Unit V: Introduction and classification of the drugs acting on: Autonomic nervous system

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Compiled and circulated by Dr. Parimal Dua, Assistant Professor, Dept. of Physiology, Narajole Raj college

Page | 21 SEC-4: Pharmacology and Toxicology

Unit V: Introduction and classification of the drugs acting on: Autonomic nervous system

 Antiadrenergic drugs and their clinical uses:

 Blockers:

(1)  blockers (like Prazosin etc.) are used in human therapeutics as vasodilators in emergency control of dangerously high blood pressure or in peripheral ischaemic diseases.

(2) The ability of  blockers to reverse the effects of xylazine has now given these drugs a veterinary role.

 Atipamezole (2 blocker) selectively antagonizes medetomidine (2 agonist).

 Idazoxan (2 blocker) selectively antagonizes xylazine (2 agonist).

 Yohimbine is in general used as 2 antagonist.

 - Blockers:

(1) Pronethalol: It was the first  blocker to be marketed. Although, effective in controlling arrhythmias and hypotension, it was found a carcinogen in mice and was later withdrawn.

(2) Propranolol: It is a non-selective  (1+2) antagonist.

 The drug is a competitive antagonist of isoprenaline at  adrenoceptors.

Useful in angina pectoris and protects the heart from sympathetic drive.

 Inhibits the metabolic actions of adrenaline like muscle and liver glycogenolysis & lipolysis.

 Bronchoconstrictor and antiarrhythmic for heart.

(3) Acebutolol, Metoprolol, Atenolol: (Cardioselective 1 blockers)

 Used for – Angina pectoris, hypertension, cardiac arrhythmias etc.

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 Drugs Acting on Autonomic Ganglia Ganglionic Transmission:

Acetylcholine (ACh) is the primary excitatory neurotransmitter in both sympathetic and parasympathetic ganglia. Drugs alter the ganglionic function by either stimulating (ganglionic stimulants) or blocking (ganglionic blockers) the impulse transmission through the autonomic ganglia. The principal pathway of impulse transmission through the ganglia involves release of ACh from the preganglionic nerve endings and the stimulation of nicotinic receptors by ACh on the post-junctional membrane (EPSP) causing rapid depolarization and subsequent propagation of the impulse through the post-ganglionic nerve fibre.

Figure: Impulse transmission in sympathetic autonomic ganglia.

ACh is discharged from the preganglionic nerve terminal and interacts with a nicotinic receptor on the ganglionic neuron to cause a rapid depolarization measured electrically as a fast excitatory post synaptic potential (EPSP). ACh also interacts with a muscarinic receptor on the ganglionic neuron to cause a

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delayed depolarization measured electrically as a slow EPSP. In addition, ACh activates nearby chromaffin cells through a muscarinic receptor, which results in a release of catecholamine (CA: dopamine or epinephrine). CA interacts with an  receptor on the ganglionic neuron to cause an inhibitory (hyperpolarization) response measured electrically as an inhibitory post synaptic potential (IPSP).

Ganglionic Stimulants:

The ganglionic stimulants stimulate the nicotinic receptors like ACh and cause EPSP and rapid depolarization.

(1) Natural Alkaloids:

(a) Nicotine: It is obtained from the leaves of Nicotiana tabacum. Small doses of nicotine stimulate the CNS. Large doses cause tremors or even convulsions. Respiratory stimulation is due to direct stimulation of medullary respiratory centre and through activation of carotid and aortic chemoreceptors. The stimulation is followed by depression of the CNS.

Nicotine can stimulate the sympathetic and parasympathetic ganglia in small doses. In large doses, it blocks ganglia. The effects of nicotine on GI tract are due to stimulation of parasympathetic ganglia which include salivation, increase in tone and motility of GI tract and defaecation. Nicotine toxicity may cause CNS excitation followed by marked depression and even death due to central respiratory failure and paralysis of peripheral respiratory muscles. [NB: Nicotine transdermal has been therapeutically used for treatment of nicotine dependence and as an aid to smoking cessation.]

(b) Lobeline: It is obtained from the leaves of Lobelia inflata.

(2) Synthetic compounds:

a) Trimethylammonium (TMA) b) Tetraethylammonium (TEA)

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c) Dimethylphenylpiperazinium (DMPP) Ganglionic Blockers:

These drugs competitively antagonize the action of ACh on the nicotinic receptors on the post-ganglionic membrane and thus block ganglionic transmission. Ganglionic blockers are all synthetic compounds.

a) Hexamethonium b) Pentolinium c) Trimethaphan d) Mecamylamine

Pharmacological effects of Ganglionic Blockers:

(i) CVS: Vasodilatation, increased peripheral blood flow, venous pooling, decreased cardiac output, hypotension and tachycardia.

(ii) GI tract: Reduced tone and motility.

(iii) Eye: Mydriasis and cycloplegia.

(iv) Bladder: Relaxation and urine retention.

(v) Sweat glands: Anhydrosis.

(vi) Salivary glands: Xerostomia (dry mouth).