindication

Sympathomimetic bronchodilator that relaxes the muscle surrounding


the bronchioles
Relieve symptoms of Asthma, chronic bronchitis and emphysema.
Fine tremor of the hands
Anxiety, tension restlessness
Inhalation is considered more effective because drug is delivered
directly to the bronchioles
Caution in diabetes, Hyperparathyroidism, CV disorders

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Onset of bronchodilation

10-20 minutes

Duration of
bronchodilation

4-5 hours

Asthma and COPD

Salmeterol (Serevent)
Mechanism

Therapeutic use
Side effects
Drug-drug interaction

A Sympathomimetic Bronchodilator, And Relaxes The Muscle


Surrounding The Airways In The Lungs But Because It Has A
Slow Onset Of Effect, It Is Not Used For Immediate Relief Of
Symptoms Of Asthma.
It Has Longest Duration Of Bronchodilation
Indicated In COPD And Emphysema
Prevention Of Nocturnal Asthma
Prevention Of Exercise Induced Asthma
Dry And Irritated Nose, Throat (Inhalations), Tremors,
Nervousness, Cough Wheezing
There is an increase risk of low blood potassium levels when high
doses of salmeterol are taken with corticosteroids, Theophylline
And Diuretics

Metaproterenol (Alupent)
Mechanism
Therapeutic use
Onset of
bronchodilation
Duration of action

Produces dilatation of the bronchioles and improved airway function


Asthma
5-10 Minutes
4-5 Hours

Terbutaline (Bricanyl)
Mechanism
Therapeutic use
Side effects

Drug-drug
interaction

A sympathomimetic bronchodilator that dilates the small airways of the


lungs
Treatment and prevention of the bronchospasm occurring with asthma,
chronic bronchitis, and emphysema
Bronchodilator and reduce uterine contractions in premature labor.
Muscle tremor, especially of the hands
Nervousness and restlessness
Administered subcutaneously and orally.
Terbutaline may interact with MAOIs to cause a dangerous rise in
blood pressure

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Asthma and COPD

Corticosteroids
Corticosteroids

Mechanism

Therapeutic use

Side effects

Recommendation
Combination
products

Prednisone PO, Prednisolone PO,


Beclomethasone
Budesonide
Fluticasone
Triamcilone
Steroids have no effect on the airway smooth muscles; rather decrease
the number and activity of cells involved in airway inflammation.
(Macrophage, eosinophils, and T-lymphocytes).
Prolonged use for several months reduces the hyperresponsiveness of
smooth muscles.
Antiinflammatory response reduced by reversal of mucosal edema
Asthma
Allergic rhinitis
Inhaled glucocorticosteroid are the drug of choice in moderate to
severe asthma that requires beta2 agonist more than once daily.
Inhaled corticosteroids are deposited in the airway and mouth
Severe asthma systemic glucocorticoids (short time use only)
Glucocorticoids most effective when taken continuous
Oral thrush (candidiasis): Can be reduced by rinsing mouth or using
spacer
Spacers: reduces systemic side effects and reduces thrush.
Nasal sprays: systemic absorption is minimal and side effects are
localized nasal irritation, nosebleed, sore throat, rarely candidiasis
To reduce corticoids side effects rinse and gargle mouth after inhalations.
Adviar = Salmeterol (LABA) + Fluticasone (steroid)
Symbicort = Formeterol (LABA) + Budesanoide

Prednisone/Prednisolone (Inflamase)
Mechanism
Therapeutic use
Side effects
Drug-Drug interaction
Recommendation

Prednisolone is the active form of Prednisone, is a powerful


corticosteroid
Skin diseases, rheumatic disorders, and certain blood disorders.
Long term treatment with high doses can cause fluid retention,
indigestion, diabetes, hypertension and acne.
It may increase the adverse effects of Diuretics
Prolonged systemic use can lead to such adverse effects as diabetes,
glaucoma, cataracts, and fragile bones, and may retard growth in
children.
Dosages are usually tailored to minimize these effects.

Fluticasone (Flovent)
Mechanism

A corticosteroid drug used to control inflammation in asthma and


allergic rhinitis.

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Mechanism
Therapeutic use
Side effects

Monitoring

Asthma and COPD

It does not produce relief immediately, so it is important to take it


regularly.
Prevent asthma attack (by inhaler)
Prevent allergic rhinitis
Fungal infection causing irritation of the mouth and throat (inhaled
form)
To minimize side effects thorough rinsing the mouth ang gargling with
water after inhalation is recommended
Periodic checks of adrenal functions may be required if large doses are
being taken.

Budesonide (Pulmicort, Rhinocort)


Mechanism
Therapeutic use

Side effects
Drug-Drug
interaction
Monitoring

A corticoisteroid in a form of slow release capsule that reduces


inflammation of whether nose, lungs, or intestines
Prevent attacks of asthma but not stop an existing attack.
Enema to treat ulcerative colitis
Relieve symptoms of Crohns disease
Fewer and less serious side effects
Ketoconazole and other azole antifungals can increase the blood level
of oral Budesonide.
When taking in a large dose, periodic checks may be needed to insure
the adrenal glands are working properly
Children inhalers may have their growth (height) monitored regularly.

Beclomethasone (Qvar)
Mechanism
Therapeutic use

Side effects
Recommendation
Monitoring

A corticosteroids that controls nasal symptoms by reducing


inflammation and mucus production in the nose.
Relieve the symptoms of allergic rhinitis and to control asthma
Helps to reduce symptoms such as wheezing and coughing
Given to people whose asthma is not responding to bronchodilators
alone.
Fungal infections causing irritation of the mouth and throat (inhalers)
Rinse mouth and gargle with water after each inhalation.
When large doses are being used, periodic checks is required to ensure
that the adrenal glands are functioning healthy.

Anticholinergics
Ipratropium Bromide Atrovent
Mechanism

An anticholinergic bronchodilator that relaxes the muscles surrounding the


bronchioles. Has longer effect but slower onset.

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Therapeutic use

Side effects
Onset of effect
Duration of action
Tiotropium (Spiriva)

Combivent
All MDI

Asthma and COPD

Maintenance treatment of reversible airway disorders, particularly Chronic


Bronchitis
Runny nose due to allergy (nasal spray)
The drug of choice for COPD
Anticholinergic side effects
Has rare side effects
5-15 minutes
8 hours
Long acting muscarinic blocker
Administered by special devise handihaler
Available as capsule
Ipratropium bromide + Salbutamol (MDI) and Nebulizers
Should shake before use

Leukotriene inhibitors
Zafirlukast
Mechanism

Leukotriene inhibitors
Inhibitors of LTC4 and LTD4 receptors
Steroid sparing properties

Therapeutic use

Have anti-inflammatory and bronchodilator activity


Reduce bronchospasm and associated symptoms that are mediated
through leukotrienes.
Used for exercise induced asthma
DOC for aspirin induced asthma
Sudden withdrawal of corticosteroid patient taking Zafirlukast
precipitated Churg-Strauss syndrome (Severe asthma with increase
eosinophil count in blood).
Vasculitis angiitis: A patchy inflammation of the walls of small blood
vessels
ZafirlukastFood reduces bioavailability take 1 hour before or 2 after
meals
Take empty stomach
Oral tablets
Used in 12 year or Over 12 year old only
Singulair
Chewable tablets and Granules
Inhibitors of LTC4 and LTD4 receptors
Have antiinflammatory and bronchodilator activity
Reduce bronchospasm and associated symptoms that are mediated
through leukotrienes.
Used in Exercise induced asthma
Headache
Nausea and diarrhea
Abdominal pain

Side effects

Drug-Food
interaction

Montelukast
Mechanism
Therapeutic use

Side effects

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Drug-Food
interaction

Asthma and COPD

Montelukast may be taken without regard to food.


Chewable tablet
Powder
Over 2 year old can be used

Theophylline and Aminophylline


Mechanism

Therapeutic use

Side Effects

Recommendation

Monitoring

Factors that alter


theophylline
clearance

(Aminophylline will breaks down to Theophylline in the body)


Induce phosphodiesterase (PDE) inhibition
Alter intracellular calcium
Adenosine antagonisms
Increase circulating catecholamines
Antiinflammatory action
Chronic asthmamainly decreases symptoms
Bronchitis and emphysema
Use as a preventive measure, and is added to standard therapy

GI effects Nausea, vomiting, abdominal cramps, Diarrhea,


headache,
CVS Palpitation
CNS effects Insomnia, seizures, dizziness, nervousness, restlessness
Overdose causes seizures, and arrhythmias.
Dosage should be adjusted based on serum levels
Sustain release theophyllines allow for a longer dosing interval and
improve compliance. Compliance to oral theophylline also may better
than that inhaled bronchodilators and corticosteroids
Oral therapy: Sustained released theophylline allows for longer dosing
interval and improve compliance
Periodic checks on blood levels are requires especially the Serum level
Theophyllines are contraindicated in patients with hypersensitivity to
xanthine compounds.
Cuation in patient with peptic ulcers and seizure diseases
Increase theophylline clearance (decrease levels): age: 1-9 years,
High protein diet, smoking (tobacco, marijuana), fever, drugs such as
carbamazepine, Phenobarbital, phenytoin and rifampin.
Decrease theophylline clearance (Increase levels): Age (elderly,
infants, under 6 months age, premature neonates), CHF, Fatty food,
High carbohydrated diet, Liver dysfunction and Drugs such as: Oral
contraceptives, Non selective beta blockers, CCBs, Macrolide antibiotics,
Clindamycin, Zafirlukast, Allopurinol.

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Asthma and COPD

Cromolyn and nedocromil


Mechanism
Therapeutic use

Side Effects

Mast cell inhibitors


Has Anti-inflammatory Action
Effective in prophylactic, has anti-inflammatory effect.
Not used in acute asthmatic attacks
Cromolyn administered by inhalation of microfine powder or as an
aerosol solution.
Cromolyn poor absorption causes more side effect that can be reduced
by powder or aerosol formulations.
Internasal cromolyn reduces allergic rhinitis symptoms
Bitter taste
Irritation of nasal mucosa, pharynx, larynx

Chronic Obstructive Pulmonary Diseases (COPD)


COPD: Chronic Obstructive Pulmonary Diseases; COPD is due to chronic obstruction in airway
passage. COPD is two types:
Emphysema (high altitude sickness)
Chronic bronchitis.
EMPHYSEMA is a disease in which the small air exchange sacs (alveoli) in the lungs become
permanently enlarged and damaged (alveoli walls destroyed) decreasing oxygen absorption and
resulting in shortness of breathe.
CHRONIC BRONCHITIS is an inflammation of the airways in the lungs that causes your lungs to
produce excessive amounts of mucus (phlegm). This reduces the flow of air to the lungs.
Onset age 45 years
Risk Factors that Cause COPD
Smoking (80-90%)
Family History
Occupational exposures to certain ducts and fumes
Air Pollution
Second Hand Smoke
Asthma
Drug used for the treatment of COPD

Beta adrenergic agonists
Corticosteroids
Ipratropium (Atrovent)
Theophylline

Asthma and COPD Tips


Theophylline inhibit activity of
Leukotrienes are chemical derivatives of
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Asthma and COPD

Leukotrienes are produced from arachidonic acid by catalization of


Long term use of oral corticosteroids may cause
Leukotriene antagonist act on
DOC for aspirin induced asthma
Patient has COPD and pneumonia, what is DOC
Oral contraceptive effect on theophylline
Dry cough is caused by accumulation of
What is differentiating symptoms of asthma from COPD
Smoking is very high risk factor for COPD
What asthma devices do not require shaking
Polycythemia
Asthma exacerbations are NOT triggered by
Obstruction of airways in lungs is referred as
Permanent enlargement of alveoli is referred as
Highest clearance of theophylline in which age group
When can we use leukotriene inhibitors
What is important to counsel in patient using steroid inhalers
Histamines are released from
What kinds of changes can you expect to see in aminophylline solutions exposed to air?

