Cholinergic Antagonists

Cholinergic Antagonists: Intro & Classes - ACh Blockade Basics

• Definition: Drugs competitively blocking acetylcholine (ACh) at muscarinic/nicotinic receptors.
  • Antimuscarinics also termed parasympatholytics.
• ACh Blockade Basics:
  • Prevent ACh binding, inhibiting cholinergic transmission.
  • Effects are generally opposite to those of cholinomimetics.
• Major Classes:
  • Antimuscarinic Agents: Selectively block muscarinic receptors (e.g., Atropine).
  • Antinicotinic Agents:
    • Ganglion Blockers (N_N blockade).
    • Neuromuscular Blockers (N_M blockade).

⭐ Atropine is a non-selective muscarinic antagonist; it blocks M1, M2, and M3 receptors.

Antimuscarinics: Actions & Uses - Parasympathetic Pause

• Core Action: Competitive blockade of muscarinic receptors (M1-M5) → ↓parasympathetic tone.
  • 📌 Effects: Dry mouth, blurred vision, tachycardia, constipation, urinary retention, "atropine fever" (anhidrosis).
• CNS:
  • Sedation, anti-motion sickness (Scopolamine).
  • Parkinsonism (Benztropine, Trihexyphenidyl): ↓tremor, rigidity.
• Eye:
  • Mydriasis, cycloplegia. Uses: Fundoscopy (Tropicamide), uveitis.
  • ⚠️ Caution: Angle-closure glaucoma (↑IOP).
• CVS:
  • Tachycardia (blocks M2). Uses: Symptomatic bradycardia, AV block (Atropine).
• Respiratory:
  • Bronchodilation, ↓secretions. Uses: COPD, Asthma (Ipratropium, Tiotropium - inhaled).
• GIT:
  • ↓Salivation, ↓motility (antispasmodic), ↓acid. Uses: IBS (Dicyclomine), pre-anaesthetic (Glycopyrrolate).
• GUT:
  • ↓Bladder contractility. Uses: Overactive bladder (Oxybutynin, Tolterodine), ↓urgency.
• Crucial Use: Atropine in organophosphate poisoning (life-saving).

⭐ In organophosphate poisoning, atropine only blocks muscarinic effects. Pralidoxime is needed to regenerate AChE and reverse nicotinic effects (muscle weakness).

Antimuscarinics: ADRs & Toxicity - Dry Side Dangers

• ADRs (Anticholinergic Effects):
  • Dryness: Mouth (xerostomia), eyes (blurred vision, mydriasis, cycloplegia), skin (anhidrosis, flushing).
  • Systemic: Tachycardia, urinary retention, constipation.
  • CNS: Confusion, delirium, hallucinations (elderly ↑ risk). 📌 "Dry as bone, blind as bat, red as beet, mad as hatter, hot as hare."
• Toxicity (Atropine Poisoning): Exaggerated ADRs; hyperthermia, agitation, seizures, coma.
• Management: Supportive care (ABC, cooling). Physostigmine for severe toxicity (monitor closely).

  ⭐ Physostigmine (cholinesterase inhibitor) reverses central & peripheral antimuscarinic effects; use cautiously due to potential for bradycardia/seizures.

• Contraindications: Narrow-angle glaucoma, benign prostatic hyperplasia (BPH), obstructive uropathy/GIT disease, tachyarrhythmias.

Nicotinic Antagonists: NMBs - Muscle Relax Masters

• Neuromuscular Blockers (NMBs): Act at nicotinic (Nm) receptors of the neuromuscular junction (NMJ).
• Classification & Mechanism:
  • Depolarizing:
    • Example: Succinylcholine
    • MOA: Phase I (persistent depolarization, initial fasciculations), then Phase II (desensitization block, flaccid paralysis).
    • Rapid onset, short duration.
  • Non-Depolarizing (Competitive):
    • Examples: "-curoniums" (Pancuronium, Vecuronium, Rocuronium); "-curiums" (Atracurium, Cisatracurium).
    • MOA: Compete with Acetylcholine (ACh) for Nm receptors.
    • Reversible by AChE inhibitors (e.g., Neostigmine, Sugammadex for Rocuronium/Vecuronium).
• Clinical Uses: Anesthesia for surgical relaxation, endotracheal intubation, mechanical ventilation.
• Key Points:
  • Atracurium: Undergoes Hofmann elimination (useful in renal/hepatic failure).
  • Cisatracurium: Less histamine release than Atracurium.

⭐ Succinylcholine can cause significant hyperkalemia in patients with burns, crush injuries, or upper motor neuron lesions, potentially leading to cardiac arrest. Use is contraindicated >24-48 hours post-injury until risk subsides (months).

High‑Yield Points - ⚡ Biggest Takeaways

• Atropine: prototype muscarinic antagonist; treats bradycardia, organophosphate poisoning.
• Antimuscarinic toxidrome: "Dry as a bone, blind as a bat, red as a beet, mad as a hatter, hot as a hare".
• Ipratropium/Tiotropium: inhaled for COPD/asthma; poor systemic absorption.
• Scopolamine: for motion sickness; preanesthetic use.
• Contraindications: Narrow-angle glaucoma, BPH, bowel obstruction.
• Oxybutynin/Tolterodine/Solifenacin: treat overactive bladder.
• Benztropine/Trihexyphenidyl: for Parkinson's disease and drug-induced EPS.