Application of Drugs Acting on Autonomic Nervous System in Hospitals

PUTERI JUANITA ZAMRI,

MASTERS IN CLINICAL PHARMACY, B(H) PHARM

The Nervous System

Central Nervous System (CNS) - Brain and spinal

cord Peripheral Nervous System (PNS) - Located outside the brain & spinal cord * Autonomic Nervous System (ANS) & the Somatic The PNS receives stimuli from the CNS & initiates responses to the stimuli after its interpreted by the brain

Peripheral Nervous System

Includes all the neurons and ganglia found outside

the CNS Includes the

Sympathetic receptors (adrenergic) Parasympathetic receptors (cholinergic)

Autonomic Nervous System

ANS acts on smooth muscles & glands

- Controls & regulation of the heart, respiratory. system, GI tract, bladder, eyes & glands - Involuntary - person has little or no control Somatic - voluntary - person has control (skeletal muscle)

ANS
ANS has 2 sets of neurons:

1. Afferent (sensory) - sends impulses to the CNS for interpretation 2. Efferent - receives impulses (info.) from the brain & transmits from the spinal cord to the effector organ cells - 2 branches a) sympathetic b) parasympathetic

Figure 20-2.

Sympathetic and Parasympathetic Effects on Body Tissues

Sympathetic Nervous System

Helps the body cope with external stimuli and

functions during stress (triggers the flight or fight response)

Vasoconstriction increase in blood pressure Increased heart rate Increased respiratory rate Cold, sweaty palms Pupil dilation

ANS - Sympathetic nervous system (Adrenergic)

A. Sympathetic Nervous System (adrenergic)

- Norepinephrine=Neurotransmitter - Drugs that mimic = adrenergic drugs, sympathomimetics, or adrenomemetics * Adrenergic agonists - Drugs initiate a response - Drugs that block = adrenergic blockers, sympatholytics or adrenolytics * Adrenergic antagonists - prevent a response

ANS
4 types of adrenergic receptor organ cells:
1. Alpha-1 = vasoconstriction of blood vessels inc. blood return to heart, inc. circulation, inc. BP 2. Alpha-2 = inhibits release of norepinephrine dec. in vasoconstriction, dec. BP 3. Beta-1 = inc. in heart rate & force on contraction 4. Beta-2 = relaxation of smooth muscle in bronchi, uterus, peripheral blood vessels Dopaminergic = dilate vessels, inc. in blood flow - only dopamine activates this receptor

Adrenergic Receptors
Found in: Cardiovascular Endocrine Gastrointestinal Genitourinary Respiratory Ocular

Alpha Receptors
Alpha 1: adrenergic receptors located on

postsynaptic effector cells.

Smooth muscles of blood vessels Bladder sphincter Penis Uterus Pupillary muscles of iris

Adrenergic Receptor
Alpha 1 Therapeutic Uses Control topical superficial bleeding Treat nasal congestion Elevate blood pressure Delay absorption of local anesthesia Decrease intraocular pressure (pressure in eye)

Alpha 2
Same as the Alpha 1 but are located in the

presynaptic nerve terminals.

Adrenergic Receptor
Beta 1 Cardiovascular Cardiac muscle: increased contractility Atrioventricular node: increased heart rate Sinoatrial node: increase in heart rate Endocrine Pancreas Beta 1 drugs: Predominately works on vascular

smooth muscle of the heart.

Adrenergic Receptor
Beta 2 Cardiovascular Dilation of blood vessels

Endocrine
Uterine relaxation Respiratory: dilation of bronchial muscles

Beta 2 Drugs
Used in Asthma to relieve bronchocontriction. Used to delay pre-term labor by relaxing the uterus.

Dopamine
Adrenergic neurotransmitter essential for normal

brain function.

Studies focus on connection between dopamine malfunction in schizophrenia and Parkinsons Disease. Role of dopamine: stimulants and depressants.