Abbrevation and Terminology


ASA
NSAIDS
SABA
LABA
COMT
EIA
COPD
CHF
CCB

Acetyl Saliaylate
Non-Steroidal Anti-inflammatory Drugs
Short Acting Beta2 Agonist
Long Acting Beta2 Agonist
Catechol-O-methyl transferase
Exercise Induce Asthma
Chronic Obstructive Pulmonary Diseases
Congestive Heart Failure
Calcium Channel Blocker

Generic and Brand


Salbutamol
Salneterol
Metaproterenol
Terbutaline
Prednisone/Prednisolone
Fluticasone
Budesonide
Beclomethasone

Ventolin
Advir, Serevent
Alupent
Brenthin, Bricanyl
Inflamase, Pediapril, Winpred
Flonase, Flovent
Entocort, Pulmicort, Rhinocort, Rhinocort Aqua
Ati-Beclomethasone, Qvar, Rivanase AQ

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Asthma and COPD

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Anticancer Drugs and Chemotherapy

33

Anticancer Drugs and Chemotherapy


Classification of Anticancer drugs

Action of DNA

Damage DNA

Inhibit
synthesis or
functions

Others
Free radicals:
Alkylation:
Actinomycin D
Bleomycin

Mechlorethamine
Etoposide
Cyclophosphamide
Teniposide
Ifosfamide
Amsacrine
Topoisomerase
Chlorambucil
Antimetabolites
inhibitors
5-fluorouracil

Melphalan
Doxorubicin
Cytarabine
Busulfan

Daunorubicin
Mercaptopurine
Lomustine

Topotecan
Thioguanine
Carmustine

Irinotecan
Thioguanine
Streptozolin

Methotrexate
Cisplatin
Carboplatin
Dacarbazine
Procarbazine
Altretamine/
Hexamethylmelamine
Action on steroid
Mitomycin
Hormones

Agonists
Androgens
Estrogens
Progestins
Leuprolide
Goserelin
Narfarelin

Cancer estimated
deaths in men
Cancer estimated
deaths in women
Warning signs of
cancers

Atagonist
Tamoxifen

Toremifene
Flutamide
Anastrozole
Letrozole

Lung cancer 31%


Prostate cancer 11%
Lung cancer 25%
Breast cancer 15%
C------ change in bowel or bladder habits
A------ a sore that does not heal
U------ unusual bleeding or discharge
T------ Thickening or lump in breast
I-------- Indigestion or difficult in swallowing
O------ Obvious change in wart or mole
N------ Nagging cough or hoarseness

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Cell Cycle Phases

Cell cycle phase


specific drugs

Cell cycle specific


drug (phase-non
specific)
Cell cycle non
specific agents

Anticancer Drugs and Chemotherapy

All cells must traverse the cell cycle phases before and during cell division.
Anticancer drugs may act on specific phase. Tumor cells are more
responsive to specific drugs
G0 phase Resting phase
G1 phase Synthesis of enzymes needed for DNA synthesis
S phase DNA replication (DNA synthesis)
G2 phase Synthesis of components needed for mitosis.
M phase Mitotic tubule formation Vincristine and vinblastine
More active against cells that are specific phase of cycle:
G1 phase L-aspraginase and prednisone
S phase Methotrexate, 6-thioguanine, cytarabine
G2 specific Bleomycin and etoposide
M phase Vincristine and vinblastine, peclitaxol
Alkylating agents, Antitumor antibiotic, Cisplatin

Effective whether cancer cells are in cycle or resting phase radiation,


nitrosoureas, mechlorethanime
M: mitotic
G2: synthesis of
cellular components
required for mitosis

phase where
cell divides

G0: resting
state where cell
is not dividing
G1: synthesis
of enzymes
needs for DNA
synthesis

S: DNA is
replicated

Class
Alkylator and alkylatorlike drugs
Antimetabolites

Examples
Melphalan, Chlorambucil,
Cisplatin, Carmustine
Fluoroucil, Methotrexate
cytarabine, Mercaptopurine
fludarabine

Mechanisms
Covalent bonds break with DNA
bases; strand breaks
Inhibit DNA synthesis by inhibiting
enzymes or incorporating into DNA
and RNA.

Antibiotics

Doxorubin, Bleomycin,
Mitomycin C, Dactinomycin
Vincristine, Vinblastine,
Paclitaxel. Docetaxel

Intercalate DNA strands and


produce oxygen free radicals
Vincas inhibit microtubule
formation
Taxanes stabilize microtubules so
cant rearrange
Inhibit unwinding and winding of
double helix; cant form or repair
DNA

Mitotic inhibitors

Topoisomerase
inhibitors

Etoposide, Irinotecan, Topotecan

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Anticancer Drugs and Chemotherapy

Alopecia is a counseling issue! The extent of hair loss varies, but is usually starts at 2-4 weeks and
is reversible when the drugs are discontinued. Doxorubicin and paclitaxel tend to cause the most
alopecia, but it is common with most combination regimens. Patients may wear wigs, hats, or may
just go bald.
Neurotoxicity: Vincristine has as its dose-limiting toxicity autonomic dysfunction and peripheral
neuropathy, both sensory and motor.
Pulmonary toxicity: Bleomycin causes a generally irreversible pulmonary fibrosis at higher lifetime
doses.

Clophosphamide (Cytoxan)
Mechanism
Therapeutic use

Side Effects

Drug-Drug
interaction
Contraindication
Monitoring

An Alkylating agent use to treat cancer.


Lymphomas (lymph gland cancers)
Leukemia
Solid tumors (breast and lung)
Also use for autoimmunediseases
Nausea, vomiting, and hair loss
Irregular menstruation
Can affect heart, lungs, and liver (acute hemorrhagic cystitis)
Bladder damage in susceptible people
Phenytoin can increase the breakdown of cyclophosphamide
Allopurinol and phenothiazines can inhibit breakdown of
cyclophosphamide.
Not advisable for pregnant and lactating mothers.
Periodic checks on blood composition and on all effects of the drug are
usually required.

Mercaptopurine, 6-MP (Purinethol)


Mechanism

Inhibits purine synthesis


Analog of hypoxanthine
Structurally similar to allopurinol (purines)
Azathioprine an immunosuppressant exert effect after converting 6-MP.
Causes RNA and DNA dysfunction

Side effects

GI Nausea, vomiting, diarrhea


Bone marrow depression
Hepatotoxicity

Doxorubicin (Adriamycin)
Mechanism
Therapeutic use

Effect maximal at S and G2 phase


Anticancer antibiotics
Widely used anticancer drug (breast, lung etc)

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Side effects

Anticancer Drugs and Chemotherapy

Irreversible cardiotoxicity
Myelosuppression
Stomatitis
Alopecia
Nausea and vomiting
Should be carried in Vertical laminar air flow hood

Compounding

Dactinomycin (Cosmegen)
Mechanism
Side effects

Anticancer antibiotics
Form stable DNA complex and interfere with DNA dependent RNA polymerase
Major dose limiting toxicitybone marrow depression.

Mechlorethamine (Mustargen)
Mechanism
Therapeutic use
Side effects

Alkylating agent

Primarily used in Hodgkins disease (malignant disease of lymphatic tissue) as
part of MOPP regimen (Mechlorethamine, Oncovin, Prednisone, Procarbazine)
Severe nausea and vomiting
Sever bone marrow depression
Myelosuppression
Anorexia
Gonadal dysfunctionz

Vincristine and vinblastine


Mechanism

Side effects

Mitotic spindle is part of cytoskeleton and essential for internal movement


occurring in the cytoplasm of all eukaryocytic cells.
Mitotic spindle is essential for partitioning two DNA daughter cells.
Myelosuppression
Paralytic ileus
Alopecia
Stomatitis

Paclitaxel (Taxol)
Mechanism
Side effects

Reversible microtubule inhibitor.


Obtained from Yew plants (from Himalayas)
Serious hypersensitivity reaction,
Patient should be premedicated with dexamethasone and
diphenhydramine as well as H2 blockers.
Myelosuppression
Peripheral neuropathy
Alopecia
Mucositis

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Anticancer Drugs and Chemotherapy

Anaphylaxis
Dyspnea

Chemotherapy
The treatment of cancer with drugs is called chemotherapy. Antineoplastic drugs, also referred to as
chemotherapeutic agents, are drugs that are used to treat cancer.
Side effects of chemotherapy:
Acute:
Extravasation (effects the adjacent tissue)
Vessicant drugs (damage to tissue / necrosis) Example: Bleomycin, cisplatin,
dactinomycin, domorubicin, vincristine, vinblastin etc.
Thrombophlebitis (inflammation associated with thrombus): Patient with cancer can
develop thrombosis after chemotherapy. Due to activation of fibrinogen.
Hypersensitive reactions. Example: Etopiside, peclitaxol, rituximab, trastuzumab.
Rapid tumor lysis syndrome
Nausea and vomiting

Chronic, organ specific:


Skinalopecia, dry skin, nail changes, pigmentation (melanoma), Xerostomia
Alopecia is the loss of hair: Drug that cause alopecia is doxorubicin, daunorubicin,
cyclophosphamide, vincristine, and paclitaxel.
Vessicant agents include: dactinomycin, doxorubicin, mechlorethamine, mitomycin, vincristine, and
vinblastine.
Hair regrowth occurs after 1-2 months after stopping chemotherapy.
Xerostomia: Dry mouth is one of the most common complication associated with radiation therapy.
Reversible after 6-12 months of therapy.
Can be managed by: Sugar free hard candy, chewing sugar free gum stimulate salivation.
Commercially available saliva substitute. Ice chips. Cholinergic agonist Pilocarpine 5mg tab.
Bone marrow depression (Myelosuppression):
Bone marrow depressionNeutropenia, Thrombocytopenia
Neutropenia treated by colony stimulating factors (G-CSF and GM CSF): Filgrastim or
pegfilgrastim
Thrombocytopenia for prevention use Oprelvekin (Inerleukin-11)
Complications: Bone marrow suppression is the most dose limiting side effect of cancer
Myelosuppression in general the onset is 7 10 days and peak is 10 14 days. Recovery count
occurs usually occurs in 2 3 weeks.
Megaloblastic anemia by methotrexateFolinic acid (leucovorin, 5-formyltetrahydrofolic acid)
Neutropenia associated anticancer drugs can be treated by filgrastim (human granulocyte
colony stimulating factor)
Least bone marrow depression anticancer drugs is: Bleomycin
Cancer patient with anemia Erythropoeitins are useful

Cardiotoxicity:

Risk of CHF, commonly seen with doxorubicin, daunorubicin, epirubicin, mitoxantrone.


5-FU, capecitabine; Cause coronary spasms, mimicking a myocardial infarction (avoid in know
coronary artery disease patients)
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Anticancer Drugs and Chemotherapy

Cardiotoxicity can prevented or lessen by using cardioprotective agent: Dexrazoxane

Pulmonary toxicity:
Pneumonitis, pulmonary fibrosis commonly seen with Bleomycin, Carmustine, Cyclophosphamide,
Mitomycin, Methotrexate, vinca alkaloids,
Symptoms of pulmonary toxicity include: SOB, non-productive cough, and rarely low grade fever.

Neurotoxicity:
Common with vincristine, vinblastine, Cytarabines, Methotrexate (very little), 5FU, interferon
alpha
Peripheral neuropathies associated with: Vincristine, peclitaxel: Peresthesia (numbness and
tingling) can occur with vincristine, which often appears within few weeks of therapy.
High dose of cytarabin may produce cerebllar toxicity that manifest initially as loss of eye-hand
coordination and progress to coma.
Fludrabine cause severe neurotoxicity
Caramustine and other alkylating agents cause little or no neurotoxicity.

GI toxicity

Mucositis or stomatitis:
Mucositis: Generalized burning, and pain on the ventral surface of tongue. Floor of tongue, mouth
looks erythromatus.
Stomatitis: generalized inflammation of oral mucosa.
Mucositis or stomatitis: Common with Doxorubicin, Methotrexate, 5-fluorouracil, Actinomycin,
Bleomycin capecitabine.
Recommend mouth hygiene, xylocaine, viscous sucralfate, nystatin, sodium bicarbonate, for
severe cases peliformin (growth factor) can be used.
Avoid alcohol, antihitamine, steroids, spicy food
Mucositis treatment and prevention:
Topical anesthetics: Viscous Lidocaine, or dyclonineHCL 0.5 or 1%
Corticosteroid provide anti-inflammatory action
Capscisin: Produces burning and pain and ultimately desensitizes pain.
Sucralfate suspension may provide benefit by coating.
For Localized effect: use benzocain in orabase
Mucositis prevention:
Chlorhexidine gluconate 0.12% (Peridex, Periogard) may reduce severity and frequency
of mucositis infections.

Nausea and vomiting


Very high emetics anticancer drugs
Cisplatin
Streptozocin
Cyclophosphamide
High emetics anticancer drugs
Doxorubicin
Methotrexate (250 mg to 1000mg)
Cytarabine
Lowest emetic anticancer drugs
Bleomycin
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Anticancer Drugs and Chemotherapy

Methotrexate (under 50 mg)


Vincristine
Vinblastine
Tamoxifen

Management of Nausea and vomiting associated with cancer chemotherapy:


Lowest emitogenic drugs Nausea and vomiting can be treated by Metoclopramide
High and very high emitogenic drugs associated Acute: nausea and vomiting can be treated by
Dexamethasone
DOC for delayed nausea and vomiting Dexamethasone

Hepatotoxicity
Hepatotoxicity monitor LFT, jaundice, or hepatitis: Asparaginase, cytarabine, mercaptopurine, and
methotrexate.

Nephropathy:
Elevate BUN and electrolyte abnormalities: methotrexate may precipitate in kidney. Cisplatin and
streptozocin. Amifostine may be used to protect the kidney from the nephrotoxicity associated
with cisplatin.

Sexual dysfunction:
Cyclophosphamide, melphalan, and procarbazine associated with significant infertility in men and
women.

Hemorrhagic cystitis
It is a bladder toxicity that is seen most commonly after administration of cyclophosphamide and
ifosfamide.
These drugs produce a metabolite called acrolein, which cause chemical irritation in bladder
mucosa, resulting in bleeding.
Hemorrhagic cystitis caused by Acrolein can be prevented by excessive hydration and subsequent
frequent urination. The other method is by administering uroprotecting agent called MESNA,
which bind acroleine and prevent from contacting the bladder mucosa.

