Pharmacology Notes - Part 2

TABLE OF CONTENTS
23. Calcium Channel Blockers (Page 1)

24. Drugs Acting on the Renin Angiotensin Aldosterone System (Page 5)
25. Diuretic Drugs (Page 8)
26. Drugs Used to Treat Congestive Heart Failure (Page 13)
27. Antianginal Drugs. Drugs That Increase Regional Blood Flow (Page 17)
28. Antihypertensive Drugs (Page 20)
29. Antiarrhythmic Drugs (Page 23)
30. Drugs Used to Treat Hyperlipoproteinemia (Page 29)
31. Anticoagulatnts. Fibrinolytics. Antifibrinolytics. Antiplatelet Drugs (Page 33)
32. Drugs Affecting Hematopoiesis (Page 39)
33. Histamine, H1 and H2 Receptor Antagonists (Page 43)
34. Serotonin, Serotonin Receptor Agonists and Antagonists (Page 47)
35. Pharmacology of Eicosanoids. Drugs Acting on the Smooth Muscle: Smooth Muscle
Relaxants; Pharmacology of the Uterine Smooth Muscle (Page 53)
36. Pharmacology of the Respiratory Tract (Page 61)
37. Pharmacology of the Gastrointestinal Tract: Drugs in the Treatment of Peptic Ulcer; Emetics,
Anti-Emetics (Page 65)
38. Pharmacology of the Gastrointestinal Tract: Prokinetic Drugs, Laxatives, Antidiarrhoeal
Agents, Drug Treatment of Inflammatory Bowel Disease and Paralytic Ileus, Digestives,
Drugs Used in Cholelithiasis (Page 72)
39. Antianxiety and Hypnotic Drugs (Page 80)
40. Alcohols: Pharmacology and Toxicology (Page 86)
41. Antipsychotic Drugs (Page 90)
42. Antidepressants (Page 94)
43. General Anaesthetics (Page 99)
44. Antiepileptic Drugs (Page 105)
45. Central Nervous System Stimulants and Nootropic Agents (Page 109)
46. Drug Treatment of Neurodegenerative Disorders. Centrally-Acting Muscle Relaxants (Page
111)
47. Drug Abuse and Dependence: General Principles, Opioids, Anti-Anxiety and Hypnotic
Drugs, Inhalants, Ethanol (Page 116)
48. Drug Abuse and Dependence: Psychomotor Stimulants, Psychedelics, Cannabis (Page 118)
49. Opioid Analgesic Drugs: Morphine and Codeine (Page 130)
50. Opioid Analgesic Drugs: Semi-Synthetic, Synthetic Opioids; Opioid Antagonists (Page 130)
51. Cyclooxygenase Inhibitors: Aspirin, Paracetamol (Page 138)
52. Cyclooxygensae Inhibitors: Pyrazolons, Propionic Acid Derivatives, Indole Derivatives and
Others. “COX-2 Inhibitors” (Page 138)
53. Drugs Used to Treat Rheumatoid Arthritis and Gout (Page 144)
A1. Drugs, 2nd Semester (Page 149)
23. CALCIUM CHANNEL BLOCKERS
Overview
- calcium channel blockers (“calcium antagonists”) are drugs that block voltage-sensitive
calcium channels (“type L-calcium channels”)
- the voltage-sensitive calcium channels are more susceptible to blockage in their active state,
thus exhibiting use-dependence
- voltage-sensitive calcium channels are responsible for the propagation of action potential in
unitary muscle fibers (cardiac- and smooth muscle), thus blockage of them causes decreased
depolarization
General Effects
- 2 types
LOCATION ACTION
BLOOD VESSELS Decreased blood pressure
- arterial vasodilation
HEART Positive tropic effect

- reflex tachycardia (due to decreased blood pressure)
Negative tropic effect

- negative chronotropic effect (decreased heart rate)
- negative ionotropic effect (decreased force of contraction)
- negative bathmotropic effect (decreased myocardial excitability)
- negative dromotropic effect (decreased AV conduction)
Relevant Drugs
- 3 categories
1) PHENYLALKYLAMINES (VERAPAMIL)
- primarily acts on the heart
- also has a weak action on blood vessels
- 1 type
DRUG NAME DESCRIPTION

VERAPAMIL General Description
- administered orally
- extensive first-pass metabolism
- extensively bound to plasma proteins
- not to be taken with other drugs with
negative tropic effects (eg. beta-blockers, see
21)
-1-
Clinical usages
- treatment of atrial fibrillation (negative
tropic effect)
- treatment of supraventricular paroxysmal
tachycardia (negative tropic effect)
- treatment of angina pectoris (negative
tropic effect and weak coronary artery
vasodilation)
- treatment of hypertension (negative tropic
effect and weak arterial vasodilation)
Side effects
- bradycardia (negative chronotropic effect)
- heart failure (negative ionotropic effect, if
symptoms of heart failure are already
present)
- supraventricular AV- junctional block
(negative dromoptropic effect)
- constipation (decreased contractility of GI
smooth muscle)
2) BENZOTHIAZEPINES (DILTIAZEM)
- acts efficaciously both on heart and blood vessels
- 1 type

DILTIAZEM General information
- same as verapamil, but less pronounced
(more reflex tachycardia)
3) DIHYDROPYRIDINES (“DHP”)
- primarily act on blood vessels
- also has a weak effect on the heart
- may be subdivided in 3 groups according to duration of action
A) SHORT/RAPIDLY-ACTING DHPS
- 4-6 hours
- 3 types

NIFEDIPINE General information
- administrated orally
- extensive first pass-metabolism
-2-
Clinical usages
- treatment of hypertension (strong arterial
vasodilation)
Side effects
- reflex tachycardia
- headache (cerebral artery vasodilation)
- flushing (cutaneous artery vasodilation)
- ancle edema (arterial vasodilation)
NIMODIPINE General information

- same as nifedipine
- exhibit some selectivity for cerebral
arteries
Clinical usages
vasodilation)
- treatment of cerebral vasospasms following
subarachnoid hemorrhage (then administered
IV)
Side effects
NICARDIPINE General information

- some selectivity for coronary arteries
Clinical usages
vasodilation)
- treatment of prinzmental angina pectoris
(strong coronary artery vasodilation)
Side effects
B) INTERMEDIATELY-ACTING DHPS
- 8-10 hours
- 2 types
-3-
NITRENDIPINE General information
Clinical usages
- same as nicardipine
Side effects
- same as nifedipine, but less pronounced
reflex tachycardia
NISOLDIPINE General information

- same as nitrendipine
C) LONG/SLOWLY-ACTING DHPS
- 40-60 hours
- 1 type

AMLODIPINE General information
Clinical usages
- same as nicardipine
Side effects
- same as nitrendipine, but even less
pronounced reflex tachycardia
-4-
24. DRUGS ACTING ON THE RENIN ANGIOTENSIN
ALDOSTERONE SYSTEM
Overview
- the renin angiotensin aldosterone system is primarily consumed with regulation of blood
pressure
- initiation of the renin angiotensin aldsterone system is done by secretion of renin from the
juxtaglomerular apparatus of the kidney nephrons in response to decreased flow rate of pre-
urine in the distal tubules of the nephrons (due to decreased blood pressure in the glomeruli
of the nephrons and following decreased glomerular filtration rate)
- activation of the renin angiotensin aldosterone system is done in 2 (3) steps
ANGIOTENSINOGEN
renin
ANGIOTENSIN I
ACE (angiotensin-converting enzyme)
ANGIOTENSIN II
ALDOSTERONE SECRETION
- the most important functions of the renin angiotensin aldosterone system include
ENZYME ACTION
ANGIOTENSIN II - arterial vasoconstriction (primarily in the kidneys, heart and
brain)
- increased sympathetic tone
- hypertrophy/hyperplasia of cardiac- and smooth muscle
- aldosterone secretion
ALDOSTERONE - sodium/water reabsorption by the kidneys

- potassium secretion by the kidneys and potassium uptake by the
cells of the body
- hydrogen ion secretion by the kidneys (pH regulation)
Relevant Drugs
- 5 categories
1) BETA-1 ADRENERGIC RECEPTOR ANTAGONISTS

- beta-1 adrenoceptors are found in macula densa cells of the juxtaglomerular
apparatus, and facilitate renin release upon activation
- beta-1 adrenoceptor antagonists thus inhibit renin release
- see 21
-5-
2) RENIN INHIBITORS
- renin inhibitors inhibit the enzymatic activity of renin, thus decrease the
conversion of angiotensinogen to angiotensin I
- 1 type

ENALKIREN
3) ACE INHIBITORS
- ACE inhibitors inhibit the enzymatic activity of ACE, thus decrease the
conversion of angiotensin I to angiotensin II
- 3 types

ENALAPRIL General information
- prodrug
- extensive first-pass metabolism (conversion to active
metabolites)
Medical uses
- treatment of hypertension (arterial vasodilation and
decreased sodium/water retention)
- prophylaxis of angina pectoris and AMI (coronary
artery vasodilation)
- treatment of cardiac failure (coronary arterial
vasodilation, decreased hypertrophy/hyperplasia of
cardiac muscle and decreased preload/afterload)
- treatment of chronic- and acute renal failure
(decreased workload of the kidneys)
Side effects
- hypotension
- renal failure (renal ischemia, if bilateral renal artery
stenosis is present)
- teratogenesis
- hyperkalemia (decreased potassium secretion and cell
uptake)
- respiratory mucosal edema (ACE is also responsible
for catabolizing bradykinin)
- dry cough (respiratory mucosal edema)
LISINOPRIL General information
-6-
- same as enalapril
RAMIPRIL General information

- same as enalapril
4) TYPE 1 ANGIOTENSIN II RECEPTOR ANTAGONISTS

- type 1 angiotensin II receptors are found in both arteries and renal tubules
and are the primary receptors for angiotensin II action
- type 1 angiotensin II receptor antagonists are competitive antagonists of
angiotensin II at type 1 angiotensin II receptors, thus decreasing their
activation
- 2 types

LOSARTAN General information
Medical uses
- treatment of hypertension (arterial vasodilation and
decreased sodium/water retention)
Side effects
- same as with enalapril (, but no respiratory mucosal
edema/dry cough)
VALSARTAN General information

- same as losartan
5) ALDOSTERONE RECEPTOR ANTAGONISTS (“POTASSIUM-SPARING

DIURETICS”)
- see 25
-7-
25. DIURETIC DRUGS
Overview
- diuretic drugs are drugs that increase the urinary output
- all diuretics (except osmotic diuretics) are drugs that inhibit sodium reabsorption from the
renal tubules
- this results in an increased tubular oncotic pressure, decreased water reabsorption, and
following increased urinary output
Relevant Drugs
- 5 categories (listed from most- to least potent)
1) LOOP DIURETICS
- “ceiling diuretics”
- may increase urinary output to 45 liters/day (25% of glomerular filtrate)
- inhibits the 1 sodium/2 chloride/1 potassium cotransported reabsorption of
the thick ascending limb of the loop of henle
- 3 types

FUROSEMIDE General information
- administered orally or IV
- extensively bound to plasma proteins
- eliminated by the organic acid
transporter of the proximal tubule of the
kidneys
Medical uses
- treatment of severe hypertension
- treatment of systemic edema (due to
right-sided congestive heart failure)
- treatment of pulmonary edema (due to
left-sided congestive heart failure)
- treatment of ascites (due to liver
cirrhosis)
- treatment of acute- and chronic renal
failure (increased water excretion)
- treatment of hypercalcemia (inhibition
of calcium reabsorption)
Side effects
- hypotension (hypovolemia)
- hypokalemia (inhibition of potassium
reabsorption and increased tubular flow
rate)
- metabolic alkalosis (due to
-8-
hypokalemia)
- hypomagnesemia (increased tubular
flow rate)
- hypocalcemia (increased tubular flow
rate)
- azotemia (competition between urea
and loop diuretics at the organic acid
transporter)
ETACRYNIC ACID General information

- same as furosemide
2) THIAZIDE DIURETICS
- inhibits the sodium/chloride cotransported reabsorption of the distal tubule
- 3 types

BENDROFLUMETHAZIDE General information
- eliminated by the organic acid
transporter of the proximal tubule of the
kidneys
Medical uses
- treatment of hypertension (due to
decreased water reabsorption and
vasodilation)
- treatment of chronic resistant edema
(together with loop diuretics)
- prophylaxis of urolithiasis (increased
tubular flow rate and no inhibition of
calcium reabsorption)
- treatment of diabetes insipidus
(paradoxal decrease in urinary output)
Side effects
- hypotension (vasodilation)
- hyperglycemia (inhibition of insulin
secretion)
- hypokalemia (increased tubular flow
rate)
- metabolic alkalosis (due to
hypokalemia)
- azotemia (competition between urea
and thiazide diuretics at the organic acid
-9-
transporter)
- hyperlipoproteinemia
- male impotence
HYDROCHLORTHIAZIDE General information

- same as bendrofluazide
CYCLOPENTHIAZIDE General information

- same as bendrofluazide
3) CA (CARBONIC ANHYDRASE) INHIBITORS

- may increase urinary output to 10 liters/day (5% of glomerlular filtrate)
- carbonic anhydrase is the main enzyme responsible for metabolic pH
buffering
CARBONDIOXIDE + WATER
CA (carbonic anhydrase)
CARBONIC ACID
HYDROGEN ION + BICARBONATE ION
- CA inhibitors inhibit intracellular carbonic anhydrase in the tubular

epithelium of the distal tubule
- this leads to decreased intracellular hydrogen ion concentration and following
disruption of the hydrogen ion/sodium antiporter
- 1 drug

ACETAZOLAMIDE General information
- not used as a diuretic
Medical uses
- treatment of glaucoma (carbonic
anhydrase is also involved in production
of the aquous humor of the eye)
- treatment of epilepsy
Side effects
- hypokalemia (increased tubular flow
rate)
- metabolic acidosis (decreased
- 10 -
hydrogen secretion and increased loss of
bicarbonate due to no hydrogen ion in
the tubular fluid to react with to form
carbondioxide and water)
4) POTASSIUM-SPARING DIURETICS (“ALDOSTERONE RECEPTOR

ANTAGONISTS”)
- potassium-sparing diuretics antagonize the effect of aldosterone in the late
distal tubule
- 3 types

SPIRONOLACTONE General information
- direct antagonist of aldosterone at the
intracellular aldosterone receptors in the
late distal tubule, thus inhibiting
expression of aldosterone-dependent
sodium reabsorption, and potassium-
and hydrogen ion secretion
Medical uses
- coadministered with non-potassium
sparing diuretics to preserve potassium
- treatment of hyperaldosteronism
(“conn’s syndrome”)
Side effects
- hyperkalemia (decreased potassium
secretion)
- metabolic acidosis (decreased
hydrogen secretion and hyperkalemia)
- testicular atrophy
- impotence
- gynecomastia
- amenorrhea
TRIAMTERENE General information

- indirect antagonist of aldosterone by
blocking the aldosterone-dependent
sodium reabsorption and potassium
secretion
Medical uses
- 11 -
- coadministered with non-potassium
sparing diuretics to preserve potassium
Side effects
- hyperkalemia
- metabolic acidosis (due to
hyperkalemia)
AMILORIDE General information

- same as triamterene
5) OSMOTIC DIURETICS
- osmotic diuretics do not increase urinary output by the way of inhibition of
sodium reabsorption
- however, osmotic diuretics also act by increasing the tubular oncotic pressure
- the osmotic diuretics are chemical compounds that are unable to leave the
intravascular fluid space except at the large fenestrations of the glomerular
capillaries (freely filtered), and are unable to be reabsorbed by the tubular
epithelium
- this results in an increased intravascular- and tubular oncotic pressure
- 1 type

MANNITOL General information
- administered IV
Medical uses
- prophylaxis of acute renal failure
(increased tubular flow rate)
- treatment of glaucoma (increased
intravascular oncotic pressure)
- treatment of cerebral edema (increased
intravascular oncotic pressure)
Side effects
- transient expansion of the intravasular
fluid space
- 12 -
26. DRUGS USED TO TREAT CONGESTIVE HEART FAILURE
Overview
- heart failure is a failure of the heart to supply the body with sufficient cardiac output
- upon occurrence of heart failure the body will initiate 2 events to try to maintain minimal
required cardiac output
EVENT CONSEQUENCE
INCREASED SYMPATHETIC TONE Positive consequences
- positive tropic effect, thus increasing heart
rate and force of contraction
Negative consequences
- vasoconstriction, and following increased
afterload (increased total peripheral
resistance for the heart to work against)
INCREASED ACTIVATION OF RAAS Positive consequences

- increased blood volume, and following
increased distribution capabilities of the
blood
Negative consequences
- increased blood pressure, and following
increased preload (increased blood volume
arriving in the atria that the heart has to
pump back out)
- congestive heart failure occurs if the negative consequences outweighs the positive
consequences, and following backwards failure symptoms occur (congestion, edema etc.)
Relevant Drugs
- 5 categories
1) CARDIAC GLYCOSIDES (“DIGITALIS”)

- affect the heart in 2 ways
A) INHIBITION OF 3 SODIUM/2 POTASSIUM ANTIPORTER

- normally consumed with maintaining normal resting membrane
potential of -90mV by continuously pumping sodium out of the cell
and potassium into the cell
- 2 consequences
CONSEQUENCE DESCRIPTION
- 13 -
POSITIVE BATHMO- - due to decreased negative
TROPIC EFFECT membrane potential and following
easier excitability of the myocytes
POSITIVE IONO- - due to increased intracellular

TROPIC EFFECT sodium and following disruption of
the sodium gradient across the
sarcolemma
- in turn, this disrupts the
sarcolemmal sodium/calcium
antiporter normally consumed with
restoring the normal intracellular
calcium balance following a
depolarization
- this leads to increased intracellular
calcium, and forces the cell to pump
more calcium into the sarcoplasmic
reticulum instead
- finally, upon the successive
depolarization more calcium will be
released from the sarcoplasmic
reticulum, thus amplifying the force
of contraction
B) INCREASED VAGAL TONE (CENTRAL STIMULATION OF

VAGAL NUCLEI)
- 2 consequences
CONSEQUENCE DESCRIPTION
NEGATIVE CHRONO- - due to depression of the SA-node
TROPIC EFFECT and following decreased heart rate
NEGATIVE DROMO- - due to depression of the AV-node

TROPIC EFFECT and following decreased AV
conduction
- 2 types

DIGOXIN General information
- found in foxgloves
- administered orally (and IV in
emergencies)
- effective dose and toxic dose has a
very small margin
- 14 -
- eliminated by the kidneys
Medical uses
- treatment of heart failure
- treatment of atrial fibrillation
(negative dromotropic effect)
Side effects
- bradycardia (negative chronotropic
effect)
- AV block (negative dromotropic
effect)
- ventricular extrasystole, ventricular
paroxysmal tachycardia and/or
ventricular fibrillation (positive
bathmotropic effect)
- vomiting (stimulation of area
postrema)
Contraindications
- kidney problems (eliminated by the
kidneys)
- hypokalemia (amplified inhibition
of the 3 sodium/2 potassium
antiporter)
- hypercalcemia (even stronger
positive ionotropic effect)
- beta-adrenergic
antagonists/verapamil (even stronger
negative chronotropic- and
dromotropic effect)
OUABAIN General information

- same as digoxin
2) DIRECT VASODILATORS
- decrease total peripheral resistance
- see 28
3) DRUGS ACTING ON THE RENIN-ANGIOTENSIN-ALDOSTERONE

SYSTEM
- decrease blood volume, decrease arterial vasoconstriction and decrease
hypertrophy/hyperplasia of cardiac muscle
- see 24
- 15 -
4) DIURETICS
- decrease blood volume
- see 25
- 16 -
27. ANTIANGINAL DRUGS. DRUGS THAT INCREASE
REGIONAL BLOOD FLOW
ANTIANGINAL DRUGS
Overview
- angina pectoris is reversible myocardial ischemia due to a coronary artery disorder
- there are 4 (5) types of angina
TYPE DESCRIPTION
SILENT MYOCARDIAL ISCHEMIA
STABLE ANGINA - narrowed coronary artery lumen
UNSTABLE ANGINA - occluded coronary artery lumen
MIXED ANGINA - both narrowed and occluded lumen at distinct

locations
PRINZMETAL ANGINA - vasospasms of the coronary arteries
- if angina pectoris remains untreated it can progress to irreversible myocardial ischemia (acute
myocardial infarction, AMI)
Relevant Drugs
- 3 categories
1) ORGANIC NITRATES
- reacts with tissue sulfhydryl (-SH) groups to form nitric oxide (NO), thus
inducing systemic vasodilation
- affects the heart in 2 ways
CAUSE CONSEQUENCE
INCREASED MYOCARDIAL Increased myocardial oxygen supply
BLOOD SUPPLY - general coronary artery vasodilation
(resolves prinzmetal angina)
- vasodilation of collaterals of the
coronary arteries to supply the
ischemic area of the myocardium
(resolves stable- unstable- and mixed
angina)
DECREASED MYOCARDIAL Decreased myocardial oxygen
- 17 -
WORKLOAD consumption
- decreased preload (venous
vasodilation)
- decreased afterload (arterial
vasodilation)
- 3 types

