Atropine Sulfate

(BANM)

💊 Chemical information

Atrop. Sulph.; Atropiinisulfaatti; Atropin Sülfat; Atropina, sulfato de; Atropine, sulfate d’; Atropine Sulphate fas; Atropini Sulfas Monohydricus; Atropino sulfatas; Atropinsulfat; Atropin-sulfát monohydrát; Atropin-szulfát; Atropiny siarczan.
Chemical formula: (C17H23NO3)2,H2SO4,H2O = 694.8.
CAS — 55-48-1 (anhydrous atropine sulfate); 5908-99-6 ATC — A03BA01; S01FA01.
ATC Vet — QA03BA01; QS01FA01.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet.

Ph. Eur. 6.2

(Atropine Sulphate). A white or almost white, crystalline powder or colourless crystals. Very soluble in water; freely soluble in alcohol. A 2% solution in water has a pH of 4.5 to 6.2. Protect from light.

USP 31

(Atropine Sulfate). Odourless, colourless crystals or white crystalline powder. It effloresces in dry air. Soluble 1 in 0.5 of water, 1 in 2.5 of boiling water, 1 in 5 of alcohol, and 1 in 2.5 of glycerol. Store in airtight containers.

Incompatibility.

Incompatibility between atropine sulfate and hydroxybenzoate preservatives has been seen, 1 resulting in a total loss of the atropine in 2 to 3 weeks. 1. Deeks T. Oral atropine sulphate mixtures. Pharm J 1983; 230: 481.

💊 Adverse Effects

The pattern of adverse effects seen with atropine and other antimuscarinics can mostly be related to their pharmacological actions at muscarinic and, at high doses, nicotinic receptors (see Actions of Antimuscarinics, below). These effects are dose-related and are usually reversible when therapy is stopped. The peripheral effects of atropine and other antimuscarinics are a consequence of their inhibitory effect on muscarinic receptors within the autonomic nervous system. At therapeutic doses, adverse effects include dryness of the mouth with difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of the pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, with palpitations and arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation. Some of the central effects of atropine and other tertiary antimuscarinics seen at toxic doses (see below) may also occur at therapeutic doses. In overdosage, the peripheral effects become more pronounced and other symptoms such as hyperthermia, hypertension, increased respiratory rate, and nausea and vomiting may occur. A rash may appear on the face or upper trunk. Toxic doses also cause CNS stimulation marked by restlessness, confusion, excitement, ataxia, incoordination, paranoid and psychotic reac tions, hallucinations and delirium, and occasionally seizures. However, in severe intoxication, central stimulation may give way to CNS depression, coma, circulatory and respiratory failure, and death. There is considerable variation in susceptibility to atropine; recovery has occurred even after 1 g, whereas deaths have been reported from doses of 100 mg or less for adults and 10 mg for children. Quaternary ammonium antimuscarinics, such as atropine methobromide or methonitrate and propantheline bromide, have some ganglion-blocking activity and high doses may cause orthostatic hypotension and impotence; in toxic doses non-depolarising neuromuscular block may be produced. Systemic toxicity may be produced by the local instillation of antimuscarinic eye drops, particularly in children and in the elderly. Prolonged application of atropine to the eye may lead to local irritation, hyperaemia, oedema, and conjunctivitis. An increase in intra-ocular pressure may occur, especially in patients with angleclosure glaucoma. Hypersensitivity to atropine is not uncommon and may occur as conjunctivitis or a skin rash.

Effects on body temperature.

Atropine can cause hyperthermia as a result of inhibition of sweating. This may be attenuated by atropine’s ability to dilate cutaneous blood vessels. However, there has been a report of hypothermia in a 14-year-old feverish patient after intravenous use of atropine.1 For reports of fatal heat stroke in patients taking an antimuscarinic with an antipsychotic see under Interactions in Benzatropine.
1. Lacouture PG, et al. Acute hypothermia associated with atropine. Am J Dis Child 1983; 137: 291–2.

Effects on the eyes.

In addition to the expected ocular effects of atropine (see above) there have been instances of acute angleclosure glaucoma in patients receiving nebulised atropine.1
1. Berdy GJ, et al. Angle closure glaucoma precipitated by aerosolized atropine. Arch Intern Med 1991; 151: 1658–60.

