Muscarinic Antagonists: Pharmacodynamics and Application

Effects on the cardiovascular system and vascular tone

The primary target of M-anticholinergics in the heart is $M_2$ muscarinic receptors. By blocking them, these drugs remove the inhibitory influence of the vagus nerve. In the sinoatrial node, this leads to increased automaticity and the development of tachycardia, while in the atrioventricular node, it improves conduction.

Interestingly, at low doses, a paradoxical effect of transient bradycardia may occur. This is attributed to the stimulation of vagal centers in the central nervous system or the blockade of presynaptic receptors, which enhances acetylcholine release.

Regarding blood vessels, at rest, M-anticholinergics do not affect vascular tone because there is no parasympathetic innervation there (receptors are localized on the endothelium). However, when agonists (cholinomimetics) are administered, these drugs can prevent the vasodilation they induce.

Effects on smooth muscle and glands

By acting on $M_3$ muscarinic receptors, the drugs eliminate the stimulating parasympathetic influence, producing a spasmolytic effect:

• Gastrointestinal motility is reduced.
• Relaxation of the urinary bladder detrusor occurs.
• Bronchial tone is decreased.
• Important feature: sphincter tone, conversely, increases.

Blockade of the same $M_3$ receptors leads to a generalized suppression of exocrine gland secretion (bronchial, salivary, lacrimal, sweat). Blockade of $M_1$ receptors in the stomach reduces histamine release, which ultimately decreases hydrochloric acid secretion.

Clinical application

Due to a wide range of pharmacodynamic effects, M-anticholinergics (especially atropine) are used in various fields of medicine:

1. Ophthalmology: For fundus examination (causing persistent mydriasis) and determination of true refraction (causing cycloplegia). They are also used in inflammatory conditions (iridocyclitis) to provide functional rest and prevent synechiae.
2. Cardiology: For atrioventricular block of vagal origin and sinus bradycardia.
3. Pulmonology: To relieve bronchospasm. Inhaled drugs (quaternary ammonium compounds) are more commonly used; unlike atropine, they are poorly absorbed from mucous membranes and do not cause systemic side effects.
4. Anesthesiology: In premedication before surgery to prevent reflex cardiac arrest, reduce glandular secretion, and lower the risk of laryngospasm.
5. Toxicology: As an antidote for anticholinesterase poisoning (including organophosphates) and M-cholinomimetics.
6. Neurology: Drugs that cross the blood-brain barrier are used in Parkinson's disease to reduce tremor and rigidity.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Specific aspects of M-anticholinergic use in gastroenterology
• Mechanisms of systemic side effects
• Comparative characteristics of tertiary and quaternary amines
• The role of M-anticholinergics in the treatment of extrapyramidal disorders

Other topics in the section «Drugs acting on cholinergic synapses»

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