GLYCEROL TRINITRATE General information
(NITROGLYCERIN) - lipophilic
- administered sublingually,
transdermally or IV
Medical uses
- prophylaxis of stable angina
(administered sublingually or
transdermally)
- treatment of stable angina
(administered sublingually)
- treatment of unstable angina
(administered IV)
- treatment of acute heart failure
(administered IV)
Side effects
- postural hypotension (venous
vasodilation)
- headache (meningeal artery
vasodilation)
AMYL NITRATE General information

- same as glycerol trinitrate
ISOSORBIDE General information

MONONITRATE - administered orally
Medical uses
- prophylaxis of stable angina
- treatment of chronic heart failure
Side effects
- same as glycerol trinitrate
- 18 -
2) CALCIUM CHANNEL BLOCKERS
- causes arterial vasodilation and decreases sympathetic action on the heart,
thus both increasing myocardial blood supply and decreasing myocardial
workload
- see 23

- decreases sympathetic action on the heart, thus decreasing myocardial
workload
- contraindicated in prinzmental angina (beta-1 adrenergic receptor antagonists
are not completely selective, thus might cause coronary artery
vasoconstriction)
- see 21
DRUGS THAT INCREASE REGIONAL BLOOD FLOW

Overview
- …
- 19 -
28. ANTIHYPERTENSIVE DRUGS
Overview
- blood pressure is given by 2 parameters
PARAMETER DESCRIPTION
CARDIAC OUTPUT - given by the rate and stroke volume of the
heart
TOTAL PERIPHERAL RESITANCE - given by the blood volume and the level of
vasoconstriction
- hypertension is a pathologically increased blood pressure due to an increase in any of these

parameters
Relevant Drugs
- 8 categories
- dilate the blood vessels, thus decreasing total peripheral resistance
- 4 types

MINOXIDIL General information
- activates potassium channels, thus causing
outflux of potassium
- this leads to hyperpolarization of the cell, and
following vasodilation
- strong, long acting vasodilator
- administered IV
Medical uses
- last resort in treatment of severe hypertension
Side effects
- reflex tachycardia
- increased blood volume (activation of the renin
angiotensin aldosterone system)
- hirsutism (increased facial- and body hair
growth)
HYDRALAZINE General information

- inhibits calcium release from sarcoplasmic
- 20 -
reticulum during depolarization, thus leading to
decreased vasoconstriction
- administered IV
Medical uses
- short-term treatment of hypertension
Side effects
- same as minoxidil
- SLE-like disorder (autoantibodies against own
DNA)
NITROPRUSSIDE General information

- inorganic nitrate
- administered IV
- same as organic nitrates (see 27)
DIAZOXIDE General information

- non-diuretic thiazide
- administered IV
- same as thiazide diuretics (see 25)

- cause arterial vasodilation and decrease the tropic effect of the heart, thus
causing both decreased cardiac output and total peripheral resistance
- see 23
3) ORGANIC NITRATES
- cause both arterial and venous vasoldilation, thus decrease total peripheral
resistance
- see 27
4) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS

- inhibit the sympathetic vasomotor center in the brain stem and the
sympathetic- and parasympathetic ganglia, thus causing vasodilation and
following decreased total peripheral resistance
- see 19
5) ALPHA-1 ADRENERGIC RECEPTOR ANTAGONISTS

- cause vasodilation, thus decreasing total peripheral resistance
- see 20
- 21 -
- decrease sympathetic action on the heart, thus decreasing cardiac output
- see 21
7) DRUGS ACTING ON THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM

- cause vasodilation and decreased blood volume, thus decreasing total
peripheral resistance
- see 24
8) DIURETICS
- decrease blood volume, thus decreasing total peripheral resistance
- see 25
- 22 -
29. ANTIARRHYTHMIC DRUGS
Overview
- action potential in myocytes has 4 (5) phases
PHASE DESCRIPTION
PHASE 0 Rapid depolarization
- due the myocyte reaching a membrane potential
of -60 mV (critical firing threshold) and following
opening of the activation gates of voltage-gated
sodium channels
- this leads to rapid influx of sodium and
following depolarization
PHASE 1 Partial repolarization

- due to the myocyte reaching +40 mV and
following closing of the inactivation (refractory)
gates of the voltage-gated sodum channels
- partial repolarization is done by outflux of
potassium through the normal potassium-sodium
leak channels
PHASE 2 Plateau
- due to the myocyte reaching 0 mV and following
activation of voltage-gated calcium channels of
the sarcoplasmic reticulum
- this leads to release of large quantities of calcium
into the sarcoplasm, and following initiation of
muscle contraction
PHASE 3 Repolarization
- due to the myocyte reaching –10 mV and
following inactivation of the voltage-gated
calcium channels
- repolarization is done by the same mechanism as
with partial repolarization (see above)
PHASE 4 Pacemaker potential

- due to the myocyte reaching -90 mV (resting
membrane potential) and following activation of a
special sodium-potassium leak channel (only
found in SA-node, AV-node, and purkinje fibers)
that opposes the normal potassium-sodium leak
channel (found in all cells capable of depolarizing)
- this leads to a steadily increasing membrane
potential, thus initiating the successive
depolarization at -60 mV (phase 0)
- 23 -
- there are 4 types of cardiac arrhythmias
TYPE DESCRIPTION
ACTIVE ECTOPIC BEATS General information
(SUPRAVENTRICULAR-, - “extrasystole”, “premature beat”
VENTRICULAR-) - 1 beat occurring before it would have been
expected originating outside the AV-node
- due to irritation of the myocardium
Causes
- excess sympathetic tone
- ischemia
- small calcified plaques
- myocardial toxins (alcohol, caffeine, nicotine,
drugs etc.)
PAROXYSMAL TACHYCARDIA General information

(SUPRAVENTRICULAR-, - heart rate above 150 BPM
VENTRICULAR-) - due to successive active ectopic beats (see
above) or the presence of a reentrant circuit (see
below)
FLUTTER (ATRIAL-) General information

- heart rate above 250 BPM
- due to the presence of 1 reentrant circuit
Causes
- presence of extranodal conducting pathways
(wolff-parkinson-white syndrome etc.)
- increased distance of conductance
(atrial/ventricular dilation)
- decreased velocity of conduction (ischemia,
excess parasympathetic activity etc.)
- decreased refractory period (excess sympathetic
activity etc.)
FIBRILLATION (ATRIAL-, General information

VENTRICULAR-) - heart rate above 350 BPM
- due to the presence of multiple reentrant circuits
(see above)
- 24 -
Relevant Drugs
- antiarrhythmic drugs may be divided in 4 classes (vaughan williams’ system)
1) CLASS I ANTIARRHYTHMIC DRUGS

- blocks the voltage-gated sodium channels (phase 0), thus decrease
excitability of the myocardium
- are use-dependent, thus blocking stronger sites of the myocardium that more
frequently depolarize
- may be further subdivided in 3 groups
A) CLASS Ia ANTIARRHYTHMIC DRUGS

- cause intermediate voltage-gated sodium channel block
- also block potassium-sodium leak channels (phase 1 and phase 3), thus
increase duration of repolarization (refractory period)
- 2 types

QUINIDINE General information
- also has an atropine-like effect
Medical uses
- treatment of ventricular arrhythmias
Side effects
- ventricular paroxysmal tachycardia
(“torsade de pointes”, due to prolonged
refractory period)
- any side effect of muscarinic antagonists
(atropine-like effect, see 15)
- thrombocytopenia (autoantibodies against
platelets)
DISOPYRAMIDE General information

- same as quinidine
PROCAINAMIDE General information

- administered IV
Medical uses
- treatment of ventricular arrhythmias
Side effects
- SLE-like disorder (autoantibodies against
own DNA)
- 25 -
B) CLASS Ib ANTIARRHYTHMIC DRUGS
- cause weak voltage-gated sodium channel block
- selectively block refractory voltage-gated sodium channels
- 2 types

LIDOCAINE General information
- local anaesthetic (see 22)
- administered IV
Medical uses
- treatment of arrhythmias associated with
irreversible myocardial ischemia (AMI, due
to selective refractory blockage)
- local anaesthesia
Side effects
- see 22
PHENYTOIN General information

- antiepileptic drug (see 43)
- same as lidocaine
Medical uses
irreversible myocardial ischemia (AMI, due
to selective refractory blockage)
Side effects
- see 43
C) CLASS Ic ANTIARRHYTHMIC DRUGS

- cause strong voltage-gated sodium channel block
- 2 types

FLECAINIDE Medical uses
reentrant circuits (strong general
suppression)
- 26 -
Side effects
- heart failure (in patients with symptoms,
due to strong general suppression)
ENCAINIDE General information

- same as flecainide
2) CLASS 2 ANTIARRHYTHMIC DRUGS

- beta-adrenergic receptor antagonists
- block voltage-gated sodium- (phase 0) and calcium channels (phase 2), thus
decrease excitability and force of contraction of the myocardium
- used in treatment of arrhythmias associated with excess sympathetic tone
- see 21

- block the potassium-sodium leak channels (phase 1 and phase 3), thus
increase duration of repolarization (refractory period)
- 3 types

AMIODARONE General information
- iodine-containing compound
- accumulates in tissues
Medical uses
reentrant circuits (prolonged refractory
period)
Side effects
(prolonged refractory period)
- hypo- or hyperthyroidism (iodine, tissue
accumulation)
- photosensitivity (iodine, tissue
accumulation)
- skin discoloration (iodine, tissue
accumulation)
- visual disturbances (accumulation in the
cornea, due to iodine-content and tissue
accumulation)
- neurological disturbances (tissue
accumulation)
- 27 -
SOTALOL General information
- also a beta-adrenergic receptor antagonist
(see 21)
Medical uses
reentrant circuits
excess sympathetic activity
Side effects
- see 21

- calcium channel blockers
- block voltage-gated calcium channels, thus decrease force of contraction
- used in treatment of supraventricular/atrial arrhythmias
- see 23
- 28 -
30. DRUGS USED TO TREAT HYPERLIPOPROTEINEMIA
Overview
- triglycerides and cholesterol are transported in lipoproteins in the circulation
- lipoproteins consists of 2 parts
PART DESCRIPTION
MEDULLA - hydrophobic
- consists of triglycerides and cholesterol esters
CORTEX - hydrophilic
- consists of phospholipids, cholesterol and
apolipoproteins
- there are 5 types of lipoproteins
TYPE DESCRIPTION
CHYLOMICRON - transports triglycerides and cholesterol from the
intestines to muscle- and adipose tissue
- here, the triglycerides are split to free fatty acids by
lipoprotein lipase and the free fatty acids taken up by
these tissues
CHYLOMICRON REMNANT - transports the cholesterol and remaining triglycerides

remaining in the chylomicron to the liver
- here, the cholesterol is converted to bile salts and
secreted through the bile into the intestines for
absorption of new lipids and cholesterol
(enterohepatic bile circulation)
VLDL Very low density lipoprotein

- transports newly synthesised triglycerides and
cholesterol from the liver back to muscle- and adipose
tissue
- here, all the triglycerides are split by lipoprotein
lipase and taken up by these tissues
LDL Low density lipoprotein

- transports the remaining cholesterol either back to
the liver for conversion to bile acids, or to extrahepatic
tissues for metabolism
HDL High density lipoprotein

- a scavenger lipoprotein that adsorbs cholesterol
- 29 -
derived from cell breakdown and transfers it to vLDL
and LDL
- if VLDL and/or LDL concentration increases, there will be a higher probability of

atherosclerosis
- if HDL increases, there will be a lower probability of atherosclerosis
Relevant Drugs
- 3 categories
1) STATINS
- statins are HMG-CoA (3-hydroxy-3- methylglutaryl-coenzyme A) reductase
inhibitors
- HMG-CoA catalyzes the rate limiting step of cholesterol synthesis in the
liver, thus blocking it will lead to a relative deficiency of cholesterol for
synthesis of bile acids
- this leads to upregulation of LDL receptors, and following removal of LDL
from the circulation
- statins also reduce VLDL production
- 4 types

MEVASTATIN General information
- found in fungus
- extensive first-pass
metabolism (, though the site
of action is the liver)
Medical uses
- reduction of LDL and
VLDL
Side effects
- mild GI disturbances
- mild sleep disturbances
- mild skin rashes
LOVASTATIN General information

- same as mevastatin
SIMVASTATIN General information

- synthetic pro-drug
- same as mevastatin
- 30 -
PRAVASTATIN General information
- same as simvastatin
2) FIBRATES
- fibrates are PPAR-alpha (peroxysome proliferator-activated receptor alpha)
agonists
- PPAR-alpha is an intracellular receptor regulating gene transcription of
proteins responsible for lipid metabolism
- consequences of PPAR-alpha upregulation include
CONSEQUENCE CAUSE
DECREASED LIPID STORES - increased deliberation of
lipids from adipose tissue
DECREASED CIRCULATING LIPIDS - increased lipoprotein lipase

activity
- increased beta-oxidation
DECREASED CIRCULATING VLDL - decreased VLDL

production
DECREASED CIRCULATING LDL - increased LDL-receptor

expression
- 3 types

FENOFIBRATE Gereral information
Medical uses
- reduction of VLDL
- reduction of VLDL and
LDL
Side effects
- myositis (inflammation of
muscle)
- acute renal failure (due to
myositis and following
hemoglobinuria)
- mild GI disturbances
- 31 -
CIPROFIBRATE General information
-same as fenofibrate
BENZAFIBRATE General information

-same as fenofibrate
3) RESINS
- resins complex with bile salts in the intestines, thus inhibiting reabsorption
through the enterohepatic circulation
- this results in deficiency of bile acids, upregulation of LDL receptors, and
following removal of LDL from the circulation
- 2 types

COLESTYRAMINE Gereral information
Medical uses
- reduction of LDL
Side effects
- nausea
- vomiting
- bloating
- constipation or diarrhea
- fat-soluble vitamin
deficiency
COLESTIPIL General information

-same as colestyramine
- 32 -
31. ANTICOAGULANTS. FIBRINOLYTICS.
ANTIFIBRINOLYTICS. ANTIPLATELET DRUGS
Overview
- hemostasis consists of 4 (5) mechanisms
MECHANISM DESCRIPTION
VASOCONSTRICTION - both neurally- and humorally mediated
PLATELET PLUG FORMATION - adhesion of platelets to the damaged endothelium
COAGULATION - blood clot formation by activation of fibrin

through the intrinsic- or extrinsic coagulation
cascade
PERMANENT CLOSURE - growth of fibrous tissue by conversion of smooth

muscle cells of the vessel walls to myofibroblasts
FIBRINOLYSIS - removal of the blood clot by activation of

plasmin
ANTICOAGULANTS
Overview
- anticoagulants are drugs that interfere with the coagulation factors (“serine proteases”) of the
extrinsic- and intrinsic coagulation pathways, thus inhibiting coagulation
Relevant Drugs
- 2 categories
1) INJECTABLE ANTICOAGULANTS
- injectable anticoagulants bind to the allosteric seat of antithrobin III, thus
activating it
- antithrombin III is a serine protease inhibitor responsible for inhibition of
activated coagulation factors
- , thus activation of antithrombin III leads to decreased activation of fibrin and
following inhibition of coagulation
- 2 types

HEPARIN General information
- 33 -
- endogenous compound found in the granules of mast
cells
- sulfated glycosaminoglycan (large, negatively
charged)
- extracted from bovine lung and/or hog intestine
- digested in the GI
- administered IV or subcutaneously (cause hematomas
if injected intramuscularly due to its large molecular
size)
- contains a second binding site for factor XII, XI, IX
and II (thrombin), thus accelerating their inactivation
by antithrombin III
- also accelerate inactivation of factor X
(independently of the second binding site)
Medical uses
- treatment of thrombosis, DIC and emboli
Side effects
- hemorrhage (clotting factor inhibition)
- thrombosis/DIC (autoantibodies against heparin-
platelet factor 4 complexes (and following
thrombocytopenia) and platelet factor 4-vascular
endothelium complexes)
- osteoporosis
LMWHS General information

- “low molecular weight heparins”
- fragments of heparin lacking the second binding site
- only accelerate inactivation of factor X
- administered subcutaneously
- same as heparin
2) ORAL ANTICOAGULANTS
- oral anticoagulants bind to the active site of vitamin K reductase, thus
inhibiting reduction of vitamin K to it’s active form
- reduced vitamin K is a cofactor of alpha-carboxylase, consumed with
modification of coagulation factor X, IX, VII and II (thrombin) after primary
protein translation
- only the modified coagulation factors are able to be activated, thus inhibition
of vitamin K reductase leads to decreased activation of fibrin and following
inhibition of coagulation
- 1 type
- 34 -
WARFARIN Gereral information
- also used in rat poison
- may cross the placenta
- only inhibits formation of new coagulation factors,
thus previously synthetized coagulation factors will
still be able to induce coagulation until they are
catabolized (around 48 hours)
Medical uses
Side effects
- hemorrhage (deceased clotting factor production)
- teratogenesis (may cross the placenta)
FIBRINOLYTICS
Overview
- fibrinolytics are drugs that increase activation of plasmin, thus increase fibrinolysis and
following removal of blood clots
Relevant Drugs
- 3 types

STREPTOKINASE General information
- streptococcal protein
- may only be administered once per year (antistreptococcal
antibodies will be formed within 1 week (!))
Medical uses
Side effects
- hemorrhage (fibrinolysis)
- stroke (hemorrhage)
- anaphylaxis (antistreptococcal antibodies)
ALTEPLASE General information

- recombinant tPA (“tissue plasminogen factor”, the physiological
- 35 -
protein responsible for plasmin activation)
- more active on plasminogen bound to fibrin (“clot selective”)
- very short half-life
- administered by IV infusion (very short half-life)
Medical uses
Side effects
- hemorrhage (fibrinolysis)
- stroke (hemorrhage)
RETEPLASE General information

- short half-life
- administered by IV bolus
- same as alteplase
ANTIFIBRINOLYTICS
Overview
- antifibrinolytics are drugs that inhibits activation of plasmin, thus decrease fibrinolysis and
following increase the integrity of blood clots
Relevant Drugs
- 1 type

TRANEXAMIC ACID General information
Medical uses
- treatment of severe hemorrhages
- treatment of fibrinolytic overdose
Side effects
- thrombosis
APOPROTININ General information

- inhibits proteolytic enzymes (including plasmin)
Medical uses
- 36 -
- treatment of fibrinolytic overdose
Side effects
- thrombosis
ANTIPLATELET DRUGS
Overview
- antiplatelet drugs are drugs that inhibit adhesion of platelets to the damaged endothelium,
thus inhibiting platelet plug formation
Relevant Drugs
- 4 categories
1) COX-1 INHIBITORS
- inhibits COX-1, thus inhibiting TXA2 (thromboxane A2) synthesis in platelets and
PGI2 (prostaglandin I2) synthesis in vascular endothelium
- TXA2 stimulates glycoprotein IIb/IIIa receptor expression on platelets while PGI2
inhibits it
- glycoprotein IIb/IIIa is the receptor responsible for platelet-platelet adhesion and
platelet-fibrinogen adhesion
- however, vascular endothelium is capable of syntethizing new COX-1 while platelets
are not, thus platelet plug formation is inhibited
- see 51/52
2) THIENOPYRIDINE DERIVATIVES
- inhibits ADP-mediated expression of glycoprotein IIb/IIIa, thus inbiting platelet plug
formation
- 2 types

TRICLOPIDINE General information
- pro-drug
Medical uses
Side effects
- hemorrhages
- blood dyscrasias
- diarrhea
- skin rashes
- 37 -
CLOPIDOGREL General information
- same as triclopidine
3) GLYCOPROTEIN IIB/IIIA RECEPTOR ANTAGONITS

- antagonizes TXA2 and ADP, thus inhibiting platelet plug formation
- 2 types

ABCIXIMAB General information
- hybride rodent/human monoclonal antibody
- administered IV
- may only be administered once (antibodies against the
rodent part will be formed)
Medical uses
Side effects
- hemorrhages
TIROFIBRAN General information

- administered IV
Medical uses
Side effects
- hemorrhages
4) PGI2 AGONISTS
- inhibit expression of glycoprotein IIb/IIIa, thus inhibiting platelet plug formation
- 1 type