Pulmonary toxicities:
The most common with bleomycin, mitomycin, carmustine
Rationale for combination therapy: Overcoming or preventing resistance, Cytotoxicity to resting and
dividing cells Biochemical enhancement of effect. Beneficial drug interactions Rescue host cells

Some agents can be administered intrathecally: Methotrexate, Cytarabine Thiotepa

Warning: Vincristine should be labelled as Intravenous only. Intrathecally vincristine causes death.

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Anticancer Drugs and Chemotherapy

Anticancer drugs Tips
















Melonoma is
Metoclopramide and dexamethasone are more effective nausea related to
Methotrexate is used for
Which anticancer drugs cause pulmonary fibrosis
Hypertropy is
Hyperplasia is
Least emetic anticancer drug is
Cancer patient on cancer chemotherapy, reports shortness of breath, non productive cough, she
may be using drug
DOC for delayed Nausea and vomiting
Mesna is
Doxorubicin preparation should be performed in
Hypertropy is
Hyperplasia is
Melatonin
Peclitaxel and docetaxel act on

Abbrevation and Terminology


MOPP
GM
CSF
LFT
MESNA

Mechlorethamine, Oncovin, Prednisone, Procarbazine


Liver Funtion Test

Generic and Brand


Melphalan
Chlorambucil
Cisplatin
Carmustine
Fluoroucil
Methotrexate
Cytarabine
Fludarabine
Bleomycin
Mitomycin C
Vincristine
Vinblastine
Docetaxel
Etoposide
Irinotecan
Topotecan
Vincristine
Cyclophosphamide
Mercaptopurine, 6-MP
Doxorubicin
Dactinomycin
Mechlorethamine
Paclitaxel

Alkeran
Leukeran
Platinol
BiCNU
Adrucil, Carac, Efudex, Fluoroplex
Rheumatrex, Trexall
Cytosar
Fludara
Blenoxane
Mitozytrex, Mutamycin
Oncovin, Vincasar PFS
Velban
TaxotereT
Etopophos, Toposar, VePesid
Camptosar
Hycamtin
Oncovin
Cytoxan, Procytox
Purinethol
Adriamycin, Rubex
Cosmegen
Mustargen
Taxol

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Gastrointestinal Drugs

34

Gastrointestinal Drugs
GERD
Mild GERD, relief of symptoms is with antacids, alginates or non-prescription strength H2RA.
Severe GERD: PPI are the Drug of choice. Use PPI for 2 4 weeks
The goal is to raise the intragastric pH 4 during periods when reflux is likely to occur.
Peptic ulcers
Gastric ulcers Due to reflux since has weak pyloric sphincter
Duodenal ulcers Excessive secretion from parietal cells
Acute stress ulcers (Curlings ulcer) Tumors
Pathologic acid-hypersecretory states (Zollinger-Ellison syndrome)
Treatment of peptic ulcers



Neutralization of gastric acid Antacids


Reduction of gastric secretion H2 antagonist, Proton Pump Inhibitors (PPI)
Cytoprotection Sucralfate
Eradication of Helicobacter pylori 2 Antibiotics + PPI (triple therapy)

To eradicate H. pylori



Triple therapy: 2 antibiotics + 1 PPI


Losec 1-2-3 A: Amoxicillin + Clarithromycin + Omeprazole
Losec 1-2-3 M: Metronidazole + Clarithromycin + Omeprazole
Quadruple therapy: Tetracycline+ Metronidazole + Bismuth subsalicylate + Omeprazole

Antacids
Antacids are used to treat stomach upset, acid indigestion (heartburn) and sometimes ulcers. They
are simple chemical compounds that are mildly alkaline, and some also act as chemical buffers. They
act by neutralizing stomach and coating the mucosal lining of the stomach. Simethicone is an agent
added to antacids that helps relieve gas.
Types of antacids

Aluminum
compounds

Aluminum compounds, Magnesium compounds, Combined


preparations
(e.g. Aluminum hydroxide, Calcium carbonate, Mg hydroxide, Mg
trisilicate, Na carbonate). Antifoaming agent (Simethicone)
Has prolonged action and widely used especially for the treatment of
indigestion and dyspepsia.
Side effects: constipation.

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Mg bicarbonate

Na bicarbonate

Combined
preparations

Calcium Carbonate

Gastrointestinal Drugs

Has prolonged action.


Side effects: in large doses they cause diarrhea
In patient with impaired kidney function, a high blood Mg level may build
up causing weakness, lethargy, and drowsiness.
The only sodium compound used as antacid
Acts quickly but its effect soon passes.
It reacts with stomach acids to produce gas, which cause bloating and
belching
Recommendation: not advisable to patients with kidney disease, as it
can lead to water accumulation (edema) in the legs, and lungs, or serious
changes in acid-base balance in blood.
Antacids combined with Alginates or antifoaming agents.
ALGINATES are intended to float on the content of the stomach to
produce a neutralizing layer to subdue acid that can otherwise rise into
esophagus, causing heartburn.
ANTIFOAMING agents are intended to relieve flatulence
Constipation

Drug interactions with Antacids:


Tetracyclins: Tetracyclin binds with bi and trivalent ions, thereby this can reduce absorption of
tetracyclins.
Ketoconazole: The antifungal ketoconazole require acidic medium for absorption. Concomitant use
of antacids can reduce absorption of ketoconazole.

H2 receptor antagonists
Ach

Atropine

Histamine

Muscarinic receptor
IP3 Ca2+

Cimetidine
H2 receptor

cAMP

PPIs

Gastrin

H+ secretion

H2-receptor antagonists inhibit the action of a special type of histamine receptor present in the
stomach. This reduces the amount of gastric acid production, which helps heal ulcers.
H2 receptor
antagonists

Therapeutic use

Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)
Acid must be produced to digest protein
Gastric acid secretion is controlled by histamine from enterochromaffin-like
cells, acetylcholine neurons and gastrin-G cells in the antrum
90% reduction in acid secretion
Useful in promoting healing of gastric ulcers
Preventing reoccurrence of ulcers
Management of Zollinger-Ellison syndrome
Gastric hypersecretory states in systemic mastocytosis which is a rare
disorder with increase number of mast cells systematically and in skin

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Side effects

Tips

Gastrointestinal Drugs

Gynecomastia elevation of prolactin (cimetidine)


Headaches famotidine and ranitidine
Hematologic abnormalities
Decreased hepatic microsomal metabolism of some drugs like cimetidine
which decreases the metabolism of warfarin, theophylline, diazepam and
phenytoin
Diarrhea
Constipation
Fatigue
Confusion
Cardiac effects
Diarrhea, constipation, fatigue, headache and confusion are more common
in elderly and decrease renal function patients.
Nizatidine is preferable used in elderly and renal disorder patients
Cimetidine and famotidine are now available without prescription in some
countries for the treatment of dyspepsia (2 weeks supply)

Ranitidine (Zantac)
Mechanism
Therapeutic use

Side Effects
Drug-drug
interaction
Contraindication

Advantage from
other drugs
Call physician NOW

Reduces the amount of stomach acid produced, allowing ulcers to


heal
Ulcers cause by H, pylori
Protect against duodenal ulcers in patients taking NSAIDs.
Reduces discomfort and ulceration of reflux esophagitis; and may
prevent gastric bleeding
Headache; nausea and vomiting; constipation; diarrhea; jaundice
Ranitidine may reduced the absorption of Ketoconazole
High doses (2g) of Sucralfate may reduce the absorption of
Ranitidine.
Avoid alcohol (may aggravate underlying condition and reduce
drugs effects)
Reduce dose to children and infants, and it may pass into beast
milk.
Not like Cimetidine, it does not blood levels of other drugs
such as anticoagulants, anti-convulsants, which might reduce the
effectiveness of treatment.
Sore throat/fever

Cimetidine
Mechanism

Therapeutic use

Is an Anti-ulcer drug that reduces the secretion of gastric acid and


pepsin in the duodenum and stomach, and promotes the healing of
ulcers.
Treat stomach and duodenal ulcers
Used for reflux esophagitis

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Side Effects
Drug-Drug
interaction
Contraindication
Monitoring

Gastrointestinal Drugs

Diarrhea
Dizziness
Increases the effects of anticoagulants. Inhibit CYP 3A4 metabolism,
thereby inhibit metabolism of warfarin, phenytoin, theophylline.
Discuss with physician about using the drugs for pregnant and
lactating mothers.
It is prescribed with caution to people who are receiving
anticoagulants and anticonvulsants
This drug will mask the symptoms of cancer, and delay diagnosis.

Proton pump Inhibitors


Omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole are proton pump inhibitors,
powerful anti-ulcerogenic drugs that work by stopping the production of stomach acid completely.
Eradication of H. pylori is considered to be a major factor in the treatment of duodenal ulcer disease.
PPI

Mechanism
Therapeutic use

Duration
Side effects

Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Irreversible inhibition of gastric parietal cell proton pump H+/K+ ATPase
Prevention of reoccurrence of duodenal ulcers and esophagitis
Pathology hypersecretory states
Multiple endocrine neoplasias
Healing of NSAID induces peptic ulcers
Systemic mastocytosis
A part of the eradication of H. pylori therapy
Drug of choice for Ellison Zollinger Syndrome
Short term treatment (4-8 weeks)
Abdominal pain
Diarrhea
Headache

Omeprazole (Losec)
Mechanism
Therapeutic use
Side Effects
Drug-drug
interaction
Contraindication
Stop taking drug
NOW

It reduces (about 70%) the amount of acid produced by the stomach.


Treat peptic ulcer
Can be given with antibiotics to kill H. pylori (bacteria that cause gastric ulcer)
Headache, diarrhea, nausea, and constipation
Warfarin and Phenytoin = the effects by omeprazole
Blood levels of cyclosporine may raised by omeprazole
Not recommended to infants and children
Alcohol
Rash

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Gastrointestinal Drugs

Lansoprazole (Prevacid)
Mechanism
Therapeutic use

Side Effects

Drug-drug
interaction


Contraindication

An anti-ulcer drug belongs to proton pump inhibitors group.


Peptic ulcer
Gastroesophageal reflux
Zollinger-Ellison syndrome (large quantities of stomach acid are
produced)
Headache and dizziness
Diarrhea and constipation
Flatulence/abdominal pain
No clinical interaction with Lansoprazole however this may reduce the
effects of oral contraceptives, phenytoin, carbamazepine, warfarin, and
theophylline.
Antacids and sucralfate should not to be taken within an hour with
lansoprazole (Lansoprazole will reduce the absorption of these drugs)
Avoid alcohol
Not recommended with infants and children

Esomeprazole (nexium) no clinical significant interaction

Cytoprotective Agents (Mucosal Protective Sulfate)


Sucralfate binds to the ulcer site by forming a viscid sticky gel that coats the ulcer site and acts as a
protectant.
Sucralfate
Mechanism

Therapeutic use

Side effects
Dose
Drug interactions

Aluminum sucrose sulfate is a Sulfated disaccharide


Selectively binds to necrotic ulcer tissues (Acts as a barrier to acid,
pepsin and bile)
Directly absorb bile thus has chelating property
Stimulates endogenous prostaglandin synthesis.
Stimulates mucus secretion
Effective in the healing of duodenal ulcers
Requires acid pH to be activated
Reduces the number of H. pylori
Causes constipation
Dose 1g qid
Should not be administered with antacids, H2 antagonists or proton
blockers

Bismuth Compounds
Mechanism

Therapeutic use

Selectively binds to necrotic ulcer tissues


Stimulation of mucous production
Inhibition of pepsin activity
Possess anti-microbial activity against H. pylori
When combined with antibiotics like metronidazole and tetracycline has
98% healing rate for ulcer

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Contraindications

Gastrointestinal Drugs

Should not be given in renal disease and pregnancy

GI disorder Tips























Lactulose is used in what type of chronic liver disorder


An example of ecosanide is
Misoprostol is
Type of pain in GERD is
Increase in bilirubin cause
Aluminum salts can cause SE
Magnesium antacids cause SE
H.pylori will cause
What type of hepatitis is chronic
What is treatment of hepatitis
NSAIDs induced ulcers can be treated by
Independent risk factors for peptic ulcers are: H.pylori and NSAIDs
Chronic hepatitis?
Epsom salt is?
Ulcerative colitis occurs at?
Antiflatulance agent?
What vaccine can be used for travelers diarrhea?
Na bicarbonate is contraindicated in-patient with hypertension, CHF, severe renal disease,
and edema. This also contraindicated in ulcers.
CaCO3 antacids have rebound acidity due to stimulation of acid secretion.
CaCO3 antacids avoid in hypercalcemia patients.
Hypophosphetemia and osteomalacia can occur with long-term use of Aluminum containing
antacids.
Antacids bind with Tetracyclins, and fluroquinolone and reduce absorption.
Antacids may destroy coating of enteric-coated drugs.
Mg antacids can cause cathartic SE.

