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Description: Atropine is a naturally occurring tertiary amine extracted from belladonna alkaloid that consists of a racemic mixture of both d- and l-hyoscyamine, which differ in their antimuscarinic potencies. Atropine is the prototype antimuscarinic from which other antimuscarinic agents were developed. Atropine counteracts cholinergic-mediated reductions in heart rate, vascular resistance, and blood pressure. Atropine has many applications in clinical medicine but most commonly is used systemically to treat symptomatic bradycardia and as a preoperative agent to reduce secretions prior to surgery. It also is used to produce mydriasis during ophthalmic examination. Atropine is no longer used in the management of parkinsonism since newer, synthetic agents were developed that possessed fewer peripheral side effects. Atropine decreases the muscarinic cholinergic adverse reactions associated with organophosphate toxicity (e.g., lacrimation, sweating, breathing problems, bradycardia) and is well known as an useful as an adjunct in nerve agent and insecticide poisoning. Atropine was formally approved by the FDA in 1938 but it had been used clinically for many years prior to that. Several dosage forms of atropine are available for clinical use. An auto-injector (Atropen®) was FDA-approved in 1973 for use in adults as an adjunct emergency antidote in nerve agent and insecticide poisoning; on June 20, 2003 the Atropen® was approved for children.

Mechanism of Action: Atropine is a competitive inhibitor at autonomic postganglionic cholinergic receptors. These include receptors found in GI and pulmonary smooth muscle, exocrine glands, the heart, and the eye. Atropine does not block the actions of acetylcholine at the neuromuscular junction. The activity of atropine is due primarily to l-hyoscyamine, which possesses all of the antimuscarinic activity, and not d-hyoscyamine, which essentially has no peripheral antimuscarinic activity. The degree of sensitivity of various muscarinic receptors to antimuscarinic agents is dose-dependent. The most sensitive receptors are those of the salivary, bronchial, and sweat glands. Next are the receptors in the eye and heart, followed by the receptors in the GI tract.

The principal clinical effects of atropine are a reduction in salivary, bronchial, and sweat gland secretions; mydriasis; cycloplegia; changes in heart rate; contraction of the bladder detrusor muscle and of the GI smooth muscle; decreased gastric secretion; and decreased GI motility. At lower doses, a paradoxical decrease in heart rate occurs, and at higher doses, effects are seen at nicotinic receptors in autonomic ganglia, causing restlessness, hallucinations, disorientation, and/or delirium. The paradoxical decrease in heart rate results as muscarinic type 2 presynaptic receptors when blocked cannot cause the reuptake of acetylcholine from the synapse. Unlike scopolamine, atropine does not produce CNS depression (drowsiness, euphoria, amnesia, fatigue, decreased REM sleep) at usual therapeutic doses. Also, atropine's antimuscarinic potency is greater in the heart, bronchial, and GI smooth muscle, and is lesser in the iris; ciliary body; and salivary, sweat, and bronchial glands.

The respiratory effects of atropine include reducing the volume of secretions from the nose, mouth, pharynx, and bronchi and relaxing smooth muscles of the bronchi and bronchioles, which decrease airway resistance. Since atropine is a potent bronchodilator, it is especially effective in blocking the acetylcholine-induced stimulation of guanyl cyclase, which is responsible for producing cyclic guanosine monophosphate (cGMP), a mediator of bronchoconstriction released from mast cells. These actions of atropine are useful, but controversial, in the treatment of antigen-, methacholine-, and exercise-induced bronchospasm in asthmatic patients.

Pharmacokinetics: Atropine is well absorbed after inhalation, IM, endotracheal, or oral administration. Following oral inhalation, peak plasma concentrations are reached in 1.5—4 hours. Peak plasma concentrations are seen within 30 minutes following IM administration and within 1 hour after oral administration. After absorption, the drug is widely distributed throughout the body and crosses the blood-brain barrier and the placenta. It is metabolized in the liver to several metabolites including tropic acid. The initial half-live of atropine is about 2 to 3 hours, and the terminal half-life is about 12.5 hours. Atropine and metabolites are primarily excreted renally and, to a lesser extent, by the pulmonary and fecal routes.