EPOPROSTENOL
- 38 -
32. DRUGS AFFECTING HEMATOPOIESIS
Overview
- all blood cells originate from pluripotent stem cells of the bone marrow
- there are 5 types of blood cells
CELL TYPE DESCRIPTION

ERYTHROCYTES - RBCs
PLATELETS - cell fragments of megakaryocytes
MONOCYTES - differentiate to macrophages
GRANULOCYTES - neutrophils
- eosinophils
- basophils
LYMPHOCYTES - B lymphocytes
- T lymphocytes
- anemia is a decrease in circulating RBCs

- there are 4 types of anemia
TYPE DESCRIPTION
APLASTIC ANEMIA - due bone marrow failure
DEFICIENCY ANEMIA - normocytic, normochromic deficiency anemia (due to

erythropoietin and/or GM-CSF deficiency)
- microcytic, hypochromic deficiency anemia (due to
iron deficiency)
- macrocytic, hyperchromic anemia (due to folic acid
(vitamin B9) and/or cobolamin (vitamin B12)
deficiency)
HEMOLYTIC ANEMIA - due to increased sequestration of RBCs
HEMORRHAGIC ANEMIA - due to hemorrhages
Relevant Drugs
- 4 categories
- 39 -
1) IRON
- needed for the heme group of hemoglobin, thus deficiency leads to decreased
hemoglobin synthesis
- is utilized by the body in the ferrous (Fe2+) form
- 5 types

FERROUS SULFATE General information
Medical uses
- treatment of microcytic, hypochromic
deficiency anemia
Side effects
- nausea
- diarrhea
- abdominal cramps
FERROUS SUCCINATE General information

- same as ferrous sulfate
FERROUS GLUCONATE General information

FERROUS FUMARATE General information

IRON-DEXTRAN General information

- administered IV
2) FOLATE (“VITAMIN B9”)

- cofactor (methyl-group donor) in the synthesis of purines and pyrimidines
used for DNA- and RNA synthesis, thus deficiency leads to decreased DNA-
and RNA synthesis
- this is especially manifested in tissues with high cell turnover (bone marrow)
- is utilized by the body in the tetrahydrofolate (FH4) form
- is carried in the circulation as methyl-FH4
- the methyl group is removed by cobolamin (“vitamin B12”), thus cobolamin
is needed for it’s utilization
- 1 type
- 40 -
FOLATE Gereral information
- administered orally (parenterally in case
of malabsorption syndromes)
Medical uses
- treatment of macrocytic, hyperchromic
deficiency anemia
3) COBOLAMIN (VITAMIN B12)

- removes the methyl group of methyl-FH4, so that it can be utilized in purine
and pyrimidine synthesis
- 1 type

HYDROXYCOBOLAMIN Gereral information
- administered intramuscularly
(cobolamin deficiency is almost always
due to malabsorption syndromes)
Medical uses
- treatment of macrocytic, hyperchromic
deficiency anemia
4) CSFS (COLONY-STIMULATING FACTORS)

- CSFs are responsible for differentiating the pluripotent stem cells to all types
of commited progenitors of blood cells (except lymphocytes)
- they are also involved in final differentiation of all these cells (except
basophils)
- 2 types

GM-CSF Gereral information
- “granulocyte-macrophage colony-
stimulating factor”
- endogenous substance
- involved in differation of all cells
mentioned above
- administered IV or subcutaneously
Medical uses
- treatment of leucopenia (mainly
neutropenia)
Side effects
- 41 -
- fever
- skin rashes
- muscle pain
- muscle weakness
G-SCF Gereral information

- “granulocyte colony-stimulating factor”
- endogenous substance
- involved in differation of neutrophils
- administered IV or subcutaneously
Medical uses
- treatment of neutropenia
Side effects
- dysuria
- vasculitis
- 42 -
33. HISTAMINE, H1 AND H2 RECEPTOR ANTAGONISTS
Overview
- histamine is a paracrine hormone and an inhibitory neurotransmitter
- histamine is primarily found in 3 locations
LOCATION DESCRIPTION
CNS - histaminergic neurons
SYSTEMIC CIRCULATION - granules of mast cells

- granules of basophils
GI TRACT - neuroendocrine cells in the glands of the GI
- histamine acts on histaminergic receptors

- there are 3 types of histaminergic receptors
RECEPTOR TYPE LOCATION

H1 - smooth muscle
- CNS
H2 - parietal cells of the castric glands

- heart
H3 - presynaptically in CNS neurons
General Effects
- 6 types
ORGAN DESCRIPTION
CNS - inhibition of neurotransmitter release
- nausea
HEART - positive chronotropic effect (increased heart rate)

- positive ionotropic effect (increased force of
contraction)
BLOOD VESSELS - vasodilation

- increased vascular permeability
- 43 -
RESPIRATORY TRACT - bronchoconstriction
GI TRACT - increased gastric acid secretion

- GI smooth muscle contraction
GENITO-URINARY TRACT - contraction of uterus
Relevant Drugs
- 2 categories
1) H1 RECEPTOR ANTAGONISTS (“ANTIHISTAMINES”)

- histamine acting on H1 receptors in smooth muscle is the main mediator of
the symptoms of anaphylaxis (type 1 hypersensitivity reactions)
- histamine acting on H1 receptors in the CNS is also a mediator of nausea
- H1 receptor antagonists are reversible competitive antagonists of histamine,
thus blocking it’s action
- many of the H1 receptor antagonists are not completely selective to
histaminergic receptors, thus may antagonize other types of receptors as well
(see below)
- 5 types

PROMETAZINE General information
- marked muscarinic receptor antagonist
action
- weak alpha-1 adrenergic receptor antagonist
action
- weak local anaesthetic action
- may cross the blood-brain barrier
Medical uses
- treatment of emesis (especially motion
sickness)
- treatment of insomnia (sedative)
Side effects
- diarrhea/constipation (GI smooth muscle
contraction)
- same as muscarinic receptor antagonists
(see 15)
DIPHENHYDRAMINE General information

- marked muscarinic receptor antagonist
- 44 -
action
- weak local anaesthetic action
- may cross the blood brain barrier
- same as prometazine
CYCLIZINE General information

Medical uses
- treatment of emesis (especially motion
sickness)
Side effects
- diarrhea/constipation
- sedation
CINNARIZINE General information

- same as cyclizine
MEQUITAZINE General information

- administered orally, topically and/or IV
- does not cross the blood-brain barrier
Medical uses
- treatment of anaphylactic reactions (allergic
rhinitis, urticaria (allergic skin rashes), insect
bites, drug hypersensitivities etc.)
Side effects
CENTRIZINE General information

- same as mequitazine
FEXOFENADINE General information

- same as mequitazine
2) H2 RECEPTOR ANTAGONISTS
- H2 receptor antagonists decrease histamine-mediated gastric acid secretion
- H2 receptors antagonists also inhibit the secondary messenger systems of
gastrin- and acetylcholine-mediated gastric acid secretion
- 45 -
- , thus H2 receptor antagonists may decrease basal- and pranial gastric acid
secretion by over 90%
- they also promote healing of duodenal ulcers by a separate mechanism
- 4 types

CIMETIDINE Gereral information
- minor androgen receptor antagonism
- also inhibit cytochrome P450
- administered orally, intramuscularly or IV
Medical uses
- treatment of peptic ulcer (gastric- and/or
duodenal)
- treatment of reflux esophagitis
Side effects
- hypergastrinemia
- diarrhea
- gynecomastia (androgen receptor
antagonism)
RANTIDINE General information

Medical uses
- same as cimetidine
Side effects
- same as cimetidine (but no gynecomastia)
FAMOTIDINE General information

- same as rantidine
NIZATIDINE General information

- same as rantidine
- 46 -
34. SEROTONIN, SEROTONIN RECEPTOR AGONISTS AND
ANTAGONISTS
Overview
- serotonin (“5-hydroxytryptamine”, “5-HT”), like histamine, is a paracrine hormone and an
inhibitory neurotransmitter
- biosynthesis and breakdown of serotonin is done in 3 steps (similar to that of catecholamines,
see 17)
TRYPTOPHAN
tryptophan hydroxylase
5-HYDROXYTRYPTOPHAN
DOPA decarboxylase
5-HYDROXYTRYPTAMINE (5-HT, SEROTONIN)

MAO + aldehyde dehydrogenase
5 HYDROXYINDOLEACETIC ACID (5-HIAA)
- serotonin is primarily found in 3 locations
LOCATION DESCRIPTION
CNS - serotonergic neurons
SYSTEMIC CIRCULATION - platelets
GI TRACT - neuroendocrine cells in the glands of the GI

- myenteric plexus
- serotonin acts on serotonergic receptors

- there are 8 types of serotonergic receptors
RECEPTOR TYPE DESCRIPTION

5-HT 1A Location
- CNS
Effect
- CNS depression
- anxiolysis
- alertness
- 47 -
5-HT 1B Location
- CNS
- pulmonary vasculature
Effect
- CNS depression
- pulmonary vasoconstriction
5-HT 1D Location
- CNS
- cerebral vasculature
Effect
- CNS depression
- cerebral vasoconstriction
5-HT 2A Location
- CNS
- smooth muscle
- platelets
Effect
- CNS excitation
- hallucination
- arterial- and venous vasoconstriction
- arteriolar vasodilation
- bronchoconstriction
- contraction of the uterus
- platelet plug formation (platelet aggregation)
5-HT 2B Location
- stomach
Effect
- gastric smooth muscle contraction
5-HT 2C Location
- choroid plexus of the CNS
Effect
- secretion of cerebrospinal fluid
5-HT 3 Location
- 48 -
- CNS
- chemoreceptive trigger zone of area postrema in the
CNS
- spinal cord analgesic system
Effect
- CNS excitation
- nausea
- vomiting
- analgesia
5-HT 4 Location
- smooth muscle of the GI tract
Effect
- increased peristalsis
- neither selective serotonin receptor agonists nor –antagonists are completely selective, thus
may exhibit other effects on any of the other types of serotonin receptors
SEROTONIN RECEPTOR AGONISTS
Relevant Drugs
- 3 categories
1) 5-HT 1 AGONISTS
- 3 types

BUSPIRONE Medical uses
- treatment of anxiety (CNS depression)
Side effects
- restlessness (alertness)
- headache
- nausea (effect on 5-HT 3 receptors)
SUMATRIPTAN General information

- 5-HT 1D selective agonist
- do not cross the blood-brain barrier
- administered orally or subcutaneously
- 49 -
Medical uses
- treatment of migraine (vasoconstriction of
meningeal blood vessels)
Side effects
- cardiac ischemia (coronary artery
vasoconstriction)
ERGOTAMINE General information

- found in the ergot fungus
- 5-HT 1 partial agonist on blood vessels
- 5-HT 1 antagonist in all other locations
- 5-HT 2 agonist
- also an alpha-adrenergic receptor agonist (see 19)
- related to ergometrine (see 35)
- administered IV, rectally or by inhalation
Medical uses
- treatment of migraine (vasoconstriction of
meningeal blood vessels and inhibition of
nocioceptive transmission)
- treatment of postpartum hemorrhage
Side effects
- hypertension (vasoconstriction)
- coronary ischemia (vasoconstriction)
- nausea
- vomiting
2) 5-HT 2 AGONISTS
- 1 type

LSD General information
- see 48
3) 5-HT 4 AGONISTS
- 1 type
- 50 -
CISAPRIDE General information
Medical uses
- treatment of reflux esoophagitis (increased tone of
lower esophageal sphincter)
- disorders of gastric emptying (increased tone of
gastric smooth muscle)
- treatment of paralytic ileus (increased peristalsis)
Side effects
- diarrhea
- abdominal cramps
SEROTONIN RECEPTOR ANTAGONISTS

Relevant Drugs
- 2 categories
1) 5-HT 2 ANTAGONISTS
- 2 types

METHYLGLYCERGIDE General information
- also partial 5-HT 2 agonist
Medical uses
- prophylaxis of migraine (cerebral blood
vessel vasodilation)
Side effects
- nausea
- vomiting
- retroperitoneal/mediastinal fibrosis
CYPROHEPTADINE General information

- also histaminergic receptor antagonist
(see 33)
Medical uses
- 51 -
- prophylaxis of migraine (cerebral blood
vessel vasodilation)
Side effects
- sedation
- weight gain
2) 5-HT 3 ANTAGONISTS
- 2 types

ONDASETRON General information
Medical uses
- treatment of emesis (vomiting)
- treatment of anxiety
TROPISETRON General information

- same as ondasetron
- 52 -
35. PHARMACOLOGY OF EICOSANOIDS. DRUGS ACTING
ON THE SMOOTH MUSCLE: SMOOTH MUSCLE
RELAXANTS; PHARMACOLOGY OF THE UTERINE
SMOOTH MUSCLE
PHARMACOLOGY OF EICOSANOIDS
Overview
- eicosanoids are autocrine- and paracrine mediator molecules of many important
physiological- and pathological processes
- there are 3 groups of eicosanoids
GROUP TYPE
PROSTAGLANDINS - PGD2
- PGE2
- PGF2-alpha
- PGI2
TROMBOXANES - TXA2
LEUKOTRIENES - LTB4
- LTC4
- LTD4
- LTE4
- they are synthesized from arachidonic acid (“5,8,11,14-eicosatetraenoic acid”) which is found
as arachidonic acid esters in phospholipids
PHOSPHOLIPIDS
phospholipase A2
ARACHIDONIC ACID
COX (“cyclooxygenase”, see 51/52) 5-lipoxygenase
PROSTAGLANDINS/ LEUKOTRIENES
TROMBOXANES
- there are 9 types of eicosanoid receptors
RECEPTOR TYPE DESCRIPTION
- 53 -
DP (PGD2) RECEPTORS Location
- blood vessels
- uterus
- GI tract
- platelets
- pituitary gland
Effect
- vasodilation
- uterine smooth muscle relaxation
- GI tract smooth muscle relaxation
- inhibition of platelet aggregation
- regulation of pituitary hormone release
EP1 (PGE2) RECEPTORS Location

- lungs
- GI tract
- CNS
- C nerve fibers
Effect
- GI tract smooth muscle contraction
- fever (increase the hypothalamic temperature set point)
- hyperalgesia (sensitization of afferent C nerve fibers, see
49)

- blood vessels
- lungs
- GI tract
Effect
- vasodilation
- bronchodilation
- GI tract smooth muscle relaxation
- intestinal fluid secretion

- uterus
- GI tract
- autonomic nervous system
- adipose tissue
- 54 -
Effect
- pregnant uterine smooth muscle contraction
- GI tract smooth muscle contraction
- inhibition of gastric acid secretion
- gastric mucous secretion
- inhibition of autonomic neurotransmitter release
- inhibition of lipolysis
FP (PGF2-alpha) Location
RECEPTORS - uterus
Effect
- uterine smooth muscle contraction
IP (PGI2) RECEPTORS Ligand

- PG12
Effect
- vasodilation
- inhibition of platelet aggregation
- renin release
- hyperalgesia (sensitization of afferent C nerve fibers)
TP (TXA2) RECEPTORS Location

- blood vessels
- platelets
Effect
- vasoconstriction
- platelet aggregation
BLT (LTB4) RECEPTORS Location

- neutrophils
- macrophages
- lymphocytes
Effect
- neutrophil/macrophage chemotaxis
- neutrophil degranulation
- macrophage/lymphocyte cytokine release
- macrophage/lymphocyte proliferation
- 55 -
CYSLT (LTC4, LTD4, Location
LTE4) RECEPTORS - blood vessels
- lungs
Effect
- vasodilation
- increase vascular permeability
- bronchial mucous secretion
SMOOTH MUSCLE RELAXANTS
Overview
- …
PHARMACOLOGY OF THE UTERINE SMOOTH MUSCLE
Overview
- the uterine smooth muscle, like the heart, contains pacemaker cells, thus possessing the
ability of spontaneous rhythmic contractions
- the rhythmic contractions are under hormonal control
ACTION HORMONE
FACILITATION - progesterone
- oxytocin
INHIBITION - estrogen
- the rhythmic contractions take part in several important events of the uterus, thus the
hormones controlling them partially- or completely give the outcome of these events
EVENT DESCRIPTION
MENSTURAL CYCLE Pre-ovulatory phase
- weak rhythmic contractions (estrogen)
Post-ovulatory phase
- strong rhythmic contractions (progesterone)
PREGNANCY Pregnancy
- very weak (or absent) rhythmic contractions
- 56 -
Delivery
- very strong rhythmic contractions (oxytocin)
- in addition, the uterine smooth muscle is also capable of contracting normally like any other
smooth muscle
- the normal contractions are under prostaglandin- and hormonal control
ACTION HORMONE
FACILITATION - PGE2 (EP3 receptors)
- PGF2-alpha
- histamine (H1 receptors)
- serotonin (5-HT 2A receptors)
INHIBITION - PGD2
- adrenalin (beta-2 receptors)
Relevant Drugs
- 2 categories
1) OXYTOCIC DRUGS
- facilitate uteral contraction
- 3 groups
A) OXYTOCIN RECEPTOR AGONISTS

- 1 type

OXYTOCIN General information
- endogenous hormone
- causes strong facilitation of the rhythmic
contractions of the uterus (labor)
- causes contraction of the mammary gland
(lactation)
- also causes vasodilation
- also has a weak antidiuretic effect
- administered IV or intramuscularly
Medical uses
- induction of labor (uteral contraction)
- augmentation of labor (uteral contraction)
- treatment of postpartum hemorrhage (uteral
- 57 -
contraction)
- treatment of milk congestion (mammary
gland contraction)
Side effects
- hypotension (vasodilation)
- reflex tachycardia (hypotension)
- water retention (antidiuretic effect)
B) ERGOT ALKALOIDS
- 2 types

ERGOMETRINE General information
- found in the ergot fungus
- 5-HT 2 receptor agonist
- beta-2 adrenergic receptor antagonist
- also a D2 receptor agonist
- causes strong contraction of the uterine
smooth muscle
- also causes vasoconstriction
Medical uses
- treatment of postpartum hemorrhage
Side effects
- angina (vasoconstriction)
- nausea (stimulation of the chemoreceptive
trigger zone)
- vomiting (nausea)
- headache
- blurred vision
ERGOTAMINE General information

- see 34
C) PROSTAGLANDIN ANALOGUES
- 3 types
- 58 -
DINOPROST General information
- synthetic PGE2 analogue
- causes simultaneous contraction of the
uterus and relaxation of the cervix
- administered orally or intravaginally
Medical uses
- induction of labor
- 2nd trimester abortion
Side effects
- uterine pain
- nausea
- vomiting
CARBOPROST General information

- synthetic PGF2-alpha analogue
- same as dinoprostone
MISOPROSTOL General information

- see 37
2) TOCOLYTIC DRUGS
- inhibit uteral contraction
- 2 groups
A) OXYTOCIN RECEPTOR ANTAGONISTS

- 1 type

ATOSIBAN General information
- oxytocin receptor antagonist
- administered IV
Medical uses
- prevention of premature labor
Side effects
- nausea
- vomiting
- hyperglycemia
- 59 -
- skin rashes
B) SELECTIVE BETA-2 ADRENERGIC RECEPTOR AGONISTS

- inhibit uteral contraction, thus preventing premature labor
- see 19
- 60 -
36. PHARMACOLOGY OF THE RESPIRATORY TRACT
Overview
- asthma is a reversible obstructive disorder of the lungs
- asthma consists of 2 phases
PHASE DESCRIPTION
ACUTE PHASE - activation of mast cells mediated by IgE and
following secretion of cytokines
LATE PHASE - chemotaxis and activation of inflammatory cells

(especially eosinophils) and following secretion of
cytokines
- secreted cytokines include
CYTOKINE DESCRIPTION
ACUTE PHASE CYTOKINES - bronchoconstrictory cytokines
- chemotactic cytokines
LATE PHASE CYTOKINES - chemotactic cytokines

- inflammatory cytokines
- vasodilatory cytokines
- growth factors
- toxic proteins
BRONCHODILATOR DRUGS
Overview
- used to treat the early phase of asthma
Relevant Drugs
- 5 categories
1) BETA-2 ADRENERGIC RECEPTOR AGONISTS

- stimulates beta-2 adrenergic receptors, thus causing bronchodilation
- also inhibits release of bronchoconstrictors from activated mast cells
- administered by aerosol, orally or IV
- may pass onto the systemic circulation, thus may cause systemic side effects
- see 19
- 61 -
2) MUSCARINIC RECEPTOR ANTAGONISTS
- blocks muscarinic receptors (M3 receptors in this case), thus causing
bronchodilation and inhibition of bronchial hypersecretion
- administered by aerosol in conjunction with beta-2 adrenergic receptor
agonists
- do not pass into the systemic circulation, thus do not cause systemic side
effects
- see 15
3) HISTAMINERGIC H1 RECEPTOR ANTAGONISTS

