A comprehensive study notes on Anticholinergic (Cholinergic Antagonist) Drugs

CHOLINERGIC ANTAGONISTS (ANTICHOLINERGIC DRUGS)

These are drugs that block the effects of acetylcholine (ACh) at cholinergic receptors. They are the opposite of cholinergic (parasympathomimetic) drugs.

Classification

Cholinergic antagonists are divided into three main groups:

1. Antimuscarinic agents (Muscarinic blockers)

2. Ganglionic blockers

3. Neuromuscular blockers

1. ANTIMUSCARINIC AGENTS (MUSCARINIC BLOCKERS)

These agents competitively block muscarinic receptors, preventing ACh from exerting its effects on organs innervated by the parasympathetic nervous system.

Mechanism of Action (MOA)

• Block muscarinic receptors (M1–M5), leading to inhibition of parasympathetic activity.

• Effects include increased heart rate, decreased secretions, relaxation of smooth muscles, and pupil dilation.

A. Atropine

Site of Action:
Eye, GI tract, heart, salivary glands, sweat glands, and lacrimal glands.

Pharmacologic Effects:

• Eye:

  • Relaxation of ciliary muscle → Mydriasis (pupil dilation)

  • Loss of accommodation → Cycloplegia (blurred near vision)

  • Unresponsiveness to light

  • Used before eye exams and surgery

• GI tract:

  • Blocks M3 receptors → Decreases GI motility

  • Delays gastric emptying and intestinal transit

• Heart:

  • Blocks M2 receptors on SA and AV nodes → Tachycardia (↑ HR by 30–40 bpm)

• Glands:

  • Inhibits salivary, sweat, and lacrimal glands → Dry mouth, dry skin, ↑ body temperature

Clinical Uses:

• Pre-anesthetic to reduce secretions

• Bradycardia treatment

• Eye examinations

• Antidote for organophosphate poisoning

Adverse Effects:

• Dry mouth, blurred vision, constipation, urinary retention, tachycardia, fever

B. Scopolamine

Key Points:

• Greater CNS penetration and longer duration than Atropine.

• Produces sedation and amnesia.

Uses:

• Prevention of motion sickness (transdermal patch lasting up to 3 days)

• Postoperative nausea and vomiting

Adverse Effects:

• Drowsiness, confusion, dry mouth, blurred vision

C. Ipratropium and Tiotropium

MOA:

• Nonselective muscarinic blockers that cause bronchodilation and decrease mucus secretion.

Uses:

• Maintenance therapy for COPD and asthma

• Ipratropium (short-acting, 4× daily)

• Tiotropium (long-acting, once daily)

• Ipratropium nasal spray → reduces rhinorrhea (runny nose)

D. Overactive Bladder Drugs

Agents:

• Tolterodine

• Darifenacin

• Solifenacin

• Oxybutynin

• Trospium

• Fesoterodine

MOA:

• Block M3 receptors in the bladder → Reduce detrusor muscle contraction

• Increase bladder capacity and delay urge to void

Adverse Effects:

• Dry mouth, constipation, blurred vision, urinary retention

E. Central Muscarinic Blockers

Agents:

• Benztropine

• Trihexyphenidyl

MOA:

• Inhibit central cholinergic activity in the CNS.

• Restore balance between dopamine and ACh in Parkinson’s disease.

Uses:

• Parkinson’s disease

• Drug-induced extrapyramidal symptoms (from antipsychotics)

Mnemonic for Anticholinergic Side Effects

ABCDS:

• A – Agitation

• B – Blurred vision

• C – Constipation and Confusion

• D – Dry mouth

• S – Stasis of urine and Sweating (↓ sweating → ↑ temperature)

2. GANGLIONIC BLOCKERS

Main Agent: Nicotine

Mechanism:

• Acts on nicotinic receptors (Nn) in autonomic ganglia of both sympathetic and parasympathetic systems.

• Initially stimulates, then blocks cholinergic transmission (functional antagonist).

Effects:

• CNS:

  • Low doses → stimulation → alertness, well-being

  • High doses → depression → convulsions, respiratory paralysis

• CV System:

  • Stimulates adrenal medulla → ↑ BP and HR (low dose)

  • High dose → hypotension

• GI System:

  • ↑ motility → nausea and vomiting

• Addiction Potential:

  • Causes dependence via dopamine and serotonin release

Clinical Use:

• Limited to smoking cessation therapy

3. NEUROMUSCULAR BLOCKERS

These agents block nicotinic receptors (Nm) at the neuromuscular junction, preventing acetylcholine from triggering muscle contraction.

Mechanism of Muscle Contraction Recap

1. ACh released → binds to nicotinic receptors

2. Sodium influx → depolarization → action potential

3. Calcium release from sarcoplasmic reticulum → contraction

Neuromuscular blockers interfere with this process.

A. Nondepolarizing Agents (Competitive Antagonists)

MOA:

• Bind to nicotinic receptors but do not open ion channels, preventing depolarization and muscle contraction.

Effects:

• Paralysis proceeds in this order:

  1. Eyes and face

  2. Neck and limbs

  3. Diaphragm (last)

  • Recovery occurs in reverse order.

Clinical Uses:

• Facilitate intubation and mechanical ventilation

• Adjunct to anesthesia for muscle relaxation

Agents & Duration:

• Cisatracurium – 90 min, safe in renal/hepatic failure

• Pancuronium – 90 min, ↑ HR

• Rocuronium – 40 min

• Vecuronium – 40 min

• Atracurium – 40 min, causes histamine release and seizures (via metabolite laudanosine)

Adverse Effects:

• Hypotension, bronchospasm (histamine release), tachycardia, prolonged paralysis

B. Depolarizing Agent (ACh Receptor Agonist)

Agent: Succinylcholine

MOA:

• Acts as ACh receptor agonist, causing persistent depolarization → muscle paralysis.

• Not rapidly degraded by acetylcholinesterase → prolonged action.

Phases:

1. Phase I Block: Persistent depolarization → fasciculations → flaccid paralysis

2. Phase II Block: Receptor desensitization → no further action potentials

Clinical Use:

• Rapid-sequence intubation

• Electroconvulsive therapy (ECT)

Pharmacokinetics:

• IV onset: within 1 min

• Duration: 5–10 min (metabolized by plasma pseudocholinesterase)

Adverse Effects:

• Prolonged apnea (in pseudocholinesterase deficiency)

• Hyperkalemia (especially in burns, trauma)

• Malignant hyperthermia (genetic predisposition; causes extreme fever and muscle rigidity)

SUMMARY 

Group	Example Drugs	Receptor Target	Main Effects / Uses
Antimuscarinic	Atropine, Scopolamine, Ipratropium, Tiotropium	Muscarinic (M1–M5)	Decrease secretions, bronchodilation, increase HR, mydriasis
Bladder Selective	Oxybutynin, Tolterodine	M3	Decrease bladder spasm
CNS Active	Benztropine, Trihexyphenidyl	M1 (CNS)	Parkinsonism
Ganglionic Blocker	Nicotine	Nn	Stimulatory then blocking; addiction
Nondepolarizing Blocker	Rocuronium, Vecuronium, Cisatracurium	Nm	Muscle relaxation (surgery)
Depolarizing Blocker	Succinylcholine	Nm	Rapid paralysis (intubation)

Mnemonics:

• ABCDS → Anticholinergic effects

• Order of paralysis: Eyes → Face → Neck → Limbs → Diaphragm

• Reversal order: Diaphragm → Limbs → Neck → Eyes