Anticholinergic Drugs Study Notes

Anticholinergic Drugs (Cholinergic Antagonists) – Study Notes

Overview

Cholinergic antagonists block the effects of acetylcholine (ACh) at muscarinic or nicotinic receptors.
They reduce parasympathetic activity (“rest and digest”) and are divided into three main groups:

1. Antimuscarinic agents – block muscarinic receptors

2. Ganglionic blockers – block nicotinic receptors at autonomic ganglia

3. Neuromuscular blockers – block nicotinic receptors at the neuromuscular junction

1. Antimuscarinic Agents

Block parasympathetic innervation at muscarinic receptors.

Common Agents

• Atropine

• Scopolamine

• Ipratropium, Tiotropium, Aclidinium

• Darifenacin, Solifenacin, Oxybutynin, Tolterodine, Fesoterodine, Trospium

• Benztropine, Trihexyphenidyl

Atropine

• Mechanism: Competitive antagonist of muscarinic receptors (central + peripheral)

• Duration: General effects last ~4 hours; ocular effects last for days

Clinical Uses:

• Cardiac: Treat bradycardia (blocks vagal stimulation)

• Antispasmodic: Reduce GI motility preoperatively

• Antisecretory: Reduce respiratory secretions before surgery

• Ophthalmic: Mydriasis and cycloplegia (long-lasting)

• Antidote: For cholinergic poisoning (e.g., organophosphates, mushrooms)

Adverse Effects:

• Up to 5 mg: Dry mouth, blurred vision, tachycardia, urinary retention, constipation, hyperthermia, ↓sweating

• High doses (~10 mg): CNS toxicity—restlessness, confusion, hallucinations, delirium

Toxicity Mnemonic:

“Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter.”

Contraindication:

• Angle-closure glaucoma (↑ intraocular pressure)

• Caution in children → risk of hyperthermia

Scopolamine

• Duration: Long-acting

• Uses:

  • Motion sickness prevention (transdermal patch – 3 days)

  • Postoperative nausea/vomiting

• CNS Effects: Sedation, amnesia, confusion at normal doses

• Adverse Effects: Similar to atropine

Respiratory Antimuscarinics

Agents: Ipratropium (SAMA), Tiotropium and Aclidinium (LAMA)
Administration: Inhalation → local delivery, minimal systemic effects

• Ipratropium: Acute management of bronchospasm in asthma

• Tiotropium: Chronic management of bronchospasm in asthma and COPD

• Tiotropium & Aclidinium: Maintenance therapy in COPD

Genitourinary Antimuscarinics

Agents: Darifenacin, Solifenacin, Oxybutynin, Tolterodine, Fesoterodine, Trospium
Uses: Overactive bladder and urinary incontinence

• Mechanism: Block M3 receptors in bladder → ↓ pressure and contractions

• Darifenacin, Solifenacin: Selective for M3 (fewer side effects)

• Extended-release/patch forms (e.g., Oxybutynin) have lower incidence of dry mouth and constipation

• Common ADEs: Dry mouth, constipation, blurred vision, confusion

CNS Antimuscarinics (Parkinsonism)

Agents: Benztropine, Trihexyphenidyl
Uses:

• Adjunct in Parkinson’s disease

• Treat extrapyramidal symptoms (EPS) caused by antipsychotics (e.g., haloperidol)
  EPS Symptoms: Tremors, rigidity, repetitive movements

2. Ganglionic Blockers

Mechanism: Block nicotinic receptors at autonomic ganglia → inhibit both sympathetic and parasympathetic activity
Agents: Nicotine (prototype)

• Limited therapeutic use due to unpredictable actions

• Nicotine effects: Stimulates transmitter release → causes arousal, appetite suppression, tachycardia, urinary retention

• Therapeutic use: Smoking cessation (nicotine replacement therapy)

3. Neuromuscular Blockers

Block nicotinic receptors at skeletal muscle NMJ → muscle relaxation
Used in: Surgery, intubation, mechanical ventilation

Types:

1. Nondepolarizing (antagonists) – compete with ACh

2. Depolarizing (agonists) – activate receptor but prevent repolarization

Nondepolarizing Neuromuscular Blockers

Agents: Cisatracurium, Pancuronium, Rocuronium, Vecuronium
Administration: IV
Onset: 1–3 minutes
Duration: 8–90 minutes (drug-dependent)
Order of paralysis: Face/eye → limbs → trunk → diaphragm

Special Notes:

• Cisatracurium: Used in organ failure (spontaneous plasma degradation)

• Reversal: AChE inhibitors (e.g., neostigmine) can reverse low-dose blockade

• Potentiated by: Inhaled anesthetics, aminoglycoside antibiotics

Adverse Effects:

• Pancuronium → Vagolytic (↑ heart rate)

Depolarizing Neuromuscular Blockers

Agent: Succinylcholine
Mechanism: Binds nicotinic receptor → depolarization → initial fasciculations → sustained paralysis

Phases:

• Phase I: Persistent depolarization (fasciculation)

• Phase II: Membrane repolarizes but is unresponsive → flaccid paralysis

Use:

• Rapid endotracheal intubation

• Electroconvulsive therapy

Pharmacokinetics:

• Rapid onset, short duration

• Metabolized by plasma cholinesterases

Adverse Effects:

• Muscle soreness, malignant hyperthermia, hyperkalemia, apnea

• Avoid in: Burns, massive trauma, renal failure, or electrolyte imbalances (↑ K⁺ risk)

Summary Table

Category	Examples	Major Use	Key Notes
Antimuscarinic	Atropine, Scopolamine	Bradycardia, Motion sickness	Drying, CNS effects
Respiratory	Ipratropium, Tiotropium	Asthma, COPD	Inhaled, few systemic effects
GU	Oxybutynin, Solifenacin	Overactive bladder	M3 blockade
CNS	Benztropine, Trihexyphenidyl	Parkinsonism, EPS	Central muscarinic blockade
Ganglionic	Nicotine	Smoking cessation	Complex systemic effects
Nondepolarizing NMB	Rocuronium, Cisatracurium	Surgery/intubation	Reversible by AChE inhibitors
Depolarizing NMB	Succinylcholine	Rapid intubation	Risk: MH, hyperkalemia