- blocks histaminergic H1 receptors, thus causing bronchodilation and
vasoconstriction (decreased capillary permeability and following decreased
pulmonary transudation)
- administered in conjunction with beta-2 adrenergic receptor agonists
- see 33
4) CYSTEINYL-LEUKOTRIENE RECEPTOR ANTAGONISTS

- the bronchoconstrictory leukotrienes secreted by the activated mast cells act
on cysteinyl-leukotriene receptors
- cysteinyl-leukotriene receptor antagonists block the cysteinyl-leukotriene
receptors, thus causing bronchodilation
- administered in conjunction with beta-2 adrenergic receptor agonists
- 2 types

MONTELUKAST General information
Medical uses
- treatment of asthma
Side effects
- headache
- constipation/diarrhea
ZAFIRLUKAST General information

- same as montelukast
5) METHYLXANTHINES
- methylxanthines inhibit adenylyl cyclase, thus leading to decreased formation
of cAMP and following broncodilation
- 62 -
- see 48
ANTI-INFLAMMATORY DRUGS
Overview
- used to treat the late phase of asthma
Relevant Drugs
- 2 categories
1) GLUCOCORTICOIDS
- inhibit synthesis all the late phase cytokines (see above), thus decreasing
inflammatory cell chemotaxis, inflammation, edema (vasodilation/increased
capillary), hypertrophy/hyperplasia and bronchial epithelial damage
- see 55
2) CROMOGLICATE
- inhibits the neuronal respones of bronchial epithelial damage, thus causing
bronchodilation, decreased bronchosecretion and decreased cough
- also inhibits secretion of chemotactic cytokines by the inflammatory cells
- 2 types

CROMOGLICATE General information
- administered by aerosol in conjunction
with glucocorticoids
Medical uses
Side effects
- irritation of the upper airways
NEDOCROMIL SODIUM General information

- same as cromoglicate
ANTITUSSIVES
Overview
- antitussives (“cough suppressants”) are opioid analogues that depress the brain stem
(including the cough center), thus suppressing the cough reflex
- 63 -
Relevant Drugs
- 3 types

CODEINE General information
- see 49
DEXTROMETHORPHAN General information

- analgesic opioid analogue
- same as codeine
PHOLCODINE General information

- non-analgesic opioid analogue
- 64 -
37. PHARMACOLOGY OF THE GASTROINTESTINAL TRACT:
DRUGS IN THE TREATMENT OF PEPTIC ULCER;
EMETICS, ANTI-EMETICS
DRUGS IN THE TREATMENT OF PEPTIC ULCER
Overview
- the lumen of the GI tract is a very extreme environment consisting of extreme amounts of
potentially damaging substances
- to maintain the integrity of the intestinal mucosa there has to be a balance between the
protective- and the aggressive factors
- these factors include
TYPE FACTOR
PROTECTIVE FACTORS - mucin
- bicarbonate (HCO3-)
- blood flow
AGGRESSIVE FACTORS - hydrochloric acid (HCl)

- pepsin (gastric protease)
- gastric acid secretion by the parietal cells are regulated by 5 (3+2) substances
REGULATION SUBSTANCE
STIMULATION - acetylcholine
- gastrin
- histamine
INHIBITION - PGE2
- PGI2
Relevant Drugs
- 5 categories
- H2 receptor antagonists decrease histamine-mediated gastric acid secretion
- H2 receptors antagonists also inhibit the secondary messenger systems of
gastrin- and acetylcholine-mediated gastric acid secretion
- , thus H2 receptor antagonists may decrease basal- and pranial gastric acid
secretion by over 90%
- they also promote healing of duodenal ulcers by a separate mechanism
- see 33
- 65 -
- muscarinic receptor antagonists decrease acetylcholine-mediated gastric acid
secretion, thus decreasing both basal- and pranial gastric acid secretion
- see 15
3) HYDROGEN ION/POTASSIUM ANTIPORTER INHIBITORS

- hydrogen ion/potassium antiporter inhibitors irreversibly inhibit the hydrogen
ion/potassium antiporter responsible for secretion of hydrogen ions into the
parietal cell canaliculi, thus decreasing both basal- and pranial gastric acid
secretion
- 3 types

OMEPRAZOLE General information
- is degraded rapidly by the gastric
acid, thus must be administered in
enteric-coated granules for absorption
into the systemic circulation in the
small intestine
- weak base, thus, once reaching the
parietal cells through the systemic
circulation, it will be trapped in the
acidic environment of the parietal cell
canaliculi
Medical uses
- treatment of peptic ulcer
- treatment of hypergastrinemia
Side effects
- severe diarrhea
- severe headache
- mild gynecomastia
- mild impotence
- mild joint/muscle pain
LANSOPRAZOLE General information

- same as omeprazole
PANTOPRAZOLE General information

- same as omeprazole
- 66 -
4) ANTACIDS
- antacids chemically neutralize gastric acid
- pepsin is only active at very low pH, thus neutralization of pH secondarily
inactivates pepsin
- 4 types

MAGNESIUM HYDROXIDE General information
Medical uses
- treatment of duodenal ulcers (not
gastric-)
- treatment of dyspepsia
Side effects
- diarrhea
MAGNESIUM TRISILICATE General information

- also adsobs pepsin
- same as magnesium hydroxide
ALUMINIUM HYDROXIDE General information

- also adsorbs pepsin
Medical uses
Side effects
- constipation
SODIUM BICARBONATE General information

- very strong neutralizer (increase
gastric ph to 7,4 (!))
- deliberates carbondioxide
Medical uses
- 67 -
Side effects
- belching (deliberates carbondioxide)
- secondary hypergastrinemia
(stimulated by carbondioxide)
- metabolic alkalosis
5) MUCOPROTECTIVE DRUGS
- 3 types

SUCRALFATE General information
- binds to positively charged proteins
(including glycoproteins of the gastric
mucous)
- forms a complex gel with the gastric
mucous
Medical uses
- treatment of gastric ulcer
Side effects
- constipation
- dry mouth
- nausea
MISOPROSTOL General information

- synthetic PGE1 analogue
- inhibits both basal- and pranial
gastric acid secretion
- increases secretion of bicarbonate
and mucous
- increases mucosal blood flow
- also causes simultaneous contraction
of the uterus and relaxation of the
cervix
- administered orally or intravaginally
(if used for 1st trimester abortion)
Medical uses
- treatment of peptic ulcer
- 1st trimester abortion (then
administered coherently with
mifepristone, see 57)
- 68 -
Side effects
- diarrhea
- abdominal cramps
CARBENOXOLONE General information

- found in liquorice root
- increases production of mucous
Medical uses
- treatment of gastric ulcer
EMETICS
Overview
- emetics are used to induce vomiting in case of ingestion of toxic substances (poisons)
Relevant Drugs
- 1 type

IPECACUANHA General information
- contains 2 mucosal irritants (emetine and cephaeline), thus acting
peripherally to induce vomiting
ANTI-EMETICS
Overview
- anti-emetics suppress one or more parts of the emetic reflex arch, thus preventing vomiting
Relevant Drugs
- 5 categories
- H1 receptor antagonists inhibit H1 receptors of the vestibular nuclei in the
CNS, thus inhibiting histamine-mediated emesis due to motion (motion
sickness)
- they also inhibit H1 receptors of the nucleus of the solitary tract (relay
nucleus for noxious stimuli of the GI tract), thus inhibiting emesis due to
ingestion of toxic substances
- see 33
- 69 -
- same as H1 receptor antagonists, though it acts on muscarinic receptors
- see 15
3) 5-HT 3 RECEPTOR ANTAGONISTS

- 5-HT 3 receptor antagonists inhibits 5-HT 3 receptors in the chemoreceptive
trigger zone, thus inhibiting emesis due to all type of noxious stimuli
(including chemotherapy-induced emesis)
- see 34
4) D2 RECEPTOR ANTAGONISTS
- D2 (dopaminergic) receptor antagonists are really antipsychotic drugs (see
41)
- D2 receptor antagonists also inhibit D2 receptors on the chemoreceptive
trigger zone, thus inhibiting emesis due to all types of noxious stimuli
- 3 groups
A) PHENOTHIAZINES
- see 41
B) BUTYROPHENONES
- see 41
C) OTHERS
- 2 types

DOMPERIDONE General information
- also increases tone of GI
smooth muscle
Medical uses
- treatment of chemotherapy-
induced emesis
(increased tone of lower
esophageal sphincter)
- treatment of disorders of
gastric emptying (increased
tone of the stomach smooth
muscle)
Side effects
- see 41
- 70 -
METOCLOPRAMIDE General information
- also increases tone if the GI
smooth muscle
- also stimulates prolactin
release
- may not cross the blood-brain
barrier, central side effects are
absent
Medical uses
- same as domperidone
Side effects
- hyperprolactinemia (increased
prolactin secretion)
5) CANABINOID RECEPTOR AGONISTS

- inhibit emesis due to substances directly stimulating the chemoreceptive
trigger zone (including chemotherapy-induced emesis)
- also decrease acetylcholine secretion of the myenteric plexus, thus decreasing
peristalsis
- 2 types

NABILONE General information
- synthetic THC derivative (see
48)
Medical uses
- conjunctive to 5-HT 3- and/or
D2 receptor antagonists in
treatment of chemotherapy-
induced emesis
- treatment of diarrhea
(decreased peristalsis)
Side effects
- see 48
DRONABINOL General information

- same as nabilone
- 71 -
38. PHARMACOLOGY OF THE GASTROINTESTINAL TRACT:
PROKINETIC DRUGS, LAXATIVES, ANTIDIARRHOEAL
AGENTS, DRUG TREATMENT OF INFLAMMATORY
BOWEL DISEASE AND PARALYTIC ILEUS, DIGESTIVES,
DRUGS USED IN CHOLELITHIASIS
Overview
- peristalsis is driven by the parasympathetic nervous system (M2- and M3 muscarinic
receptors, see 14)
- the parasympathetic tone of the GI tract may be regulated in 2 ways
REGULATION RECEPTOR
STIMULATION - 5-HT 4 serotonergic receptors
INHIBITION - alpha-2 adrenergic receptors

- D2 dopaminergic receptors
- cannabinoid receptors
PROKINETIC DRUGS
Relevant Drugs
- 4 categories
1) LAXATIVES
- increase peristalsis without interfering with the normal neurohormonal
regulation
- 2 groups
A) BULK LAXATIVES (“FIBER”)

- bulk laxatives are polysaccaride polymers that are not broken down in
the GI tract
- they bind water physically in the intestinal lumen, thus increasing the
amount of feces left in the intestines
- this causes increased stretch of the wall of the GI tract, increased
activation of the cholinergic axons of the myenteric plexus, and
following increased peristalsis
- 3 types

METHYLCELLULOSE
- 72 -
BRAN
AGAR
B) OSMOTIC LAXATIVES
- osmotic laxatives are solutes that are not absorbed from the intestines
- they increase the colloid osmotic pressure of the intestinal lumen, thus
increasing the amount of water and following increased amount of
feces left in the intestines
- 3 types

LACTULOSE General information
- disaccaride of fructose and
galactose
- hydrolyzed and fermented by
bacteria to lactic- and acetic acid
which is not absorbed by the
enterocytes
Medical uses
- treatment of constipation
Side effects
- diarrhea
- flatulence
- abdominal cramps
MAGNESIUM SULFATE General information

- insoluble salt
Medical uses
Side effects
- diarrhea
MAGNESIUM HYDROXIDE General information

- same as magnesium sulfate
2) STIMULANT PURGATIVES
- 73 -
- increase GI secretion into the intestinal lumen, thus increasing the water
content and following amount of feces in the intestines
- also increase peristalsis

BISACODYL General information
- administered rectally
Medical uses
Side effects
- diarrhea
SODIUM PICOSULFATE General information

- same as bisacodyl
SENNA General information

- glycoside containing
anthracene derivatives
- hydrolyzed by bacteria to free
the antracene derivatives
- same as bisacodyl
3) PERISTALTICS
- fascilitate the parasymphatetic innervation of the intestines, thus increasing
acetylcholine release and following increased peristalsis
- 2 types
A) 5-HT 4 RECEPTOR AGONISTS

- see 34
B) D2 RECEPTOR ANTAGONISTS
- see 37
4) FECAL SOFTENERS
- decrease the surface tension of the feces, thus easing it’s transition through
the intestines
- 1 type

DOCUSATE SODIUM General information
- 74 -
- detergent
- also a weak laxative
Medical uses
ANTIDIARRHOEAL AGENTS
Relevant Drugs
- 3 categories
1) ORAL REHYDRATION
- solutions of water, sodium chloride (water follows sodium uptake), and
glucose (glucose enhances sodium uptake by the sodium/glucose
cotransporter system)
- see 33
2) ANTIMOTILITY AGENTS
- decrease peristaltic activity
- 3 groups
A) OPIOIDS
- increase the tone of smooth muscle of the GI generally and the
sphincters of the GI specially thus retarding the flow of the feces
- see 49
B) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS

- presynaptically inhibit release of acetylcholine, thus decreasing
peristalsis and following retardation of the flow of the feces
- see 19
C) BISMUTH SUBSALICYLATE
- decreases GI secretions, thus decreasing the flow of the feces
- may cause tinnitus and blackening of the feces (contains bismuth)
3) ADSORBENTS
- adsorb and bind microorganisms and toxins in the GI lumen that might be
responsible for the diarrhea
- 4 types

CHARCOAL
- 75 -
CHALK
PECTIN
MAGNESIUM ALUMINIUM SILICATE
DRUG TREATMENT OF INFLAMMATORY BOWEL DISEASE
Relevant Drugs
- 3 categories
1) 5-AMINOSALICYLIC ACID
- scavenges free radicals produced by neutrophils, thus decreasing the
inflammatory response
- 3 types

SULFASALAZINE General information
- 5-aminosalicylic acid combined with
sulfonamide sulfapyridine
Medical uses
- treatment of inflammatory bowel disease
- prophylaxis of inflammatory bowel disease
- treatment of rheumatoid arthritis (see 53)
Side effects
- diarrhea
- interstitial nephritis
- headache
- skin lesions
- leucopenia
MESALAZINE General information

- 5-aminosalicylic acid itself
- same as sulfasalazine
OLSALAZINE General information

- 2 diazo-linked 5-aminosalicylic acids
- same as sulfasalazine
- 76 -
2) GLUCOCORTICOIDS
- inhibit synthesis inflammatory cytokines, thus decreasing the inflammatory
response
- administered rectally
- see 36
3) IMMUNOSUPPRESSANTS
- powerfully suppress the immune defense system, thus decreasing the
- 2 types

AZATHIOPRINE
CICLOSPORIN
DRUG TREATMENT OF PARALYTIC ILEUS
Relevant Drugs
- 3 categories
1) MUSCARINIC RECEPTOR AGONISTS

- increase activity of GI tract smooth muscle, thus increasing peristalsis
- see 14
2) CHOLINESTERASE INHIBITORS
- inhibit cholinesterase, thus increasing acetylcholine half-life, increase activity
of GI smooth muscle, and following increase peristalsis
- see 14
3) 5-HT 4 RECEPTOR AGONISTS

- see above
DIGESTIVES
Overview
- digestives are supplements to normal substances of the GI preoccupied with digestion
- digestives are administered in case of maldigestions due to deficiency of any of these
substances
Relevant Drugs
- 3 categories
- 77 -
1) GASTRIC ACID SUPPLEMENTS
- 2 types

HYDROCHLORIC ACID General information
- given alone or together with pepsin
2) BILE SUPPLEMENTS
- 1 type

DIHYDROCHOLIC ACID General information
- increases production of bile
3) PANCREATIC ENZYME SUPPLEMENTS

- 3 types

LIPASE
TRYPSIN
AMYLASE
DRUGS USED IN CHOLELITHIASIS
Relevant Drugs
- 3 categories
1) BILE ACIDS
- form micelles around free cholesterol in the bile, thus preventing further
aggregation
- 2 types

CDCA Medical uses
(CHENODEOXYCHOLIC ACID) - treatment of cholesterol
cholelithiasis
UDCA General information
- 78 -
(URSODEOXYCHOLIC ACID) - same as CDCA

- decrease release of acetylcholine, thus decreasing cholic spasms
- see 15
3) OPIOIDS
- decrease pain associated with cholic spasms
- see above
- 79 -
39. ANTIANXIETY AND HYPNOTIC DRUGS
Overview
- anxiety is a fear response due to an appropriate stimulus
- the fear response is executed in the body by an extensive increase in noradrenalin release
- the fear response consists of 2 components
COMPONENT LOCATION
CENTRAL COMPONENT - locus ceruleus of the CNS
PERIPHERAL COMPONENT - the sympathetic nervous system
- anxiety disorder is a pathological fear response due to an inappropriate stimulus

- there are 3 main types of anxiety disorders
DISORDER DESCRIPTION
GENERALIZED ANXIETY DISORDER - chronic fear response without any
definite stimulus
PANIC DISORDER - extensive repeating attacks of fear

response
PHOBIA - fear response due to an inappropriate

stimulus
Relevant Drugs
- anxiety and sleep disorders are pharmacologically interconnected, thus normally (but not
necessary) drugs treating one may also be used in treating the other
- 4 categories
1) BENZODIAZEPINES
- bind to the allosteric seat of presynaptic GABA A receptors, thus facilitate
increased responsiveness to GABA
- GABA is an inhibitory neurotransmitter of the CNS, thus increased
responsiveness to GABA leads to increased inhibition of neuronal
transmission
- effects of benzodiazepines include
EFFECT DESCRIPTION
ANXIOLYTIC/ - inhibit adrenergic neurons of
ANTIAGGRESSIVE locus ceruleus
- 80 -
SEDATIVE - decrease time to fall asleep
- increase duration of sleep
- decrease REM sleep
- decrease slow wave sleep
ANTICONVULSIVE - decrease chemically induced

convulsions by convulsants
inhibiting GABA A receptors
ANTEROGRADE AMNESIC - obliterate memory of events

during their influence
MUSCLE TONE/ - unknown mechanism

COORDINATION DEPRESSANT
- benzodiazepines cause dependence by 2 out of the 4 mechanisms of

dependence of abuse-drugs (see 47)
MECHANISM CAUSE
TOLERANCE - downregulation of GABA A
receptors
NEGATIVE REINFORCEMENT - anxiety

- dizziness
- loss of appetite
- tremor
- convulsions
- the shorter-acting the benzodiazepines are, the more pronounced dependence

will occur
- 3 groups
A) SHORT-ACTING
- 12-18 hours
- 2 types

LORAZEPAM General information
- lipophilic, thus accumulate in fat over time
Medical uses
- treatment of insomnia (sleeping pills)
- 81 -
Side effects
- drowsiness
- sedation
- confusion
- amnesia
- impaired coordination
TEMAZEPAM General information

- same as lorazepam
B) INTERMEDIATELY-ACTING
- 18-24 hours
- 2 types

NITRAZEPAM General information
- same as lorazepam
ALPRAZOLAM General information

- same as lorazepam
- has an active metabolite, thus prolonging it’s
effect
- also has an antidepressive action
Medical uses
- treatment of depression (antidepressive
action)
Side effects
- same as lorazepam
B) LONG-ACTING
- 24-48 hours
- 2 types

DIAZEPAM General information
- same as lorazepam
- 82 -
- has an active metabolite (nordazepam)
- nordazepam has yet another active
metabolite (oxazepam), thus prolonging it’s
action even further
Medical uses
- treatment of excessive muscle tension
- treatment of status epilepticus (, then
administered IV)
Side effects
- same as lorazepam
CLONAZEPAM General information

- same as lorazepam
Medical uses
Side effects
- same as lorazepam
2) BARBITURATES
- general depressants of the CNS
- largely obsolete as anxiolytic- and hypnotic drugs
- are also abuse-drugs
- like any other abuse-drug they have 4 mechanisms by which they cause
dependence (see 47)
MECHANISM TYPE
POSITIVE REINFORCEMENT - see 47
CONDITIONING - see 47
TOLERANCE - upregulation of the hepatic

cytochrome P450 system (the
enzyme system by which they are
metabolized)
NEGATIVE REINFORCEMENT - hallucinations

- same as benzodiazepines
- 83 -
- 3 groups
A) SHORT-ACTING
- less than 1 hour
- 2 types

METOHEXITAL General information
- administered IV
- lipophilic, thus accumulate in adipose
tissue over time
Medical uses
- induction of general anaesthesia
Side effects
- euphoria
- drowsiness (sedation)
- respiratory depression
- cardiovascular depression
- death (if overdosed)
THIOPENTAL General information

- same as metohexital
- 1-6 hours
- 2 types

PENTOBARBITAL General information
- not especially lipophilic, thus will not
accumulate in adipose tissue
Medical uses
- treatment of insomnia
Side effects
- 84 -
BUTOBARBITAL General information
- same as pentobarbital
B) LONG-ACTING
- 6-12 hours
- 1 type