Effects on the gast

rointestinal tract. Antimuscarinics reduce gastrointestinal tone and paralytic ileus has been reported1in a 77-year-old man with Parkinson’s disease who had been receiving atropine sulfate orally to control excess salivation. An increased risk of oesophageal cancer has also been reported2with antimuscarinics, possibly due to reductions in lower oesophageal sphincter tone increasing the risk of gastrooesophageal reflux.
1. Beatson N. Atropine and paralytic ileus. Postgrad Med J 1982; 58: 451–3
2. Lagergren J, et al. Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma. Ann Intern Med 2000; 133: 165–75.

Effects on the heart.

Atropine sulfate, to a total of 1 mg per 70 kg body-weight, given intravenously to 79 patients before surgery produced arrhythmias in over 20% of patients, especially in the young.1 Atrioventricular dissociation was the most common disturbance in adults and in children atrial rhythm disturbances were common. In another study2 premedication including atropine or glycopyrronium given intramuscularly resulted in a significantly greater incidence of tachycardia during anaesthetic induction and intubation compared with controls who received no antimuscarinic drug. Patients who received glycopyrronium also had a higher incidence of tachycardia during surgery than the controls. No significant difference in bradycardia or extrasystoles was found in the atropine- or the glycopyrronium-treated patients. Atrial fibrillation has been reported in 2 elderly glaucoma patients after post-surgical application of atropine ointment or eye drops to the eye.3
1. Dauchot P, Gravenstein JS. Effects of atropine on the electrocardiogram in different age groups. Clin Pharmacol Ther 1971; 12: 274–80
2. Shipton EA, Roelofse JA. Effects on cardiac rhythm of premedication with atropine or glycopyrrolate. S Afr Med J 1984; 66: 287–8
3. Merli GJ, et al. Cardiac dysrhythmias associated with ophthalmic atropine. Arch Intern Med 1986; 146: 45–7.

Effects on mental function.

A study1 in patients with Parkinson’s disease and healthy control subjects suggested that although short-term memory was impaired in patients receiving long-term antimuscarinic therapy the effect was reversible on stopping. An epidemiological study2 similarly reported lower cognitive performance in elderly patients receiving antimuscarinics. See also under Trihexyphenidyl and under Oxybutynin.
1. Van Herwaarden G, et al. Short-term memory in Parkinson’s disease after withdrawal of long-term anticholinergic therapy. Clin Neuropharmacol 1993; 16: 438–43
2. Lechevallier-Michel N, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study. Br J Clin Pharmacol 2005; 59: 143–51.

Hypersensitivity.

A report1 of anaphylactic shock developing in a 38-year-old woman after an intravenous injection of atropine.
1. Aguilera L, et al. Anaphylactic reaction after atropine. Anaesthesia 1988; 43: 955–7.

Overdosage.

Reports of atropine poisoning or overdosage have included a respiratory therapist1 who had given 10 atropine sulfate aerosol treatments in the preceding 24 hours and children who had taken overdoses of a preparation containing diphenoxylate and atropine.2
1. Larkin GL. Occupational atropine poisoning via aerosol. Lancet 1991; 337: 917
2. McCarron MM, et al. Diphenoxylate-atropine (Lomotil) overdose in children: an update (report of eight cases and review of the literature). Pediatrics 1991; 87: 694–700.

💊 Treatment of Adverse Effects

If a patient presents within an hour of an overdose of atropine by mouth the stomach may be emptied or activated charcoal given to reduce absorption. Supportive therapy should be given as required. Physostigmine has been tried for antimuscarinic poisoning but such use can be hazardous and is not generally recommended. Diazepam may be given to control marked excitement and convulsions; phenothiazines should not be given as they may exacerbate antimuscarinic effects. Antiarrhythmics are not recommended if arrhythmias develop; hypoxia and acidosis should be corrected and sodium bicarbonate may be given even if acidosis is not present.

