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• Cholinergic antagonists


  Agents that bind to cholinoceptors (muscarinic or nicotinic) and prevent the effects of acetylcholine (ACh) and other cholinergic agonists
• Anticholinergic agents


  Also known as antimuscarinic agents or parasympatholytics, selective blockers of muscarinic receptors
• Atropine


  The prototype of antimuscarinic drugs, also called hyoscyamine, found in the plant Atropa belladona (deadly nightshade), and Datura stramonium (Jimsonweed/ Jamestown weed; sacred Datura or thorn apple)
• Mechanism of action of atropine

  Causes reversible (surmountable) blockade of cholinomimetic actions at muscarinic receptors
• Effects of atropine in specific organs

  • Eye (mydriasis, cycloplegia, reduced lacrimation)
  • Gastrointestinal tract (dry mouth, reduced motility, intestinal paralysis)
  • Cardiovascular system (bradycardia at low doses, tachycardia at high doses)
  • Respiratory system (bronchodilation, reduced secretion)
  • Genitourinary tract (relaxes smooth muscles, urinary retention)
  • Sweat glands (suppresses thermoregulatory sweating)
  • Central nervous system (minimal stimulant effects, sedative effect)
• Clinical applications of atropine

  • Mydriatic & cycloplegic agent
  • Antispasmodic
  • Treatment of bradycardia
  • Antisecretory agent used before surgery
  • Antidote for cholinergic agonists poisoning
• Adverse effects of atropine

  • Dry mouth
  • Blurred vision
  • Sandy eyes
  • Tachycardia
  • Urinary retention
  • Constipation
  • CNS effects (restlessness, confusion, hallucination, delirium, depression, respiratory & CV collapse, death)
• Antidote for atropine toxicity

  Low doses of cholinesterase inhibitors, such as physostigmine
• Contraindications of atropine


  • Glaucoma (Angle-closure glaucoma)
  • Prostatic hyperplasia
• Scopolamine (Hyoscine)


  Has greater action on the CNS compared to atropine
• Actions of scopolamine


  • One of the most effective anti-motion sickness drug
  • Short-term memory block
  • Can cause sedation
  • Can cause excitement at higher doses
  • May produce euphoria and is susceptible to abuse
• Therapeutic uses of scopolamine

  • Motion sickness (topical patch - 3 days)
  • Postoperative nausea & vomiting
• Drugs for respiratory disorders

  • Ipratropium - synthetic analog of atropine, used as inhalational drug in asthma & COPD
  • Tiotropium - has longer bronchodilator action and can be given once daily
• Other antimuscarinic drugs


  • Oxybutinin - used to relieve bladder spasm after urologic surgery, valuable in reducing involuntary voiding in patients with neurologic disease
  • Trospium - a nonselective antagonist, comparable in efficacy and side effects to oxybutinin
  • Darifenacin & Solifenacin - has the advantage of once-daily dosing
  • Tolterodine & Fesoterodine - available for use in adults with urinary incontinence
  • Imipramine - a tricyclic antidepressant with strong antimuscarinic functions, used to reduce incontinence in institutionalized elderly patients
  • Propiverine - a newer antimuscarinic drug approved to reduce incontinence in elderly patients
• Ganglion-blocking drugs


  Competitively block the action of acetylcholine and similar agonists at nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia
• Ganglion-blocking drugs


  • Nicotine
  • Tetraethylammonium (TEA)
  • Hexamethonium
  • Decamethonium
  • Mecamylamine
  • Trimethaphan
• Mechanism of action of ganglion-blocking drugs

  Competitively block ganglionic nicotinic receptors
• Motion sickness drugs


  • Scopolamine - unknown mechanism of action in CNS, reduces vertigo and postoperative nausea & vomiting
• Gastrointestinal disorder drugs


  • Dicyclomine (Bentyl) - competitive antagonist at M3 receptor, reduces smooth muscle and secretory activity of the gut
  • Hyoscyamine - longer duration of action
  • Glycopyrrolate - similar to dicyclomine
• Ophthalmology drugs


  • Atropine - competitive antagonist at all M receptors, causes mydriasis and cycloplegia, contraindicated in glaucoma
• Respiratory drugs (asthma, COPD)

  • Ipratropium (Atrovent) - competitive, non-selective antagonist at M receptors, reduces/prevents bronchospasm
• Urinary drugs


  • Oxybutinin (Ditropan) - non-selective muscarinic antagonist, reduces detrusor smooth muscle tone and spasms
• Cholinergic poisoning treatments


  • Atropine - mandatory antidote for severe cholinesterase inhibitor poisoning
  • Pralidoxime (Protopam) - regenerates active acetylcholinesterase, can relieve skeletal muscle and plate block, usual antidote for early stage (48hrs) cholinesterase inhibitor poisoning
• Cholinesterase regenerator compounds like pralidoxime (PAM) and diacetylmonoxime (DAM) given IV, not recommended for poisoning caused by carbamates
• Mushroom poisoning treatments


  • Rapid-onset type - apparent within 30 mins to 2 hrs, characterized by early signs of muscarinic excess, atropine is an effective treatment
  • Delayed-onset type - usually caused by Amanita phalloides, A virosa, Galerina autumnalis, G marginata, first symptoms 6-12 hours after ingestion, major toxicity involves hepatic and renal cellular injury, atropine is of no use
• Neuromuscular blocking agents


  Block cholinergic transmission between motor nerve endings & nicotinic receptors on the skeletal muscle
• Types of neuromuscular blocking agents

  • Nondepolarizing (competitive) blockers - antagonist
  • Depolarizing agents - agonist
• Nondepolarizing blockers


  • Curare
  • Tubocurarine
  • Atracurium
  • Cisatracurium
  • Pancuronium
  • Rocuronium
  • Vecuronium
• Mechanism of action of nondepolarizing blockers

  Low dose - competitively block ACh at the nicotinic receptor (reversed by cholinesterase inhibitors)

  High dose - block the ion channels of the motor endplate (cannot be reversed by cholinesterase inhibitors)
• Sequence of paralyzed muscles by nondepolarizing blockers

  • Small, rapidly contracting muscles of the face and eyes
  • Fingers, limbs, neck, trunk muscles, intercostal muscles
  • Diaphragm
• Adverse effects of nondepolarizing blockers

  • Pancuronium - increased heart rate
• Drug interactions of nondepolarizing blockers

  • Cholinesterase inhibitors
  • Halogenated hydrocarbon anesthetics
  • Aminoglycoside antibiotics
  • Calcium channel blockers
• Depolarizing agent


  Works by depolarizing the plasma membrane of the muscle fiber, similar to the action of ACh, resistant to degradation by acetylcholinesterase
• Succinylcholine


  The only depolarizing muscle relaxant in use today
• Mechanism of action of succinylcholine

  Attaches to the nicotinic receptors and acts like ACh, causes opening of Na channel which results in depolarization (Phase I - transient twitching), then continuous depolarization gives way to gradual repolarization as the Na channel closes or is blocked (Phase II - flaccid paralysis)
• Actions of succinylcholine


  • Initially produces brief muscle fasciculations causing muscle soreness
  • Respiratory muscles are paralyzed last
  • Duration of action is extremely short due to pseudocholinesterase
• Therapeutic uses of succinylcholine

  • Useful for rapid endotracheal intubation required during induction of anesthesia
  • Electroconvulsive shock treatment
• Adverse effects of succinylcholine

  • Malignant hyperthermia (antidote: Dantrolene)
  • Apnea
  • Hyperkalemia