BMS161 Cholinergic Pharmacology: Antimuscarinic

Antimuscarinic Pharmacology

• Antimuscarinics are competitive antagonists of acetylcholine (Ach) at muscarinic (M) receptors.

Effects of Atropine

CNS

• Stimulation of respiratory center
• Antiemetic effects by blocking M receptors in vomiting center
• Antiparkinsonian effects
• Eye effects:
  • Passive mydriasis (paralysis of constrictor)
  • Cycloplegia (loss of accommodation)
  • Increased intraocular pressure (IOP) → acute glaucoma in narrow chamber

CVS

• Tachycardia and increased AVN conduction
• No effect on blood pressure (M3 has no role in regulating blood pressure)
• Vasodilation (histamine release in toxic dose)

Smooth Muscle

• Decreased salivation (dry mouth)
• Decreased lacrimation (dry, sandy eyes)
• Bronchodilation
• Decreased sweating (increased body temperature)
• Decreased gastric secretion (least affected)
• Urinary retention
• Decreased bronchial secretions

Adverse Effects and Contraindications

• Confusion, restlessness, hallucinations, delirium, and mania
• Blurred vision and photophobia
• Acute glaucoma in patients with narrow anterior chamber (contraindication)
• Dry mouth and skin
• Hyperthermia (complete skin dryness)
• Vasodilation and flushing
• Tachycardia
• Urine retention in old patients with enlarged prostate (contraindication)
• Constipation

Atropine Toxicity and Treatment

• Treatment:
  • Physostigmine
  • Diazepam
  • Cooling blankets

Clinical Uses of Atropine and Atropine Substitutes

Pre-anesthetic Medication

• Decreased salivary and bronchial secretion
• Anti-emetic effects
• Bronchodilation
• Stimulation of respiratory center
• Decreased severe vagal bradycardia in anesthesia

Hyoscine (Scopolamine)

• Mydriatic (briefer than atropine)
• More safe in thyrotoxicosis and cardiac patients (less risk of arrhythmia)
• More CNS depressant action → drowsiness and amnesia
• Disadvantage: May induce CNS excitement and hallucination in females → vivid dreams

Antiparkinson (PD)

• Drug used: Benztropine (Benzhexol)
• Used for tremors or antipsychotic-induced PD

Vomiting of Motion Sickness and Minieres Disease

• Drug used: Hyoscine (more effective than atropine)

Mydriatic Cycloplegics

• Drugs used: Cyclopentolate, tropicamide, and homatropine
• Advantages: shorter-acting and easier to reverse (except in children)
• Uses:
  • Iridocyclitis
  • Measuring refractive errors
  • Fundus examination

Bronchial Atropine Substitutes

• Advantages: 4ry amines given by inhalation with no systemic effect and not drying secretions
• Used in asthma and COPD: delayed onset
• Drugs used:
  • Ipratropium (M2/M3 blocker)
  • Tiotropium (selective M3 blocker)
• Longer-acting with no tolerance

Antisecretory Antispasmodics

• Used before neostigmine to decrease its side effects (bradycardia, bronchospasm) during reversal of action of competitive muscle blockers
• Drugs used:
  • Glycopyrrolate
  • Hyoscine butylbromide
  • 3ry drugs: Dicyclomine (selective M1 blocker in Myenteric plexus) → antispasmodic

Urinary Atropine Substitutes

• Used in nocturnal enuresis and in urge incontinence and overactive bladder
• Drugs used:
  • Oxybutynin
  • Darifenacin
  • Solifenacin
  • Tolterodine
  • Trospium
  • Emepronium

Atropine Still Used In:

• CVS:
  • Hyperactive carotid sinus
  • Heart block (AV block)
  • Bradycardia (in infarction or digitalis toxicity)
• Organophosphate poisoning
• Mushroom poisoning (Amanita muscaria)
• Cycloplegic in children
• Pre-anesthetic medication

Drugs with Atropine-Like Action

• Additive atropine effects:
  • Antiarrhythmics: quinidine, procainamide, and disopyramide
  • Antihistamines (1st generation)
  • Tricyclic antidepressants, antipsychotics, and pethidine