💊 Precautions

Atropine should be used with caution in children and the elderly, who may be more susceptible to its adverse effects. It is contra-indicated in patients with prostatic enlargement, in whom it may lead to urinary retention, and in those with paralytic ileus or pyloric stenosis. In patients with ulcerative colitis its use may lead to ileus or megacolon, and its effects on the lower oesophageal sphincter may exacerbate reflux. Caution is generally advisable in any patient with diarrhoea. It should not be given to patients with myasthenia gravis except to reduce adverse muscarinic effects of an anticholinesterase. Atropine should not be given to patients with angleclosure glaucoma or with a narrow angle between the iris and the cornea, since it may raise intra-ocular pressure and precipitate an acute attack. Acute angle-closure glaucoma has been reported in patients receiving nebulised atropine. Some licensed product information recommends that atropine eye drops should not be used in infants aged less than 3 months due to the possible association between the induced cycloplegia and the development of amblyopia. Systemic reactions have followed the absorption of atropine from eye drops; overdosage is less likely if the eye ointment is used. In the event of blurred vision after topical application of atropine to the eye patients should not drive or operate machinery. Systemic use of antimuscarinics may also cause blurred vision, dizziness, and other effects that may impair a patient’s ability to perform skilled tasks such as driving. Because of the risk of provoking hyperthermia, atropine should not be given to patients, especially children, when the ambient temperature is high. It should also be used cautiously in patients with fever. Atropine and other antimuscarinics need to be used with caution in conditions characterised by tachycardia such as thyrotoxicosis, heart failure, and in cardiac surgery, where they may further accelerate the heart rate. Care is required in patients with acute myocardial infarction, as ischaemia and infarction may be made worse, and in patients with hypertension. Atropine may cause confusion, especially in the elderly. Reduced bronchial secretion caused by systemic atropine may be associated with the formation of mucous plugs. In the treatment of parkinsonism, increases in dosage and transfer to other forms of treatment should be gradual and the antimuscarinic should not be withdrawn abruptly. Minor reactions may be controlled by reducing the dose until tolerance has developed. Persons with Down’s syndrome appear to have an increased susceptibility to some of the actions of atropine, whereas those with albinism may have a reduced susceptibility.

Breast feeding.

No adverse effects have been observed in breast-feeding infants whose mothers were receiving atropine, and the American Academy of Pediatrics1 considers that it is therefore usually compatible with breast feeding.
1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: http://aappolicy.aappublications.org/cgi/content/full/ pediatrics%3b108/3/776 (accessed 01/06/04)

💊 Interactions

The effects of atropine and other antimuscarinics may be enhanced by use with other drugs having antimuscarinic properties, such as amantadine, some antihistamines, phenothiazine antipsychotics, and tricyclic antidepressants. Inhibition of drug-metabolising enzymes by MAOIs may possibly enhance the effects of antimuscarinics. The reduction in gastric motility caused by antimuscarinics may affect the absorption of other drugs. Antimuscarinics may also antagonise the gastrointestinal effects of cisapride, domperidone, and metoclopramide. Antimuscarinics and parasympathomimetics may counteract each others effects.

💊 Pharmacokinetics

Atropine is readily absorbed from the gastrointestinal tract; it is also absorbed from mucous membranes, the eye, and to some extent through intact skin. It is rapidly cleared from the blood and is distributed throughout the body. It crosses the blood-brain barrier. It is incompletely metabolised in the liver and is excreted in the urine as unchanged drug and metabolites. A half-life of about 4 hours has been reported. Atropine crosses the placenta and traces appear in breast milk. Quaternary ammonium salts of atropine, such as the methonitrate, are less readily absorbed after oral doses. They are highly ionised in body fluids and being poorly soluble in lipids they do not readily cross the bloodbrain barrier.

Pregnancy.

Studies of the pharmacokinetics of atropine in mother and fetus in late pregnancy1-3 indicated that atropine rapidly crosses the placenta. However, whereas peak concentrations of atropine in fetal cord blood were reached about 5 minutes after intravenous doses, the maximum effect on fetal heart rate occurred after about 25 minutes.
1. Barrier G, et al. La pharmacocinétique de l’atropine chez la femme enceinte et le foetus en fin de grossesse. Anesth Analg Reanim 1976; 33: 795–800
2. Onnen I, et al. Placental transfer of atropine at the end of pregnancy. Eur J Clin Pharmacol 1979; 15: 443–6
3. Kanto J, et al. Placental transfer and pharmacokinetics of atropine after a single maternal intravenous and intramuscular administration. Acta Anaesthesiol Scand 1981; 25: 85–8.

