Mechanism of action and effects on organ systems
These drugs block muscarinic receptors in tissues, eliminating the effects of the parasympathetic nervous system. Consequently, effects completely opposite to parasympathetic stimulation develop:
- Visual system: relaxation of the sphincter pupillae muscle leads to pupillary dilation (mydriasis). Simultaneous relaxation of the ciliary muscle causes tension on the suspensory ligaments (zonules of Zinn), flattening of the lens, and accommodation for distance vision (inducing cycloplegia). The combination of these effects disrupts the outflow of aqueous humor, which can trigger a rise in intraocular pressure (making these drugs strictly contraindicated in glaucoma).
- Respiratory system: smooth muscle tone is reduced (bronchodilation occurs) and bronchial gland secretion is decreased.
- Gastrointestinal tract and urinary system: motility is suppressed and the tone of smooth muscles in the intestines and urinary bladder decreases. The production of digestive secretions is significantly reduced.
- Sweat glands: a special case. They receive sympathetic innervation, but signal transmission relies on acetylcholine. By blocking these receptors, the drugs reduce sweating, causing dry skin.
Plant sources and chemical structure
Historically, the group is represented by tropane alkaloids extracted from plants of the Solanaceae family (Solanaceae): deadly nightshade (belladonna), henbane, jimsonweed, and scopolia.
The classic representative is atropine. In the living plant, it exists as L-hyoscyamine, but during chemical extraction, it transforms into a racemic mixture of isomers. This is a lipophilic, non-polar compound, ensuring good penetration across tissue barriers.
Other plant alkaloids include scopolamine (an ester of scopine and tropic acid) and platyphylline (an alkaloid from broadleaf ragwort, a methylpyrrolizidine derivative).
Clinical application
Muscarinic antagonists are widely used in gastroenterology, urology, and surgery:
- Peptic ulcer disease: the drugs reduce hydrochloric acid secretion. Atropine acts non-selectively, whereas the more modern pirenzepine selectively blocks only M1 muscarinic receptors, providing a better safety profile.
- Spasmodic conditions: due to their potent antispasmodic effect, these agents are effective for intestinal and biliary colic (their effect is weaker in renal colic).
- Acute pancreatitis: atropine inhibits trypsinogen secretion, preventing its premature activation and protecting the pancreas from autodigestion.
- Urology (overactive bladder): tolterodine and oxybutynin relax the detrusor muscle of the bladder. Newer agents include the non-selective trospium chloride and drugs with high affinity for M3 muscarinic receptors — darifenacin and solifenacin.
Related group: Ganglionic blockers
The classification of agents blocking cholinergic synapses also includes ganglionic blockers (blocking N-cholinergic receptors in autonomic ganglia). They are divided into two subgroups:
- Hydrophilic (polar): bisquaternary amines (hexamethonium, pentamin) and sulfonium compounds (trimethaphan). They do not cross the blood-brain barrier. Medium-acting drugs are used to manage hypertensive crises, while short-acting ones are used for controlled hypotension during surgical procedures.
- Lipophilic (non-polar): the secondary amine mecamylamine. It readily penetrates the central nervous system. It is used to treat nicotine dependence because it displaces nicotine from receptors and eliminates the feeling of euphoria.
Briefly: answers to topical questions
How do anticholinergics affect the cardiovascular system?
Muscarinic antagonists increase heart rate and improve atrioventricular conduction. By eliminating parasympathetic influence, pronounced tachycardia develops.
- Tachycardia (Tachycardia) — an increased heart rate.
- Atrioventricular conduction (Conductio atrioventricularis) — its improvement and acceleration.
What are the systemic side effects of atropine?
Systemic side effects of atropine are caused by the blockade of muscarinic receptors in various organs and include disturbances in secretion, cardiac activity, and urination.
- Dry skin and mucous membranes — severe thirst, dry mucous membranes, and dry skin resulting from decreased glandular secretion.
- Tachycardia — pronounced increase in heart rate; possible development of extrasystoles.
- Urinary retention — bladder atonia and urinary retention.
What are the contraindications for prescribing anticholinergics, other than glaucoma?
In addition to glaucoma, the prescription of anticholinergics is contraindicated in benign prostatic hyperplasia, cardiovascular disorders, and gastrointestinal pathologies.
- Benign prostatic hyperplasia — risk of acute urinary retention.
- Cardiovascular pathologies — tachyarrhythmias.
- GI pathologies — intestinal atony.
How do anticholinergics affect the central nervous system?
The effect on the central nervous system depends on the drug and the dose. Scopolamine in therapeutic doses causes central nervous system depression, manifested by a sedative effect, drowsiness, and amnesia. In toxic doses, scopolamine's effect becomes similar to that of atropine: psychomotor agitation develops, followed by a potential comatose state. Acute atropine poisoning can cause hallucinations, delirium, seizures, and coma.
The logic behind the pharmacological effects of anticholinergics is based on the "anti-parasympathetic" rule. If the parasympathetic system is responsible for moisture (secretion), pupillary constriction, and active peristalsis, then blocking these receptors produces the exact opposite effect: dryness, dilated pupils, smooth muscle relaxation, and an accelerated heart rate.
Class and exam questions
Why are anticholinergics strictly contraindicated in glaucoma?
These drugs cause mydriasis and cycloplegia, leading to a mechanical disruption in the outflow of aqueous humor. Consequently, a sharp and dangerous increase in intraocular pressure may occur.
Why is pirenzepine better than atropine in the treatment of gastric ulcers?
Pirenzepine is a selective drug. It selectively blocks only M1 muscarinic receptors, thereby effectively inhibiting hydrochloric acid secretion while causing virtually none of the systemic side effects characteristic of non-selective atropine (such as dry mouth or tachycardia).
Why do drugs of this group cause severe skin dryness?
Sweat glands are innervated by the sympathetic nervous system; however, signal transmission at these nerve terminals is mediated by acetylcholine (cholinergic innervation). Blocking these receptors halts glandular stimulation, and sweating stops.
What else to study on this topic
- The process of L-hyoscyamine racemization into atropine during chemical extraction from plants.
- Differences in the mechanisms of action of antispasmodics in the treatment of overactive bladder (tolterodine, oxybutynin).
- Prevention of pancreatic autodigestion: molecular targets of atropine in pancreatitis.
- Features of the clinical use of lipophilic ganglionic blockers in the treatment of nicotine dependence.
- Curare-like agents as a third major branch of substances blocking cholinergic synapses.
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