Pharmacology 4th Lecture

Nicotinic Receptors

• Nicotinic receptors are of two types: Neural nicotinic (Nn) located in autonomic ganglia, and Muscular nicotinic (Nm) located in the neuromuscular junction.

Cholinergic Antagonists (Parasympatholytics)

• Cholinergic antagonists bind to cholinergic receptors (M/N) but do not trigger an intracellular response.
• Muscarinic blockers: inhibit efferent impulses to skeletal muscle via the nicotinic muscle receptor (Nm).
• Ganglionic blockers: inhibit the nicotinic neuronal receptor (Nn) of both parasympathetic and sympathetic ganglia.

Antimuscarinics

• Antimuscarinics are drugs that compete with Ach for muscarinic receptors.
• Classification: according to selectivity, they can be non-selective (e.g., Atropine) or selective (e.g., pirenzepine, a selective M1 blocker).

Antimuscarinic Classification

• Classification according to their nature:
  • Natural alkaloids: Atropine and Scopolamine (hyoscine).
  • Synthetic atropine substitutes: used as mydriatics, antiasthmatics, antispasmodics, and for urinary incontinence and parkinsonism.

Atropine

• Atropine is a belladonna alkaloid that binds competitively and prevents Ach from binding to its sites.
• Acts both centrally and peripherally, with a duration of action of about 4 hours.
• Pharmacokinetics: readily absorbed, partially metabolized by the liver, and eliminated primarily in urine, with a half-life of about 4 hours.
• Pharmacodynamics: causes competitive reversible blockade of ACh at muscarinic receptors, and also has an effect on the extrapyramidal system, reducing the rigidity of patients with parkinsonism.

Therapeutic Uses of Atropine

• In pre-anaesthetic medication to decrease salivary and bronchial secretions, prevent lung collapse and bronchopneumonia, and protect the heart from excessive vagal tone.
• As an antispasmodic for intestinal, renal, and biliary conditions.
• Treatment of severe bradycardia and syncope associated with hyperactive carotid sinus reflex.
• Hyperhidrosis (excessive sweating), anti-Parkinsonism, peptic ulcer, nocturnal enuresis, and antidote to parasympathomimetics.

Atropine Substitutes

• Mydriatics: cyclopentelate, homatropine, and eucatropine.
• Antisecretory: pirenzepine and telenzepine.
• Antispasmodic: Hyoscine butyl bromide (Buscopan).
• Antiparkinsonian: Benztropine and Trihexyphenidyl (Artane).

Adverse Effects and Toxicity of Atropine

• Dry mouth, blurred vision, tachycardia, constipation, urine retention, increased IOP, flush, agitation, delirium, and hyperthermia.
• In acute toxicity, patient is "dry as a bone, blind as a bat, red as a beet, and mad as a hatter".

Contraindications of Atropine

• Glaucoma.
• Enlarged prostate (benign prostatic hyperplasia).

Hyoscine (Scopolamine)

• Therapeutic uses: pre-anaesthetic medication, prophylaxis of motion sickness, sedative in cases of mania, and antiemetic.

Nicotinic Antagonists

• Neuromuscular blockers: Tubocurarine, gallamine, and succinylcholine.
• Ganglionic blockers: Trimethaphan, hexamethonium, and mecamylamine.

Neuromuscular Blockers

• Classified into non-depolarizing (e.g., Tubocurarine, Pancuronium, and Atracurium) and depolarizing agents (e.g., Succinylcholine).
• Mechanism of action: competitively block cholinergic transmission at the nicotinic receptors by preventing the binding of Ach to its receptor.
• Route of administration: must be given I.V because oral absorption is poor.

Succinylcholine

• Mechanism of action: binds to nicotinic receptors, leading to open Na channels and cause membrane depolarization.
• Duration of action: 3-6 minutes if given as a single dose.
• Therapeutic use: used as an adjuvant drug for general anesthesia, to facilitate rapid intubation.
• Adverse effects: bronchoconstriction and hypotension caused by histamine release, hypotension, arrhythmias, apnea due to respiratory paralysis, and malignant hyperthermia.

This quiz covers the 4th lecture on pharmacology, focusing on nicotinic receptors, their locations, and functions.