indication

For the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides.

pharmacology

Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and l-hyoscyamine, whose activity is due almost entirely to the levo isomer of the drug. Atropine is commonly classified as an anticholinergic or antiparasympathetic (parasympatholytic) drug. More precisely, however, it is termed an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters. Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine may also lessen the degree of partial heart block when vagal activity is an etiologic factor. Atropine in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure.

mechanism of action

Atropine binds to and inhibit muscarinic acetylcholine receptors, producing a wide range of anticholinergic effects.

toxicity

Oral, mouse: LD₅₀ = 75 mg/kg. Symptoms of overdose includes widespread paralysis of parasympathetically innervated organs. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever and cutaneous flush are especially prominent, as are mental and neurological symptoms. In instances of severe intoxication, respiratory depression, coma, circulatory collapse and death may occur.

biotransformation

Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver. From 13 to 50% is excreted unchanged in the urine.

absorption

Atropine is rapidly and well absorbed after intramuscular administration. Atropine disappears rapidly from the blood and is distributed throughout the various body tissues and fluids.

half life

3.0 ± 0.9 hours in adults. The half-life of atropine is slightly shorter (approximately 20 minutes) in females than males.

route of elimination

Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted unchanged in the urine.

drug interactions

Cinitapride: Anticholinergic agents like atropine may reduce the action of cinitapride.

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Haloperidol: The anticholinergic increases the risk of psychosis and tardive dyskinesia

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Atropine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Trimethobenzamide: Trimethobenzamide and Atropine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Atropine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trospium: Trospium and Atropine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.