Anticholinergic Drugs (Muscarinic Receptor Antagonists)

Anticholinergic Drugs

Definition: Cholinergic antagonists (also known as cholinergic blockers, parasympatholytics, or anticholinergic drugs).

  • Bind to cholinoceptors but do not trigger the usual receptor-mediated intracellular effects.

Prototype: Atropine.

  • Highly selective for muscarinic receptors.
  • Some synthetic substitutes may have nicotinic blocking properties.
  • All anticholinergics are competitive antagonists.

Classification of Anticholinergic Drugs

  1. Natural Alkaloids:

    • Atropine
    • Hyoscine

  2. Semisynthetic Derivatives:

    • Homatropine
    • Atropine methonitrate
    • Hyoscine butyl bromide
    • Ipratropium bromide

  3. Synthetic Compounds:

    • Mydriatics: Cyclopentolate, Tropicamide.
    • Antisecretory-antispasmodics:
    • Quaternary Compounds:
      • Propantheline
      • Oxyphenonium
      • Clidinium
      • Pipenzolate methyl bromide
      • Isopropamide
      • Glycopyrrolate.
    • Tertiary Amines:
      • Dicyclomine
      • Oxybutynin
      • Flevoxate
      • Pirenzepine
      • Telenzipine.

  4. Antiparkinsonian: Trihexyphenidyl, Procyclidine, Biperiden, Benztropine.

  5. Other Drugs with anticholinergic properties:

    • Tricyclic Antidepressants
    • Phenothiazines
    • Antihistamines
    • Disopyramide

Pharmacological Action of Atropine

Cardiovascular System:

  • Main Effect: Tachycardia.
  • Low doses (0.2-0.3 mg) may cause a transient decrease in heart rate initially due to central effects; peripheral blockade then increases heart rate.
  • Therapeutic doses lead to vagal blockade at SA and AV nodes resulting in tachycardia.
  • Little effect on blood pressure at usual doses; large doses (> 2 mg) may increase BP.

Respiratory System:

  • Produces bronchodilation; effects evident with cholinergic-induced bronchoconstriction.
  • Reduces bronchial secretions.

Gastrointestinal System:

  • Reduces tone and motility across GIT.
  • Antagonizes spasmogenic action of morphine on intestines.
  • Partially blocks effects of vagus nerve stimulation without affecting normal peristalsis.

Eye:

  • Causes mydriasis by blocking cholinergic nerves in iris sphincter.
  • Produces cycloplegia (inability to accommodate for near vision).

Central Nervous System:

  • Mild vagal excitation from therapeutic doses.
  • Toxic doses can cause restlessness, irritability, disorientation, hallucinations, depression, and potentially lead to circulatory collapse and respiratory failure.

Glands:

  • Decreases secretions leading to dry mouth, reduced sweating, and lacrimation.
  • Contraindicated in children due to risk of hyperthermia from decreased sweating.

Pharmacokinetics

  • Absorption: 10-25% from GIT; major sites are duodenum and jejunum.
  • Plasma protein binding: ~50%.
  • Half-Life: 3-4 hours.
  • Excretion: Up to 80% in urine within 8 hours; 95% in 24 hours.
  • Metabolism: Processed in the liver to tropine and tropic acid; only a small fraction is excreted unchanged.
  • Crosses: Placenta; Blood-brain barrier passage is restricted.

Dosage & Administration

  • Usual Adult Dose: 0.6 – 2 mg (IM/IV); 1 – 2% topically for eyes.
  • Child Dosage: 0.02 mg/kg, maximum of 0.6 mg.
  • Often used with anti-AChE agents to reverse NMJ blockade (0.6-1.2 mg).

Therapeutic Uses

  1. CNS:

    • Parkinson’s Disease: Benztropine and Benzhexol reduce tremors and rigidity.
    • Motion Sickness: Scopolamine prevents symptoms.

  2. Eye:

    • Pupil dilation for fundoscopic exam: Atropine and homatropine.
    • Treats keratitis and iritis.

  3. CVS:

    • Treats sinus bradycardia post-myocardial infarction and digitalis toxicity.

  4. Respiratory System:

    • Treats Bronchial asthma and COPD (Ipratropium).
    • Pre-anesthetic medication with Atropine and Scopolamine.
    • Glycopyrrolate is more effective anti-sialogogue than Atropine.

  5. GIT:

    • Spasmolytics for intestinal/biliary colic; previously used for peptic ulcers, now less common due to H2 blockers and PPIs.

  6. Antidote: Atropine is effective for cholinesterase inhibitor overdose and certain mushroom poisonings.

Precautions with Atropine Therapy

  • Use caution in patients over 40; risk of acute congestive glaucoma.
  • Avoid in those with tendencies to tachycardia (hyperthyroidism, CVD); Scopolamine may be preferred.

Overdosage Symptoms:

  • Dry mouth
  • Blurred vision, mydriasis
  • Hot dry skin, hyperpyrexia
  • Restlessness,