Abbrevation and Terminology


IBD
IBS
IFN alfa
GERD

Inflammatory Bowel Disease


Inflammatory Bowel Syndrome
Interferon alfa
Gastro Esophogeal Reflux Disease

Generic and Brand


Omeprazole
Lansoprazole
Cimetidine
Nizatidine
Ranitidine

Losec
Prevacid
Tagamet
Axid
Zantac

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Cell Wall Synthesis Inhibitors

35

Cell Wall Synthesis Inhibitors


Antibiotics classifications

Protein Synthesis
inhibitors

Cell Wall synthesis


inhibitors

Aminoglycosides
Macrolides
Tetracyclines
Lincosamide

Penicillins
Cephalosporins
Vancomycin

DNA Synthesis
inhibitors
Quinolones/
Fluoroquinolones
Metronidazole

Folate Inhibitors
Sulfonamides
Trimethoprin

Penicillins
Acid labile (acid sensitive)
Penicillin G...b-lactamase sensitive
Methicillinb-lactamase resistant
Nafcillin....b-lactamase resistant

Acid stable (acid resistant)


Penicillin Vb-lactamase sensitive
Oxacillinb-lactamase resistant
Amoxicillinb-lactamase sensitive
Ampicillin..b-lactamase sensitive

Tips: PAPA is sensitive to beta lactamases


Beta-Lactamase Inhibitors
Clavulanate
Sulbactam
Tazobactam
Clavulanic acid
Beta-lactamase inhibitors such as clavulanic acid can be combined with sensitive Beta-lactams to
yield an active combination with resistant organisms
Penicillins

Aminopenicillins

Penicillin G
Penicillin V
Methicillin
Nafcillin
Oxacillin
Carbenicillin
Ticarcillin
Piperacillin
Amoxicillin
Ampicillin

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Mechanism
Therapeutic uses

Cell wall synthesis inhibitors


Gram + ve and Gram ve

Side effects

Cell Wall Synthesis Inhibitors

Hypersensitive reactions, rash,


Nausea & Vomiting,
Pseudomembranous colitis diarrhea
Intestinal nephritis

Penicillins G
Mechanism

Cell wall synthesis inhibitors

Therapeutic uses
Side effects

Gram + ve (all of them), Gram ve for Neisseria


Hypersensitive reactions, rash,
Nausea & Vomiting
Pseudomembranous colitis diarrhea
Intestinal nephritis
Take empty stomach

Side effects
management
Drug interactions

Interferes and alters test results for urine and serum protein levels. It
does not interfere with test using bromophenol blue.
Aminoglycoside causes synergistic effect. Most effective endocarditis
infections.

Penicillin V
Mechanism
Uses
Side Effects
SE management
Drug interactions

Cell wall synthesis inhibitors


Gram + ve (all of them)
Gram ve for Neisseria
Hypersensitive reactions, rash,
GI effects Nausea & Vomiting, Pseudomembranous colitis
Give 1 hour before or 2 hour after meals for max absorption.
Interferes and alters test results for urine and serum protein levels. It
does not interfere with test using bromophenol blue.

Piperacillin and Carbenicillin


Therapeutic use
Side Effects
Drug interaction

Gram ve (E.coli, Enterobacter, Klebsiella, Pseudomonas.


Used combination with b-lactamase inhibitors.
Often mixed with aminoglycoside (not in same IV bag)

Amoxicillin (Amoxil)

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Therapeutic use

Side Effects

Drug interaction

Cell Wall Synthesis Inhibitors

Gram + ve (mainly)
Gram ve Neisseria
Synergistic effect with aminoglycoside
Hypersensitivity, Anaphylaxis
GI affects Nausea& Vomiting, P. Colitis (diarrhea).
Blood related
Thrombocytopenia
Leucopenia
Agranulocytosis
AllopurinolIncreases rashes
Hormonal contraceptiveDecreases contraceptive effect.
Methotrexate-effects renal tubular absorption.

Ampicillin (Principen)
Clinical use
Drug interaction
Side Effects

Gram + ve (mainly)
Gram ve Neisseria
AllopurinolIncreases rashes
Hormonal contraceptiveDecreases contraceptive
Hypersensitivity, Anaphylaxis
GI Nausea & Vomiting, P. colitis (diarrhea).
Blood related Thrombocytopenia
Leukopenia
Agranulocytosis

Cephalosporins
1st generation

2nd generation

Cefazolin
Cephalothin
Cephalexin
Cephapirin
Cephradine
Cefadroxin
Cefaclor
Cefamandole
Cefoxitin
Cefuroxime
sodium
Cefuroxime
auxetil
Cefotetan
Cefproxil
Cefonicid
Loracarbef

Long duration of action in 1st gen.


Oral (DOC pharyngitis, cellulites)
Renal and hepatic elimination
Shortest half life (0.6 0.8 h)
Oral
Oral (Associated with serum sickness)

Can cross BBB, can be used in community aquired


bronchitis or pneumonia in elderly
oral

Oral

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3rd generation
Contain
methylthiotetrazole
side chain. Can cause
hypoprothrombonemia
and bleeding problems

1th generation

Cefixime
Cefoperazone
Cefotaxime
Cefpodoxime
Ceftazidime
Ceftriaxone
Cefdinir
Ceftibuten
Cefepime

Cell Wall Synthesis Inhibitors


Oral
Hepatic elimination only
Renal and hepatic elimination, Can penetrate in CSF.

Longest half life (8 hours) Single dose


Oral
Oral

Cephalosporins 1st Generation


1st Generation
Therapeutic use
Side effects

Dose

Cefazolin
Cephalothin
Surgical prophylaxis (best for Gram + ve)
Allergic reaction (5-15%)
Anaphylaxis
Skin rash
Fever
Hemolytic anemia
Granulocytopenia
Local irritation at site of injection.
Seizure in high doses in IV form
IV and PO

Cephalosporins - 2nd Generation


2nd Generation

Clinical use
Side effects

Dose

Cefaclor
Cefamandole
Cefoxitin
Cefuroxime
Gram -ve coverage.
Parenteral administration except: cefaclor
Allergic reaction (5-15%) Skin rash, Anaphylaxis
Fever,
Local irritation at site of injection
Blood related Hemolytic anemia, Granulocytopenia
IV and PO

Cephalosporins-3rd Generation
3rd Generation

Cefixime
Cefoperazone
Cefotaxime
Cefpodoxime
Ceftazidime
Ceftriaxone

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Clinical use

Side effects
Dose

Cell Wall Synthesis Inhibitors

Gram negative only


Reserved for serious infections (bacterial meningitis)
These drugs can penetrate Cerebrospinal fluids (CSF) thereby it indicated
for bacterial meningitis infections.
Nosocomial infections (hospital acquired infections),
Unknown origin infections Sepsis in immunocompramized patients.
Allergic reaction (5-15%) Skin rash, Anaphylaxis
Fever, Local irritation at site of injection
Blood related Hemolytic anemia, Granulocytopenia
IV and PO

Cephalosporins - 4th Generation


4th Generation
Clinical use

Cefepime
Best for Gram -ve
Higher potency

Side effects

Allergic reaction (5-15%) Skin rash, Anaphylaxis


Fever, Local irritation at site of injection
Blood related Hemolytic anemia, Granulocytopenia
IV and IM

Dose

Vancomycin (Vancocin)
Mechanism
Therapeutic use

Side effects

Precautions
Dosage

Cell wall synthesis inhibitor


A very important drug for treating methicillin-resistant staphylococcus
aureas infections (MRSA), and it is an alternate drug for treating
superinfection (Superbug) by Clostridium difficile in patients with P. colitis.
Narrow spectrum of activity - active against Staphylococcus, Streptococcus
and Clostridium sp. (Gram + ve bacteria)
Chills, Fever
Ototoxicity
Nephrotoxicity
Rapid administration causes red man syndrome (flushing)
In renal failure patient drug will accumulate
IV and Oral
Renal elimination
Oral is used in only treatment of P. Colitis
Half life 6 8 h

Abbrevation and Terminology


PAPA
GI

Penicillin G, Amoxicillin, Penicillin V, Ampicillin

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Cell Wall Synthesis Inhibitors

Generic and Brand


Penicillins G
Penicillins V
Piperacillin
Carbenicillin
Amoxicillin
Ampicillin
Cephalosporins
Vanconycin
Cefazolin
Cephalothin
Cefaclor
Cefoxitin
Cefuroxime Sodium
Cephradine
Cefadroxil
Cefamandole
Cefoxitin
Cefuroxime axetil
Cefotetan
Cefproxil
Cefonicid
Loracarbef
Cefixime
Cefoperazone
Cefotaxime
Cefpodoxime
Ceftazidime
Ceftriaxone
Cefdinir
Ceftriaxone
Ceftibuten
Cefepime

Pfizerpen
Beepen-VK, V-Cillin-K, Veetids
Pipracil
Amoxil, Dipermox, Trimox
Principen
Vancocin, Vancoled
Ancef, Kefzol
Keflin
Ceclor, Ceclor CD, Raniclor, Raniclor
Mefoxin
Alti, Ceftin, Kefurox, Zinacef
Velosef
Duricef
Mefoxin
Ceftin
Cefotan
Cefzil
Lorabid
Suprax
Cefobid
Claforan
Banan, Vantin
Ceptaz, Fortaz, Tazicef, Tazidime
Rocephin
Omnicef
Rocephin
Cedax
Maxipime

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Protein Synthesis Inhibitors

36

Protein Synthesis Inhibitors


Protein Synthesis
Inhibitors
50 S Antibacterial Agents

Chloramphenicol
Lincosamides
Clindamycin
Lincomycin

Macrolides
Erythromycin
Azithromycin
Clarithromycin

30 S Antibacterial Agents

Aminoglycosides
Gentamycin
Streptomycin
Kanamycin

Tetracyclines
Demeclocycline
Doxycycline
Minocycline

TEST CC: T = tetracycline, E = erythromycin S = Sulfadrugs, T = trimethoprin, C = clindamycin C = Chloramphenicol,


are bactereostatic.

Aminoglycosides
Gentamicin, Streptomycin, Tobramycin, Kanamycin, Amikacin
Pharmacokinetics
All aminoglycosides renally eliminated
Half-life 2 4 hours.
Post dose antibiotic effect (PDAE)
Only Kanamycin and neomycin have oral and topical
Commonly aminoglycosides used as IM or IV
Streptomycin has only IM
Pharmacokinetics is not completely understood
Contain aminosugars structures and have low bioavailablity
Primarily used in infections associated with gram ve.
Aminoglycoside have little activity against anaerobic.

Gentamicin (Garamycin)
Therapeutic Uses

Side Effects

Gram ve
Drug uptake depends of oxygen: active against aerobes
Second line treatment for tuberculosis (mainly streptomycin)
Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
Combined with cephalosporins (2nd and 3rd) to reduce resistance
Respiratory paralysis (decrease Ach at NMJ)
Nephrotoxicity (proximal tubular cell)
Ototoxicity (also occurs in unborn fetus)

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Protein Synthesis Inhibitors

Streptomycin
Uses

Side Effects

Gram -ve
Second line treatment for tuberculosis (mainly streptomycin)
Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
Combined with cephalosporins (2nd and 3rd) to reduce resistance
Otic nerve toxicity-8th cranial nerve (mainly streptomycin)
Highest ototoxicity
Least Nephrotoxic

Ototoxicity

Streptomycin = Kanamycin > amikacin = gentamycin = tobramcycin > netilmycin

Tobramycin (Tobrex)
Uses

Side Effects

Gram -ve
Second line treatment for tuberculosis (mainly streptomycin)
Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
Combined with cephalosporins (2nd and 3rd) to reduce resistance
Respiratory paralysis (decrease Ach at NMJ)
Nephrotoxicity (proximal tubular cell)
Ototoxicity (also occurs in unborn fetus).

Amikacin (Amikin)
Uses

Side Effects

Gram -ve
Second line treatment for tuberculosis (mainly streptomycin)
Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
Combined with cephalosporins (2nd and 3rd) to reduce resistance
Respiratory paralysis (decrease Ach at NMJ)
Nephrotoxicity (proximal tubular cell)
Ototoxicity (also occurs in unborn fetus)

Aminoglycoside summary
Side effects
A = Allergy
M = neuroMascular Blockade
I = Inactivated when physically mixed with b-lactams
N = Nephrotoxicity
O = Ototoxicity, Optic nerve toxicity
Half life is 2 4 h
Aminoglycoside have post antibiotic effect
Highest ototoxicity is with Streptomycin
Highest nephrotoxic is Neomycin
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Protein Synthesis Inhibitors

Ototoxicity symptoms associated with gentamycin and streptomycin are: Vestibular damage this
can cause Tinnitus, vertigo, and ataxia.
Ototoxicity symptoms associated with amikacin and kanamycin are: Auditory damage this can
cause hearing loss.
Tobramycin can cause both vestibular and auditory damage
To prevent serious side effects associated with aminoglycosides monitor: Blood drug levels,
BUN, Serum creatinin levels
Blood levels are monitored by peak and trough levels:
Trough levels of gentamycin greater than 2mcg/ml can cause nephrotoxic.

