INFORMATION FOR HEALTH PROFESSIONALS
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0.4 mg/mL injection: a clear, colourless, particle-free solution containing 0.4 mg/mL atropine sulphate.
0.6 mg/mL injection: a clear, colourless, particle-free solution containing 0.6 mg/mL atropine sulphate.
1.2 mg/mL injection: a clear, colourless, particle-free solution containing 1.2 mg/mL atropine sulphate.
Atropine (dl-hyoscyamine) is often classified as an anticholinergic drug but is more accurately described as an antimuscarinic agent since it inhibits the muscarinic actions of acetylcholine, possessing both central and peripheral activity.
Atropine has activity both 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 antagonised by atropine in therapeutic doses are primarily the peripheral structures that are stimulated or inhibited by muscarine (ie. 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 hyoscine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of hyoscine. Unlike the latter, atropine in therapeutic doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centres. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) 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 parasympathetic drugs, and cardiac arrest produced by stimulation of the vagus.
Atropine sulfate injection in therapeutic 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 the 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 is well absorbed following IM administration. Peak plasma levels are observed within 30 minutes of injection, accompanied by an increase in heart rate which reaches a maximum at 15 to 50 minutes. The duration of effect on the heart rate is reported to be up to 5 hours. The effect on salivation is delayed, with a peak effect occurring approximately 100 minutes after the injection and persisting for up to 4 hours.
Following intravenous administration serum levels of atropine drop rapidly within the first ten minutes and then decrease more gradually. One hour after either IM or IV injection atropine levels are very similar.
Atropine is well distributed throughout the body , crossing both the blood-brain and placental barriers, and distributing into the milk in small quantities. It has a large apparent volume of distribution (2-4 L/kg).
Atropine shows a high interindividual variability in serum protein binding, ranging from 22.5% ± 20.6%.
Atropine is metabolised by the liver and excreted mainly in the urine. About 30 to 50% of a dose is excreted in urine unchanged, the rest as metabolites. Atropine has a plasma half life of approximately 4 hours in adults, with a longer half-life of approximately 6.5 hours in children.
Atropine may be given as a pre-anaesthetic medication to inhibit excessive salivary and bronchial secretions and to diminish the risk of vagal inhibition of the heart. The use of atropine as an antisialagogue is rarely necessary since the introduction of halothane and similar anaesthetics in place of ether anaesthesia.
Atropine maybe administered concurrently with anticholinesterase agents (e.g. neostigmine, physostigmine) to block the adverse muscarinic effects of these latter agents when they are used after surgery to terminate curarisation.
It may be used in the management of patients with acute myocardial infarction and sinus bradycardia who have associated hypotension and increased ventricular irritability.
It is also used concomitantly with a cholinesterase reactivator (e.g. pralidoxime) to reverse muscarinic effects associated with toxic exposure to anticholinesterase compounds (e.g. organophosphate pesticides).
Atropine may be used in conjunction with morphine or other agents for the relief of biliary or renal colic.
Atropine may be administered by subcutaneous, intramuscular or direct intravenous injection.
300-600 mcg of atropine sulfate IM or SC, approximately 1 hour before anaesthesia, usually in conjunction with a narcotic. Alternatively, 300-600 mcg atropine sulfate may be given IV immediately prior to induction of anaesthesia.
To reverse the effects of non depolarising muscle relaxants, 600 mcg-1.2 mg atropine sulfate may be given to adults as a slow IV injection in conjunction with the anticholinesterase agent (e.g. neostigmine methylsulfate) of choice.
Suitable premedication doses to be given subcutaneously 30-60 minutes prior to surgery in children are suggested below:
| Infants weighing less than 3 kg: | 100 mcg |
| Children weighing 7 to 9 kg: | 200 mcg |
| Children weighing 12 to 16 kg: | 300 mcg |
| Children weighing 20 to 27 kg: | 400 mcg |
| Children weighing 32 kg: | 500 mcg |
| Children weighing 41 kg: | 600 mcg |
Atropine sulphate 0.4-1 mg IV may be repeated every 5 minutes until the desired effect on heart rate or asystole is achieved. The total dose should not exceed 2 mg.
