Core pharmacology

Introduction

anticholinergic activity

Onset Peak Duration

onset / duration rapid / 1-2 hours

Physiological effects

CVS
- In low doses may produce a bradycardia (Bezold-Jarisch reflex, partial agonist at M2) followed by tachycardia (usual effect
- Cardiac output is increased with little effect on blood pressure
- Decreases AVN conduction time and may promote arrhythmias

Resp
- Bronchodilation with increase in physiological dead space
- Bronchial secretions decrease
- RR increased
- Decreased laryngospasm has been reported

CNS
- Central depression or excitation may occur (anticholinergic syndrome)- characterized by hallucinations, agitation, confusion, dysarthria, ataxia, delirium
- Has antiemetic and antiparkinsonian effects

GIT
- Decreased salivation
- Decreased GIT motility
- Antispasmodic in biliary tree
- Decreased LOS tone

GU- Tone and peristalsis in urinary tract decreased

Metabolic/other
- Sweating inhibited (children may develop pyrexia)
- BMR increased
- Suppresses ADH release

Distribution

Crosses BBB and placenta

Class Group

Muscarinic antagonist

Presentation

Clear, colourless atropine sulfate solution for injection. The referenced text lists 0.5-0.6 mg/mL and 3 mg in 10 mL preparations, with 0.6 mg tablets also described.

Mechanism of action

Competitive antagonism of acetylcholine at muscarinic receptors, with little effect at nicotinic receptors except at high doses.

Adverse Effects Toxicity

Painful on intramuscular injection. Dry mouth. Central anticholinergic syndrome, especially in older patients. Hyperpyrexia in children due to inhibition of sweating. Urinary retention. Ocular administration may precipitate glaucoma.

Protein binding

Approximately 50% protein-bound in plasma.

Volume of distribution

Large apparent Vd, approximately 2–4 L/kg.

Half-life

Plasma half-life approximately 2–3 hours after parenteral administration.

Excretion

Predominantly urinary; approximately 30–50% of a dose may be excreted unchanged.

Metabolism

Hepatic metabolism to several metabolites; enzymatic hydrolysis contributes importantly to elimination.

Chemical Pharmaceutics

Tertiary alkaloid supplied as a racemic mixture. Antimuscarinic activity is predominantly due to the L-enantiomer.

Absorption

Rapidly absorbed from the gastrointestinal tract with oral bioavailability about 10-25%. After intramuscular administration, peak concentration is reached at about 30 minutes. Intravenous administration bypasses absorption.

Route And Dose

Intramuscular or intravenous administration: 0.015-0.02 mg/kg in the referenced text. Adult oral dose 0.2-0.6 mg. A total dose of about 3 mg is described for complete vagal blockade in adults.

Indications Uses

Treatment of bradycardia, antagonism of muscarinic effects from anticholinesterase drugs, treatment of organophosphate poisoning, management of oculocardiac reflex crises, and ophthalmic mydriasis or cycloplegia. Tetanus is also listed in the legacy source.