Macrolides
Erythromycin. Clarithromycin, Azithromycin
Pharmacokinetics:
All of macrolides hepatically eliminated, except: clarithromycin, which is renally eliminated.
All macrolides have oral dosage and erythromycin gluceptate and lactobionate is IV.
Azithromycin has long half-life 68h and used single daily doses.
Erythromycin has short half-life 1.2 2.6 hours.
Erythromycin are preferred drug for treatment of Mycoplasma infection.
Important alternate in patient allergic to penicillins
Erythromycin estolate may cause cholestatic jaundice in-patient used more than 10-14 days.
(Resolved after discontinued treatment)
Erythromycin is inhibitor of CYP3A4, thereby potentiates toxicities of drugs that are metabolized
by CYP3A4, eg: digoxin, corticosteroids, lovastatin or (ALS), Carbamazepine.
Clarithromycin increase warfarin INR (monitor PT), increases digoxin and theophylline levels.
Azithromycin is more active against gram ve H.influenza than erythromycin.
Clarithromycin is effective for H.pylori (used along with PPIs in triple therapy)

Erythromycin
Use
Side effects

Drug
Interactions

Gram + ve (all of them), Gram ve for Neisseria


Epigastric distress (poor compliance)
Cholestatic jaundice (in estolate form):
Estolate is salt of lauryl ester.
Ototoxicity (more with erythromycin)
Contraindicated in patient with hepatic dysfunction (it accumulate in liver)
Theophylline, Warfarin, Terfenadine, Statins

Clarithromycin (Biaxin)
Use
Side Effects
Contraindication

Same as erythromycin: H. influenza, Chlamydi, Legionella


GI Epigastric distress (Nausea, vomiting, Burning stomach, Diarrhea),
Renal (azotemia), Liver Hepatitis
Patient with hepatic dysfunction

Azithromycin (Zithromax)
Use

Less active for Staph. and Strep than Erythromycin


Far more active H. influenza, Moraxella catarrhalis
Mycobacterium avium, except HIV

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Side Effects
Contraindicated
Counselling

Protein Synthesis Inhibitors

Epigastric distress.
Oral has less N and V.
in patient with hepatic dysfunction
Suspension do not refrigerate

Tetracycline
Tetracycline
Therapeutic Uses

Side Effects
Contraindication
Counselling

Broad spectrum antibiotics


Acne treatment
Chlamydia (lymphogranuloma, Psittacosis)
Rickettsia (Rocky mountain spotted fever)
Mycoplasma pneumonia
Lyme disease
Tetracyclines should not be treated to renally impaired patient.
(Accumulated increase azotemia.
Pregnancy, breast-feeding, children under 8 old,
Must take empty stomach with glass of water.
Tetracycline may stain teeth and for topical can stain cloth
Avoid prolong sun exposure.
Topical: Can continue use of cosmetics.
Stinging may occurs and that may resolve shortly.
Tell patient to report continuous nausea, vomiting,
Yellowing of eye and skin.

Doxycycline
Uses

Side Effects

Contraindication
Counseling

Broad spectrum
Prophylaxis in travellers diarrhea
Lyme disease, Chlamydia (lymphogranuloma, Psittacosis), Rickettsia (Rocky
mountain spotted fever)
Mycoplasma pneumonia
Gastric discomfort.
Effect on calcified tissues (deposition in the bone and primary dentination
occurs during growing children.
Discoloration and hypoplasia of the teeth and temporary stunting of growth,
Fetal hepatotoxicity
Phototoxicity-Severe sunburn
Super infection (over growth of candida in vagina or resistance to
Staphylococcus in intestine)
Pregnancy, children under 8 old, breast feeding
Take entire medication even if you feel better
Oral: take with or after meal with glass of water.
(Food decreases GI side effects avoid milk, antacids, iron)
Tell patient to check tongue for fungal infection.
Stress good oral hygiene.
Avoid prolong sun exposure

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Protein Synthesis Inhibitors

Minocycline
Minocycline
Therapeutic use
Side Effects

Broad spectrum antibiotic


Acne, Rheumatoid arthritis
Less phototoxicity
Vestibular problems: dizziness, nausea, vomiting
Pregnancy, breast-feeding, children under 8 old
Take with or without food

Contraindication

Clindamycin
Clindamycin
Uses
Side Effects

Contraindication
Counseling

Precaution

Lincosamides class of drug


Gram +ve anaerobic bacteria Bacteroid fragilis (abdominal infection)
Diarrhea (C. difficile is resistant to clindamycintreatmentTreatment: Discontinue medication, and start vancomycin or
metronidazole (oral)
History of colitis, regional entities, or antibiotic associated colitis.
Take With or without food (Discourage with food)
Capsule: take with full glass (240 ml) of water to prevent dysphagia.
Do not refrigerate the reconstituted solution since under condition of low
temp, the solution may thicken and difficult to pour.
Stable at room temp for 14 days.
I.M injection may be painful

Abbrevation and Terminology


PDAE
NMJ
AcH
ALS
INR
PT

Post Dose Antibiotic Effect

Generic and Brand


Gentamicin
Streptomycin
Tobramycin
Amikacin
Erythromycin
Clarithromycin
Azithromycin
Tetracycline
Doxycycline
Minocycline
Clindamycin

Garamycin, Genoptic, Gentacidin


Ak-Tob, Nebcin, Tobi, Tobrex
Amikin
Biaxin
Azasite, Zithromax, Zmax
Emtet, Panmycin, Sumycin, Tetra 250
Adoxa Pak, Atridox, Bio-Tab, Doxy
Cleeravue, Dynacin, Minocin, Myrac
Dalacin, Clinacin, Cleocin, Evoclin

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Protein Synthesis Inhibitors

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Quinolones and fluroquinolones

37

Quinolones & Fluoroquinolones


Quinolones & Fluoroquinolones
Quinolones
Nalidixic acid (disinfectant)
Fluoroquinolones
1st Gen
Nalidixic acid
Norfloxacin
nd
2
Ciprofloxacin
Oflaxacin
rd
3
Gatifloxacin
Moxifloxacin
Levofloxacin
4th Travofloxacin

Ciprofloxacin (Cipro, Cipro XR )


Mechanism
Therapeutic Uses

Side Effects

Counseling

Auxiliary labels

Phototoxicity

Inhibits DNA replication of bacterial DNAg (gyrase)


UTI E.coli
STD Gonorrhea
Respiratory alternate to ampicillin in pneumonia
GI infections E.coli travellers diarrhea
Nephrotoxicity
Cartilage toxicity-Avoid under 18years and pregnancy
Tendonitis/tendon rupture-common in elderly and renal failure patient
Most common: Nausea and Vomiting, light-headedness.
Cipro otic suspension:
Store cipro otic suspension at room temp (15 to 25oC).
Do not use otic suspension under 2 year of age
With or without food. The preferred time is 2 hours after meal (for faster
absorption)
With full glass of water. (avoid dairy products)
Avoid taking with antacid, iron, or calcium together
Sunscreens may not effective; drug should be discontinued at the first of
sign of toxicity-sun burn like rashes.

Ofloxacin (Floxin)
Mechanism
Uses

Inhibits DNA replication of bacterial DNA gyrase


Mainly for E. coli in UTI and STD with exception syphilis.
Alternate in gonorrhea

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Side effects
Counseling

Quinolones and fluroquinolones

Hypoglycemia, Leukopenia, Neutropenia


Tell patient to drink fluids liberally.
Separate doses of vitamins, antacids by 2 hours.

Gatifloxacin (Tequin)
Mechanism
Therapeutic use
Side Effects
Drug-drug
interaction
Contraindication
Monitoring

A quinolone, use to treat several types of bacterial infections.


Chest infections (pneumonia), Sinus infection, Urinary tract infection
Q-T prolongation
Oral iron preparation and antacids containing magnesium and aluminum
can interfere the absorption of gatifloxacin
Not recommended in children

Metronidazole (Flagyl)
Metronidazole
Mechanism
Therapeutic use

Side effects

Drug-Drug
interaction

Precautions
Pregnancy and
lactations
Dosage

Classified as antiprotozoal drug and has antibiotic actions (anaerobic)


Mode of action is thought to be breakage of cell DNA.
Indicated in anaerobes such as Bacteroides, C. difficile, C.vaginalis
Protozoans (Entamoeba, Giardia, Trichomonas)
This drug is also active against trophozoites in the intestinal lumen and
walls.
Metronidazole has direct anti-inflammatory effect (antioxidant action that
contributes to its anti-inflammatory activity).
Giardiasis and trichomoniasis metronidazole used orally
Metallic taste, furry tongue, glossitis,
Must avoid taking alcohol while on this drug can cause disulfiram like
reactions
Rarely be neurotoxic.
Cimetidine prolongs metronidazole half-life and decrease its plasma
concentration
Warfarin: Potentiates effects resulting in prolongation of prothrombin time.
Disulfiram: Causes acute psychosis ever if taken within two weeks.
Phenobarbitone: Increases metronidazole metabolism
It can cause dark urine
Do not mix i.v metronidazole with any other drug.
Caution require in pregnancy and lactation




Injection: to treat anaerobic infections and protozoal infection


Oral capsule
Oral tablets
Vaginal cream and inserts, vaginal gel: for treatment of bacterial vaginitis
Topical cream or gel: Drug of choice for Rosacea applied effected twice
daily morning and evening for 9 weeks, then as needed.

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Quinolones and fluroquinolones

Abbrevation and Terminology


UTI
STD

Sexually Transmitted Disease

Generic and Brand


Ciprofloxacin
Ofloxacin
Gatifloxacin
Metronidazole

Cipro, Cipro XR, Proquin XR


Floxin, Tarivid
Tequin, Zymar
Flagyl, Metrocream, Metron, Vandazole

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Quinolones and fluroquinolones

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Folate Antagonist Sulfa Drugs

38

Folate antagonist Sulfa drugs


Sulfa drugs

Combination
drugs
Mechanism
Therapeutic Use

Sulfamethoxazole
Sulfadiazine
Sulfisoxazole
Sulfasalazine
Trimethoprim
Cotrimoxazole
Folate Antagonists

UTI E. coli
Drug of choice in Traveller diarrhea
Trachoma-chlamydia trachoma-most
common cause of preventable blindness
Topical: Burns and wounds
Side effects
Crystalluria: adequate hydration and
alkalinization prevent this problem
Hypersensitivity: rashes, StevensJohnson syndrome-occurs with longer
acting agents: (diuretics, acetazolamide,
thiazide, furosemide, bumetanide,
diazoxide).
Hemolytic anemia-G6 PD deficiency
Kernicterus: newborns because sulfas
displace bilirubin from binding
Counseling
Sulfasalazine: drugs colors urine and may
color skin orange yellow.
May permanently stain soft lenses
Take drug after meals to reduce GI
distress and to facilitate passage into
intestine.
Stevens-Johnson syndrome
Sulfa Drugs = Antiseizure drugs ; Allopurinol
Management of SJS: by discontinuing medication.
Folate antagonist Mechanism

Pteridine + PABA

Dihydropteroate
synthase

Sulfonamide

Dihydropteroic acid

Dihydrofolic acid
Dihydrofolate
reductase

Trimethoprim,
pyrimethamine

Tetrahydrofolic acid (THF)

THF cofactors

Thymine

Purines

DNA

DNA
RNA

Methionine
Glycine
f-met-tRNA

Proteins

Sulfasalazine (Salazopyrin)
Mechanism
Therapeutic use

A combination of sulfanamide and salycilate, is use to treat two


inflammatory disorders affecting the bowels
Ulcerative Colitis (mainly affects the large intestine); Crohns disease
(usually affects small intestine)

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Side effects

Drug-drug
interactions
Monitoring

Folate Antagonist Sulfa Drugs

Stomach irritation (can be avoided by taking the coated tabled form)


Allergic reactions, such as fever and rash (can be avoided or minimized by
low initial doses followed by gradual increases).
Nausea and vomiting
Aplastic anemia
Sulfasalazine inhibits the absorption of folic acid
Decrease the bioavailability of digoxin
Cholestyramine decreases the metabolism of sulfasalazine
Periodic test of blood composition and liver function are usually required.
Blood disorders may occur with prolonged use of this drug.

