L17 Adrenergic Transmission and Adrenoceptors

• Anti Cholinergic Drugs


  Drugs that blocks or inhibit the action of acetylcholine in the parasympathetic nervous system

  
• Antimuscarinic drugs


  Drugs which specifically antagonizing 'muscarinic' receptors
• Atropine


  Prototype of antimuscarinic drugs, a tertiary amine extracted from belladonna alkaloid
• Classification of Antimuscarinics


  • Natural alkaloids: Atropine, Scopolamine, Hyoscine
  • Semisynthetic & Synthetic: Tertiary amines - Pirenzepine, Dicyclomine, Homatropine, Cyclopentolate, Tropicamide
  • Quaternary amines - Propantheline, Glycopyrrolate, Ipratropium
  • Antiparkinsonism: Procyclidine, benztropine
• Mechanism of action of Antimuscarinics

  Reversibly/competitively block muscarinic receptors, highly selective to muscarinic receptors
• Pharmacological actions of Atropine

  • Blocks all muscarinic receptors, has both central and peripheral effects, highly sensitive to salivary, bronchial and sweat glands
• Pharmacological actions of Antimuscarinics

  • Cardiovascular effects - tachycardia, facilitates AV conduction
  • Eye effects - mydriasis, cycloplegia, reduced lacrimal secretion
  • GI effects - relaxes smooth muscles, reduces secretions
  • Respiratory effects - bronchodilation, reduces secretions
  • Urinary effects - relaxation of detrusor, constriction of sphincter
  • Glandular effects - reduces sweating, lacrimal, salivary secretions
  • CNS effects - sedation, drowsiness, amnesia, high doses - excitement, hallucinations

  
• Uses of Atropine and its substitutes

  • Peptic ulcer - Pirenzepine, Telenzepine
  • Antispasmodic - Hyoscine, Glycopyrrolate, Dicyclomine
  • Mydriatic and cycloplegic agent - Tropicamide, Cyclopentolate, Homatropine
  • Bronchial asthma - Ipratropium bromide
  • Bradycardia and AV block after MI
  • Parkinsonism and drug-induced extrapyramidal dysfunction - Procyclidine, Benztropine
  • Motion sickness, sea sickness - Scopolamine, Hyoscine
  • Pre-anesthetic medication
  • Antidote to organophosphorus and mushroom poisoning

  
• Natural atropine is not used clinically due to prolonged duration of action and wide range of adverse effects
• Advantages of atropine substitutes over atropine

  Shorter duration of action, more specific action and less adverse effects
• Adverse effects of atropine and its substitutes

  • Blurring of vision, dry mouth, constipation, fever, urinary retention, tachycardia, agitation, hallucinations, delirium

  
• Dose-dependent effects of atropine
• Clinical features of atropine poisoning

  • Eye - blurred vision, raised IOP, mydriasis, loss of accommodation reflex, dry eye
  • Cardiovascular - tachycardia
  • GI - constipation
  • Genitourinary - urinary retention
  • Exocrine - dry skin, dry mouth
  • CNS - restlessness, agitation, drowsiness, convulsion

  
• Classical clinical features of atropine poisoning

  • Red as beet (skin flushed)
  • Hot as hare (hyperthermia)
  • Dry as bone (dry mucous membrane, no sweating)
  • Blind as bat (cycloplegia, blurred vision)
  • Mad as hatter (confusion, delirium)
• Management of atropine poisoning

  • General management - vital sign monitoring, gastric suction, catheterization, diazepam for seizures, symptomatic treatment
  • Specific management - Physostigmine
• Relative contraindications of atropine

  • Glaucoma
  • Urinary retention (especially in BPH)
  • Gastrointestinal obstruction