Anti-Muscarinic Agents – Study Notes

Anti-Muscarinic Agents – Study Notes

1. Concept

• Anti-muscarinics = anticholinergic drugs that block muscarinic ACh receptors.

• Act as parasympatholytics (oppose parasympathetic system).

• Effects = opposite of parasympathetic physiology.

2. Normal Parasympathetic Actions (via ACh on M receptors)

• CNS:

  • Basal ganglia → modulates movement (balance of dopamine & ACh).

  • Emetic center (medulla) → vomiting reflex.

• Eye:

  • Pupil constriction (miosis).

  • Ciliary muscle contraction → accommodation & ↑ aqueous humor drainage.

• Glands:

  • Lacrimal → ↑ tears.

  • Salivary → ↑ saliva.

• Heart:

  • ↓ HR & ↓ cardiac output (via M2 receptors).

• Lungs:

  • Bronchoconstriction.

• GI Tract:

  • ↑ motility & ↑ secretions.

  • ↑ bile release.

• Sweat glands:

  • Sympathetic cholinergic → sweating.

• Bladder:

  • Contraction of detrusor → urination.

• Pelvic/Lower GI:

  • Sacral nerves (S2–S4) → ↑ motility, defecation.

3. Effects of Anti-Muscarinic Agents

• Eye: Mydriasis (dilation), cycloplegia (loss of accommodation), ↑ intraocular pressure.

• Glands: ↓ lacrimation & salivation → dry eyes, dry mouth.

• Heart: ↑ HR, ↑ cardiac output.

• Lungs: Bronchodilation.

• GI tract: ↓ motility, ↓ secretions → constipation.

• Sweat glands: ↓ sweating → hyperthermia.

• Bladder: ↓ contraction → urinary retention.

• CNS: Altered cognition, movement modulation, ↓ vomiting reflex.

4. Muscarinic Receptor Subtypes

• M2, M4 → Gi-coupled → inhibitory (↓ cAMP, ↑ K+ efflux → hyperpolarization).

  • Example: heart (↓ HR).

• M1, M3, M5 → Gq/Gs-coupled → stimulatory (↑ Ca²⁺, ↑ cAMP, ↑ contractions/secretion).

  • Examples: glands, GI tract, bladder.

Anti-muscarinics block both inhibitory and stimulatory muscarinic actions.

5. Major Drugs & Uses

A. Atropine

• Eye: Mydriasis, cycloplegia (used for eye exams; contraindicated in glaucoma).

• Glands: ↓ secretions (used pre-op or pre-intubation).

• Heart: ↑ HR (first-line for bradycardia).

• Antidote for cholinergic crisis (e.g., organophosphate or AChE inhibitor toxicity).

B. Scopolamine

• Crosses BBB (tertiary amine).

• Blocks muscarinic receptors in emetic center.

• Uses: motion sickness, post-op nausea/vomiting.

C. Benztropine, Trihexyphenidyl

• CNS action on basal ganglia.

• Rebalances dopamine–ACh in movement disorders.

• Uses: Parkinson’s disease (especially tremor), treatment of extrapyramidal symptoms from antipsychotics.

D. Oxybutynin, Tolterodine, Solifenacin

• M3 receptor antagonists in bladder.

• ↓ detrusor contraction → treat overactive bladder/urge incontinence.

E. Dicyclomine, Hyoscyamine

• GI selective (M3 blockade).

• ↓ GI motility, ↓ secretions.

• Use: IBS-D (spasms, diarrhea-predominant IBS).

F. Glycopyrrolate

• Quaternary amine → poor CNS penetration.

• ↓ secretions → used in drooling (e.g., cerebral palsy) or pre-op to reduce airway secretions.

G. Ipratropium, Tiotropium

• Inhaled muscarinic antagonists.

• Block M3 receptors in bronchi → bronchodilation.

• Uses: COPD, asthma.

• Ipratropium = short-acting (SAMA).

• Tiotropium = long-acting (LAMA).

6. Adverse Effects – Anticholinergic Toxicity

Mnemonic: "Hot as a hare, Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter"

• CNS: delirium, confusion, hallucinations, seizures.

• Eyes: mydriasis, blurry vision.

• Glands: dry eyes, dry mouth.

• Heart: tachycardia, hypertension.

• Skin: ↓ sweating → hyperthermia, flushed skin.

• GI/GU: constipation, urinary retention.

Causes: overdose of anti-muscarinics, TCA overdose, antipsychotics, 1st-gen antihistamines, belladonna plant.

Physiology → drug effects → receptor mechanism → drugs by system → toxicity.