Cotrimoxazole (SMX + TMP)


Therapeutic Use

Side effects

Counseling

Contraindications

Chronic treatment of UTI


Gram ve: H. influenza, Gonorrhea, E. coli, Klebsiella, Salmonella, shigella
sp. V. cholera
Gram +ve: S. pyogenes (GAS), S. viridans, S. aureus
UTI-Acute, recurrent, chronic.
Upper and lower raspchronic bronchitis.
Immunocompromised children: P. carinii
Not indicated in infections associated with pseudomonas, mycoplasma.
Skin reaction (severe in elderly)
GI --> N and V
Blood related: Megaloblastic anemia, Thrombocytopenia, Leukopenia: The
above three effects can be reversed by concurrent administration of folinic
acid.
Hemolytic anemia-G6 PD deficiency due to SMX
Drug is not for IM
Shake oral suspension thoroughly before use
Take drug as prescribe even feel better
Take oral dose with full glass of water.
With or without food. (food decreases GI side effect)
Store in amber glass of bottle.
Store at room temp until expiry and protect from moisture.
Last trimester of Pregnancy, lactation.
Children under 2 months. May cause kernicterus

Antibiotics Tips
Steven-Johnsons Syndrome: Rash, skin peeling, and sores on the mucus membrane. In Steven
Jhonsons syndrome, a person has blistering of mucus membrane, typically in mouth, eyes and
vagina. Patchy areas of rash. SJS can occur in all age groups.
Due to: SASPAN
Sulfonylurea
Anticonvulsant (phenytoin)
Sulphonamide
Penicillin
Allopurinol
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Folate Antagonist Sulfa Drugs

NSAIDs
Sulfa drugs Stevens Jhonsons Syndrome
Topical sulfa is contraindicated because it may cause disease like SJS, this disease is life threatening.
Treatment of SJS is Cortisone
Summary of Cell wall synthesis inhibitors















Methicillin is only IV and IM


Penicillin G benzathine has long half life
Naficillin is mainly hepatic elimination
Beta lactamase sensitive drugs: Pen G, Amoxi, Pen V and Ampicillin
Endocarditis prophylaxis is (Dental extraction prophylaxis)
A child less than 2 y allergic penicillin, what is the drug choice for otitis media treatment
A patient has heart diseases and underwent prostatic valve surgery. Dentist plans to tooth
extraction, what antibiotic is suitable for endocarditis prophylaxis
Chewable antibiotics
Beta lactams that should be taken empty stomach
Aminopenicillins are:
Penicillin allergic patient, alternate drug of choice is?
Penicillins are ineffective in treatment of bacterial infections associated with
MRSA infections are treated by
P.colitis associated diarrhea is treated by
Bacteria is inhabitant in GI, what location of GI tract is commonly found
Type of bacteria mainly present in colon is

Macrolides Practice Test


Azithromycin suspension stored at
Clarithromycin suspension stored at
Which macrolide suspension have to refrigerate after reconstitution
What antibiotics should caution and require monitoring in patient receiving warfarin What antibiotic potentiate the effect of digoxin and can cause digitalis toxicity
Azithromycin is the drug of choice in traveler diarrhea for patient traveling to
Tetracyclin Practice Tests
Tetracyclin are contraindicated are contraindicated in pregnancy and children.
Tetracyclin can stain teeth and discoloration.
Oral or topical tetracycline are drug of choice for acne treatment
Tetracyclin MUST BE taken empty stomach.
Tetracyclin binds
GI distress (abdominal discomfort, diarrhea) most common SE. This can be resolved by taking
with food or decreasing dose.
Expired tetracycline can lead
Doxycyclin is the DOC
Doxycyclin should be taken
Minocyclin may take with or without food.
Phototoxic reactions (sever skin lesions) can develop with exposure to sunlight. Photoxicity is the
most common with doxycyclin or demeclocyclin.
Epimerization is a
Tetracyclins = Take empty stomach
Doxycyclins = Take with or after food
Minocyclins = Regardless of food

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Folate Antagonist Sulfa Drugs

Clindamycin Practice Tests


Most common complication of clindamycin is
Clindamycin active against
Pseudomembranous colitis symptoms include: fever, abdominal pain, bloody stools.
Clindamycin can cause
Clindamycin drug associated diarrhea is treated by
Clindamycin suspension stored at
Clindamycin should taken
Quinolone and fluroquinolone Practice Test
Fluroquinolones are indicated for UTI, Infectious diarrhea (Travellers diarrhea), lower respiratory
tract infections, bone and joint infections (osteomylitis).
Gatifloxacin, Moxifloxacin SE are
FluroquinolonesContraindicated in children, under 18 y, pregnant women due to its
Antacids, bivalent and trivalent ions significantly decrease absorption of
Fluroquinolone increase INR in patient receiving warfarin, therefore monitor
Fluroquinolones can cause hypo or hyperglycemia, therefore monitor
Fluroquinolones at higher alkaline pH can cause
Cipro is the drug of choice in
Metronidazole Practice Tests
Alcohol with metronidazole can cause
Metronidazole is classified as: Antiprotozoal drug
Metronidazole is effective against
Metronidazole discolor urine
Metronidazole caution in pregnancy
Sulfadrugs Practice Test
Sulfamethoxazole + trimethoprim have
A 22 year old patient currently using cotrimoxazole for UTI, reported sever rashes on arms, neck
and back, what are the possible reactions
What are the folic acid synthesis inhibitors
Patient with G6PD deficiency, takes sulfadrugs can cause
Hypersensitive reactions of sulfadrugs most commonly involve
Life threatening hepatitis caused by sulfadrug toxicity or sensitization rare SE, the signs and
symptoms include
Sulfamethoxazole have high frequency of skin hypersensitive reaction in patient with
If used in last trimester of pregnancy, can cause kernecterus in new born.
Cotrimoxazole suspension stored at room temperature in amber color glass bottle.
P. carinii pneumonia (PCP) drug of choice is Cotrimoxazole.

Abbrevation and Terminology


SJS
THF
SMX
TMP
UTI
GAS
IM
INR

Generic and Brand


Sulfasalazine
Cotrimoxazole

Salazopyrin, Salazopyrin En-Tabs


Septrin, Bactrim

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Antifungals

39

Antifungal agents
Mechanisms of Action and Classification of Antifungal Agents
Antifungal Agents
After cell membrane permeability
Azoles

Allylamine
* Terbinafine
* Naftifine

Imidazoles
* Ketoconazole
* Miconazole
* Clotrimazole

Systemic
antifungals

Triazoles

Disrupt microtubule function

Pyrimidine
Analog

Polyene
macrolide
antibiotics

* Flucytosine

Penicillin
derivative
* Griseofulvin

* Amphotericin B
*Nystatin

* Fluconazole
* Itraconazole

Allylamines
Antifungal Antibiotics

Echinocandins
Imidazole
Pyrimidines
Triazoles
Topical
Antifungals

Block nucleic acid synthesis

Allylamines
Antifungal Antibiotics
Imidazoles

Other topical antifungals

Terbinafine hydrochloride
Amphotericin B
Amphotericin B (lipid-based)
Griseofulvin
Caspofungin acetate
Ketoconazole
Flucytosine
Fluconazole
Itraconazole
Naftifine hydrochloride
Terbinafine hydrochloride
Nystatin
Clotrimazoles
Econazole nitrate
Ketoconazole
Miconazole nitrate
Oxiconazole nitrate
Tioconazole
Chlorphenesin
Ciclopirox olamine
Clioquinol
Selenium sulfide
Tolnaftate
Undecylenic acid

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Antifungals

Amphotericin B (Fungicidal)
Therapeutic use

Mechanism
Side effects

Contraindication
WARNING

Drug interaction

Precaution
Counselling
References

Widest of any agent, systemic fungal infections; candidiasis; cryptococcos;


blastomycosis; histoplasmosis; coccodiodomycosis; aspergillosis;
sprorotichosis; mycosis; leishmaniasis
Availability: 3% cream/lotion/oral suspension
Not absorbed in the GIT
Bind to ergosterol from pores resulting in the leakage of cellular contents
Infusion related fever and chills; anorexia; muscle pain; headache
Non-infusion related: nephrotoxic, hyperkalemia, hypomagnesemia,
tachycardia, anemia, thrombocytopenia, arrhythmias, VF, HTN, tachypnea,
leukoencephalopathy, dry skin, skin discoloration, SJS, toxic epidermal
necrolysis, agranulocytosis, jaundice, hemorrhage, sore throat
Allergies
Apply only to patients with progressive, potentially fatal infections and
should not be used to treat non-serious infection
Monitor Lab test sp. Renal function (frequently), liver function, serum
electrolytes particularly magnesium and potassium, blood count, Hgb conc.
Not use for dosage adjustment
Does not penetrate CSF
Antineoplastic= increase renal toxicity, bronchospasm, hypotension
Corticosteroids/ACTH= increase amphotericin B-induced hypokalemia,
renal toxicity;
Nephrotoxic agents (Cisplatin, pentamidine, aminoglycoside, cyclosporine=
increase renal toxicity
Digitalis glycosides= Amphotericin B-induced hypokalemia, increase
digitalis toxicity
Skeletal muscle relaxants= enhance cureiform
Others: AZT, chloramphenicol, antithyroid, colchicine, deferoxamine,
streptozocin, plicamycin, lithium, penicillamine
Overdose: cardiorespiratory arrest
Storage of dry powder; 2-8 deg, protect from light
Give slow IV infusion
When applying topicals on the skin, protect nails and clothes as it may stain
CPS 2004, 854-855,
Comprehensive Pharmacy Review, 5th Ed. Page 795,

Nystatin
Category
Therapeutic use

Mechanism
Side effects

Polyene antibiotic, structurally similar to Amphotericin B, fungicidal,


fungistatic
Active against Candida sp. Primarily use as a topical agent in vaginal
and oral candidiasis
Not very effective against dermatophytes (Tinea)
Inhibit growth of yeast, binds to sterol in the fungal cell membrane,
increasing permeability and causing leakage of intracellular components
Irritation e.g. mild digestive upset, Nausea & Vomiting diarrhea; cream/
vaginal tablet- itching, burning, irritation

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Advantage
Drug interaction
Precaution
Counselling

Can be use by pregnant women

Reference:

Antifungals

Application of vaginal tablet


Nystatin liquid-3-5x a day by mouth for mouth infections, intestinal
infection-3x per day. Shake bottle well before each use. Place half of the
liquid on one side and the other half on the other side. Hold; swish it
for several times in the mouth before swallowing. For intestinal use, just
swallow liquid.
Skin ointment or cream. Use several times a day. Wash thoroughly the
affected area. Apply a small amount of the cream or ointment and gently
massage it. Keep away from eyes.
Powder. Dust the powder inside shoes and socks.
Nystatin vaginal tab and cream. Use OD/ BID as directed for vaginal
infections. Use vaginal tab or cream for two week in women who are not
pregnant and 3-6 weeks before delivery in pregnant women. Continue to
use medication even if symptoms improve for a few days.
CPS 2004 1308-1309
Comprehensive Pharmacy Review, 5th Ed. Page 795.
Comparison of Fluconazol And Ketoconazol

Fluconazol
Triazole type antifungal
Inhibitors of Ergosterol synthesis by
binding to CYP
Single doses
Penetrate CNS (AIDS chemotherapy)
CNS SE: dizziness
No interaction with cimetidine, antacids
For systemic infection UTI, peritonitis,
pneumonia

Potent inhibitor of CYP 2C9 (high) and


CYP 3A4
Fluconazole taken with or without food.

Ketoconazol
Imidazole type antifungal
Inhibitor Ergosterol synthesis
Not a single dose
Doesnt penetrate CNS
SE: Hormonal effects such as gynecomastia and
menstrual disturbances
Interaction with cimetidine, antacids
Require acidic conditions for absorption (avoid
antacids concomitantly)

Potent inhibitor of CYP 3A4 (high) and CYP


2C9
Ketoconazole taken with food or after food
(with cola beverage if achlorhydric or on acid
secrete suppressor)

Ketoconazole (Nizoral)
Ketoconazole (Imidazole type)
Therapeutic use

Miconazole; Clotrimazole
Chronic mucocutaneous candidiasis, systemic and vaginal
candidiasis, Tinea corporis (ringworm), T. cruris (jock itch),
T. pedis (Athletes foot), Tinea versicolor (sun fungus),
histoplasmosis, blastomycosis, paracoccidioidomycosis, oral
thrush
Relative bioavailability: 75 % with meals
Available as tablet, cream

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Antifungals

Mechanism

Block the synthesis of ergosterol 14a demethylase in the


fungal CYP 450 complex; hepatic elimination

Side effects

Hormonal effects Decreased male libido and potency,


gynecomastia, decreased plasma testosterone levels, affects
female menstrual problems, Cardio effects hypertension,
fluid retention,
GI effects GI upset, hepatotoxicity, dizziness, anorexia,
Nausea & Vomiting
Hypersensitivity; teratogenicity
Rebound effect. Apply mild topical corticosteroids in the
morning and ketoconazole at night and gradually decrease
steroid over a period of 2-3 weeks. Cross sensitivity
Allergies with imidazoles
Increased absorption on an empty stomach.
Shampoo, 1%: Wet scalp and work lather. Massage. Leave
for 3-5 minutes then rinse zwell with warm water. Repeat
application. Rinse and dry hair. Wash eyes if shampoo gets
into them. Treatment is 2x a week for 2-4 weeks whereas as
a prophylaxis, use once every 1-2 week; Shampoo, 2% : Wet
hair and scalp.
Apply shampoo the affected area. Work up lather and leave for
5 minutes. Rinse hair and scalp well. Dry hair. Protect eyes.
Cream: Apply Ketoconazole cream to cover affected area and
surrounding skin areas. Rub gently. Keep using cream for the
full treatment even if symptoms begin to clear up after a few
days to several weeks. Recurrent infection if you stop meds
too soon. Do not miss a dose
CPS 2004, 1379-1380
Comprehensive Pharmacy Review, 5th Ed. Page 794-795,

Contraindication
WARNING

Precaution
Counselling

References

Fluconazole (Diflucan)
Mechanism
Therapeutic use

Side effects

Block The Synthesis Of Ergosterol By Inhibit 14A-Demethylase In The


Fungal CYP450 Complex
Mucocutaneous Candidiasis (Esophageal); Alternative For
Amphotericin B For Treatment Of Systemic Candidiasis, Cryptococcal
Meningitis, Coccidioidomycosis, Cryptococcosis, HIV Associated
Infections
aRelative Bioavailability: 85- 92% With Meals
Skin Rash
GI Effects Nausea, Vomiting Diarrhea Or Commonly Causing GI
Disturbances.
Liver Effect Increase Liver Enzymes, Yellowing Of The Skin, And
Eyes, Flu-Like Symptoms,
CNS Dizziness, Headache, Exfoliative Skin Reactions, Altered Taste
Buds, Extreme Tiredness, Seizures.