💊 Uses and Administration

Atropine is a tertiary amine antimuscarinic alkaloid with both central and peripheral actions (see below). It is usually given as the sulfate. It first stimulates and then depresses the CNS and has antispasmodic actions on smooth muscle and reduces secretions, especially salivary and bronchial secretions; it also reduces perspiration, but has little effect on biliary or pancreatic secretion. Atropine depresses the vagus and thereby increases the heart rate. When given orally atropine reduces smooth-muscle tone and diminishes gastric and intestinal motility but has little effect on gastric secretion in usual therapeutic doses. Quaternary ammonium derivatives, such as the methonitrate, have less effect on the CNS but strong ganglion-blocking activity. Because of its effects on heart rate, atropine is used in the treatment of bradycardia and asystole of various causes, including in acute cardiopulmonary resuscitation procedures. It has also had many other uses, including: in anaesthetic practice as a premedicant and to counteract the muscarinic effects of anticholinesterases such as neostigmine and other parasympathomimetics; as an antispasmodic in gastrointestinal disorders; as an adjunct to opioid analgesics for the symptomatic relief of biliary or renal colic; to treat or prevent bronchospasm; and in the treatment of poisoning with mushrooms that contain muscarine and in organophosphorus pesticide poisoning. Atropine is used topically as a mydriatic and cycloplegic in ophthalmology. See under headings below for details of dosage and administration of atropine and its derivatives in specific indications.

Actions of antimuscarinics.

Antimuscarinic drugs such as atropine are competitive inhibitors of the actions of acetylcholine at the muscarinic receptors of autonomic effector sites innervated by parasympathetic (cholinergic postganglionic) nerves; they are also inhibitors of the action of acetylcholine on smooth muscle lacking cholinergic innervation. They have been described as parasympatholytic, atropinic, atropine-like, and as anticholinergic, although the latter term should encompass compounds that also have antinicotinic actions. At least 5 different pharmacologically identifiable types of muscarinic receptor (M1, M2, M3, M4, and M5) have been described as have 5 different molecular forms (m1, m2, m3, m4, and m5) of these receptors. While the traditional antimuscarinics appear to be relatively non-specific, newer compounds like pirenzepine and telenzepine have a selective action on the M1 receptors within ganglia supplying cholinergic postganglionic nerves to the gastrointestinal tract. Antimuscarinics can be classified as tertiary amine or quaternary ammonium compounds. Atropine and other naturally occurring alkaloids such as hyoscine and hyoscyamine are tertiary amines, that is they have a tertiary nitrogen atom; semisynthetic derivatives or synthetic antimuscarinics may be either tertiary (e.g. homatropine or trihexyphenidyl) or quaternary ammonium (e.g. homatropine methylbromide or ipratropium) compounds. At therapeutic doses tertiary amine antimuscarinics have little effect on the actions of acetylcholine at nicotinic receptors. However, the quaternary ammonium antimuscarinics exhibit a greater degree of antinicotinic potency, and some of their effects at high doses are due to ganglionic blockade; excessively high doses may even produce neuromuscular block. There are also pharmacokinetic differences between tertiary amine and quaternary ammonium antimuscarinics. Quaternary ammonium compounds are less lipid soluble than tertiary amines; their gastrointestinal absorption is poor and they do not readily pass the blood-brain barrier or conjunctiva. Antimuscarinics can produce a wide range of effects at therapeutic doses. The peripheral antimuscarinic effects that are produced as the dose increases are:
decreased production of secretions from the salivary, bronchial, and sweat glands
dilatation of the pupils (mydriasis) and paralysis of accommodation (cycloplegia)
increased heart rate
inhibition of micturition and reduction in gastrointestinal tone
inhibition of gastric acid secretion As for central effects, with the exception of hyoscine, which causes CNS depression at therapeutic doses, tertiary amines stimulate the medulla and higher cerebral centres producing mild central vagal excitation and respiratory stimulation. At toxic doses all tertiary amines, including hyoscine, cause stimulation of the CNS with restlessness, disorientation, hallucinations, and delirium. As the dose increases stimulation is followed by central depression and death from respiratory paralysis. Synthetic tertiary amines are less potent in their central effects than natural tertiary amines; quaternary ammonium compounds have negligible central effects.

