Cholinergic Antagonists Overview

Cholinergic Antagonists

• Cholinergic antagonists are drugs that block the action of acetylcholine.
• Learning objectives include understanding the pharmacology of major muscarinic antagonists, their pharmacokinetics, mechanism of action (MOA), effects on organ systems, therapeutic applications, and associated risks.
• Anticholinergic drugs are classified as antimuscarinic and antinicotinic.
• Examples of antimuscarinic drugs include: M₁-selective (pirenzepine), and nonselective (atropine).
• Examples of antinicotinic drugs include ganglion blockers (hexamethonium) and neuromuscular blockers (tubocurarine).

Muscarinic Receptor Antagonist

• Muscarinic antagonists block the action of acetylcholine at muscarinic receptors.
• The process involves the antagonist competing with acetylcholine for binding sites on the receptor, preventing acetylcholine from activating the receptor.

Recap of Parasympathetic System Effects

• Parasympathetic nervous system effects can be blocked by muscarinic antagonists.
• This leads to changes in organ function including pupil dilation, reduced bronchial constriction, reduced heart rate, blood vessel dilation, decreased gastric motility and secretions, bladder relaxation, and decreased salivary gland activity.

Physiological Response to Muscarinic Blockade

• Muscarinic blockade affects various tissues.
• The eye shows dilation (mydriasis) and relaxation of sphincter/ciliary muscles.
• The heart experiences an increased heart rate and improved conduction.
• Lung function results in bronchial dilation and decreased secretions.
• The stomach demonstrates decreased motility, tone, and secretion. Other effects in the bladder, adrenal medulla, exocrine glands (pancreas, salivary, lacrimal, pharyngeal) and sweat glands include a similar pattern of blockade.

Clinically Used Muscarinic Antagonists

• Commonly used muscarinic antagonists include atropine, hyoscine, ipratropium, tiotropium, cyclopentolate, and pirenzepine.

Atropine

• Atropine is a natural alkaloid, a relatively lipid-soluble tertiary amine that crosses the blood-brain barrier (BBB).
• It competitively blocks acetylcholine (ACh) binding to muscarinic receptors.
• Clinical uses include sinus bradycardia, pre-anesthetic medication to reduce secretions, and organophosphate poisoning treatment.

Sinus Bradycardia

• Sinus bradycardia is a slow heart rate.
• Atropine treatment increases heart rate by blocking parasympathetic influences on the heart.

Organophosphate Poisoning

• Organophosphates irreversibly inhibit acetylcholinesterase (AChE).
• This leads to a buildup of acetylcholine, triggering cholinergic toxicity with symptoms like diarrhea, urination, miosis (constricted pupils), bronchospasms, bradycardia (slow heart rate), excitation of skeletal muscles and central nervous system (CNS), salivation, sweating, and vomiting.

Side Effects of Atropine

• Atropine can cause side effects at therapeutic doses, including constipation, urinary retention, mydriasis, bronchodilation, cycloplegia, tachycardia, dry mouth, hyperthermia, decreased sweating, flushed skin, and hallucinations or disorientation.

Scopolamine (Hyoscine)

• Scopolamine is a competitive antagonist of acetylcholine at muscarinic receptors.
• It readily penetrates the blood-brain barrier.
• It is used to prevent nausea and vomiting in motion sickness.

Scopolamine Butylbromide (Hyoscine Butylbromide)

• Scopolamine butylbromide is a competitive antagonist of acetylcholine at muscarinic receptors.
• It has poor absorption and primarily affects the central nervous system.
• It is used as an antispasmodic for irritable bowel syndrome (IBS).

Ipratropium and Tiotropium

• These are synthetic amines used as short- and long-acting anticholinergic drugs, respectively.
• They are primarily used in the treatment of bronchospasm associated with asthma, chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Cyclopentolate

• Used to produce mydriasis and cycloplegia for diagnostic purposes.

Pirenzepine

• A M₁ selective antagonist.
• Primarily used in the treatment of peptic ulcer disease.