Norepinephrine and epinephrine

Both always present in the blood. Norepinephrine varies according to the amount of

stress present and will cause transient changes in heart rate and systemic arteries and veins. Epinephrine is a constant in regulating heart rate, vasoconstriction in systemic arteries and veins and vasodilation of muscles and liver.

Body Responses fight or flight

Increase in blood pressure and cardiac output. Increase blood flow to brain, heart and skeletal

muscles. Decrease blood flow to skin and organs not needed for flight. Increase in glycogen for energy, mental activity, muscle strength, blood coagulation, respiratory rate, pupil dilation to aid vision, and increase in sweating.

Parasympathetic Nervous System

Works to save energy, aids in digestion, and supports

restorative, resting body functions.

Decrease in heart rate Increased gastro intestinal tract tone and peristalsis Urinary sphincter relaxation Vasodilation decrease in blood pressure

ANS - Parasympathetic Nervous System (Cholinergic)

B. Parasympathetic or Cholinergic Nervous System Acetylcholine = neurotransmitter - Drugs that mimic = cholinergic drugs, parasympathomimetics Cholinergic agonists - initiates a response - Drugs that block = anticholinergic, parasympatholytics Cholinergic antagonists - prevents a response

Body Responses rest and digest

Dilation of blood vessels in skin Decrease heart rate (bradycardia) Increase secretion of digestive enzymes

Constriction of smooth muscle of bronchi

Increase in sweat glands - cooling Contraction of smooth muscles of urinary bladder

Contraction of smooth muscle of skeletal system

APPLICATIONS IN THE HOSPITAL

Adrenergic Drugs

Indications
Respiratory conditions Topical nasal congestion Ophthalmic conditions

Cardiovascular

1) Lungs
1) Asthma and COPD (Chronic Obstructive

Pulmonary Disease):
1)

2) 3)

Beta 2 drugs or bronchodilators are used to relieve bronchoconstriction and broncho-spasm. Salmeterol, salbutamol Combination with anticholinergic: Combivent, Berodual

2)Topical Nasal Congestion

Common cold: anti-histamines Allergy: nasal or oral to relieve nasal congestion

Pseudoephedrine
Trade names: Actifed, Afrin nose spray Therapeutic classification: allergy, cold and cough

remedies, nasal drying agents / decongestants Action: stimulates alpha and beta adrenergic receptors

3) Heart
Direct stimulation of receptors Alpha 1
Vasoconstriction of blood vessels which increases blood pressure Pressor or vasopressor effect to maintain blood pressure

Beta 1
Increased force of myocardial contraction Increased speed of electrical conduction in the heart.

Vasopressive Drugs
Pressor drugs or pressors or inotropes Used to support the cardiovascular system during

cardiac failure or shock. Common vasopressors:

Dobutamine Dopamine Ephedrine Epinephrine

Dopamine
In hospital: Indicated for non-hypovolemic

hypotension Dose: Initial 2-5mcg/kg/min with increm 510mcg/kg/min at 10-15mins intervals until adequate response, usually main at 20mcg/kg/min (Max:50mcg/kg/min) I ampoule:40mg/ml (5ml)

Dobutamine
Indication: Hypotension and heart failure Dose: IV initial 0.5-1mcg/kg/min, maint: 2.5-

5mcg/kg/min, titrate according to response (Max:40mcg/kg/min)

Norepinephrine (Noradrenaline)
Ind: Septic shock and shock where peripheral

vascular resistance is low Dose: 0.01-0.1mcg/kg/min (infuse, titrate) Strength:Inj 4mg/4ml

Epinephrine
Ind: Cardiopulmonary resuscitation Dose: 0.5-1mg SC/IM, repeated every 5mins if

necessary Strength:1mg/ml (1ml) Action: affects both the beta 1 (cardiac) and beta 2 (pulmonary) receptors

produces bronchodilation inhibits hypersensitivity reaction of mast cells.