Anaesthesia.

Antimuscarinics, including atropine, hyoscine, and glycopyrronium, have been used pre-operatively to inhibit salivation and excessive secretions of the respiratory tract during anaesthesia, although this use is less important now that less irritating anaesthetics are used. Atropine and glycopyrronium are also given to reduce intra-operative bradycardia and hypotension induced by drugs such as suxamethonium, halothane, or propofol, or following vagal stimulation. Glycopyrronium causes less tachycardia than atropine when given intravenously. When hyoscine is used as a premedicant it also provides some amnesia, sedation, and antiemesis but, unlike atropine, may cause bradycardia rather than tachycardia. Atropine or, preferably, glycopyrronium is also used before, or with, anticholinesterases such as neostigmine to prevent their muscarinic adverse effects. For premedication 300 to 600 micrograms of atropine sulfate may be given by subcutaneous or intramuscular injection, usually 30 to 60 minutes before anaesthesia. Alternatively 300 to 600 micrograms of atropine sulfate may be given intravenously immediately before induction of anaesthesia. Suitable paediatric subcutaneous or intramuscular premedication doses of atropine sulfate are:
children up to 3 kg in weight: 100 micrograms
children 7 to 9 kg in weight: 200 micrograms
children 12 to 16 kg in weight: 300 micrograms
children over 20 kg in weight: the adult dose. For intra-operative bradycardia the BNF states that 300 to 600 micrograms may be given intravenously; larger doses may be used in emergencies. Children may be given 10 to 20 micrograms/kg. To counteract the muscarinic effects of anticholinesterases when they are used to reverse the effects of competitive muscle relaxants adults are given atropine sulfate 0.6 to 1.2 mg by intravenous injection before or with the anticholinesterase. Neonates, infants, and children may be given a dose of 20 micrograms/kg (maximum dose 600 micrograms).

Anoxic seizures.

A reflex anoxic seizure is a paroxysmal event triggered by a noxious stimulus which, by vagal stimulation, causes pronounced bradycardia or cardiac arrest and consequent relative cerebral ischaemia.1 Certain features of the attack may lead to a misdiagnosis of epilepsy. To avoid confusion with epileptic seizures, reflex anoxic seizures have also been called white or type 2 breath holding attacks. Depending on the degree of vagal hypersensitivity or noxious stimulus, attacks may occur infrequently or several times a day. Infants and young children are mainly affected, however, the condition usually resolves by early childhood. It is generally benign and children do not suffer cardiac or cerebral damage. Treatment is seldom necessary, but atropine has been advocated to prevent vagal hypersensitivity in those children with frequent, persistent attacks. As atropine may require frequent doses with an attendant risk of overdosage, transdermal hyoscine has been tried as an alternative.2
1. Appleton RE. Reflex anoxic seizures. BMJ 1993; 307: 214–5
2. Palm L, Blennow G. Transdermal anticholinergic treatment of reflex anoxic seizures. Acta Paediatr Scand 1985; 74: 803–4.

Biliary and renal colic.

Atropine has been used as an adjunct to opioid analgesics for symptomatic relief of biliary or renal colic.

Cardiac disorders.

