Antimuscarinic Drugs: Mechanism & Types

• Cholinergic antagonists bind to cholinoceptors and prevent the actions of acetylcholine and other cholinergic agonists.
• Muscarinic antagonists (antimuscarinic drugs) and neuromuscular blockers are types of cholinergic antagonists.

Antimuscarinic Drugs

• Also known as muscarinic antagonists, atropinic drugs, or parasympatholytics.
• Classified into natural alkaloids, semisynthetic derivatives, and synthetic molecules.
• Natural alkaloids include atropine and hyoscine (scopolamine).
• Semisynthetic derivatives include homatropine.
• Synthetic molecules include benztropine.
• Examples of antimuscarinic drugs include: oxyphenonium, dicyclomine, cyclopentolate, tropicamide, oxybutynin, and benztropine.

Mechanism of Action of Antimuscarinic Drugs

• Atropine non-selectively blocks muscarinic receptors (M1, M2, and M3) by competing with acetylcholine, preventing its binding.
• Some antimuscarinics are moderately selective for specific muscarinic receptor subtypes.

Pharmacological Actions of Antimuscarinic Drugs

Central Nervous System Effects

• Atropine has minimal stimulatory effects in therapeutic doses, specifically on parasympathetic medullary centers, and a minimal central depressant effect.
• Scopolamine has a central depressant effect, causing drowsiness and amnesia in sensitive individuals at therapeutic dosages.
• Centrally acting antimuscarinic drugs like benztropine can reduce tremor and rigidity in Parkinson's disease by counteracting excess cholinergic activity.

Cardiovascular System Effects

• Tachycardia can occur due to the blockade of the vagal slowing effect on the sinoatrial (SA) and AV nodes.
• Antimuscrarinic drugs generally have no effect on blood vessels or blood pressure
• Vasodilation can occur with cutaneous vasodilatation in adults at toxic doses and children with therapeutic doses, causing atropine flush and fever.

Gastrointestinal Tract Effects

• Antimuscarinics decrease gastrointestinal smooth muscle motility from the stomach to the colon, reducing tone and propulsive movements.
• They reduce some of the secretory functions of the gut, such as gastric secretion.

Genitourinary Tract Effects

• Antimuscarinics relax smooth muscle of the ureters and bladder, potentially leading to urinary retention.

Exocrine Glands Effects

• Antimuscarinics reduce most exocrine secretions, including salivary, lacrimal, and sweat secretions.

Respiratory System Effects

• Antimuscarinics induce bronchodilatation and reduction of bronchial secretion.

Eye Effects

• Topical application or systemic administration of atropine can cause paralysis of the constrictor pupillae muscle, resulting in mydriasis.
• Paralysis of the ciliary muscle (cycloplegia) leads to loss of accommodation to near objects.
• Increased intraocular pressure results from narrowing of the anterior chamber angle, decreasing drainage of the aqueous humor.
• Inhibition of lacrimation leads to dry eye.
• Atropine has a duration of action of 7-10 days when applied locally to the eye, but only a few hours when given systemically.

Therapeutic Uses of Muscarinic Anatagonists

• Used in various systemic disorders and to treat organophosphorus compound poisoning.

Central Nervous System Disorders

• Benztropine is used to control tremors and rigidity in Parkinson's disease.
• Scopolamine is effective for motion sickness prophylaxis. Transdermal patches can protect for up to 3 days.

Ophthalmologic Disorders

• Atropine or its substitutes are used topically as eye drops to produce mydriasis with cycloplegia.
• Essential for accurate measurement of refractive error in uncooperative patients, like young children, through ciliary paralysis.
• Facilitates retinal examination by inducing mydriasis, with short-acting tropicamide being preferred.
• Helps prevent adhesion formation and decrease local pain in uveitis or iritis by relaxing ciliary muscle spasm; cyclopentolate is valuable for this.

Respiratory Disorders

• Atropine may be administered as a pre-anesthetic medication to decrease airway secretions and prevent laryngospasm, protect the heart from excessive vagal tone, and treat chronic obstructive pulmonary disease (COPD).

Cardiovascular Disorders

• Parenteral atropine is used to treat vasovagal attacks.

Gastrointestinal Disorders

• Used as antispasmodics for intestinal colics and to relieve traveler's diarrhea.
• Often combined with diphenoxylate (opioid antidiarrheal) under the name Lomotil.

Urinary Disorders

• Oxybutynin is selective for M3 receptors, relieving bladder spasms after urologic surgery.
• Valuable in reducing involuntary voiding in patients with neurologic diseases.

Organophosphorus Toxicity

• Atropine is used as an antidote for organophosphorus compound toxicity.

Adverse Effects of Muscarinic Antagonists

• Mydriasis and cycloplegia leading to blurred vision and acute glaucoma.
• Dry mouth.
• Hot and flushed skin, especially in children/infants.
• Tachycardia.
• Toxic doses of scopolamine (and to a lesser extent, atropine) can cause agitation, hallucinations, and coma.

Contraindications of Muscarinic Antagonists

• Glaucoma or a history of glaucoma.
• Elderly men with benign prostatic hyperplasia.