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.