Mechanism of Action:
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.
Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles, which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism, which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents, which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine, (i.e., exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation may also be inhibited by atropine, but this occurs less readily than with responses to injected (exogenous) choline esters.
Atropine reduces secretions in the mouth and respiratory passages, relieves the constriction and spasm of the respiratory passages, and may reduce the paralysis of respiration, which results from actions of the toxic agent on the central nervous system. Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Although mild vagal excitation occurs, the increased respiratory rate and occasionally increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.
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. In some individuals with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized. Occasionally, a large dose may cause atrioventricular (A-V) block and nodal rhythm.
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. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the “blush” area (atropine flush), and may cause atropine “fever” due to suppression of sweat gland activity especially in infants and small children.
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. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted unchanged in the urine. Traces are found in various secretions, including milk. Atropine readily crosses the placental barrier and enters the fetal circulation.
The approximate Cmax of atropine following 1.67 mg atropine given intramuscularly to adults by the 2 mg AtroPen® delivery system was 9.6 ± 1.5 (mean ± SEM) ng/mL. The mean Tmax was 3 minutes. The T1/2 of intravenous atropine in pediatric subjects under 2 years is 6.9 ± 3.3 (mean ± SD) hours; in children over 2 years, the T1/2 is 2.5 ± 1.2 (mean ± SD) hours; in adults 16-58 years the T1/2 is 3.0 ± 0.9 (mean ± SD) hours; in geriatric patients 65-75 years it is 10.0 ± 7.3 (mean ± SD) hours. The protein binding of atropine is 14 to 22% in plasma. There are gender differences in the pharmacokinetics of atropine. The AUC(0-inf) and Cmax were 15% higher in females than males. The half-life of atropine is slightly shorter (approximately 20 minutes) in females than males.