PHENOBARBITAL General information
- same as pentobarbital
Medical uses
- treatment of epileptic convulsions
Side effects
3) 5-HT 1 AGONISTS
- bind to presynaptic 5-HT 1 receptors, thus increasing inhibition of neuronal
transmission (including locus ceruleus) and following anxiolysis
- their effect takes weeks to develop, thus are ineffective in panic
- also have an arousing effect, thus are ineffective in sedation
- see 34
3) NON-SELECTIVE BETA ADRENERGIC RECEPTOR ANTAGONISTS

- inhibit the systemic sympathetic response to anxiety
- see 21
- 85 -
40. ALCOHOLS: PHARMACOLOGY AND TOXICOLOGY
ETHANOL
Overview
- ethanol is a low potency abuse-drug
- it has 3 effects on CNS neuronal transmission
EFFECT DESCRIPTION
FACILITATION OF GABA-A RECEPTORS - facilitation of GABA-mediated
neuronal inhibition
INHIBITION OF NMDA RECEPTORS - inhibition of glutamate-mediated

neuronal excitation
INHIBITION OF VOLTAGE-GATED - presynaptic inhibition of

CALCIUM CHANNELS neurotransmitter release
- the effects of ethanol consumption are classified according to the circulating amount of
ethanol
QUANTITY EFFECT
50 MG/100 ML - decreased intellectual function
- decreased motor coordination
- increased self-confidence
- euphoria
150 MG/100 ML - all of the effects above

- melancholy
- aggression
- submission
300 MG/100 ML - coma
500 MG/100 ML - cessation of respiration

- death
- , thus the overall effect closely resembles that of general anaesthetics (see 43)
- like any other abuse-drug it has 4 mechanisms by which it causes dependence (see 47)
- 86 -
MECHANISM CAUSE
POSITIVE REINFORCEMENT - inhibition of voltage-gated calcium
channels, thus inhibiting release of
inhibitory neurotrasmitters that
regulate the mesolimbic-mesocortical
dopaminergic pathway
TOLERANCE - downregulation of GABA-A

receptors
- upregulation of NMDA receptors
- upregulation of voltage-gated
calcium channels
NEGATIVE REINFORCEMENT - tremor

- nausea
- sweating
- fever
- epilepsy-like seizures
- hallucinations
- confusion
- agitation
- aggression
- it is used orally and is absorbed by the mucosa of the stomach and the small intestine
- 90% is metabolized in the liver, while the remaining 10% is excreted unchanged by the
kidneys and lungs
- metabolism of ethanol is done in 2 steps
ETHANOL
alcohol dehydrogenase
ACETALDEHYDE
aldehyde dehydrogenase
ACETIC ACID
- both of the enzymes envolved in is dependent on NAD+ as a cofactor for its enzymatic
action, thus the availability of NAD+ is the rate-limiting factor of ethanol metabolism
- 87 -
- for the same reason hepatic metabolism of ethanol exhibit early saturation kinetics, thus if
high amounts of alcohol is absorbed (eg. if empty stomach) most of it will escape first-pass
metabolism
- consequences of ethanol consumption include
LOCATION EFFECT
CNS - ventricular enlargement
- cerebellar neuronal degeneration
- dementia
PERIPHERAL NERVOUS SYSTEM - periphral neuropathy
BLOOD VESSELS - cutaneous vasodilation (gives the

perception of being warm though a
great heat loss is occurring)
LIVER - alcoholic hepatitis

- jaundice/cirrhosis
GI TRACT - increased gastic acid secretion by

the parietal cells of the stomach
- peptic ulcer
- gastritis
ENDOCRINE SYSTEM - increased ACTH secretion by the

pituitary gland
- secondary adrenocortical
hyperactivity
- immunosuppression
- decreased ADH secretion by the

pituitary gland
- increased urinary output
- decreased oxytocin secretion by the

pituitary gland (females)
- delayed labor at term
- decreased testosterone production in

the testes (males)
- impotence
- femininization
GENITO-URINARY TRACT - severe teratogenesis

- alcohol-related neurodevelopmental
disorder (decreased brain size,
- 88 -
decreased intellectual function,
decreased motor coordination)
- fetal alcohol syndrome (mental
retardation, hyperactivity, decreased
brain size, retardation of growth,
abnormal facial development)
METHANOL
Overview
- methanol is metabolized by the same enzymes as ethanol
METHANOL
alcohol dehydrogenase
FORMALDEHYDE
FORMIC ACID
- formaldehyde is extremely reactive binding covalently to proteins, especially enzymes of the

citric acid cycle, thus inactivating them
- this leads to severe lactic acidosis
- methanol may also be converted to formaldehyde by retinol dehydrogenase in the retina, thus
causing blindness
- 89 -
41. ANTIPSYCHOTIC DRUGS
Overview
- there are 3 main D2 dopaminergic pathways of the CNS
PATHWAY DESCRIPTION
MESOLIMBIC-MESOCORTICAL - between the midbrain, hippocampus and
PATHWAY cerebral cortex
- “reward center”
NIGROSTRIATAL PATHWAY - between substantia nigra and corpus

striatum
- facilitates voluntary movement
TUBEROINFUNDIBULAR PATHWAY - between hypothalamus and pituitary

gland
- inhibits pituitary secretion of prolactin
and GH
- schizophrenia is the major type of psychosis

- it is due to hyperactivity of the mesolimbic-mesocortical pathway
- there are 4 groups of symptoms of schizophrenia
GROUP DESCRIPTION
POSITIVE SYMPTOMS General information
- mental processes absent in well
individuals, but present in schizophrenia
Symptoms
- delusion
- hallucination
- disturbance of thinking
- aggression
NEGATIVE SYMPTOMS General information

- mental processes present in well
individuals, but absent in schizophrenia
Symptoms
- isolation
- apathy/anhedonia
- memory impairment
- 90 -
- intellectual impairment
- speech impairment
ANXIETY General information

- see 39
BIPOLAR DEPRESSION General information

- see 42
Relevant Drugs
- antipsychotic drugs are D2 receptor antagonists
- they work by decreasing the activity of the mesolimbic-mesocortical pathway, thus
decreasing the positive symptoms of schizophrenia
- however, the negative symptoms remain unaffected
- their antipsychotic effect takes weeks to develop
- they are effective in 70% of the cases, while ineffective in the last 30% (treatment-resistant
schizophrenia, the cause is unknown)
- the effective dose is also highly variable, thus administration must be adjusted on a trial-and-
error basis
- antipsychotic drugs are administered orally or intramuscularly (, then esterified with
heptanoic or decanoic acid to increase lipophilicity)
- they also cause upregulation of D2 receptor expression, thus decreasing their effectiveness
over time
- they are also partial muscarinic-, alpha-adrenergic-, H1-, and 5-HT 2 antagonists to varying
degree
- general side effects of antipsychotic drugs include
SIDE EFFECTS DESCRIPTION

MESOLIMBIC-MESOCORTICAL SIDE EFFECTS - sedation
- confusion
- coma (if overdosed)
NIGROSTRIATAL SIDE EFFECTS - acute dystonias (acute

reversible involuntary
movements including muscle
spasms, torticollis and
protruding tongue due to
antagonism of the nigrostriatal
pathway)
- tardive dyskinesia (delayed
irreversible involuntary
movements of the face and
tongue due to upregulation of
D2 receptors in the nigrostratal
pathway)
- convulsions (if overdosed)
- 91 -
TUBEROINFUNDIBULAR SIDE EFFECTS - hyperprolactinemia
- lactation (even in males (!))
- gynecomastia
- amenorrhea
- impotence (males)
- infertility (females)
MUSCARINIC RECEPTOR SIDE EFFECTS - see 15
ALPHA-ADRENERGIC SIDE EFFECTS - see 20
5-HT 2 SIDE EFFECTS - see 34
OTHER SIDE EFFECTS - cholestatic jaundice

- skin photosensitivity
- 2 categories
1) CLASSIC ANTIPSYCHOTIC DRUGS

- exhibit most (if not all) of the side effects of antipsychotic drugs
- 2 groups
A) PHENOTHIAZINES
- 2 types

CHLOROPROMAZINE Medical uses
- treatment of schizophrenia
- treatment of huntington’s
disease (see 46)
- treatment of chemotherapy-
indiced emesis (see 37)
Side effects
- see above
THIORIDAZINE General information

- same as chloropromazine
B) BUTYROPHENONES
- 2 types
- 92 -
HALOPERIDOL General information
DROPERIDOL General information

2) ATYPICAL ANTIPSYCHOTIC DRUGS

- have increased muscarinic receptor antagonist activity, thus magnifying this
side effect
- however, this also counteracts the nigrastriatal side effects
- 4 types

SULPIRIDE
RISPERIDONE
CLOZAPINE General information

- also shows a tendency to treat
negative symptoms and
treatment-resistant
schizophrenia
OLANZAPINE General information

- same as clozapine
- 93 -
42. ANTIDEPRESSANTS
Overview
- there are 3 types of monoamine neurotransmitters
TYPE DESCRIPTION
SEROTONIN - see 34
NORADRENALINE - see 18
DOPAMINE - see 41
- not relevant in depression
- depression is a disorder of mood due to functional deficit of monoamine neurotransmitters

(primarily serotonin)
- there are 2 types of depression
TYPE DESCRIPTION
UNIPOLAR DEPRESSION
BIPOLAR DEPRESSION - “manic depression”

- alteration between depression and mania every 2-3
weeks
- there are 2 groups of symptoms of depression
GROUP DESCRIPTION
EMOTIONAL SYMPTOMS - misery
- apathy
- pessimism
- low self esteem
- loss of motivation
- indecisiveness
BIOLOGICAL SYMPTOMS - retardation of thought

- loss of libido
- loss of appetite
- sleep disturbance
- 94 -
Relevant Drugs
- 3 categories
1) TRICYCLIC ANTIDEPRESSANS (TCAS)

- TCAs are competitive non-selective monoamine uptake 1 inhibitors, thus
inhibiting reuptake of monoamines released into the synaptic cleft (see 17)
- they have active metabolites, thus increasing their effectiveness and duration
of action
- they also downregulate presynaptic autoreceptors, thus further increasing their
effectiveness
- their antidepressive effect takes weeks to develop due to latency in receptor
downregulation
- they are administered orally
- they are lipophilic, thus accumulate in adipose tissue over time
- they are also partial muscarinic receptor antagonists, thus having atropine-like
side effects
- general side effects of TCAs may be divided in 2 groups
SIDE EFFECT DESCRIPTION

CNS SIDE EFFECTS Therapeutic dose
- sedation
- confusion
- orthostatic hypotension
(hyperactivity of the vasomotor center
of the CNS)
Overdose
- excitement
- delirium
- convulsions
- coma
PERIPHERAL SIDE EFFECTS Therapeutic dose

- muscarinic receptor antagonist side
effects (see 15)
- ECG disorders (prolongation of QT
interval)
- impotence
Overdose
- ventricular fibrillation (prolongation
of QT interval
- death (ventricular fibrillation)
- 95 -
- 2 groups
A) NON-SELECTIVE TCAS
- 2 types

IMIPRAMINE
AMITRIPTYLINE
B) NORADRENALINE-SELECTIVE TCAS
- 2 types

DESIPRAMINE
CLOMIPRAMINE
2) SEROTONIN-SELECTIVE UPTAKE 1 INHIBITORS

- inhibits serotonin reuptake by monoamine uptake 1 specifically
- like TCAs, their antidepressive effect takes weeks to develop
- 4 types

FLUOXETINE General information
Medical uses
- treatment of depression
- treatment of obsessive-compulsive
disorders
Side effects
- nausea
- anorexia
- insomnia
- decreased libido
- failure of orgasm
FLUVOXAMINE General information
- 96 -
- same as fluoxetine
PAROXETINE General information

SERTALINE General information

3) MONOAMINE OXIDASE INHIBITORS (MAOIS)

- MAOIs allosterically inhibit enzymatic catabolism of monoamines by
monoamine oxidase in the presynaptic neuronal cytoplasm
- this increases cytoplasmic concentration of monoamines, and following
passive diffusion of monoamines into the synaptic cleft (see 17)
- like TCAs, they also downregulate presynaptic autoreceptors, thus increasing
their effectiveness
- their antidepressive effect takes weeks to develop due to latency in receptor
downregulation
- 2 groups
A) IRREVERSIBLE MAOIS
- 3 types

PHENELZINE General information
Medical uses
- treatment of depression
Side effects
- excitement
- insomnia
- tremor
- convulsions (if overdose)
- increased appetite
- weight gain
- atropine-like side effects
- severe hypertension (if simultaneous
administration of indirectly acting
sympatomimetics (see 17))
IPRONIAZID General information

- same as phenelzine
- 97 -
TRANYLCYPROMINE General information
B) REVERSIBLE MAOIS
- 1 type

MOCLOBEMIDE General information
- 98 -
43. GENERAL ANAESTHETICS
Overview
- general anaesthetics act by decreasing excitatory neurotransmitter release and decreasing the
postsynaptic excitability in response to those excitatory neurotransmitters
- this is done by binding to the hydrophobic domains of ligand-gated ion channels of neurons,
thus inhibiting their depolarization
- there are 4 stages of anaesthesia
STAGE DESCRIPTION
STAGE I “Analgesia”
- conscious
- drowsy
- amnesic
- voluntary movement is still present
- coherent speech is still present
- reduced reaction to stimuli
STAGE II “Excitement”
- loss of consciousness
- delirious
- involuntary movement
- incoherent speech
- loss of reaction to non-painful stimuli
- reflex reactions to painful stimuli
- exaggerated reflexes
- irregular respiration
- irregular heart rate
STAGE III “Surgical anaesthesia”

- loss of movement
- loss of speech
- regular respiration
- regular heart rate
- muscle tone is still present
STAGE IV “Overdose”
- medullary paralysis
- cessation of respiration
- cardiovascular collapse
- cessation of muscle tone
- death
- 99 -
Relevant Drugs
- 2 categories
1) INHALATION ANAESTHETICS
- inhalation anaesthetics are volatile gasses
- they enter and leave the systemic circulation through the pulmonary capillaries
- the pharmacokinetic aspects of inhalation anaesthetics are primarily given by
2 parameters
PARAMETER DESCRIPTION
OIL/GAS PARTITION General information
COEFFICIENT - the oil/gas partition coefficient describes
the solubility of the gas in oil (ie. the
lipophilicity of the inhalation anaesthetic)
- partially or completely determines 2 of
the characteristics of the inhalation
anaesthetics
Potency
- the higher the oil/gas partition
coefficient is, the more efficacious it can
bind to the hydrophobic domains of the
ligand-gated ion channels to produce
general anaesthesia
- , thus the higher the oil/gas partition
coefficient is, the smaller alveolar partial
pressure of the inhalation anaesthetics is
needed to produce general anaesthesia
Recovery
- however, higher oil/gas partial pressure
also results in higher amounts of gas to be
redistributed to adipose tissue by
secondary distribution
- , thus the higher the oil/gas partition
coefficient is, the longer time is needed
for it’s elimination
BLOOD/GAS PARTITION General information

COEFFICIENT - the blood/gas partition coefficient
describe the solubility of the gas in blood
(ie. the hydrophilicity of the inhalation
anaesthetic)
- partially or completely determines 2 of
the characteristics of the inhalation
anaesthetics
- 100 -
Induction
- the higher the blood/gas partition
coefficient is, the more gas is needed to be
dissolved in blood before it can diffuse out
of the blood stream and into the neurons
to produce general anaesthesia
- , thus the higher the blood/gas partition
coefficient is, the longer time is needed to
produce general anaesthesia
Recovery
- also, the higher the blood/gas partition
coefficient is, the more gas is dissolved in
blood
- , thus the higher the blood/gas partition
coefficient is, the longer time is needed
for it’s elimination
- , thus inhalation anaesthetics ideally need to exhibit of moderate oil/gas

partition coefficient (for as little alveolar partial pressure of inhalation
anaesthetic as possible needed, with as little redistribution to adipose tissue as
possible) and of small blood/gas partition coefficient (for as little solubility in
blood as possible)
- inhalation anaesthetics are usually used for maintenance of general anaesthesia
- 6 types (listed from high potency with slow induction and slow recovery to
low potency with fast induction and fast recovery)

ETHER General information
- has paralytic properties
- has analgesic properties
- large blood/gas partition coefficient
(slow induction and slow recovery)
- large oil/gas partition coefficient (high
potency, but even slower recovery)
- highly explosive
Side effects
- irritation of the respiratory tract
- postoperative nausea and vomiting (long
recovery)
HALOTHANE General information

- intermediate blood/gas partition
coefficient (intermediate induction and
- 101 -
intermediate recovery)
- high oil/gas partition coefficient (high
potency and slower recovery)
- is the only inhalation anaesthetic that is
notably metabolized by the liver (30%)
- metabolites (mainly trifluoroacetic acid)
binds covalently to proteins of the liver
Side effects
- hypotension (vasodilation and
myocardial depression)
- ventricular extrasystoles (myocardial
sensitization to adrenaline)
- malignant hyperthermia (excessive
calcium release from skeletal muscle
sarcoplasmic reticulum)
- hepatic failure (immune reaction to
trifluoroacetic acid-bound proteins)
recovery)
ENFLURANE General information

- intermediate blood/gas partition
coefficient (intermediate induction and
intermediate recovery)
- intermediate oil/gas partition coefficient
(intermediate potency and intermediate
recovery)
Side effects
- hypotension
- ventricular extrasystoles
- malignant hyperthermia
- seizures
ISOFLURANE General information

- irritate the respiratory tract
- same as eflurane (but no seizures)
SEVOFLURANE General information

- low blood/gas partition coefficient (fast
induction and fast recovery)
- low oil/gas partition coefficient (low
potency and fast recovery)
- same as isoflurane (but no irritation of
the respiratory tract)
- 102 -
NITROUS OXIDE General information
- low blood/gas partition coefficient (fast
induction and fast recovery)
- very low oil/gas partition coefficient
(very low potency and fast recovery)
- can only be used as an adjunct to other
general anaesthetics (very low potency)
- inhibits methionine synthase if
administered for more than 6 hours, thus
decreasing DNA- and protein synthesis
Side effects
- anemia (bone marrow depression due to
decreased DNA synthesis)
- leucopenia (bone marrow depression)
2) INTRAVENOUS ANAESTHETICS
- causes much faster induction of general anaesthesia than inhalation
anaesthetics (less that 20 seconds) due to their direct introduction into the
circulatory system
- however, they also are very short-acting (5-10 minutes) due to their high
lipophilicity and following rapid redistribution to adipose tissue
- from this point on, recovery is solely given by hepatic metabolism
- , thus intravenous anaesthetics are usually used for induction of anaesthesia
- 5 types (listed from fast induction and slow recovery to slow induction and
fast recovery)

METOHEXITAL General information
- slowly metabolized (slow recovery)
- a short-acting barbiturate (see 39)
THIOPENTAL General information

ETOMIDATE General information

- intermediately metabolized
(intermediate recovery)
Side effects
recovery)
- adrenal cortical suppression
- 103 -
FENTADYL General information
- rapidly metabolized (fast recovery)
- synthetic opioid derivative (see 50)
- may be used as a general anaesthetic
alone by continuous infusion
- also used for analgesia
Side effects
- see 50
KETAMINE General information

- phencyclidine analogue (see 48)
- produces dissociative anaesthesia
(analgesia, amnesia, paralysis, and
relative sensory loss, without loss of
consciousness (!))
- may be used as a general anaesthetic
agent alone by continuous infusion
Side effects
- see 48
- 104 -
44. ANTIEPILEPTIC DRUGS
Overview
- epilepsy is a neurologic disorder characterized by epileptic seizures
- epileptic seizures are sudden high frequency neuronal discharges (hyperactivity) in the CNS
- there are 2 groups of epileptic seizures
TYPE DESCRIPTION
PARTIAL SEIZURES General information
- localized seizure not exceeding the cerebral
hemisphere from which it originates
- 2 types
Simple Seizure
- the seizure stays in it’s location of origin
- no loss of consciousness
- symptoms depend on where the seizure is located
(motor seizure, sensory seizure, autonomic seizure,
psychomotor seizure etc.)
Complex seizure
- the seizure spreads from it’s location of origin to other
areas of the CNS, including the reticular formation
- loss of consciousness (hyperactivity of the reticular
formation)
- symptoms depend on where the seizure originates
from and where it spreads
GERERALISED SEIZURES General information