When cardiac arrest has occurred, external cardiac massage or other method of resuscitation is required to distribute the drug after intravenous injection.
An initial dose of 1-2 mg for mild poisoning, and up to 6 mg for severe poisoning; this is given IV preferably, or IM. Atropine can be given as often as every 5 minutes until secretions are minimal and ventilation is adequate. In moderate to severely poisoned adult, atropine is given for at least two days. In severe cases atropine therapy should be withdrawn gradually. Pralidoxime enhances the effect of atropine.
As an antispasmodic in the symptomatic relief of biliary or renal colic, 600 microgram IM up to three times a day may be given.
Known hypersensitivity to atropine or other anticholingergic agents. Patients with obstructive disease of the gastrointestinal tract (e.g. pyloroduodenal stenosis), cardiospasm, paralytic ileus or intestinal atony (especially in geriatric or debilitated patients). Megacolon complicating ulcerative colitis. Prostatic enlargement. Unstable cardiovascular status in acute haemorrhage. Tachycardia secondary to cardiac insufficiency of thyrotoxicosis. Toxaemia of pregnancy.
It is also contraindicated in patients with obstructive uropathy (e.g. bladder neck obstruction caused by prostatic hypertrophy). Due to risk of provoking hyperpyrexia, atropine should not be given to patients, especially children, where the ambient temperature is high.
Atropine should not be given to patients with closed angle glaucoma.
Atropine should be used cautiously in patients over 40 years old as they may be more susceptible to adverse effects, particularly those with any severe heart disease, hypertension, ulcerative colitis, ileus, chronic lung disease, hyperthyroidism, autonomic neuropathy, hepatic or renal disease or prostatic hypertrophy, oesophageal reflux or hiatus hernia.
Elderly patients may react with excitement, agitation, drowsiness or confusion to even small doses of atropine. Changes in dosage should be gradual.
Atropine should be used with caution in infants and small children.
Atropine should be used with caution in debilitated patients. These patients, especially those with chronic pulmonary disease, may be susceptible to the formation of bronchial mucous plugs due to decreased bronchial secretions.
In patients over 40 years, conventional parenteral doses of atropine may precipitate acute glaucoma in susceptible individuals.
Atropine should be used with extreme caution in patients with myasthenia gravis.
In conditions characterised by tachycardia, such as cardiac insufficiency or failure, extreme caution must be exercised (see Contraindications ). Care is also required in patients with acute myocardial infarction or ischaemia as atropine may worsen the symptoms.
Patients with known cardiac problems have developed angina following administration of atropine.
Atropine has been associated with the development of arrhythmias in adult and paediatric patients. Accelerated heart rate and intraventricular conduction delays have been associated with the development of ventricular fibrillation.
Category A
Although atropine has been taken by a large number of pregnant women and women
of child-bearing age without an increase in the frequency of malformations or
other direct or indirect harmful effects on the foetus being observed, the
safety of atropine in pregnancy has not been positively established. As with all
other drugs, caution must be exercised in the use of atropine in pregnant women
and women of child-bearing age.
Small amounts of atropine have been found in human breast milk, therefore atropine should only be administered to nursing mothers if absolutely necessary.
Most side effects are directly related to the antimuscarinic actions of atropine. Adverse effects following single or repeated doses are most often the result of excessive dosage.
Cardiovascular
Tachycardia and palpitations.
Central Nervous System
Dryness of the mouth, thirst. These are due to the reduction of salivary,
bronchial and sweat secretions and are dose related.
Gastrointestinal
Urinary difficulty and retention, and constipation; due to inhibition of
parasympathetic control of the bladder and GI tract respectively.
Ocular
Dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia)
and photophobia can occur with increasing doses of atropine.
Skin
Flushing and dryness of the skin.
Cardiovascular
The development of angina in patients with known cardiac problems has been
reported.
Central Nervous System
Tremor, fatigue, drowsiness, ataxia, vomiting, mental confusion and/or
excitement, dizziness. Anhidrosis also may occur and produce heat intolerance in
patients living in a hot environment.
