DESCRIPTION

• Atropine is an anticholinergic agent used as an antidote for various toxic and anticholinesterase agents.
• It is also an antisecretory, mydriatic, and cycloplegic drug.

FORMS AND USES

Atropine sulfate injection is available in:

• 400 µg/ml vials and ampules
• 1 mg/ml dosette vials
• 0.5 mg/5 ml and 1 mg/10 ml prefilled syringes

MECHANISM OF ACTION

• Atropine is an antimuscarinic agent because it is a competitive antagonist of acetylcholine at the muscarinic receptors on autonomic synapses.
• The decreased activity of acetylcholine at the muscarinic receptor site explains characteristic symptoms of atropism, which are anticholinergic by definition: mental status changes, hyperthermia, visual disturbances, mydriasis, urinary retention, flushing, constipation, and absence of sweat or secretions.
• Atropine has little effect on nicotinic receptor sites.

DRUG AND DISEASE INTERACTIONS

• The anticholinergic properties of atropine are potentiated by the sympathomimetic drugs:
  • Catecholamines: epinephrine, norepinephrine, isoproterenol, dopamine, and dobutamine
  • Noncatecholamines: amphetamine, methamphetamine, ephedrine, and phenylephrine
  • Selective beta-adrenergic agonists: metaproterenol, terbutaline, albuterol, and ritodrine
• The anticholinergic effects of atropine can be reversed by the cholinergic effects of bethanechol, methacholine, and, more commonly, physostigmine.

PREGNANCY AND LACTATION

US FDA Pregnancy Category C: The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Conditions involving symptomatic bradycardia, such as hypotension, lightheadedness, nausea, and vomiting
• Cholinergic poisoning that produces bronchospasm or bronchorrhea, such as organophosphate, carbamate, and edrophonium intoxication
• As a preinduction agent in pediatric sedation to prevent vagally mediated bradycardia
• Production of mydriasis and cycloplegia for examination of the retina and in the management of inflammatory conditions of the iris and uveal tract

CONTRAINDICATIONS

Ophthalmic preparations are contraindicated in known or suspected acute angle closure glaucoma because of the likelihood of increasing intraocular pressure. This is especially true for the elderly.

ADVERSE EFFECTS

• Anticholinergic effects (tachycardia, pupillary dilation, fever, etc.) may develop.
• Irritation, hyperemia, and edema of the eye may occur after prolonged use.
• Ophthalmic application has been associated with systemic absorption and generation of cardiac dysrhythmias.
• High environmental temperatures may precipitate heat-related illness in patients treated with anticholinergic medications such as atropine.
• Atropine should be used with extreme caution in patients who are already tachycardic or hypertensive because these conditions may be exacerbated.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

• Symptomatic bradycardia
  • The initial adult dose is 0.5 to 1.0 mg intravenously. The initial dose for a child is 0.01 mg/kg.
  • The dose may be repeated every few minutes until the heart rate increases.
  • Administer in the emergency department or intensive care unit with continuous cardiac monitoring.
• Bronchospasm or bronchorrhea from organophosphate, carbamate, or other cholinesterase inhibitor intoxication (e.g., nerve agents)
  • Administration should begin with a full vagolytic dose of a 2-mg intravenous push.
  • The dose should be repeated at 5-minute intervals until the bronchial secretions are attenuated.
  • Doses in excess of a gram have been required over 24 hours for severe poisoning.
  • When treating severe bronchorrhea secondary to cholinergic toxicity or organophosphate poisoning, the clinical endpoint is resolution of bronchial hypersecretion.
• Cycloplegia
  • A 0.6-mg (approximately one drop of a 1% solution) dose will act as an effective cycloplegic and mydriatic for as long as 1 to 2 weeks.

• Provide atropine in vagolytic doses during bradycardia.
• Provide enough atropine to reverse muscarinic effects of cholinergic poisoning (e.g., by an organophosphate or carbamate). Significant poisoning by these agents may require the entire atropine stores of a hospital for one patient.

Discontinuation of atropine based on development of tachycardia may not provide control of bronchial secretions.

Poisoning by drugs primarily affecting the autonomic nervous system: parasympatholytics (anticholinergics and antimuscarinics) and spasmolytics.

RECOMMENDED READING

Brown JH, Taylor P. Muscarinic receptor agonists and antagonists. In: Gilman A, Goodman LS, Rall TW, et al., eds. Goodman and Gilman's the pharmacologic basis of therapeutics, 9th ed. New York: McGraw-Hill, 1996:149.

Kaiser SC, McClain PL. Atropine metabolism in man. Clin Pharmacol Ther 1970;11:214-227.

Lahdes K, Kaila T, Hunponen R, et al. Systemic absorption of topically applied ocular atropine. Clin Pharmacol Ther 1988;44:310-314.

Author: Gerald F. O'Malley

Reviewer: Katherine M. Hurlbut