- global seizure involving both hemispheres
- 2 types
Grand mal seizures

- “tonic-clonic seizures”
- rigid extensor spasm
- cessation of respiration
- micturition
- defecation
- salivation
- all of this is followed by series of violent synchronous
jerks that gradually dies out
- 105 -
Petit mal seizures
- “absence seizures”
- rhythmic oscillating seizure of thalamic relay neurons
- vacant stare
- no motor abnormalities
- the exact pathophysiological origin of epilepsy is unknown, and the same applies to the
pharmacological mechanisms of the drugs used to treat it
Relevant Drugs
- 3 categories
1) DRUGS AFFECTING PARTIAL- AND GRAND MAL SEIZURES

- 3 types

PHENYTOIN General information
- inhibits sodium channels, thus blocking the
initiation and propagation of action potentials
- use dependent, thus inhibiting more efficacious
sodium channels that more frequently open (eg.
sodium channels of seizure-affected neurons)
- metabolized by the liver
- causes induction of hepatic enzymes, thus
causing increased metabolism of itself and
following tolerance over time
Medical uses
- treatment of partial- and grand mal epileptic
seizures
- treatment of cardiac arrhythmias (see 29)
Side effects
- vertigo
- ataxia
- nystagmus
- headache
- confusion
- intellectual deterioration
- gum hypertrophy
- hirsutism (abnormal growth of body hair, due
to increased androgen secretion)
- macrocytic, hyperchromic anemia (disorder of
- 106 -
folate metabolism)
- skin rashes
- teratogenesis
CARBAMAZEPINE General information

- also mood-stabilizing
- same as phenytoin
Medical uses
- treatment of partial- and grand mal epileptic
seizures
- treatment of manic depression (mood
stabilizer)
Side effects
- sedation
- ataxia
- mental deterioration
- water retention
- leucopenia (bone marrow depression)
- skin rashes
PHENOBARBITAL General information

- a barbiturate
- also facilitates increased sensitivity of GABA
A receptors, thus increasing inhibition of
excitatory neurotransmission
- see 39
2) DRUGS AFFECTING PETIT MAL SEIZURES

- 1 type

ETHOSUXIMIDE General information
- inhibits T-type calcium channels, thus
blocking rhythmic oscillations of thalamic relay
neurons
Medical uses
- treatment of petit mal seizure
Side effects
- 107 -
- vertigo
- nausea
- apathy
- anorexia
3) DRUGS AFFECTING ALL TYPES OF EPILEPTIC SEIZURES

- 2 types

VALPROATE General information
- fascilitates increased sensitivity of GABA A
receptors, thus increasing inhibition of
excitatory neurotransmission
- also inhibits GABA transaminase, thus
decreasing inactivation of GABA in the
neuromuscular junction and following even
stronger inhibition of excitatory
neurotransmission
- also inhibits sodium channels, thus blocking
the initiation and propagation of action
potentials
- also mood-stabilizing
Medical uses
- administered in conjunction with other
antiepileptic drugs in treatment of all types of
epilepsy
- treatment of manic depression (mood
stabilizer)
Side effects
- hair loss
- liver damage
- teratogenesis
LONG-ACTING General information

BENZODIAZEPINES - see 39
- 108 -
45. CENTRAL NERVOUS SYSTEM STIMULANTS AND
NOOTROPIC AGENTS
CENTRAL NERVOUS SYSTEM STIMULANTS
Overview
- see 48
NOOTROPIC AGENTS
Overview
- nootropic drugs are drugs that enhance the intellectual capacity
- they act by one or more of 4 mechanisms
MECHANISM DESCRIPTION
ENHANCEMENT OF CEREBRAL - increasing cerebral blood flow (vasodilation)
MICROCIRCULATION - increasing RBC plasticity
- inhibiting platelet aggregation
- reducing blood viscosity
ENHANCEMENT OF CEREBRAL - increasing cerebral energy supply

METABOLISM - enhancing cerebral energy utilization
ENHANCEMENT OF CEREBRAL - increasing availability and/or effect of

NEUROTRANSMISSION acetylcholine
- increasing availability and/or effect of
monoamines (see 42)
NEUROPROTECTION - neutralizing free radicals (“antioxidation”)
Relevant Drugs
- 3 types

PIRACETAM General information
- enhances cerebral microcirculation
- enhances cerebral metabolism
- enhances cerebral neurotransmission (acetylcholine)
- neuroprotective
- 109 -
Medical uses
- treatment of stroke
- treatment of dementia (including alzheimer’s disease, see 46)
Side effects
- hyperactivity
- insomnia
VINPOCETINE General information

- enhances cerebral metabolism
- administered IV
Medical uses
- treatment of perfusion disorders of the eye and the inner ear
(including tinnitus)
Side effects
- hypotension
- tachycardia
PENTOXYFILLINE General information

- theobromine derivative (see 48)
Medical uses
- treatment of perfusion disorders of the eye and the inner ear
Side effects
- hypotension
- cardiac arrythmias
- dizziness
- 110 -
46. DRUG TREATMENT OF NEURODEGENERATIVE
DISORDERS. CENTRALLY-ACTING MUSCLE
RELAXANTS
DRUG TREATMENT OF NEURODEGENERATIVE DISORDERS
Overview
- there are 3 main types of neurodegenerative disorders
TYPE
ALZHEIMER’S DISEASE
PARKINSON’S DISEASE
HUNTINGTON’S DISEASE
ALZHEIMER’S DISEASE
Overview
- alzheimer’s disease is a progressive dementia of idiopathic origin
- it occurs primarily due to loss of neurons in 2 locations of the CNS
LOCATION NEURONS AFFECTED

HIPPOCAMPUS - unselective neuronal loss
BASAL FOREBRAIN - cholinergic neuronal loss
Relevant Drugs
- 2 categories
1) CHOLINESTERASE INHIBITORS
- cholinesterase inhibitors inhibit cholinesterase in the cholinergic synapses,
thus inhibiting acetylcholine breakdown and following increased acetylcholine
concentration in those synapses (see 14)
- however, different cholinesterase inhibitors are used centrally to treat
alzheimer’s disease than those used peripherally to treat peripheral disorders
- 4 types
- 111 -
TACRINE Side effects
- cholinergic side effects (see 14)
- hepatotoxicity
DONEPEZIL Side effects

- cholinergic side-effects
RIVASTIGMINE General information

- selective for the CNS
GALANTHAMINE General information

- also an nicotinic acetylcholine receptor allosteric
activator (see 14)
Side effects
- cholinergic side-effects
2) NOOTROPIC DRUGS
- enhances the intellectual capacity, thus counteracting the dementia
- see 45
PARKINSON’S DISEASE
Overview
- parkinson’s disease is a progressive motility disorder
- it occurs primarily due to loss of dopaminergic neurons running from substantia nigra to
corpus striatum (“nigrostriatal tract”, see 41)
- these dopaminergic neurons are inhibitory neurons that act on D2 receptors of cholinergic
neurons in the corpus striatum, thus loss of inhibition causes hyperactivity of these
cholinergic neurons
- parkinson’s disease is characterized by 3 (4) symptoms
SYMPTOM DESCRIPTION
HYPOKINESIA - voluntary movement is hard to initiate and -to stop
- due to loss of dopaminergic neurons
TREMOR - at rest
- due to hyperactivity of cholinergic neurons
RIGIDITY - increased resistance to voluntary movement

- due to loss of dopaminergic neurons and hyperactivity of
cholinergic neurons
- 112 -
(DEMENTIA) - decreased mental capacity
- due to loss of other types of neurons elsewhere in the CNS
- biosynthesis and breakdown of dopamine is done in 5 steps (similar to that of

catecholamines, see 17)
TYROSINE
tyrosine hydroxylase
L-DOPA
DOPA decarboxylase
DOPAMINE
MAO (MAO-A peripherally, MAO-B centrally)
3,4-DIHYDROXYPHENYLACETALDEHYDE
3,4-DIHYDROXYPHENYLACETIC ACID
COMT
HOMOVANILLIC ACID
Relevant Drugs
- 2 categories
1) DOPAMINE REPLENISHERS
- 4 types

L-DOPA General information
- precursor of dopamine
- increases dopamine biosynthesis
- coadministered with carbidopa (a peripheral
DOPA decarboxylase inhibitor, see 17) to inibit
peripheral use of dopamine
- causes downregulation of dopamine receptors,
thus tolerance will develop over time
Side effects
- dyskinesia (involuntary movements of face and
limbs)
- on-off effect (rapid fluctuations of symptoms)
- schizophrenia-like syndrome (see 41)
- nausea
- 113 -
- anorexia
SELEGILINE General information

- selective MAO-B inhibitor (, thus only acts in
the CNS, see 17)
- decreases central monoamine breakdown
ENTACAPONE General information

- COMT inhibitor
- decreases central- and peripheral monoamine
breakdown
AMANTIDINE General information

- antiviral drug
- increases presynaptic dopamine release and
decreases presynaptic dopamine reuptake
2) D2 RECEPTOR AGONISTS
- 3 types

BROMOCRIPTINE Medical uses
- treatment of galactorrhea
- treatment of gynecomastia
- treatment of parkinson’s disease
LISURIDE
PERGOLIDE

- block muscarinic receptors, thus inhibiting the effect of the hyperactive
cholinergic neurons in the corpus striatum
- see 15
HUNTINGTON’S DISEASE
Overview
- huntington’s disease is, like parkinson’s disease, a progressive motility disorder
- 114 -
- however, huntington’s disease is due to loss of GABA neurons running in opposite direction
to that of the dopaminergic neurons affected in parkinson’s disease (from corpus striatum to
substantia nigra)
- these GABA neurons are inhibitory neurons of the dopaminergic neurons in the substantia
nigra, thus loss of inhibition causes hyperactivity of these dopaminergic neurons
- , thus huntington’s disease exhibit opposite symptoms to that of parkinson’s disease
Relevant Drugs
- 2 categories
1) GABA AGONISTS
- 1 type

BACLOFEN
2) D2 RECEPTOR ANTAGONISTS
- “antipsychotic drugs”
- block D2 receptors, thus inhibiting the effect of the hyperactive dopaminergic
neurons
- see 41
CENTRALLY-ACTING MUSCLE RELAXANTS
Overview
- …
- 115 -
47. DRUG ABUSE AND DEPENDENCE: GENERAL
PRINCIPLES, OPIOIDS, ANTI-ANXIETY AND HYPNOTIC
DRUGS, INHALANTS, ETHANOL
Overview
- drug abuse is recurrent use of drugs that are illegal and/or cause harm to the subject of
interest
- drug dependence is the state of mind when drug use becomes compulsory (rather than
voluntarily) and takes precedence over other needs of the subject of interest
- drug dependence has 2 components
COMPONENT TYPE
PSYCHOLOGICAL DEPENDENCE Positive reinforcement
- occurs when the abuse-drug is used
- stimulation of the mesolimbic-
mesocortical dopaminergic pathway of the
CNS (reward center, see 41) and following
feeling of reward
Conditioning
- occurs when the abuse-drug is withdrawed
- the association of items, locations or
people with the abuse-drug induced feeling
of reward
PHYSIOLOGICAL DEPENDENCE Tolerance

- occurs when the abuse-drug is used
- physiological opposition of the
biochemical responses of the abuse-drug
over time, thus decreasing its effectiveness
- see 6
Negative reinforcement
- occurs when the abuse-drug is withdrawed
- the physiological result of the
physiological contradiction of the
biochemical responses of the abuse-drug,
when the abuse-drug is not used
OPIOIDS
Overview
- 116 -
- see 49
ANTI-ANXIETY AND HYPNOTIC DRUGS

Overview
- see 39
INHALANTS
Overview
- …
ETHANOL
Overview
- see 40
- 117 -
48. DRUG ABUSE AND DEPENDENCE: PSYCHOMOTOR
STIMULANTS, PSYCHEDELICS, CANNABIS
PSYCHOMOTOR STIMULANTS
Overview
- psychomotor stimulants are abuse-drugs that exhibit both physical- and psychological effects
in the subject of interest
Relevant Drugs
- 3 categories
1) AMPHETAMINE ANALOGUES
- amphetamines are abuse-drugs that fascilitate secretion of monoamines
(dopamine, noradrenaline and serotonin) into the synaptic cleft
- they are taken up by the neuron by way of the uptake 1 monoamine transporter
in exchange for cytoplasmic monoamines, thus facilitating the release of
monoamines
- further, they are taken up by the cytoplasmic neurotransmitter vesicles by the
way of VMAT in exchange for monoamines, thus displacing monoamines
from the neurotransmitter vesicles and into the cytoplasm
- the effects of amphetamines are classified according to the monoamines
released
MONOAMINE EFFECT
DOPAMINE Abuse dose
- euphoria
- pleasure
- excitement
- increased confidence
- increased sex drive
- increased mental performance
- increased physical performance
- insomnia
Overdose
- hallucinations
- paranoia
- aggression
NORADRENALINE - increased motor activity
SEROTONIN - anorexia
- 118 -
- like any other abuse-drug they have 4 mechanisms by which they cause
dependence (see 47)
MECHANISM CAUSE
POSITIVE REINFORCEMENT - release of dopamine, and following
stimulation of the mesolimbic-
mesocortical dopaminergic pathway
TOLERANCE - depletion of dopamine

- depletion on noradrenaline
(- depletion of serotonin)
NEGATIVE REINFORCEMENT - apathy

- axiety
- depression
- suicidality
- consequences of amphetamine consumption include
ORGAN EFFECT
HEART - tachycardia
- cardiac arrhythmias
BLOOD VESSELS - vasoconstriction

- hypertension
SKELETAL MUSCLE - tremor

- hyperthermia
ENDOCRINE SYSTEM - increased ADH secretion by the

pituitary gland
- hypotonic hypervolemia
UPON OVERDOSE - sudden death (even from just a

single moderate dose (!))
- 119 -
- they are used orally or nasally and absorbed from the nasal- and/or small
intestinal mucosa
- 6 types

AMPHETAMINE General information
- abuse-drug
Medical uses
- treatment of narcolepsy
- treatment of obesity
METHAMPHETAMINE General information

- “speed”
- abuse-drug
METHYLENEDIOXY- General information

METHAMPHETAMINE - “ecstasy”
- abuse-drug
MESACAINE General information

- abuse-drug
METHYLPHENIDATE Medical uses

- treatment of ADHD (paradoxically
(!))
FENFLURAMINE General information

- has a stronger action of serotonin
release, thus producing more
pronounced anorexia
2) COCAINE ANALOGUES
- cocaine is an abuse-drug found in coca leaves
- it inhibits presynaptic reuptake of monoamines uptake 1, thus increasing
monoamine concentration (dopamine and noradrenaline) in the synaptic cleft
- it also blocks sodium channels, thus is clinically used as a local surface
anaesthetic (see 22)
- the effects of cocaine are classified according to the monoamines increased in
the synaptic cleft
MONOAMINE EFFECT
DOPAMINE - euphoria
- pleasure
- 120 -
- garrulity
NORADRENALINE Abuse Dose

- increased motor activity
- hyperthermia
- tachycardia
- vasoconstriction
- hypertension
Overdose
- tremor
- convulsions
- vasomotor depression
- like any other abuse-drug it has 4 mechanisms by which it causes dependence

(see 47)
MECHANISM CAUSE
POSITIVE REINFORCEMENT - inhibition of presynaptic dopamine
reuptake, and following stimulation
of the mesolimbic-mesocortical
dopaminergic pathway
TOLERANCE - downregulation of dopaminergic

receptors
- downregulation of adrenergic
receptors
NEGATIVE REINFORCEMENT - dysphoria

- depression
- decreased mental performance
- decreased physical performance
- consequences of cocaine consumption include
ORGAN EFFECT
HEART - tachycardia
- cardiac arrhythmias
- 121 -
- myocardial damage
BLOOD VESSELS - vasoconstriction

- hypertension
- coronary- and/or cerebral artery
thrombosis
SKELETAL MUSCLE - tremor

- hyperthermia
UPON OVERDOSE - convulsions

- death
- 2 types

HYDROCHLORIDE SALT General information
COCAINE - “snow”
- abuse-drug
- used nasally or IV
FREE BASE COCAINE General information

- “crack”
- abuse-drug
- used by inhalation, nasally or IV
3) NICOTINE
- nicotine is an abuse-drug found in nicotiana (“tobacco”)
- tobacco is a compound substance consisting of several pharmacologically
active components
- the pharmacologically active components of tobacco are divided in 2 groups
according to the chemical phase of the components
A) SOLID PHASE COMPONENTS

- “particular phase components”
- include
TYPE DESCRIPTION
NICOTINE
- 122 -
POLYCYCLIC
AROMATIC
HYDROCARBONS
(TAR)
B) GASSEOUS PHASE COMPONENTS

- include
TYPE DESCRIPTION
CARBON MONOXIDE
NITROGEN DIOXIDE
HYDROGEN CYANIDE
AMMONIA
FORMALDEHYDE
NITROSAMIDES
- of these, nicotine is the most pharmacologically active component causing

both ALL the immediate effects and the ALL the mechanisms of dependence
of tobacco (see below)
- nicotine is a nicotinergic receptor agonist, thus causing excitation of
nicotinergic cholinergic receptors (see 14)
- the effects of nicotine are classified according to the nicotinergic receptor it
acts on
TYPE EFFECT
CNS TYPE - satiety
- analgesia
- sedation
- alertness
- increased physical performance
- decreased skeletal muscle tone
GANGLION TYPE - positive chronotropic effect

(increased heart rate)
- positive ionotropic effect
(increased force of heart contraction)
- vasoconstriction
- increased circulating free fatty
- 123 -
acids
- decreased glomerular filtration
- decreased peristalsis
- sweating
MUSCLE TYPE - increased skeletal muscle tone

(completely overridden by the
decreased skeletal muscle tone of the
CNS type nicotinergic receptors (see
above))
- like any other abuse-drug it has 4 mechanisms by which it causes dependence

(see 47)
MECHANISM CAUSE
POSITIVE REINFORCEMENT - stimulation of the mesolimbic-
mesocortical dopaminergic pathway
TOLERANCE - desensitization of nicotinic

receptors (partly opposed by a
simultaneous upregulation of the
same nicotinic receptors (!))
NEGATIVE REINFORCEMENT - irritability

- insomnia
- decreased physical performance
- consequences of tobacco consumption may be divided in 2 groups according

to the causative agents
A) CONSEQUENCES OF NICOTINE AND CARBON MONOXIDE

- include
TYPE CONSEQUENCE
CARDIOVASCULAR - hypertension
DISORDERS - hyperlipoproteinemia
- coronary- and/or cerebral artery
thrombosis
- gangrene
- 124 -
FETAL DISORDERS - spontaneous abortion
- placenta praevia (obstruction of the
cervical canal by the placenta)
- premature delivery
- increased perinatal death
- decreased birth weight
B) CONSEQUENCES OF TAR AND ALL OTHER GASSEOUS STATE

COMPONENTS
- include
TYPE CONSEQUENCE
PULMONARY - chronic obstructive pulmonary
DISORDERS disorders (COPD)
CANCERS - respiratory tract cancers

- oesophageal cancers
- pancreatic cancers
- urinary bladder cancers
4) CANNABIS
- cannabis is an abuse drug found in cannabis sativa (“hemp”)
- the pharmacologically active components of cannabis are cannabinoids
- there are 3 main types of cannabinoids
TYPE DESCRIPTION
THC - “delta-9 tetrahydrocannabinol”
- the only pharmacologically active
cannabinoid
CANNABIDOL - THC precursor
CANNABINOL - THC metabolite
- cannabinoids are cannabinoid receptor agonists

- there are 2 types of cannabinoid receptors
RECEPTOR TYPE LOCATION

CB1 RECEPTOR - mesolimbic-mesocortical pathway
- hippocampus
- substantia nigra
- crebellum
- 125 -
CB2 RECEPTOR - lymphoid system
- cannabinoid receptors inhibit adenylyl cyclase, thus leading to decreased

formation of cAMP
- cannabinoid receptors also activate potassium channels and inhibit calcium
channels, thus inhibiting neuronal depolarization and inhibiting release of
neurotransmitters respectively and following inhibition of neuronal
transmission
- the effects of cannabinoids include
ORGAN EFFECT
CNS - euphoria
- sensory amplification (visual-,
auditory- and tactile-)
- sedation
(with subjective perception of
increased mental performance)
- decreased motor coordination
- catalepsy
- analgesia
- antiemesis
- increased appetite
HEART - tachycardia
BLOOD VESSELS - vasodilation
EYES - decreased intraocular pressure

- blood-shot eyes (conjunctival
blood vessel vasodilation)
BRONCHI - bronchoconstriction
LYMPHOID SYSTEM - decreased immune function
GENITO-URINARY TRACT - teratogenesis

- decreased testosterone production
- decreased sperm production
- it causes little or no dependence
- 126 -
- it is used by inhalation, orally or IV
- it is lipophilic, thus will accumulate in adipose tissue over time
- 2 types
TYPE DESCRIPTION
MARIJUANA General information
- dried leaves and flowers of
cannabis sativa
HASHISH - resin of cannabis sativa
5) METHYLXANTHINES
- methylxanthines inhibit adenylyl cyclase, thus leading to decreased formation
of cAMP
- effects of xanthines include
ORGAN EFFECT
CNS - CNS excitation
- insomnia
- nervousness
- increased motor activity
- tremor
- increased respiration
HEART - increased heart rate

- increased force of contraction
BLOOD VESSELS - systemic vasodilation

- cerebral vasoconstricion
BRONCHI - bronchodilation
KIDNEYS - increased glomerular filtration

- decreased reabsorption
- increased diuresis
- they cause little or no dependence

- 4 types
- 127 -
THEOPHYLLINE General information
- found in tea (and coffee)
Medical uses
Side effects
- any other effect of xanthines (see
above)
AMINOPHYLLINE General information

- administered IV
- same as theophylline
CAFFEINE General information

- found in coffee (and tea) and cola
nuts (coca cola)
THEOBROMINE General information

- found in cocoa
PSYCHEDELICS (PSYCHOMIMETIC DRUGS)
Overview
- psychedelics are abuse-drugs that exhibit only psychological effects in the subject of interest
Relevant Drugs
- 3 categories
1) LSD ANALOGUES
- LSD is an extremely potent abuse-drug
- it is a 5-HT 2 receptor agonist in the CNS and –antagonist in the periphery
- the CNS effects of LSD are classified according to dose
DOSE EFFECT
ABUSE DOSE - hallucinations (visual-, auditory-,
olfactory-, tactile-, and cross-
connections (eg. auditory stimuli
are perceived as visual stimuli (!)))
- illogical mental performance
- 128 -
OVERDOSE - “bad trip”
- horrific halucinations
- paranoia
- suicide
- homicide
- it causes little or no dependence (!)

