Atropine is one of the World Health Organization's core medicines on the "essential drug list", which is known as the list for minimum medical needs for a basic health care system.
PHARMACOLOGY: Atropine is commonly classified as anticholinergics or antiparasympathetic (parasympatholyic) drug.
More precisely however, it is termed an antimuscarinic agent since it antagonizes the muscarinic-like actions of acetylcholine and other 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 atreceptor 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 solution also may be inhibited by atropine, but this occurs less readily than with responses to injected (exogenous) choline esters.
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.Atropine exerts a more potent and prolonged effect on the heart, intestine and bronchial muscle
than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weakerthan that of scopolamine.Unlike the latter, atropine in clinical doses does not depress the CNS, but may stimulate the medula and higher cerebral centres.Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth ofrespiration produced by atropine are 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 anticholinesterase agents or other parasympatomimetic 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 patients 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 (AV) block and nodal rhythm.
Atropine injection 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 in infants and small children.
Atropine disappears rapidly from the blood flow following injection and is distributed throughout the body. Much of the drug is destroyed by enzymatic hydrolysis,
particularly in the liver:from 3 to 50% is excreted unchanged in the urine.Traces are destroyed in various secretions, including milk.Atropine readily crosses the placental barrier and enters the fetal circulation.
Sodium chloride added to renderthe solution isotonic forinjection of the active ingredients is present in amounts sufficient to affect serum electrolyte balance of sodium and chloride ions.
INDICATIONS: Atropine is indicated forthe treatment of conditions where relaxation of gastrointestinal, biliary and genito-urinary tracts is desirable, or where suppression of salivary, gastric, and respiratory secretion is required.
It is also indicated for the prophylaxis of syncope from Adams-stokes or hypertensive carotid sinus syndrome, treatment of bradycardia caused by excessive vagal
stimulation and the symptomatic treatment of idiopathic and postencephalitic Parkinsonism.
It may be used as an antidote for cholinesterase inhibitors and parasympatomimetic. Atropine may be given before the induction of general anesthesia to diminish the risk of vagal inhibition of the heart and to reduce salivary and bronchial secretions.
CONTRAINDICATIONS: Glaucoma, pyloric stenosis or prostatic hypertrophy, except in doses ordinarily used for preanesthetic medication.
Atropine is contraindicated for patients known to be hypertensive to the product.
Atropine should not be used in patients with asthma since an excessive drying effect upon mucus plugs in the bronchi may occur.
WARNINGS: Atropine is a highly potent drug and due care is essentialto avoid overdosage,especiallywith I.V.administration.
Children are more susceptible than adults to the toxic effects of anticholinergic agents.
PRECAUTIONS: Do not administer unless solution is clear. Discard unused portion.
Use with caution in all individuals over 40 years of age. Atropine may cause mental confusion, especially in the elderly.
Conventional systemic doses may precipitate acute glaucoma in susceptible patients, convert partial organic pyloric stenosis into complete obstruction, and lead to
complete urinary retention in patients with prostatic hypertrophy or cause inspissations of bronchial secretions and formation of dangerous viscid plugs in patients with chronic lung disease.
Atropine should be used cautiously in patients with fever.
Atropine should be used with caution in conditions characterized by tachycardia such as thyrotoxicosis, cardiac insufficiency or failure, and in cardiac surgery where it
may further accelerate the heart rate.
The effects of Atropine and other anticholinergic agents may be enhanced by the concomitant administration of other drugs with anticholinergic properties such as
amantadine, some antihistamines, butyrophenones, phenothiazines and tricyclic antidepressants.
Pregnancy: Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproductive capacity.Atropine should be given to a pregnant woman only if clearly needed.
ADVERSEEFFECTS: Most of the side effects of atropine are directly related to an antimuscarinic action.Dryness of mouth, blurred vision, photophobia and tachycardia
commonly occur with chronic administration of therapeutic doses.Anhidrosis also may occur and produce heat intolerance or impair temperature regulation in persons living in a hot environment. Constipation and difficulty in micturition may occur in elderly patients.Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation.
Adverse effects following single or repeated injections of atropine are most often the result of excessive dosage. These include palpitation, dilated pupils, difficulty in
swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia.Toxic doses lead to marked palpitation, restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma.
OVERDOSE: SYMPTOMS AND TREATMENT: In the event of toxic overdosage (see the adverse effects), a short acting barbiturate of diazepam may be given as
needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning. Central stimulants are not recommended. Physostigmine, given as an atropine antidope by slow I.V. injection of 1 to 4 mg (0.5 to 1.0 mg in children), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after 1 to 2 hours, and repeated doses may be required. Artificial respiration with oxygen may be necessary. Ice bags help to reduce fever, especially in children.
The fatal adult dose of atropine is not known: 200 mg doses have been used and doses as high as 1000 mg have been given.
In children, 10 mg orless may be fatal. With doses as low as 0.5 mg, undesirable minimal symptoms orresponses of overdosage may occur. These increase in severity and extent with larger doses of the drug (excitement, hallucinations, delirium and coma with a dose of 10 mg or more.
DOSAGE AND ADMINISTRATION: Adults: The usual dose of atropine sulphate is 0.4 to 0.6 mg administered by S.C., I.M. or I.V.routes. The complete atropinizing
dose for man is usually believed to be in the order of 2 mg.
For pre-medication priorto anesthesia: 300 to 600 µg may be given by subcutaneous or intramuscular injection, usually in conjunction with 10 to 15 mg of morphine
sulphate, about an hour before anesthesia.Alternatively 300 to 600 µg may be given intravenously immediately before induction of anesthesia.
Reversal of Competitive Neuromuscular Block: 0.6 to 1.2 mg is given by slow intravenous injection in conjunction with neostigmine methylsulfate to reverse the
effects of non-depolarizing muscle relaxants.
Biliary or Renal Colic : 600 µg may be given intramuscularly up to three times daily as an antispasmodic to provide symptomatic relief in conjunction with morphine
or other opiates. Organophosphate Poisoning: 1 to 2 mg may be given intravenously. Additional 2 mg doses may be administered intramuscularly or intravenously every 5 to 60 minutes until symptoms subside, and repeated if they reappear.For severe cases 2 to 6 mg may be administered intravenously, with subsequent additional doses of 2 to 6 mg being administered until symptoms subside.
Children: Premedication doses up to 65 µg subcutaneously for premature infants, 100 µg for full-term infants, 200 µg at 6 months to 1 year , and 10 to 20 µg per kg
body weight for older children , with reduced doses on hot days or for a febrile child.
Atropine is also a specific antidote for cardiovascular collapse resulting from injudicious administration of choline ester. When cardiac arrest has occurred, external
cardiac massage or other method of resuscitation is required to distribute the drug after I.V. injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (see
AVAILIBILITY: Atropine Injection BP0.4 mg/ml:Each ml of sterile solution contains atropine sulphate of 0.4 mg, sodium chloride 8.9 mg and sulphuric acid (to adjust
pH).Ampoules of 1 ml, boxes of 10.
Atropine Injection BP 0.6 mg/ml : Each ml of sterile solution contains atropine sulphate 0.6 mg, sodium chloride 8.9 mg and sulphuric acid (to adjust pH). Ampoules
of 1 ml, boxes of 10.
STORAGE: Store at room temperature (15 to 30°C).