Gastrointestinal
Vomiting, retrosternal pain due to increased gastric reflux
Skin
Hypersensitivity reactions may manifest as conjunctivitis or skin rash which, in
some instances, progresses to exfoliation.
The effect of atropine may be enhanced by concomitant administration of other drugs with antimuscarinic properties, such as:
amantadine
some antihistamines, including cyproheptadine, promethazine.
butyrophenones eg. Haloperidol
phenothiazines eg. chlorpromazine, fluphenazine, perphenazine, proclorperazine,
promazine, thioridazine, trifluoperazine.
tricyclic antidepressants eg. amitryptiline, desipramine, doxepin, imipramine,
nortriptyline.
The absorption of other drugs may be affected by the reduction in gastric motility caused by atropine.
Atropine antagonises the actions of a number of compounds, including:
synthetic choline esters eg. bethanecol, carbachol
anticholinesterase drugs eg. physostigmine, neostigmine, pyridostigmine
cholinomimetic alkaloids eg. pilocarpine.
Atropine has been reported to be incompatible with solutions containing the following: adrenaline hydrochloride, amylobarbitone sodium, ampicillin sodium, chloramphenicol sodium succinate, chlortetracycline hydrochloride, heparin sodium, metaraminol bitartrate, methicillin sodium, nitrofurantoin sodium, novobiocin sodium, oxacillin sodium, pentobarbitone sodium, promazine hydrochloride, sodium bicarbonate, sulphadiazine sodium, sulphafurazole diethanolamine, tetracycline hydrochloride, thiopentone sodium, vitamin B complex and ascorbic acid, warfarin sodium. This list is not exhaustive.
Acute overdosage of atropine produces both peripheral and central signs and symptoms. Peripheral symptoms may include vasodilatation, tachycardia and hypertension with arrhythmias, diminution of gastrointestinal motility, urinary retention and dryness of mucous membranes. Central toxic effects include anxiety, delirium, disorientation, hallucinations, hyperactivity and convulsions. In severe overdosage, CNS depression, circulatory collapse and hypotension may occur. Coma and skeletal muscle paralysis may also occur and may be followed by death from respiratory failure.
Maintenance of an adequate airway is important and respiratory assistance may be necessary. Symptomatic and supportive therapy may include fluid therapy; cold packs, mechanical cooling devices or sponging with tepid water to treat hyperthermia; and urinary catheterisation.
Diazepam may be given to control marked excitement and convulsions; phenothiazines should not be given since they may exacerbate antimuscarinic effects.
Delirium, hallucinations, coma and cardiac arrhythmias often respond to physostigmine. Relative contraindications to the use of physostigmine include asthma, gangrene, cardiovascular disease and mechanical obstruction of the gastrointestinal or genitourinary tract. Physostigmine should be used in these situations only if a life-threatening emergency occurs.
IV propanolol may be useful for treating supraventricular tachyarrhythmias unresponsive to physostigmine or when physostigmine is contraindicated.
If indicated, physostigmine salicylate is usually administered by slow IV injection.
The usual initial dose is 2 mg. A second dose of 1 to 2 mg may be attempted after 20 minutes if no reversal has occurred. If initial doses of the drug are effective, additional doses of 1 to 4 mg may be given every 30 to 60 minutes as necessary.
The usual initial dose is 0.5 mg. Additional doses of 0.5 mg may be administered every 5 minutes until a response is obtained, adverse cholinergic effects develop, or a total dose of 2 mg is given. Thereafter, the lowest effective dose may be repeated as necessary. Atropine should be available to reverse life-threatening toxic cholinergic effects, e.g. bronchoconstriction, which might result from physostigmine.
Polyamps:
Store below 25°C. Protect from light. Shelf-life 18 months.
Prescription Medicine.
1 mL Polyamp DuoFit®:
400 mcg/mL packs of 50
600 mcg/mL packs of 50
1 200 mcg/mL packs of 50
Nil.
AstraZeneca Ltd
303 Manukau Rd
Epsom, Auckland
Ph: (09) 623 6300
23 July 1999