Cholinergic Antagonists

Cholinergic Antagonists

• Cholinergic antagonists are agents that bind to cholinoceptors (muscarinic or nicotinic) and prevent the effects of acetylcholine (ACh) and other cholinergic agonists.
• The most clinically useful of these agents are selective blockers of muscarinic receptors, also known as anticholinergic agents, antimuscarinic agents, or parasympatholytics.
• A second group of drugs, the ganglionic blockers, shows a preference for the nicotinic receptors of the sympathetic and parasympathetic ganglia.
• The third family of compounds, the neuromuscular-blocking agents, interfere with transmission of efferent impulses to skeletal muscles.

Antimuscarinic Agents

• Antimuscarinic agents block muscarinic receptors, causing inhibition of muscarinic functions.
• They also block the few exceptional sympathetic neurons that are cholinergic, such as those innervating the salivary and sweat glands.
• These drugs do not block nicotinic receptors and have little or no action at skeletal neuromuscular junctions (NMJs) or autonomic ganglia.

Atropine

• Atropine is a tertiary amine belladonna alkaloid with a high affinity for muscarinic receptors.
• It binds competitively and prevents ACh from binding to those sites.
• Atropine acts both centrally and peripherally.
• Therapeutic uses include:
  • Ophthalmic: Topical atropine exerts both mydriatic and cycloplegic effects.
  • Antispasmodic: Atropine is used to relax the GI tract.
  • Cardiovascular: The drug is used to treat bradycardia of varying etiologies.
  • Antisecretory: Atropine is used to block secretions in the upper and lower respiratory tracts prior to surgery.
  • Antidote for cholinergic agonists: Atropine is used to treat organophosphate poisoning and overdose of clinically used anticholinesterases.

Pharmacokinetics and Adverse Effects of Atropine

• Atropine is readily absorbed, partially metabolized by the liver, and eliminated primarily in urine.
• It has a half-life of about 4 hours.
• Adverse effects include:
  • Dry mouth
  • Blurred vision
  • Tachycardia
  • Urinary retention
  • Constipation
  • Effects on the CNS include restlessness, confusion, hallucinations, and delirium, which may progress to depression, collapse of the circulatory and respiratory systems, and death.

Ganglionic Blockers

• Ganglionic blockers specifically act on the nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia.
• These drugs show no selectivity toward the parasympathetic or sympathetic ganglia and are not effective as neuromuscular antagonists.
• They block the entire output of the autonomic nervous system at the nicotinic receptor.

Nicotine

• Nicotine is a poison with many undesirable actions and is deleterious to health.
• It is without therapeutic benefit.
• Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis of all ganglia.
• The stimulatory effects are complex and result from increased release of neurotransmitters, due to effects on both sympathetic and parasympathetic ganglia.

Learn about cholinergic antagonists, agents that bind to cholinoceptors and prevent the effects of acetylcholine, and their clinical uses.