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Drug interaction

Precaution

Reference:

Antifungals

Decrease Levels With Carbamazepine, H2 Blockers, INH, Phenytoin;


Increase Levels Of Phenytoin, Warfarin, Sulfonylureas; ROH;
Anticancer Drugs, Amiodarone, Astemizole, Benzodiazepine,
Cyclosporine, Disopyramide, OCP, Diuretics, Moxifloxacin, Sotalol,
Terfenadine, Quinidine, Valproic Acid, Thioridazine And Tacrolimus
Decrease Elimination Of Enzyme Inducers Like Rifampin, Allergies To
Fluconazole And Other Antifungals, Irregular Heart Beat; Kidney Or
Heart Disease
Applied T. Handbook; Chapter. 67, Pp. 67.4 - 67.5
TC Page 4th Ed Page 1056.

Itraconazole (Sporanox)
Therapeutic use

More active treatment against Aspergillus spp.; blastomycosis; other


mycosis like mucor, fusarium pseudoallescherria boydii; HIV associated
infections; invasive and non-invasive pulmonary aspergillosis;
oral and esophageal candidiasis; chronic histoplasmosis (acute
immunocompromised, an alternative to amphotericin); cutaneous and
lymphatic sporotrichosis; paracoccioidomycosis; chromomycosis
Dose Aspergillosis: 200mg IV Q8H X 72 H then 200mg IV Q12H
Blastomycosis; 200mg po BID
Histoplasmosis: 200-400mg QD po
Take with meals for adequate absorption

Mechanism

Block the synthesis of ergosterol 14a demethylase in the fungal CYP 450
complexz

Side effects

Nausea, epigastric pain rash, headache, edema, hypokalemia, loss of


appetite, shaking, dyspnea, bleeding gums, yellowing of eyes and skin;
hypertriglyceridemia; decrease libido

Contraindication

CHF; Ventricular dysfunction

Warning

Cause CHF; heart attack; irregular heart beat/ dse; lung/ kidney/liver
disease or other serious problems; SOB; coughing up white phlegm;
weakness; excessive tiredness; fast heart beat; swelling of the feet, ankle or
leg; sudden weight gain

Drug interaction

Cisapride, pimozide, dofetilide, ergot meds, triazolam, midazolam,


quinidine, - all may cause irregular heart beat
Take antacid one hour before or two hours after itraconazole

Drug interaction

Increased by Itraconazole: antiarrhythmics, anticonvulsantsCBZ, antimycobacterial-rifabutin, antineoplastics, antipsychotics,


Benzodiazepine, Ca-channel blockers, gastrointestinal motility agents,
HMG-CoA reductase inhibitors, Immunosuppressants, oral hypoglycemics,
protease inhibitors, buspirone, macrolides;
Decrease by Itraconazole anticonvulsant, antimycobacterial, gastric acid
suppressants, NNRTI

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Counselling

Reference:

Antifungals

Oral solution: Swish 10ml (2tsp) in the mouth for a few seconds and
swallow. Repeat is necessary until entire dose is taken. The solution is
usually taken on an empty stomach once daily or BID for 1-4 weeks.
Tell Doctor if taking Itraconazole. Do not substitute the capsules for the
liquid because they have different use.
CPS 2004, page 1973-1978
Comprehensive Pharmacy Review, 5th Ed. Page 794-795

Clotrimazole
Therapeutic use

Mechanism
Side effects

Contraindication
Management

Precaution
Reference

Yeast infection, skin infections, high concentration needed in bacterial


infection
Availability: cream, lotion or solution- dermatophytes (skin infections);
intravaginal suppositories for vaginal candidiasis, lozenge
Block the synthesis of ergosterol 14a demethylase in the fungal CYP 450
complex
Topical: blisters, edema, pruritus, burning, stinging, peeling skin tissue,
increase urinary frequency
Abdominal pain
Irritation
Abnormal liver function test in patient taking lozenge
Not for first tri semester of pregnancy
In case of vaginal infection, refrain from sexual intercourse cause an
ingredient in the cream may weaken certain latex condoms / diaphragms.
If first time of vaginal itching and discomfort, see a doctor. Do not use
products within 72 hours of this med. Wear cotton underwear and loose
fitting pants; no lozenge for children under 3y/o
Pregnancy
CPS, 2004, 361-362;
Comprehensive Pharmacy Review, 5th Ed. Page 797

Miconazole
Category
Mechanism

Therapeutic use

Side effects
Contraindication
Drug interaction

Broad spectrum fungistatic


Block synthesis of ergosterol by inhibiting 14a-demethylase in the fungal
cytochrome P450 complex; selective inhibition of RNA & DNA and
mucopolysaccharide precursor
Covers both dermatophytes and candidiasis (Advantage Over Tolnaftate
and Nystatin; Also, effective against Tinea infections by T. pedis, T. cruris,
T. corporis, T. versicolor
Itching, skin rash,
Nausea &Vomiting, burning on the site of application
Sensitivity to any of the components of Miconazole, not for children > 2y/o
unless directed by a doctor, do not use for the infection of the nail
Anticoagulants,
Phenytoin,
Terbinafine,

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Drug interaction

Availability
Application

Reference

Antifungals

Atypical anti-psychotics,
Cyclosporins
Some statins
Topical 2%, aerosol powder, 2 % cream, a kit-2% powder 2y/o and 2%
tincture, 2% vaginal cream and 100 and 200 mg vaginal suppositories
Aerosol powder
Cleanse skin with soap and water.
Dry thoroughly.
Shake aerosol well before using.
Apply or spray a thin layer over the affected area in the morning and up to
bedtime.
Do it from a distance of 6-10 inches to the affected area of the feet. Do not
inhale powder.
If no improvement in 2 weeks time, see doctor But continue fir 1-2
weeks after symptoms disappear to a maximum of 4 weeks. Jock itch and
ringworm is 1-2 weeks resolution; athletes foot-4 weeks.
Cream Apply sparingly, smoothen well and avoid maceration. Massage
area gently. Athletes foot: dry feet, wear cotton socks
CPS, 2004, page 1246

Tolnaftate
Category
Mechanism
Therapeutic use

Side effects
Administration

Administration
Warning
Contraindication
Reference:

Fungistic, fungicidal
Damage hyphae and stunt mycelial growth in susceptible fungi
Jock itch, athletes foot, ringworm; T. pedis, M. canis, Aspergillus niger,
C. albicans, M. gypseum, M. audounii, M. japonicum, T. rubrum, T,
mentagrophytes, T. schonleinii, A. fumigatus
Slight irritation, sting (aerosol solution), burning and itching of athletes
foot and jock itch should decrease with in 2-3 days
Do not apply dressings, or mix cosmetics or other skin medications with
tolnaftate treatment.
Powder: Clean and dry affected area. Sprinkle it b/n toes and in socks and
shoes treated lightly.
Spray should be shaken well before use. Apply it from a distance of at
least six inches away. Continue treatment until symptoms disappear. A
total of 4-6 weeks necessary. Do not inhale powder, bring close to a hot
object or flame
Cream. Thoroughly clean the infected area. Allow it to dry and then rub
gently the medication until most of it disappears. Use sufficient quantity
to cover the affected area. Wash hands after application.
Solution. If it solidifies, dissolve by warming the closed container in
warm water then follow dosage as directed.
Usually, applied in affected areas 2x a day. If no effect in 4 weeks, check
with health care professional.
Aerosols: Flammable
Allergies to tolnaftate or any preservatives, dyes; pregnancy; children, 2
y/o
Comprehensive Pharmacy Review, 5th Ed. Page 801

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Antifungals

Antifungals Tips









Nystatin is indicated
Ketoconazole require acidic conditions for higher bioavailability therefore
Meningitis fungal infections other CNS infections can be treated by
If a child swallowed 5g of nystatin, and parents are panic, comes to your pharmacy, what is
appropriate action
Nystatin is ineffective for
DOC for oral thrush
DOC for vaginal candidasis
Topcal Drug of choice for Atheletes foot
Nystatin suspension counseling
Amphotericin B is act by inhibiting the cell membrane function

Abbrevation and Terminology


GIT
VF
HTN
SJS
CSF
ACTH
AZT
OCP
NNRTI
IV
CYP
SOB
CBZ
BID
CPS

Generic and Brand


Amphotericin B
Nystatin
Fluconazole
Itraconazole
Clotrimazole
Miconazole
Tolnaftate

Fungistic, Fungicidal
Tri-Statin, Mycolog, Mytrex
Diflucan
Sppranox
Clotrimazole, Cruex, Lotrimin, Mycelex
Aloe Vesta, Cruex, Desenex Jock Itch
Asorbine, Afate, Genaspore, Pitrex

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Anti-Mycobacterial Drugs

40

Anti-Mycobacterial Drugs
Antimycobacterial drugs
Isoniazid
Rifampin
Streptomycin
Pyrazinamide
Ethambutol
Capreomycin
Rifabutin
Tuberculosis treatment:
Goal of treatment is must eradicate mycobacterium.
Important issues in tuberculosis treatment are resistance to drugs.
Drugs that have lowest resistance is:Isoniazid, rifampin, streptomycin and combination of these
drugs with pyrazinamide, or ethambutol.
Drug of choice is combination of Isoniazid + rifampin + pyrazinamide.
Antimycobacterial Drugs
Rifampin
Chemical structure of rifampin is a macrocyclin.
This drugs is bactericidal
Mechanism
Inhibits RNA synthesis
Therapeutic Use
Effective against M. tuberculosis, and M. leprae
Prophylactic for house hold members of exposed to meningitis caused by
meningococci or H. influenza type b
Side Effects
Serious liver toxicity (hepatotoxicity) thereby LFT should be performed
regularly
GI SE: nausea, vomiting, abdominal pain
CNS SE: Headache, drowsiness, confusion, fatigue
Rifampin discolor urine, sweat, tears, saliva and feces to orange-red.
Drug interactions
Rifampin is inducer of CYP 1A2, 2D6, 2C9, 2C19, 3A4
Reduce efficacy oral contraceptive.
Isoniazid (INH)
Mechanism
Therapeutic Use
Side Effects

Chemical structure is hydrazide of isonicotinic acid.


Targets enzyme responsible for mycolic acid synthesis
First line treatment for tuberculosis
Most common: Peripheral neuritis (because of pyridoxine deficiency)
Vitamin B6 supplements. Skin rash, jaundice and fever are common SE.
Supplementing breast fed mothers can provide pyridoxine deficiency in
children.

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Side Effects

Anti-Mycobacterial Drugs

Most common: Hepatitis: Most severe-fatal, the risk of hepatitis increases


with patient age and alcohol abuse. Monitor LFT
Blood dyscariasis (agranulocytosis, aplastic anemia, hemolytic anemia
Thrombocytopenia) thereby monitor CBC routinely
CNS toxicity due to decrease in pyridoxine levels: Administer 15 50 mg/dy
pyridoxine to minimize the peripheral neuropathy.
Symptoms of CNS toxicity are: insomnia, restlessness, hyperreflexia, and
convulsions.

Pyrazinamide (ZIN) It is pyrazine analog of nicotinamide


Mechanism
Therapeutic Use
Side effects

Pyrazinamidase enzyme converts into pyrazinoic acid (active form)


Combination with INH and rifampin. Pyrazinamide has activity only against
M.Tuberculosis
Liver dysfunction
Urate retention.
May precipitate gouty attacks

Antimycobacterials Tips




Drugs that discolor urine, tears, saliva, feces, sweat


Drug of choice to treat tuberculosis
Peripheral neuritis caused by isoniazid can managed by administering
XDR TB = Extensive Drug Resistance Tuberculosis.
All antitubercular drug should be taken on:

Abbrevation and Terminology


INH
LFT
CYP
XDR TB
ZIN

Isoniazid
Liver Funtion Test
Extensive Drug Resistance Tuberculosis.
Pyrazinamide

Generic and Brand


Isoniazid
Rifampin
Streptomycin
Pyrazinamide
Ethambutol
Capreomycin
Rifabutin

Isoniazid, INH, Nydrazid


Rifadin, Rimactane
Myambutol
Mycobutin

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Anti-viral Drugs

41

Anti-viral Drugs
Antivir al Agents

Tricyclic
amines
Amantadine
Rimantadine

Guanosine
analogs
Ribavirin

Glycoproteins

Nucleoside
analogs

Nucleoside
RTIs

NNRTIs

Interferon-alfa
Interferon-beta

Acyclovir
Valacyclovir
Ganciclovir
Trifluridine
Vidarabine

Zidovudine
Didanosine
Zalcitabine
Lamivudine
Stavudine
Abacavir

Nevirapine
Delavirdine
Efavirenz

Neuroamindiase inhibitor
Osaltamavir
Zanamavir
Antivirals Drugs classifications
For RNA viruses Amantadine
Ribavirin
Rimantadine
Zidovudine
Didanosine
Zalcitabine
Stavudine
Lamivudine
Nevirapine
For DNA viruses Acyclovir
Ganciclovir
Famciclovir
For RNA and
Foscarnet
DNA viruses
Ribavirin

