Pharm 101: Atropine

Class

Antimuscarinic agent

Pharmacodynamics

• Atropine is a tertiary amine alkaloid ester of tropic acid
• Competitive, reversible muscarinic ACh receptor antagonist
  • Binding prevents release of IP3 (inositol triphosphate), DAG (diacyglycerol), and inhibition of adenylyl cyclase, which are caused by muscarinic agonists
• Equipotent at M1, M2, M3 receptors
• No significant nicotinic effect

Organ system effects

• CNS:
  • Sedation
  • Delirium
  • Decreased tremor in Parkinson’s disease
• Eye:
  • Mydriasis (pupillary constrictor muscle depends on muscarinic cholinoceptor activation)
  • Cyclopegia (weakened contraction of ciliary muscle)
• CVS:
  • Initial bradycardia at lower doses (blocks prejunctional M1 receptors)
  • Tachycardia
• Resp: bronchodilation and decreased secretions
• GIT:
  • Decreased secretions
  • Decreased gastric emptying
  • Decreased gut motility
  • Increased intestinal transit time
• GUT:
  • Relaxation of ureteric and bladder wall smooth muscle
  • Urinary retention
• Skin: decreased sweating

Pharmacokinetics

• Route of administration: IV, PO, nebulised, topical
• Well absorbed orally
• Significant levels in CNS within 30-60 minutes, wide Vd
• Two phases of elimination:
  • Rapid: half-life 2 hours
  • Slow: half-life 13 hours
• Hepatic metabolism and subsequent renal excretion:
  • 40% phase I and phase II metabolism
  • 60% unchanged

Clinical uses

• Symptomatic bradyarrhythmias / bradycardia
• Opthalmological: mydriatic and cyclopegic
• Drying of secretions e.g. cholinergic nerve agonist, OP poisoning, palliative care
• Traveller’s diarrhoea

Adverse effects

• Extension of organ system effects, typical antimuscarinic effects

Precautions

• Glaucoma
• Prostate hyperplasia
• Gastric ulcers (slow gastric emptying thus worsen symptoms)

Further reading

• Buttner R. Pharm 101: Benzotropine. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 124-131