Pharmacology: Anticholinergics and Glaucoma

Cholinergic Antagonists

• Cholinergic antagonists are agents that bind to cholinoceptors and prevent the effects of acetylcholine (ACh) and other cholinergic agonists.
• There are three types of cholinergic antagonists:
  • Antimuscarinic agents (e.g., atropine, scopolamine)
  • Ganglionic blockers (e.g., nicotine)
  • Neuromuscular-blocking agents (e.g., curare, tubocurarine, cisatracurium, pancuronium, rocuronium, vecuronium)

Antimuscarinic Agents

• Atropine is a tertiary amine belladonna alkaloid with a high affinity for muscarinic receptors.
• Atropine acts both centrally and peripherally, with a duration of action of about 4 hours.
• Atropine blocks muscarinic activity in the eye, resulting in:
  • Mydriasis (dilation of the pupil)
  • Unresponsiveness to light
  • Cycloplegia (inability to focus for near vision)
• Atropine is used to:
  • Treat bradycardia of varying etiologies
  • Block secretions in the upper and lower respiratory tracts prior to surgery
  • Counteract organophosphate poisoning, overdose of anticholinesterases, and certain types of mushroom poisoning

Atropine Pharmacokinetics and Adverse Effects

• Atropine is readily absorbed, partially metabolized by the liver, and eliminated primarily in urine.
• Atropine has a half-life of about 4 hours.
• Adverse effects of atropine include:
  • Dry mouth
  • Blurred vision
  • “Sandy eyes”
  • Tachycardia
  • Urinary retention
  • Constipation
  • Effects on the CNS (e.g., restlessness, confusion, hallucinations, delirium, collapse of the circulatory and respiratory systems, death)

Scopolamine

• Scopolamine is another tertiary amine plant alkaloid that produces peripheral effects similar to those of atropine.
• Scopolamine has greater action on the CNS (unlike atropine, CNS effects are observed at therapeutic doses) and a longer duration of action than atropine.
• Extended-release formulations and the transdermal patch have a lower incidence of adverse effects and may be better tolerated.

Ganglionic Blockers

• Ganglionic blockers specifically act on the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia.
• These drugs show no selectivity to the parasympathetic or sympathetic ganglia and are not effective as neuromuscular antagonists.
• Examples of ganglionic blockers include nicotine and other nondepolarizing, competitive antagonists.

Neuromuscular-Blocking Agents

• These drugs block cholinergic transmission between motor nerve endings and the nicotinic receptors on skeletal muscle.
• They possess some chemical similarities to ACh and act as:
  • Antagonists (nondepolarizing) or
  • Agonists (depolarizing) at the receptors on the endplate of the NMJ
• Examples of nondepolarizing blockers include:
  • Curare
  • Tubocurarine
  • Cisatracurium
  • Pancuronium
  • Rocuronium
  • Vecuronium
• Mechanism of action:
  • At low doses, nondepolarizing agents competitively block the nicotinic receptors without stimulating it.
  • At high doses, nondepolarizing agents can block the ion channels of the motor endplate.
• Actions:
  • Muscles have differing sensitivity to blockade by competitive agents.
  • Small, rapidly contracting muscles of the face and eye are most susceptible and are paralyzed first.
  • Sugammadex is a selective relaxant-binding agent that terminates the action of both rocuronium and vecuronium and can be used to speed recovery.

This quiz covers the effects of atropine and other anticholinergics on the body, including their use in treating glaucoma and gastrointestinal issues. Learn about the impact on intraocular pressure and gastric acid secretion.