Anaphylactic Shock

How it is given?
Sub-Q or IV or inhaled Epi-pen is given to clients with severe allergy

reactions Not given by mouth because drug is inactivated by gastric juices Can be inhaled in asthma attack

Adrenergic-blocking Drugs

Antiadrenergic Drugs
Blocks the effects of the sympathetic nerve

stimulation, endogenous catecholamine and adrenergic drugs.

Mechanism of Action
Act on alpha or beta receptors Receptors are blocked by adrenergic antagonists or

pre-synaptic alpha 2 receptors are stimulated.

When Used?
To manage hypertension and a number of

cardiovascular disorders.

Beta 1 blocking drugs: acute MI, angina, hypertension

Metoprolol, Atenolol Prazosin

A1 blocking drugs: heart failure, angina, hypertension

Cholinergic Drugs

Mechanism of Action
Cholinergic drugs stimulate the parasympathetic

nervous system. Direct acting cholinergic drugs are synthetic derivative of choline. Effects of drug

Decrease heart rate, vasodilation, and changes in BP Increase tone and contractibility of smooth muscle Increase tone and contractibility of bronchial smooth muscles Increased respiratory secretions

Indications for Use

Urinary retention without obstruction Postoperative abdominal distention due to paralytic

ileus Myasthenia gravis muscle weakness During surgery to reverse the effects of muscle relaxants used during surgery

Myasthenia Gravis
Signs and symptoms: muscle weakness, ptosis

(droopy eye lid), diplopia (double vision), difficulty chewing and swallowing, decreased activity intolerance.

Pyridostigmine
Trade name: Mestinon Pharmacologic classification:

cholinergics/neuromuscular disorder drugs Indications: used to increase muscle strength in the symptomatic treatment of myasthenia gravis Dose: 30-120mg at suitable intervals throughout the day (total dose: 0.3-1.5g

Cholinergic-Blocking Drugs

Colinergic-Blocking Drugs
Anticholinergics are a class of medications that

inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells.

Mechanism of Action
Drugs act by occupying receptor sites on target

organs innervated by parasympathetic nervous system leaving fewer receptor sites free to respond to acetylcholine. Parasympathetic response is absent or decreased depending on number of receptors blocked.

Effects of Anticholinergic Drugs

CNS stimulation followed by depression Decreased cardiovascular response to

parasympathetic (vagal) stimulation that slows heart rate. Bronchodilation and decrease respiratory secretions Antispasmodic effects in GI system Change in intra-ocular pressure in patients with glaucoma

Uses
GI disorders peptic ulcer disease, gastritis, increased

gastric acid secretion relax gastric smooth muscle Genitourinary anti-spasmodic urgency Excessive secretions Ophthalmology relax eye for exam Respiratory disorder asthma or bronchitis inhaled form only Cardiac disorders bradycardia or heart block Parkinsons disease

Atropine
Pharmacological classification: anticholinergic Therapeutic classification: antiarrhythmic Action: Inhibits the action of acetylcholine at

postganglionic sites located in the smooth muscle, secretory glands, CNS. Low doses decrease: sweating, salivation and respiratory secretions.

Atropine
Therapeutic effects: Increased heart rate Decreased GI and respiratory secretions May have spasmodic action on the biliary and genitourinary tracts. Side effects: Drowsiness Blurred vision Tachycardia Dry mouth Urinary hesitancy

Atropine
Indication: Reduce vagal inhibition, salivary and bronchiol secretion in anaesthesia Reversal of bradycardia Reversal of effect of competetive muscle relaxants Organophosphate poisoining Dose: 1) IM/SC 300-600mcg 30-60 mins before anaesthesia 4) IV/IM 2mg, every 30mins according to clinical response.

Questions:
1. 2.

3.
4.

5.

What is the neurotransmitter which plays role in the sympathetic nervous system? Name 3 agents of adrnergic drugs. Combinations of beta2 agonist and anticholinergic agent in asthma/COPD What is used in organophosphate poisoining Side effects of atropine (3 at least)

 Thank you