Cholinergic Antagonists Overview

Cholinergic Antagonists

• Cholinergic antagonists are agents that bind to cholinoceptors and prevent the effects of acetylcholine (ACh) and other cholinergic agonists.

Antimuscarinic Agents

• Antimuscarinic agents, also known as anticholinergic drugs, block muscarinic receptors, causing inhibition of muscarinic functions.
• These agents block some sympathetic neurons that are cholinergic, such as the salivary and sweat glands.
• They do not block nicotinic receptors, and therefore 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, with effects lasting about 4 hours.
• Neuroeffector organs have varying sensitivity to atropine, with the greatest inhibitory effects on bronchial tissue and the secretion of sweat and saliva.

Actions of Atropine

• Eye: • Atropine blocks muscarinic activity in the eye, resulting in mydriasis (dilation of the pupil), unresponsiveness to light, and cycloplegia (inability to focus for near vision). • In patients with angle-closure glaucoma, intraocular pressure may rise dangerously.
• Gastrointestinal (GI): • Atropine can be used as an antispasmodic to reduce activity of the GI tract. • Although gastric motility is reduced, hydrochloric acid production is not significantly affected.
• Cardiovascular: • Atropine produces different effects on the cardiovascular system, depending on the dose. • At low doses, the predominant effect is a slight decrease in heart rate. • Higher doses of atropine cause an increase in heart rate by blocking the M2 receptors on the sinoatrial node.
• Secretions: • Atropine blocks muscarinic receptors in the salivary glands, producing dryness of the mouth (xerostomia). • The salivary, sweat, and lacrimal glands are sensitive to atropine.

Therapeutic Uses of Atropine

• Ophthalmic: • Topical atropine exerts both mydriatic and cycloplegic effects, allowing for the measurement of refractive errors without interference by the accommodative capacity of the eye.
• Antispasmodic: • Atropine is used to relax the GI tract.

Scopolamine

• Scopolamine is one of the most effective anti–motion sickness drugs available.
• It also has the unusual effect of blocking short-term memory.
• In contrast to atropine, scopolamine produces sedation, but at higher doses, it can produce excitement.
• Scopolamine may produce euphoria and is susceptible to abuse.

Therapeutic Uses of Scopolamine

• The therapeutic use of scopolamine is limited to prevention of motion sickness and postoperative nausea and vomiting.
• For motion sickness, it is available as a topical patch that provides effects for up to 3 days.

Ipratropium, Tiotropium, Aclidinium, and Glycopyrrolate

• These agents are quaternary derivatives or synthetic quaternary compounds.
• They are approved as bronchodilators for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD).
• They are delivered via inhalation and do not enter the systemic circulation or the CNS, restricting effects to the pulmonary system.

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.
• Except for nicotine, the other drugs mentioned in this category are 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 either antagonists (nondepolarizing) or agonists (depolarizing) at the receptors on the endplate of the NMJ.

Succinylcholine

• Succinylcholine is a nondepolarizing neuromuscular blocker used to relax skeletal muscles.
• It is useful when rapid endotracheal intubation is required during the induction of anesthesia.
• It is also used during electroconvulsive shock treatment.
• Its brief duration of action results from redistribution and rapid hydrolysis by plasma pseudocholinesterase.
• Adverse effects of succinylcholine include: • Hyperthermia • Apnea • Hyperkalemia