- consequences of LSD, see 34
- 2 types

LSD General information
- “lysergic acid diethylamide”
- abuse-drug
- semisynthetic compound
synthesized from ergot alkaloids
(found in fungus)
PSILOCYBIN General information

- found in fungus
2) PHENCYCLIDINE
- phencyclidine is an abuse-drug with 2 effects in the CNS
EFFECT CONSEQUENCE
FACILITATION OF SIGMA NON-
OPIOID RECEPTORS
INHIBITION OF NMDA - inhibition of glutamate-mediated
RECEPTORS neuronal excitation
- it causes little or no dependence

- the effects of phencyclidine are divided according to dose
MONOAMINE EFFECT
ABUSE DOSE - analgesia
- same as LSD
OVERDOSE - same as LSD
- 129 -
49. OPIOID ANALGESIC DRUGS: MORPHINE AND CODEINE
50. OPIOID ANALGESIC DRUGS: SEMI-SYNTHETIC,
SYNTHETIC OPIOIDS; OPIOID ANTAGONISTS
Overview
- there are 2 types of pain
TYPE DESCRIPTION
ACUTE PAIN - excited by mechanical- and/or thermal stimuli
- conveys surface pain
- transmitted by A-delta nerve fibers from the
dorsal horns of the spinal cord through the
neospinothalamic tract to the basal ganglia and the
somatosensory cortex
- the main neurotransmitter is glutamate
CHRONIC PAIN - excited by mechanical-, thermal- and/or chemical

stimuli
- conveys both surface- and visceral pain
- transmitted by C nerve fibers from the dorsal
horns of the spinal cord through the
paleospinothalamic tract to the brain stem
(including the periaqueductal grey area)
- the main neurotransmitter is substance P
- the endogenous analgesic system is a CNS reflex arch that inhibit the excitation of A-delta-
and C nerve fibers
- it originates in the periaqueductal grey area in response to chronic pain afferens and transmit
efferent excitatory signals down to nucleus raphe magnus and nucleus reticularis
paragigantocellularis of the brain stem
- these nuclei transmit the efferent signal through the dorsolateral column to the dorsal horn of
the spinal tract where they secrete serotonin (see 34) and enkephalins, respectively
- both serotonin and enkephalins inhibit excitation of A-delta- and C nerve fibers by action on
5-HT 3- and opioid receptors respectively, thus inhibiting spinal pain transmission
- there are 5 types of endogenous opioids classified according to their location of action
LOCATION TYPE
SPINAL CORD - met-enkephalin
- leu-enkephalin
CNS - beta-endorphin
- dynorphin A
- nociceptin
- 130 -
- opioids act on opioid receptors
- there are 3 types of opioid receptors
RECEPTOR TYPE EFFECT

MY OPIOID RECEPTOR - supraspinal analgesia (fascilitation of the
periaqueductal grey area and nucleus
paragigantocellularis)
- spinal analgesia (inhibition of the A-delta- and C
nerve fibers)
- peripheral analgesia (inhibition of neural
transmission from nocioceptors)
- euphoria
- pleasure
- sedation
- emesis
- vomiting
- increased tone of GI smooth muscle (spincters
especially)
- myosis
KAPPA OPIOID RECEPTOR - spinal analgesia

- peripheral analgesia
- dysphoria
- sedation
- myosis (pupillary constriction)

especially)
DELTA OPIOID RECEPTOR - spinal analgesia
especially)
- 131 -
- the opioid receptors are G-protein coupled receptors, thus inhibiting adenylate cyclase and
following decreased cAMP formation
- they also activate potassium channels and inhibit calcium channels, thus inhibiting
depolarization and inhibiting release of neurotransmitters respectively and following
inhibition of neuronal transmission
- many (but not all) exogenous opioid analgesic drugs are also abuse-drugs
- like any other abuse-drug they have 4 mechanisms by which they cause dependence (see 47)
MECHANISM CAUSE
POSITIVE REINFORCEMENT - see 47
TOLERANCE - substantially increased activity of adenylyl

cyclase (!)
NEGATIVE REINFORCEMENT - distress

- insomnia
- nausea
- diarrhea
- sweating
- fever
- midriasis (pupillary dilatation)
- piloerection (“cold turkey”)
- they may cause coma if overdosed
Relevant Drugs
- 3 categories
1) MORPHINE ANALOGUES
- include morphine and semisynthetic morphine derivatives
- 3 types

MORPHINE General information
- strong agonist of all opioid
receptor types
- administered orally, IV or
intrathecally
- causes dependence (see above)
Medical uses
- treatment of acute- and chronic
- 132 -
pain
Side effects
- see above
DIAMORPHINE General information

- “heroin”
- strong agonist of all opioid
receptor types
- metabolized to morphine
- very high lipid solubility, thus
crossing the blood- brain barrier
very rapidly
- causes dependence
- same as morphine
3-METHOXYMORPHINE General information

- “codeine”
- weak agonist of all opioid
receptor types
- does not cause dependence
Medical uses
- treatment of mild pain
- treatment of cough (antitussive)
Side effects
- inhibition of bronchial
secretions and bronchial ciliary
activity, thus shoud not be
administered as a treatment of
asthmatic cough
- same as morphine
2) SYNTHETIC OPIOID DERIVATIVES

- 4 groups
A) PHENYLPIPERIDINE ANALOGUES
- 2 types
- 133 -
FENTANYL General information
- strong my opioid receptor
agonist
- administered IV, transdermally
or intravenously
- causes dependence
Medical uses
- treatment of acute pain
- general anaesthesia (, then
administered intravenously)
Side effects
- same as morphine
PENTHIDINE General information

agonist
- metabolized to the active
metabolite norpentidine
- also has muscarinic antagonist
activity
- administered orally or
intramuscularly
- causes dependence
Medical uses
Side effects
- excitement (norpentidine)
- hallucinations (norpentidine)
- convulsions (norpentidine)
- muscarinic antagonist side
effects (see 15)
- same as morphine
B) METHADONE DERIVATIVES
- 2 types

METHADONE General information
agonist
- 134 -
- binds extensively to the
extravascular compartment and is
slowly released from there, thus
may accumulate in the body over
time
- also causes less euphoria and
dependence for the same reason
Medical uses
- treatment of chronic pain
- treatment of morphine/heroin
addiction
Side effects
- same as morphine (but less
euphoria or dependence)
DEXTROPROPOXYPHENE General information

- weak agonist of all opioid
receptor types
- metabolized to the active
metabolite norpropoxyphene
- does not cause dependence
Medical uses
- treatment of mild pain
Side effects
- convulsions (norpropoxyphene)
- same as morphine
C) BENZOMORPHAN DERIVATIVES
- 1 type

PENTAZOCINE General information
- kappa opioid receptor agonist
and my opioid receptor antagonist
- causes dysphoria (kappa opioid
receptor agonist)
- 135 -
Medical uses
Side effects
- see above
D) THEBAINE DERIVATIVES
- 1 type

BUPRENORPHINE General information
- my opioid receptor agonist and
kappa opioid receptor antagonist
- administered sublingually, IV or
intrathecally
Medical uses
- treatment of acute- and chronic
pain
Side effects
- same as morphine
E) OTHERS
- 1 type

LOPERAMIDE General information
- does not cross the blood-brain
barrier
- selective for the GI tract
- also decrease intestinal
secretions
Medical uses
Side effects
- constipation
- abdominal cramps
- 136 -
3) OPIOID ANTAGONISTS
- 2 types

NAXOLONE General information
- antagonizes all opioid receptor
types
- short-acting
- administered IV
Medical uses
- treatment of opioid receptor
agonist induced respiratory
depression
NALTREXONE General information

- long-acting
- same as naxolone
- 137 -
51. CYCLOOXYGENASE INHIBITORS: ASPIRIN,
PARACETAMOL
52. CYCLOOXYGENASE INHIBITORS: PYRAZOLONS,
PROPIONIC ACID DERIVATIVES, INDOLE DERIVATIVES
AND OTHERS. “COX-2 INHIBITORS”
Overview
- cyclooxygenase inhibitors (“non-steroidal anti-inflammatory drugs”, “NSAIDs”) inhibit
cyclooxygenase (“COX”), thus inhibiting the formation of prostaglandins and thromboxanes
(see 35)
- there are 3 types of COX
TYPE DESCRIPTION
COX-1 Location
- most tissues
Effect
- normal tissue homeostasis
COX-2 Location
- inflammatory cells
Effect
- edema (vasodilation and potentiation of the
effect of the inflammatory mediators that
cause increased capillary permeability)
- pain (potentiation of the effect of the
inflammatory mediators that cause irritation of
afferent C nerve fibers)
- fever (increase in the hypothalamic
temperature set point in response to bacterial
endotoxins)
COX-3 Location
- CNS
Effect
- pain (cerebral vasodilation)
- induction of fever (see above)
- COX inhibitors are primarily administered to obliterate the effects of COX-2 and COX-3
- 138 -
- , thus the general medical uses of COX inhibitors include
MEDICAL USE
TREATMENT OF INFLAMMATION
TREATMENT OF PAIN
TREATMENT OF FEVER
- however, most COX inhibitors are non-selective reversible inhibitors of COX, thus also
inhibiting COX-1
- the effects of COX-1 inhibition are usually considered side effects, and include
ORGAN SIDE EFFECT

GI TRACT Increased gastric acid production and
decreased mucous production
- dyspepsia
- nausea
- vomiting
- peptic ulcers
KIDNEYS Vasoconstriction and following renal ischemia

- acute renal insufficiency
- chronic nephritis
- renal papillary necrosis
SKIN Increased arachidonic acid available for 5-

lipoxygenase and following increased
leukotriene production (see 35)
- rashes
- urticaria (“hives”)
- photosensitivity
Relevant Drugs
- 6 categories
1) SALICYLIC ACID DERIVATIVES

- salicylic acid derivatives are non-selective irreversible COX inhibitors
- 1 type
- 139 -
ASPIRIN General information
- “acetylsalicylic acid”
- severe side effects (irreversible COX
inhibition)
Medical uses
- see above
(inhibition of platelet aggregation, due to
irreversible COX-1 inhibition)
- treatment of radiation-induced diarrhea
- prophylaxis of colonic- and rectal cancer
- prophylaxis of alzheimer’s disease
Side effects
- see above
- hemorrhages (inhibition of platelet
aggregation)
- salicylism (deafness, tinnitus and vertigo, due
to repeated administration of large doses of
aspirin)
- salicylate poisoning (respiratory acidosis (due
to respiratory center depression), metabolic
acidosis (due to uncoupling of oxidative
phosphorylation), hyperpyrexia (due to
uncoupling of oxidative phosphorylation and
following increased metabolic rate) and finally
coma, due to aspirin overdose)
- reye’s syndrome (hepatic insufficiency and
encephalopathy in children, due to aspirin
administration during a viral infection)
2) ACETIC ACID DERIVATIVES

- “indole derivatives”
- 3 types

INDOMETACIN General information
- potent COX inhibitor
- has severe side effects (potent COX
inhibitor)
- also inhibits phagocytosis of urate crystals by
neutrophils
- 140 -
Medical uses
- see above
- treatment of gout (inhibition of urate crystal
phagocytosis)
SULINDAC General information

- pro-drug
DICLOFENAC General information

- accumulates in synovial fluid
Medical uses
- see above
- treatment of rheumatoid arthritis
(accumulates in synovial fluid)
3) PROPIONIC ACID DERIVATIVES

- 3 types

IBUPROFEN General information
- weak COX inhibitor
- has little or no side effects (weak COX
inhibitor)
KETOPROFEN
FENOPROFEN General information

- pro-drug
4) ENOLIC ACID DERIVATIVES

- “pyrazolon derivatives”
- 1 type

PHENYLBUTAZONE General information
- potent COX inhibitor
- has severe side effects (potent COX
inhibitor)
- 141 -
5) COXIBS
- “COX-2 inhibitors”
- coxibs are selective reversible COX-2 inhibitors
- 3 types

CELECOXIB General information
- has little or no side effects (selective COX-2
inhibitor)
ROFECOXIB General information

- same as celecoxib
PARECOXIB General information

- same as celecoxib
- administered orally or parenterally
6) ANILINE DERIVATIVES
- “COX-3 inhibitors”
- aniline derivatives are selective reversible COX-3 inhibitors
- 1 type

PARACETAMOL General information
- “acetaminophen”
- has little or no anti-inflammatory effect
(selective COX-3 inhibitor)
- has little or no side effects in therapeutic
doses (selective COX-3 inhibitor)
- metabolized by the liver by glucoronidation
and/or sulfation
Medical uses
- treatment of pain
- treatment of fever
Side effects
- paracetamol overdose (nausea and vomiting
followed by hepatic- and renal tubular
necrosis, due to saturation of the hepatic
- 142 -
enzymes responsible for it’s metabolism and
following metabolism by the cytochrome P450
enzyme system leading to the formation of a
toxic metabolite (n-acetyl-p-benzoquinone
imine))
- 143 -
53. DRUGS USED TO TREAT RHEUMATOID ARTHRITIS
AND GOUT
DRUGS USED TO TREAT RHEUMATOID ARTHRITIS
Overview
- rheumatoid arthritis is an autoimmune disorder leading to inflammation of the joints and
following erosion of the joint cartilage and –bone
Relevant Drugs
- 5 categories
1) DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

- “DMARDs”
- act by unknown mechanisms in treating rheumatoid arthritis
- have very slow onsets (months (!))
- 5 types

SODIUM AUROTHIOMALATE General information
- gold-containing compound
Side effects
- blood dyscrasias
- proteinuria
- skin rashes
- stomatitis
- hepatitis
- encephalopathy
- peripheral neuropathy
AURANOFIN General information

- gold-containing compound
- same as sodium aurothiomalate
D-PENICILLAMIDE General information

- hydrolysate of penicillin
- may celate metals
Side effects
- 144 -
- blood dyscrasias
- proteinuria
- skin rashes
- stomatitis
- anorexia
- nausea
- vomiting
- taste disturbance (celation of zinc)
CHLOROQUINE General information

- also an antimalarial drug (see 71)
- may accumulate in the retina
Medical uses
- treatment of malaria
- treatment of SLE
Side effects
- visual disturbance (accumulates in
the retina)
METHOTREXATE General information

- folic acid antagonist
Medical uses
Side effects
- pulmonary fibrosis
2) NON-STEREOIDAL ANTI-INFLAMMATORY DRUGS

- inhibit COX, thus inhibiting formation of inflammatory cytokines and
following inhibition of inflammation
- see 51/52
3) IMMUNOSUPPRESSANTS
- powerfully suppress the immune defense system, thus decreasing the
- see 36
- 145 -
4) GLUCOCORTICOIDS
- inhibit synthesis inflammatory cytokines, thus decreasing the inflammatory
response
- see 36
5) 5-AMINOSALICYLIC ACID
- scavenges free radicals produced by neutrophils, thus decreasing the
- see 38
DRUGS USED TO TREAT GOUT
Overview
- gout is a deposition of urate crystals in the synovia of joints due to excess formation of urate
- this leads to phagocytosis of the urate crystals by neutrophils and following initiation of
inflammation (“gouty arthritis”)
- urate formation is done in 2 steps
HYPOXANTHINE
xanthine oxidase
XANTHINE
xanthine oxidase
URATE
Relevant Drugs
- 4 categories
1) XANTHINE OXIDASE INHIBITORS

- xanthine oxidase inhibitors inhibit xanthine oxidase, thus decreasing
formation of urate
- 1 type

ALLOPURINOL General information
- hypoxanthine analogue
- binds to the active seat of xanthine oxidase,
thus inhibiting it
- is converted by xanthine oxidase to
alloxanthine
- alloxanthine binds to the allosteric seat of
xanthine oxidase, thus further inhibiting it
- may cause gout when first administered (!),
thus may not be used for treatment of gout
- 146 -
Medical uses
- prophylaxis of gout
Side effects
- gastrointestinal disturbances
- skin rashes
2) URICOSURIC DRUGS
- uricosuric drugs inhibit reabsorption of urate, thus increasing urate excretion
- 2 types

PROBENECID General information
- may cause gout when first administered (!),
thus may not be used for treatment of gout
Medical uses
Side effects
- uolithiasis
SULFINPYRAZOLE General information

- same as probenecid
3) ANTI-INFLAMMATORY DRUGS
- 1 type

COLCHICINE General information
- binds to tubulin leading to depolymerization
of microtubules and following decreased
motility of neutrophils
Medical uses
- treatment of gout
Side effects
- 147 -
- nausea
- vomiting
- severe diarrhea
- abdominal pain
- gastrointestinal hemorrhage
- renal tubular necrosis
- peripheral neuropathy
- skin rashes
4) NON-STEREOIDAL ANTI-INFLAMMATORY DRUGS

- NSAIDS inhibit COX-2, thus inhibiting production of inflammatory
prostaglandins and thromboxanes and following inhibition of inflammation
(see 51/52)
- used in prophylaxis and treatment of gout
- 148 -
A1. DRUGS, 2ND SEMESTER
23. CALCIUM CHANNEL BLOCKERS
1) PHENYLALKYLAMINES
- Verapamil
2) BENZOTHIAZEPINES
- Diltiazem
3) DIHYDROPYRIDINES (“DHP”)
A) SHORT/RAPIDLY-ACTING
- Nifedipine
- Nimodipine
- Nicardipine
B) INTERMEDiATELY-ACTING
- Nintrendipine
- Nisoldipine
C) LONG/SLOWLY-ACTING
- Amlodipine
24. DRUGS ACTING ON THE RENIN ANGIOTENSIN ALDOSTERONE SYSTEM
2) RENIN INHIBITORS
- Enalkiren
3) ACE INHIBITORS
- Enalapril
- Lisinopril
- Ramipril
4) TYPE 1 ANGIOTENSIN II RECEPTOR ANTAGONISTS

- Losartan
- Valsartan
5) ALDOSTERONE RECEPTOR ANTAGONISTS (“POTASSIUM-SPARING

DIURETICS”)
25. DIURETIC DRUGS
1) LOOP DIURETICS
- Furosemide
- Etacrynic Acid
- 149 -
2) THIAZIDE DIURETICS
- Berndroflumethazide
- Hydrochlorthiazide
- Cyclopenthiazide
3) CARBONIC ANHYDRASE INHIBITORS

- Acetazolamide
4) POTASSIUM-SPARING DIURETICS
- Spironolactone
- Triamterene
- Amiloride
5) OSMOTIC DIURETICS
- Mannitol
26. DRUGS USED TO TREAT CONGESTIVE HEART FAILURE
1) CARDIAC GLYCOSIDES (“DIGITALIS”)

