11. CHOLINERGIC AND ANTICHOLINERGIC DRUGS AND NEUROMUSCULAR BOCKERS

Introduction

The cholinergic system controls many involuntary body functions through the neurotransmitter acetylcholine (ACh). Drugs that increase ACh actions are called cholinergic drugs. Drugs that block its actions are called anticholinergic drugs. Another important category is neuromuscular blockers, which act at skeletal muscle junctions and are widely used during surgical procedures.

Cholinergic System Overview

ACh is produced inside the nerve terminal from choline and acetyl-CoA. It is stored in vesicles and released when the nerve is stimulated. After acting on receptors, ACh is immediately broken down by acetylcholinesterase (AChE).

Types of Cholinesterase Enzymes

  • True cholinesterase (AChE): Found in nerves, RBCs, neuromuscular junction.
  • Pseudocholinesterase: Found in plasma and liver; breaks many ester drugs.

Cholinergic Receptors

Cholinergic receptors are of two main types:

  • Muscarinic receptors (M1–M5): Found in smooth muscles, glands, heart.
  • Nicotinic receptors (Nn & Nm): Found in autonomic ganglia and skeletal muscles.

Cholinergic (Parasympathomimetic) Drugs

These drugs increase parasympathetic activity by either directly stimulating receptors or by increasing ACh levels.

1. Direct-Acting Cholinergic Drugs

a) Choline Esters

  • Acetylcholine: Not clinically useful due to rapid breakdown.
  • Carbachol: Used in glaucoma.
  • Bethanechol: Increases bladder contraction and GI motility.

Bethanechol – Uses and Effects

  • Treats postpartum or postoperative urinary retention.
  • Used in non-obstructive bladder atony.
  • Side effects: sweating, salivation, diarrhoea, bronchospasm.

b) Cholinomimetic Alkaloids

  • Pilocarpine: causes miosis, increases salivation and tears; used in glaucoma and dry mouth.

2. Indirect-Acting Cholinergic Drugs (Anticholinesterases)

These drugs inhibit AChE and increase ACh levels at synapses.

Reversible Anticholinesterases

  • Physostigmine
  • Neostigmine
  • Pyridostigmine
  • Edrophonium
  • Donepezil, Rivastigmine (used in Alzheimer’s)

Important Uses

  • Myasthenia gravis
  • Glaucoma
  • Reversal of non-depolarising muscle blockers
  • Postoperative ileus and urinary retention

Organophosphate (Irreversible) Anticholinesterases

Examples: parathion, malathion, echothiophate. They cause dangerous accumulation of ACh.

Organophosphate Poisoning – Key Features

  • Muscarinic effects: sweating, salivation, miosis, diarrhoea, bronchospasm.
  • Nicotinic effects: muscle weakness, paralysis.
  • CNS effects: confusion, convulsions, respiratory failure.

Treatment

  • Atropine: blocks muscarinic effects.
  • Oximes (Pralidoxime): reactivates AChE if given early.
  • Supportive care and decontamination.

Anticholinergic Drugs (Parasympatholytics)

These drugs block muscarinic receptors and reduce parasympathetic activity.

Important Anticholinergic Drugs

1. Atropine

  • Causes pupil dilation, decreases secretions.
  • Used in bradycardia, pre-anaesthetic medication.
  • Antidote for organophosphate poisoning.

2. Scopolamine

  • Effective in motion sickness.
  • Causes sedation and amnesia.

3. Ipratropium & Tiotropium

  • Inhalational bronchodilators for COPD and asthma.

4. Tropicamide & Cyclopentolate

  • Used for short-acting pupil dilation.

5. Oxybutynin, Tolterodine, Solifenacin

  • Used for overactive bladder.

Side Effects of Anticholinergics

  • Dry mouth
  • Blurred vision
  • Constipation
  • Urinary retention
  • Tachycardia

Neuromuscular Blockers

These drugs block transmission at neuromuscular junctions and cause muscle relaxation. They are used during surgery and intubation.

Types of Neuromuscular Blockers

  • Non-depolarising blockers (competitive antagonists)
  • Depolarising blockers (persistent depolarisation)

1. Non-Depolarising Blockers

Examples: atracurium, cisatracurium, vecuronium, rocuronium, pancuronium.

Mechanism

They compete with ACh at nicotinic receptors at the neuromuscular junction and prevent muscle contraction. Effects can be reversed with neostigmine or pyridostigmine.

Clinical Uses

  • Muscle relaxation during surgery
  • Facilitation of intubation

Adverse Effects

  • Hypotension (due to histamine release)
  • Prolonged paralysis in liver/kidney disease

2. Depolarising Blocker

Succinylcholine

Only depolarising blocker used clinically.

Mechanism

  • Binds nicotinic receptors and causes continuous depolarisation.
  • Leads to muscle fasciculations → paralysis.

Uses

  • Rapid sequence intubation
  • Short surgical procedures

Adverse Effects

  • Hyperkalemia
  • Malignant hyperthermia (treated with dantrolene)
  • Prolonged apnea in cholinesterase deficiency

Detailed Notes:

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