Mechanism
Therapeutic use

Foscarnet

Protease
inhibitors
Indinavir
Saquinavir
Ritonavir
Amprenavir

Antiretroviral

Retrovirus are the virus the consist of


reverse transcriptase enzyme, reverse
transcriptase helps to copy virus.
For HIV treatment
Reverse transcriptase enzyme
present in HIV
There are three types of antiretroviral
drugs
NRTI
NNRTI
Protease inhibitors
Nucleoside Reverse
Zidovudine (AZT)
Transcriptase
Stavudine
Inhibitors (NRTI)
Lamivudine
Didanosine
Zalcitabine
Non-Nucleoside
Nevirapine
Reverse Transcriptase Efavirenz
Inhibitors (NNRTI)
Delavirdine
Protease Inhibitors

Acyclovir (zovirax)

Prophosphanate
derivative

Saquinavir
Ritonavir
Indinavir

Guanosine analog and lacks true sugar moiety


Herpes Simplex Virus (HSV-1)
Herpes Simplex Virus (HSV-2)
Varicella zoster (Vericella is referred chicken pox and zoaster is referred as
Shingles)
Epstein-Barr virus

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Side effects

Advantage

Dosage

Anti-viral Drugs

Depends on route of administration


Topical local irritation
Oralnausea, vomiting
IVtransient renal dysfunction in dehydrated patients
Greater specificity for herpesvirus.
Sensitive to HSV-1 and HSV-2, Epstein-Barr virus, Varicella zoster,
Drug of choice for HSV.
Most commonly used in genital herpes.
Oral
Topical (5% cream, ointment) Recurrent orolabial herpes infections

Antiretroviral drugs:
Retrovirus: Virus that contain reverse transcriptase enzyme such as HIV is referred as retrovirus
There are three classes of antiretroviral drugs: NRTI, NNRTI and Protease Inhibitors;
Nucleoside reverse transcriptase inhibitors (NRTI) phosphorylate by human cellular kinases.
Non nucleoside reverse transcriptase inhibitors (NNRTI)- phosphorylate by human cellular kinases.
Protease inhibitors: viral protease

Zidovudine (AZT)
Mechanism

Therapeutic use
Side effects

AZT is converted to the nucleoside triphosphate and incorporated into


growing chain of virus DNA by reverse Transcriptase. Thus synthesis of
DNA is terminated.
Chemically it is synthetic thymidine analog (Azidothymidine: AZT)
Only clinical use in HIV
Most common SE is Bone marrow toxicity: Bone marrow toxicity can
be treated by antianemic supplements: Erythropoeitins (stimulates RBC
production)
Reversible neuropathy
Sever anemia
Leukopenia
Headache
Seizure

Didanosine (ddl)
Mechanism

Therapeutic use

Side effects

It is a synthetic purine analog.


Biotransformed into didanosine ATP, through several reactions and
incorporated into viral DNA.
Long intracellular half-life 8 24 hours.
Dose dependent activity against HIV-1 as result decrease in production of
virus.
This drug also increases in appetite and weight gain and energy.
Pancreatitis (which of may be fatal)major Black Box warning.
Avoid drug that cause pancreatitis: Sulfonamides, Zalcitabine
Peripheral neuropathy
Require acidic content in stomach for absorption (like ketoconazole)

Monitor

Monitor serum amylase and triglyerides

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Anti-viral Drugs

Zalcitabine (ddc)
Mechanism

Synthetic pyrimidine analog active against HIV

Therapeutic use

Indicated in patient advance HIV disease (Serum CD4 count <300/mm2),


and combined with Zidovudine
Rash and stomatitis (pin feeling)
Peripheral neuropathy (major)
Pancreatitis
Neuropathic pain
High triglyceride levels
Drugs that cause peripheral neuropathies: Cisplatin, isoniazid, ethambutol,
metronidazole, phenytoin, dapsone, ribavirin, vincristine, nitrofurantoin,
lithium, and chloramphenical.
Do not take with Mg, Ca, and Al antacids
Do not combine with stavudine, didonasine, lamivudine

Side effects

Monitor
Avoid

Stavudine (d4T)
Mechanism
Side effects

Monitor

A synthetic thymidine neucloside analog active against HIV


Peripheral neuropathy (21%)
Pancreatitis
Drug is not affected by food
Do not combine with zidovudine and zalzitabine

Lamivudine (3TC)
Mechanism
Therapeutic use
Side effects
Monitor

Synthetic neucloside analong structurally similar to zalcitabine


Indicated to treat HIV and chronic hepatitis B in patients with active liver
inflammation
CNS toxicity: dizziness, insomnia, neuropathy
Pancreatitis toxicity in children

Antiviral drugs Tips














CD4 count 100 patient require prophylaxis for the infections of


Pancreatitis is SE of
Peripheral neuropathy is SE of
Didanosine should be avoided with what are the other antiretroviral drugs
Flu season in Canada
Flu immunization in Canada
Who should get flu vaccination
Who is vector (carrier) of flu
Zidovudine induced anemia may be treated by
Acyclovir is the DOC for HSV-1 and HSV-2 infections
Famcyclovir and Valacycyclovir are alternate treatment for HSV-1 and HSV-2
Cold sore can be treated by calamine lotion, oatmeal bath, and antihistmines.
Genetal herpes:

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Anti-viral Drugs

Keratoconguntivitis: Triflurohexidine ophthalmic or acyclovir.


Influenza A and B virus causes flu:
Amantadine: for Influenza A
Rimantadine: for influenza A
Neuroaminidase inhibitors: Oselatamavir (Tamiflu): for influenza A and B
Zanamavir: for influenza A and B
Herpes simpex virus causes infections of Genital herpes, Keratoconjuctivitis, Cold sores

Abbrevation and Terminology


NNRTI
NRTI
HIV
AZT
HSV
RBC
ATP
RBC

Non-Nucleoside Reverse Transcriptase Inhibitors


Nucleoside Reverse Transcriptase Inhibitors

Generic and Brand


Acyclovir
Zoviraxc
Didanosine (ddl)
Zalcitabine (ddc)
Stavudine (d4T)
Lamivudine (3TC)
Oselatamavir

Zovirax
AZT Retrovir
Videx, Videx EC
Hivid
Zerit
Epivir
Tamiflu

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Anti-Malarial Drugs

42

Anti-Malarial Drugs
Malaria is infection of red blood cells with the single-celled parasite Plasmodium, which causes
fever, an enlarged spleen, and anemia.
Four species of malaria parasites--Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale,
and Plasmodium malariae--can infect people.
Falciparum malaria, caused by Plasmodium falciparum, is the most dangerous form of malaria and
can be fatal.
Blackwater fever is an uncommon complication of falciparum malaria.
Chloroquine is the drug of choice for treatment in a person who has malaria caused by Plasmodium
vivax, Plasmodium ovale, or Plasmodium malariae--except in a very few areas where resistance to
chloroquine in people with Plasmodium vivax has been reported.
Chloroquine is the preferred drug for prevention of malaria caused by Plasmodium falciparum in
Mexico, areas of Central America west of the Panama Canal, Haiti, the Dominican Republic, and
some areas of the Middle East.
Primaquine is added to kill persistent parasites in the liver of a person infected with Plasmodium
vivax or Plasmodium ovale. Before primaquine is given, a blood test is done to look for a relatively
common enzyme deficiency (G6PD deficiency). People with G6PD deficiency who are given
primaquine may have a breakdown of their red blood cells.
Treatment of malaria
Prophylaxis
P. falciparum
P. malariae
P. vivax
P. ovale
Chloroquine resistant
prohylaxis
Treatment

Pyrimethamine/sulfadoxine
Chloroquine
Chloroquine
Chloroquine + primaquine
Chloroquine + primaquine
Primaquine, Quinine + doxycycline: Mefloquine, atovaquoneproguanil.
Quinine or mefloquine or pyrimethamine/sulfoxine

Side effects of antimalarial drugs


Mefloquine

Retinopathy
Nausea, dizziness, and trouble sleeping, may rarely produce seizures
or psychiatric problems. Should also be avoided in people with
certain heart conditions.

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Quinine

Atovaquone-proguanil

Anti-Malarial Drugs

Headache, nausea, vomiting, visual disturbances, and ringing in the


ears--a condition known as cinchonism
Retinopathy
Nausea, vomiting, or abdominal pain and is not used in people with
poor kidney function, pregnant women, or infants.

Prevention: pyrimethamine-sulfadoxine or atovaquone-proguanil

Anti-malarial drugs Tips







Mefloquin prophylaxis:
Chloroquin resistant area prophylaxis is:
Chloroquin resistant area treatment:.
Plasmodium vivax and ovale infections, treatment must include
Cinchonism is caused by?
Chloroquine side effect include:

Abbrevation and Terminology


G6PD

Glucose-6-phosphate dehydrogenase

Generic and Brand


Chloroquine
Primaquine
Doxycyckine
Mefloquine
Atovaquone-proguanil.
Pyrimethamine

Ara;em
Radical cure
Adoxa Pak, Adoxa, Alodox , Atridox, Bio-Tab
Lariam
Malarone, Malarone Pediatric
Daraprim

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Travellers Diarrhea

43

Travellers Diarrhea
Travellers diarrhea also known as infections diarrhea. Organisms commonly implicated in the
cause of Travellers Diarrhea:
Escherichia coli.
Shigella sp.
Compylobacter jejuni
Shigella diarrhea diarrhea characterized as dysentery (bloody diarrhea).
Effective drugs in the prevention of Travellers Diarrhea:
Ciprofloxacin is the DOC for travelers diarrhea.
Alternate DOC is Cotrimoxazole
PreventionDoxycycline or ciprofloxacin
Traveller to Thailand: Azithromycin is the DOC for travelers diarrhea
The antibiotic most commonly recommended is ciprofloxacin.
Non prescription drugs:
Bismuth subsalicylate, a nonprescription drug. Causes black stools and tongue.
Loperamide (immodium): Treatment of diarrhea.
Bismuth subsalicylate can be used as prophylaxis or treatment. However loparamide is only used
upon appear of symptoms of diarrhea
When symptoms occur, treatment includes drinking plenty of fluids and eating a bland diet (for
example, cooked cereals, bananas, rice, applesauce, and toast). In addition, antibiotics (such as
ciprofloxacin) and antidiarrheal drugs (such as Lopramide or bismuth) are usually recommended.
Travelers are encouraged to seek medical care if they develop fever or blood in the stool.

Travellers diarrhea Tips






Travellers diarrhea commonly caused by


Prophylaxis of traveler diarrhea include:
If patient allergic to aspirin, what antidiarrheal drug should be avoided:
Loperamide belong what class of drug:
A patient currently taking over the counter antidiarrheal medication and notice black stools
and tongue, which drug can cause these symptoms?
What is the vaccine for travelers diarrhea and cholera?

Abbrevation and Terminology


DOC

Drug of Choice

Generic and Brand


Loperamide

Immodium

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Travellers Diarrhea

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Anti-Helments Drugs

44

Anti-HelminthicDrugs
Helminthic
Species

Common infections

Diseases and medication


Mode of
Treatment
transmission

Round worm

Ingestion

Hook worm

Percutaneous

Trichuris trichuria

Whipworm

Ingestion

Enterobius
vermiculars
Strongyloides

Pinworm
Threadworm

Ingestion/inhalation Pyrantel pamoate


Mebendazole
Ingestion
Thianendazole

Filariasis

Percutaneous

Diethylcarbamzine

River blindness/
onchoceriasis
Trichinosis

Percutaneous

Livermectin

Ingestion

Thiabendazole

Pork
beef

Ingestion
ingestion

Niclosamide
Niclosamide

Fish

ingestion

Niclosamide

Intestinal
nematodes
Ascaris
lumbricoides
Necator
americanus

Tissue nematodes
Wuchereria
bancrofti
Onchocerca
volvulus
Trichinella spiralis
Cestodes
(tapeworms)
Taenia solium
Taenia saginata
Diphyllobothrium
latum
Hymenolepis nana
Trematodes
(flukes)
Schistosoma
mansoni
Schistosoma
haematobium
Clonorchis sinesis
Fasciolopsis
Pragonimus

Dwarf

Blood

Mebendazole

Praziquantel, niclosamide

Percutaneous

bilharziasis
Liver
Intestinal
Lung

Pyrantel pamoate,
mebendazole
Pyrantel pamoate,
mebendazole

Praziquantel
Praziquantel

ingestion
Ingestion
Ingestion

Praziquantel
Praziquantel
Praziquantel

Mebendazole:
Mechanism: Inhibits microtubule synthesis and glucose uptake in nematodes
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Anti-Helments Drugs

Clinical Use: Pinworm and whipworm infections


Contraindicated in pregnancy
Pyrantel pamoate:
Mechanism: Depolarizing neuromuscular blocker, which causes paralysis of nematodes.
Clinical use: Hookworm infections, pinworm infections, Roundworm.
Caution: Red color urine, feces, stains on vomiting.
Praziquantel:
Mechanism: Increase membrane permeability to Ca2+ using muscular contraction and paralysis of the
nematode muscles.
Clinical Use: Drug of choice for Schistosomiasis, clonorchiasis, and pranomiasis.
Niclosamide:
Clinical Use: Infections from ingestion of beef, pork, and fish.

Anti-Helminth Drugs Tips


Pinworm infections can treated by:
Non-medical recommendation in patients with pinworm infection include: Bathing every
morning, regular cleaning of undergarments, bedding etc. Handwash, during the following week
of treatment all family members should wear cotton underpants. Frequent washing of toilet seats.
Which antihelmenthic drug can cause red color body fluids, such as urine, saliva etc? Pyrantel
pamoate

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