- Digoxin
- Ouabain
2) DIRECT VASOLDILATORS
3) DRUGS ACTING ON THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
4) DIURETICS
26. ANTIANGINAL DRUGS. DRUGS THAT INCREASE REGIONAL BLOOD FLOW
1) ORGANIC NITRATES
- Glycerol Trinitrate (“Nitroglycerin”)
- Amyl Nitrate
- Isosorbide Mononitrate
27. ANTIHYPERTENSIVE DRUGS
- Minoxidil
- Hydralazine
- Nitroprusside
- Diazoxide
3) ORGANIC NITRATES
- 150 -
4) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS
5) ALPHA-1 ADRENERGIC RECEPTOR ANTAGONISTS
7) DRUGS ACTING ON THE RENIN-ANGIOTENSIN-ALDOSTERONE. SYSTEM
8) DIURETICS
28. ANTIARRYTHMIC DRUGS
1) CLASS I ANTIARRYTHMIC DRUGS
A) CLASS Ia ANTIARRYTHMIC DRUGS

- Quinidine
- Disopyramide
- Procainamide
B) CLASS Ib ANTIARRYTHMIC DRUGS

- Lidocaine
- Phenytoin
C) CLASS Ic ANTIARRYTHMIC DRUGS

- Flecainide
- Encainide
2) CLASS 2 ANTIARRYTHMIC DRUGS (“BETA-ADRENERGIC RECEPTOR

ANTAGONISTS”)
3) CLASS 3 ANTIARRYTHMIC DRUGS

- Amiodarone
- Sotalol
4) CLASS 4 ANTIARRYTHMIC DRUGS (“CALCIUM CHANNEL BLOCKERS”)
30. DRUGS USED TO TREAT HYPERLIPOPROTEINEMIA
1) STATINS
- Mevastatin
- Lovastatin
- Simvastatin
- Pravastatin
2) FIBRATES
- Fenofibrate
- Ciprofibrate
- Benzafibrate
3) RESINS
- 151 -
- Colestyramine
- Colestipil
31. ANTICOAGULANTS. FIBRINOLYTICS. ANTIFIBRINOLYTICS. ANTIPLATELET DRUGS
1) ANTICOAGULANTS
A) INJECTABLE ANTICOAGULANTS
- Heparin
- LMWHS (“Low Molecular Weight Heparins”)
B) ORAL ANTICOAGULANTS
- Warfarin
2) FIBRINOLYTICS
- Streptokinase
- Alteplase
- Reteplase
3) ANTIFIBRINOLYTICS
- Tranexamic Acid
- Apoprotinin
4) ANTIPLATELET DRUGS
A) COX-1 INHIBITORS
B) THIENOPYRIDINE DERIVATIVES
- Triclopidine
- Clopidogrel
C) GLYCOPROTEIN IIB/IIIA RECEPTOR ANTAGONISTS

- Abciximab
- Tirofibran
D) PGI2 AGINISTS
- Epoprostenol
32. DRUGS AFFECTING HEMATOPOIESIS
1) IRON
- Ferrous Sulfate
- Ferrous Succinate
- Ferrous Gluconate
- Ferrous Fumarate
- Iron-Dextran
2) FOLIC ACID (“VITAMIN B6”)

- Folic Acid
3) COBOLAMIN (“VITAMIN B12”)
- 152 -
- Hydroxycobolamin
4) CSFS (“COLONY-STIMULATING FACTORS”)

- GM-CSF
- G-CSF
33. HISTAMINE, H1 AND H2 RECEPTOR ANTAGONISTS
1) H1 RECEPTOR ANTAGONISTS (“ANTIHISTAMINES”)

- Prometazine
- Diphenhydramine
- Cyclicine
- Cinnarizine
- Mequitazine
- Centrizine
- Fexofenadine
- Cimetidine
- Rantidine
- Famotidine
- Nizatidine
34. SEROTONIN, SEROTONIN RECEPTOR AGONISTS AND ANTAGONISTS
1) SEROTONIN RECEPTOR AGONISTS
A) 5-HT 1 AGONISTS
- Buspirone
- Sumatriptan
- Ergotamine
B) 5-HT 2 AGONISTS
- LSD
C) 5-HT 4 AGONISTS
- Cisapride
2) SEROTONIN RECEPTOR ANTAGONISTS
A) 5-HT 2 ANTAGONISTS
- Methylglyceride
- Cyproheptadine
B) 5-HT 3 ANTAGONISTS
- Ondasetron
- Tropisetron
35. PHARMACOLOGY OF EICOSANOIDS. DRUGS ACTING ON THE SMOOTH MUSCLE:

SMOOTH MUSCLE RELAXANTS; PHARMACOLOGY OF THE UTERINE SMOOTH
- 153 -
MUSCLE
1) PHARMACOLOGY OF EICOSANOIDS
A) PROSTAGLANDINS
- PGD2
- PGE2
- PGF2-alpha
- PGI2
B) TROMBOXANES
- TXA2
C) LEUKOTRIENES
- LTB4
- LTC4
- LTD4
- LTE4
2) SMOOTH MUSCLE RELAXANTS

-…
3) PHARMACOLOGY OF UTERINE SMOOTH MUSCLE
A) OXYTOCIC DRUGS
I) OXYTOCIN RECEPTOR AGONISTS

- Oxytocin
II) ERGOT ALKALOIDS

- Ergometrine
- Ergotamine
III) PROSTAGLANDIN ANALOGUES

- Dinoprost
- Carboprost
- Misoprostol
B) TOCOLYTIC DRUGS
I) OXYTOCIN RECEPTOR ANTAGONISTS

- Atosiban
II) SELECTIVE BETA-2 ADRENERGIC RECEPTOR AGONISTS
36. PHARMACOLOGY OF THE RESPIRATORY TRACT
1) BRONCHODILATOR DRUGS
A) BETA-2 ADRENERGIC RECEPTOR AGONISTS
B) MUSCARINIC RECEPTOR ANTAGONISTS
- 154 -
C) HISTAMINERGIC H1 RECEPTOR ANTAGONISTS
D) CYSTEINYL-LEUKOTRIENE RECEPTOR ANTAGONISTS

- Montelukast
- Zafirlukast
2) ANTI-INFLAMMATORY DRUGS
A) GLUCOCORTICOIDS
B) CROMOGLICATE
- Cromoglicate
- Neddocromil Sodium
3) ANTITUSSIVES
- Codeine
- Dextromethorphan
- Pholcodine
37. PHARMACOLOGY OF THE GASTROINTESTINAL TRACT: DRUGS IN THE

TREATMENT OF PEPTIC ULCER; EMETICS, ANTI-EMETICS
1) DRUGS IN THE TREATMENT OF PEPTIC ULCER
A) H2 RECEPTOR ANTAGONISTS
C) HYDROGEN ION/POTASSIUM ANTIPORTER INHIBITORS

- Omeprazole
- Lansoprazole
- Pantoprazole
D) ANTACIDS
- Magnesium Hydroxide
- Magnesium Trisilicate
- Aluminium Hydroxide
- Sodium Bicarbonate
E) MUCOPROTECTIVE DRUGS
- Sucralfate
- Misoprostol
- Carbenoxolone
2) EMETICS
- Ipecacuanha
3) ANTI-EMETICS
A) H1 RECEPTOR ANTAGONISTS
- 155 -
C) 5-HT 3 RECEPTOR ANTAGONISTS
D) D2 RECEPTOR ANTAGONISTS
I) PHENOTHIAZINES
II) BUTYRPHENONES
III) OTHERS
- Domperidone
- Metoclopramide
E) CANABINOID RECEPTOR AGONISTS

- Nabilone
- Dronabinol
38. PHARMACOLOGY OF THE GASTROINTESTINAL TRACT: PROKINETIC DRUGS,

LAXATIVES, ANTIDIARRHOEAL AGENTS, DRUG TREATMENT OF INFLAMMATORY
BOWEL DISEASE AND PARALYTIC ILEUS, DIGESTIVES, DRUGS USED IN
CHOLELITHIASIS
1) PROKINETIC DRUGS
A) LAXATIVES
I) BULK LAXATIVES
- Methylcellulose
- Bran
- Agar
II) OSMOTIC LAXATIVES

- Lactulose
- Magnesium Sulfate
- Magnesium Hydroxide
B) STIMULANT PURGATIVES
- Bisacodyl
- Sodium Picosulfate
- Senna
C) PERISTALTICS
I) 5-HT 4 RECEPTOR AGONISTS
II) D2 RECEPTOR ANTAGONISTS
D) FECAL SOFTENERS
- Docusate Sodium
2) ANTIDIARRHOEAL AGENTS
- 156 -
A) ORAL REHYDRATION
B) ANTIMOTILITY AGENTS
I) OPIOIDS
II) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS
III) BISMUTH SUBSALICYLATE
C) ADSORBENTS
- Charcoal
- Chalk
- Pectin
- Magnesium Aluminium Silicate
3) DRUG TREATMENT OF INFLAMMATORY BOWEL DISEASE
A) 5-AMINOSALICYLIC ACID
- Sulfosalazine
- Mesalazine
- Olasalazine
B) GLUCOCORTICOIDS
C) IMMUNOSUPPRESSANTS
- Azathioprine
- Ciclosporin
4) DRUG TREATMENT OF PARALYTIC ILEUS
A) MUSCARINIC RECEPTOR AGONISTS
B) CHOLINESTERASE INHIBITORS
C) 5-HT 4 RECEPTOR AGONISTS
5) DIGESTIVES
A) GASTIC ACID SUPPLEMENTS

- Hydrochloric Acid
B) BILE SUPPLEMENTS
- Dihydrocholic Acid
C) PANCREATIC ENZYME SUPPLEMENTS

- Lipase
- Trypsin
- Amylase
6) DRUGS USED IN CHOLELITHIASIS
- 157 -
A) BILE ACIDS
- CDCA (“Chenodeoxycholic Acid”)
- UDCA (“Ursodeoxycholic Acid”)
C) OPIOIDS
39. ANTIANXIETY AND HYPNOTIC DRUGS
1) BENZODIAZEPINES
A) SHORT-ACTING
- Lorazepam
- Temazepam
- Nitrazepam
- Alprazolam
C) LONG-ACTING
- Diazepam
- Clonazepam
2) BARBITURATES
A) SHORT-ACTING
- Metohexital
- Thiopental
- Pentobarbital
- Butobarbital
C) LONG-ACTING
- Phenobarbital
3) 5-HT 1 AGONISTS
4) NON-SELECTIVE BETA ADRENERGIC RECEPTOR ANTAGONISTS
40. ALCOHOLS: PHARMACOLOGY AND TOXICOLOGY
1) ETHANOL
2) METHANOL
41. ANTIPSYCHOTIC DRUGS
1) CLASSIC ANTIPSYCHOTIC DRUGS
- 158 -
A) PHENOTHIAZINES
- Chloropromazine
- Thioridazine
B) BUTYROPHENONES
- Haloperidol
- Droperidol
2) ATYPICAL ANTIPSYCHOTIC DRUGS

- Sulpiride
- Risperidone
- Clozapine
- Olanzapine
42. ANTIDEPRESSANTS
1) TCAS (“TRICYCLIC ANTIDEPRESSANTS”)
A) NON-SELECTIVE TCAS
- Imipramine
- Amitriptyline
B) NORADRENALINE-SELECTIVE TCAS
- Desipramine
- Clomipramine
2) SEROTONIN-SELECTIVE INHIBITORS
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertaline
3) MAOIS (“MONOAMINE OXIDASE INHIBITORS”)
A) IRREVERSIBLE MAOIS
- Phenelzine
- Iproniazid
- Tranylcypromine
B) REVERSIBLE MAOIS
- Moclobemide
43. GENERAL ANAESTHETICS
1) INHALATION ANAESTHETIC
- Ether
- Halothane
- Enflurane
- Isoflurane
- Sevoflurane
- 159 -
- Nitrous Oxide
2) INTRAVENOUS ANAESTHETICS
- Metohexital
- Thiopental
- Etomidate
- Fentadyl
- Ketamine
44. ANTIEPILEPTIC DRUGS
1) DRUGS AFFECTING PARTIAL- AND GRAND MAL SEIZURES

- Phenytoin
- Carbamazepine
- Phenobarbital
2) DRUGS AFFECTING PETIT MAL SEIZURES

- Ethosuximide
3) DRUGS AFFECTING ALL TYPES OF EPILEPTIC SEIZURES
A) VALPROATE
B) LONG-ACTING BENZODIAZEPINES
45. CENTRAL NERVOUS SYSTEM STIMULANT AND NOOTROPIC AGENTS
1) CENTRAL NERVOUS SYSTEM STIMULANTS
2) NOOTROPIC AGENTS
- Piracetam
- Vinpocetine
- Pentoxyfilline
46. DRUG TREATMENT OF NEURODEGENERATIVE DISORDERS. CENTRALLY ACTING

MUSCLE RELAXANTS
1) DRUG TREATMENT OF NEURODEGENERATIVE DISORDERS
A) ALZHEIMER’S DISEASE
I) CHOLINESTERASE INHIBITORS
- Tacrine
- Donepezil
- Rivastigmine
- Galanthamine
II) NOOTROPIC DRUGS
B) PARKINSON’S DISEASE
- 160 -
I) DOPAMINE REPLENISHERS
- L-DOPA
- Selegiline
- Entacapone
- Amantidine
II) D2 RECEPTOR AGONISTS

- Bromocriptine
- Lisuride
- Pergolide
III) MUSCARINIC RECEPTOR ANTAGONISTS
C) HUNTINGTON’S DISEASE
I) GABA AGONISTS
- Baclofen
II) D2 RECEPTOR ANTAGONIST
2) CENTRALLY-ACTING MUSCLE RELAXANTS

-…
47. DRUG ABUSE AND DEPENDENCE: GENERAL PRINCIPLES, OPIOIDS, ANTIANXIETY

AND HYPNOTIC DRUGS, INHALANTS, ETHANOL
1) OPIOIDS
2) ANTI-ANXIETY AND HYPNOTIC DRUGS
3) INHALANTS
-…
4) ETHANOL
48. DRUG ABUSE AND DEPENDENCE: PSYCHOMOTOR STIMULANTS, PSYCHEDELICS,

CANNABIS
1) PSYCHOMOTOR STIMULANTS
A) AMPHETAMINE ANALOGUES
- Amphetamine
- Metamphetamine (“Speed”)
- Methylenedioxymethamphetamine (“Ecstasy”)
- Mesacaine
- Methylphenidate
- Fenfluramine
B) COCAINE ANALOGUES
- Hydrochloride Salt Cocaine (“Snow”)
- 161 -
- Free Base Cocaine (“Crack”)
C) METHYLXANTHINES
- Theophylline
- Aminophylline
- Caffeine
- Theobromine
2) PSYCHEDELICS (“PSYCHOMIMETIC DRUGS”)
A) LSD ANALOGUES
- LSD
- Psilocybin
B) PHENCYCLIDINE
C) CANNABIS
- Marijuana
- Hashish
49./50. OPIOID ANALGESIC DRUGS: MORPHINE AND CODEINE. OPIOID ANALGESIC

DRUGS: SEMI-SYNTHETIC, SYNTHETIC OPIOIDS; OPIOID ANTAGONISTS
1) MORPHINE ANALOGUES
- Morphine
- Diamorphine (“Heroin”)
- 3- Methoxymorphine
2) SYNTHETIC OPIOID DERIVATIVES
A) PHENYLPIPERIDINE ANALOGUES
- Fentadyl
- Penthidine
B) METHADONE DERIVATIVES
- Methadone
- Dextropropoxyphene
C) BENZOMORPHAN DERIVATIVES
- Pentazocine
D) THEBAINE DERIVATIVES
- Buprenorphine
E) OTHERS
- Loperamide
3) OPIOID ANTAGONISTS
- Naxolone
- Naltrexone
- 162 -
51./52. CYCLOOXYGENASE INHIBITORS: ASPIRIN. PARACETAMOL.
CYCLOOXYGENASE INHIBITORS: PYRAZOLONS, PROPIONIC ACID
DERIVATIVES, INDOLE DERIVATIVES AND OTHERS. “COX-2 INHIBITORS”
1) SALICYLIC ACID DERIVATIVES

- Aspirin (“Acetylsalicylic Acid”)
2) ACETIC ACID DERIVATIVES (“INDOLE DERIVATIVES”)

- Indometacin
- Sulindac
- Diclofenac
3) PROPIONIC ACID DERIVATIVES

- Ibuprofen
- Ketoprofen
- Fenoprofen
4) ENOLIC ACID DERIVATIVES (“PYRAZOLON DERIVATIVES”)

- Phenylbutazone
5) COXIBS (“COX-2 INHIBITORS”)

- Celecoxib
- Rofecoxib
- Parecoxib
6) ANILINE DERIVATIVES (“COX-3 INHIBITORS”)

- Paracetamol
53. DRUGS USED TO TREAT RHEUMATOID ARTHRITIS AND GOUT
1) DRUGS USED TO TREAT RHEUMATOID ARTHRITIS
A) DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS

- Sodium Aurothiomalate
- Auranofin
- D-Penicillamide
- Chloroquine
- Methotrexate
B) NON-STEREOIDAL ANTI-INFLAMMATORY DRUGS (“NSAIDS”)
C) IMMUNOSUPPRESSANTS
D) GLUCOCORTICOIDS
E) 5-AMINOSALICYLIC ACID
2) DRUGS USED TO TREAT GOUT
A) XANTHINE OXIDASE INHIBITORS

- Allopurinol
- 163 -
B) URICOSURIC DRUGS
- Probenecid
- Sulfinpyrazole
C) ANTI-INFLAMMATORY DRUGS
- Colchicine
D) NON-STEREOIDAL ANTI-INFLAMMATORY DRUGS (“NSAIDS”)
- 164 -

Pharmacology Notes - Part 2

Загружено:

Сведения о документе

Исходное описание:

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Pharmacology Notes - Part 2

Загружено:

Авторское право:

Доступные форматы

TABLE OF CONTENTS

23. Calcium Channel Blockers (Page 1)

HEART Positive tropic effect

Negative tropic effect

DRUG NAME DESCRIPTION

DRUG NAME DESCRIPTION

DRUG NAME DESCRIPTION

NIMODIPINE General information

NICARDIPINE General information

DRUG NAME DESCRIPTION

NISOLDIPINE General information

DRUG NAME DESCRIPTION

ALDOSTERONE - sodium/water reabsorption by the kidneys

1) BETA-1 ADRENERGIC RECEPTOR ANTAGONISTS

DRUG NAME DESCRIPTION

DRUG NAME DESCRIPTION

LISINOPRIL General information

RAMIPRIL General information

4) TYPE 1 ANGIOTENSIN II RECEPTOR ANTAGONISTS

DRUG NAME DESCRIPTION

VALSARTAN General information

5) ALDOSTERONE RECEPTOR ANTAGONISTS (“POTASSIUM-SPARING

DRUG NAME DESCRIPTION

ETACRYNIC ACID General information

DRUG NAME DESCRIPTION

HYDROCHLORTHIAZIDE General information

CYCLOPENTHIAZIDE General information

3) CA (CARBONIC ANHYDRASE) INHIBITORS

HYDROGEN ION + BICARBONATE ION

- CA inhibitors inhibit intracellular carbonic anhydrase in the tubular

DRUG NAME DESCRIPTION

4) POTASSIUM-SPARING DIURETICS (“ALDOSTERONE RECEPTOR

DRUG NAME DESCRIPTION

TRIAMTERENE General information

AMILORIDE General information

DRUG NAME DESCRIPTION

INCREASED ACTIVATION OF RAAS Positive consequences

1) CARDIAC GLYCOSIDES (“DIGITALIS”)

A) INHIBITION OF 3 SODIUM/2 POTASSIUM ANTIPORTER

POSITIVE IONO- - due to increased intracellular

B) INCREASED VAGAL TONE (CENTRAL STIMULATION OF

NEGATIVE DROMO- - due to depression of the AV-node

DRUG NAME DESCRIPTION

OUABAIN General information

3) DRUGS ACTING ON THE RENIN-ANGIOTENSIN-ALDOSTERONE

STABLE ANGINA - narrowed coronary artery lumen

UNSTABLE ANGINA - occluded coronary artery lumen

MIXED ANGINA - both narrowed and occluded lumen at distinct

PRINZMETAL ANGINA - vasospasms of the coronary arteries

DECREASED MYOCARDIAL Decreased myocardial oxygen

DRUG NAME DESCRIPTION

AMYL NITRATE General information

ISOSORBIDE General information

3) BETA-1 ADRENERGIC RECEPTOR ANTAGONISTS

DRUGS THAT INCREASE REGIONAL BLOOD FLOW

- hypertension is a pathologically increased blood pressure due to an increase in any of these

DRUG NAME DESCRIPTION

HYDRALAZINE General information

NITROPRUSSIDE General information

DIAZOXIDE General information

2) CALCIUM CHANNEL BLOCKERS

4) ALPHA-2 ADRENERGIC RECEPTOR AGONISTS