6/5/13

Atropine

Atropine [A-troe-peen], a tertiary amine belladonna alkaloid, has a high affinity for muscarinic receptors, where it binds competitively, preventing acetylcholine from binding to those sites


Figure : Competition of atropine and scopolamine with acetylcholine for the muscarinic receptor. 

Atropine acts both centrally and peripherally. Its general actions last about 4 hours except when placed topically in the eye, where the action may last for days

1.Actions:

 a. Eye: Atropine blocks all cholinergic activity on the eye, resulting in persistent mydriasis (dilation of the pupil ), unresponsiveness to light, and cycloplegia (inability to focus for near vision). In patients with narrow-angle glaucoma, intraocular pressure may rise dangerously. Shorter-acting agents, such as the antimuscarinic tropicamide, or an αadrenergic drug, like phenylephrine, are generally favored for producing mydriasis in ophthalmic examinations

b. Gastrointestinal (GI): Atropine can be used as an antispasmodic to reduce activity of the GI tract. Atropine and scopolamine (which is discussed below) are probably the most potent drugs available that produce this effect. Although gastric motility is reduced, hydrochloric acid production is not significantly affected. Thus, the drug is not effective in promoting healing of peptic ulcer. [Note: Pirenzepine , an M1-muscarinic antagonist, does reduce gastric acid secretion at doses that do not antagonize other systems.]

c. Urinary system: Atropine is also employed to reduce hypermotility states of the urinary bladder. It is still occasionally used in enuresis (involuntary voiding of urine) among children, but α-adrenergic agonists with fewer side effects may be more effective.

d. Cardiovascular: Atropine produces divergent effects on the cardiovascular system, depending on the dose


Figure : Dose-dependent effects of atropine


At low doses, the predominant effect is a decreased cardiac rate (bradycardia). Originally thought to be due to central activation of vagal efferent outflow, the effect is now known to result from blockade of the M1 receptors on the inhibitory prejunctional (or presynaptic) neurons, thus permitting increased acetylcholine release. With higher doses of atropine, the M2 receptors on the sinoatrial node are blocked, and the cardiac rate increases modestly. This generally requires at least 1 mg of atropine, which is a higher dose than ordinarily given. Arterial blood pressure is unaffected, but at toxic levels, atropine will dilate the cutaneous vasculature.

e. Secretions: Atropine blocks the salivary glands, producing a drying effect on the oral mucous membranes (xerostomia). The salivary glands are exquisitely sensitive to atropine. Sweat and lacrimal glands are also affected. [Note: Inhibition of secretions by sweat glands can cause elevated body temperature).



2. Therapeutic uses:

a. Ophthalmic: In the eye, topical atropine exerts both mydriatic and cycloplegic effects, and it permits the measurement of refractive errors without interference by the accommodative capacity of the eye. [Note: Phenylephrine or similar α-adrenergic drugs are preferred for pupillary dilation if cycloplegia is not required. Also, individuals 40 years of age and older have decreased ability to accommodate, and drugs are not necessary for an accurate refraction.] Shorter-acting antimuscarinics (cyclopentolante and tropicamide) have largely replaced atropine due to prolonged mydriasis observed with atropine (7–14 days versus 6–24 hours with other agents). Atropine may induce an acute attack of eye pain due to sudden increases in eye pressure in individuals with narrow-angle glaucoma.

b. Antispasmodic: Atropine is used as an antispasmodic agent to relax the GI tract and bladder.

c. Antidote for cholinergic agonists: Atropine is used for the treatment of overdoses of cholinesterase inhibitor insecticides and some types of mushroom poisoning (certain mushrooms contain cholinergic substances that block cholinesterases). Massive doses of the antagonist may be required over a long period of time to counteract the poisons. The ability of atropine to enter the central nervous system (CNS) is of particular importance. The drug also blocks the effects of excess acetylcholine resulting from acetylcholinesterase inhibitors, such as physostigmine.

d. Antisecretory: The drug is sometimes used as an antisecretory agent to block secretions in the upper and lower respiratory tracts prior to surgery.


3. Pharmacokinetics:
Atropine is readily absorbed, partially metabolized by the liver, and eliminated primarily in the urine. It has a half-life of about 4 hours.


4. Adverse effects:
Depending on the dose, atropine may cause dry mouth, blurred vision, “sandy eyes,” tachycardia, and constipation. Effects on the CNS include restlessness, confusion, hallucinations, and delirium, which may progress to depression, collapse of the circulatory and respiratory systems, and death. Low doses of cholinesterase inhibitors such as physostigmine may be used to overcome atropine toxicity. In older individuals, the use of atropine to induce mydriasis and cycloplegia is considered to be too risky, because it may exacerbate an attack of glaucoma in someone with a latent condition. In other older individuals, atropine may induce urinary retention that is troublesome. Children are sensitive to effects of atropine—in particular, the rapid increases in body temperature that it may elicit. This may be dangerous in children.



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