Atropine depresses the vagus and thereby increases the heart rate. It is therefore used in a variety of disorders or circumstances in which bradyarrhythmias occur. It is frequently used in sudden onset bradyarrhythmias and although it may also be given for the initial treatment of chronic arrhythmias, cardiac pacing is generally preferred for long-term control. Examples of acute use include the prevention and treatment of arrhythmias associated with anaesthesia (see above), the treatment of other drug-induced arrhythmias, and in cardiac arrest due to asystole or electromechanical dissociation. Atropine sulfate has been used in the management of bradycardia of acute myocardial infarction; however, caution is required, as atropine may exacerbate ischaemia or infarction in these patients. For advanced life support in adults with asystole or electromechanical dissociation, European1 and UK guidelines2 recommend atropine in a single dose of 3 mg intravenously; US guidelines3 recommend repeated doses of 1 mg to a total maximum dose of 3 mg. In bradycardia, atropine is given1-3 in doses of 500 micrograms intravenously repeated every 3 to 5 minutes to a total dose of 3 mg. If an intravenous line cannot be established, atropine can be given via an endotracheal tube; 2 to 3 times the intravenous dose should be given, diluted in 10 mL of sterile water or sodium chloride 0.9%.
1. European Resuscitation Council. European Resuscitation Council guidelines for resuscitation 2005. Resuscitation 2005; 67 (suppl 1): S1–S190. Also available at: http://www.erc.edu/ index.php/guidelines_download_2005/en/? (accessed 07/03/06
2. Resuscitation Council (UK). Resuscitation Guidelines 2005. Available at: http://www.resus.org.uk/pages/guide.htm (accessed 07/03/06
3. The American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005; 112 (suppl 1): IV1–IV203. Also available at: http://intl-circ.ahajournals.org/ content/vol112/24_suppl/ (accessed 09/02/06)

Eye disorders.

Atropine is used to produce mydriasis and cycloplegia for ophthalmic examination. One local application can take up to 40 minutes or more to produce mydriasis, which lasts for a week or more; marked paralysis of accommodation is obtained in 1 to 3 hours with recovery in 6 to 12 days. However, other antimuscarinics such as cyclopentolate, homatropine, or tropicamide may be preferred because they have a more rapid onset and shorter duration of action than atropine. Atropine is also used in the management of uveitis and iritis, and in strabismus. It is used in the treatment of iritis and uveitis to immobilise the ciliary muscle and iris and to prevent or break down adhesions. Because of its powerful cycloplegic action atropine is also used in the determination of refraction in children below the age of 6 and in children with convergent strabismus. In the treatment of inflammatory eye disorders such as uveitis or iritis, the dose of atropine sulfate for adults is 1 or 2 drops of a 0.5 or 1% solution instilled into the eye(s) up to four times daily. The dose in children is 1 or 2 drops of a 0.5% solution (or one drop of a 1% solution) instilled up to three times daily. For refraction in adults the dose is one drop of a 1% solution of atropine sulfate; this may be instilled either twice daily for 1 or 2 days before the procedure or on a single occasion one hour before the procedure. In children the dose for refraction is 1 or 2 drops of a 0.5% solution (or one drop of a 1% solution) instilled twice daily for 1 to 3 days before the procedure, with a further dose given one hour before the procedure. An ophthalmic ointment of atropine sulfate 1% may be preferred for children under 5 years and particularly in infants under 3 months who are at increased risk of systemic effects with eye drops. Some manufacturers recommend that atropine sulfate should not be used in the eyes of children younger than 3 months due to a possible association between the cycloplegia produced and the development of amblyopia. Atropine borate has also been used in ophthalmic preparations.
1. Stolovitch C, et al. Atropine cycloplegia: how many instillations does one need? J Pediatr Ophthalmol Strabismus 1992; 29: 175–6
2. Foley-Nolan A, et al. Atropine penalisation versus occlusion as the primary treatment for amblyopia. Br J Ophthalmol 1997; 81: 54–7
3. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002; 120: 268–78.

Gastrointestinal disorders.

Antimuscarinics may be used in gastrointestinal disorders as antispasmodics, because of their marked inhibitory effect on gastrointestinal motility, and for their antisecretory effects. Atropine (as the sulfate or quaternary derivatives such as the methobromide or methonitrate) has been used to reduce smooth-muscle tone and diminish motility, but has little effect on gastric secretion at usual therapeutic doses (about 200 micrograms of atropine sulfate). It has been tried as an adjunct to the treatment of benign gastric and duodenal ulcers and the antispasmodic action of atropine has been used to facilitate radiological examination of the gut. Atropine sulfate has also been used in the treatment of irritable bowel syndrome. Atropine oxide hydrochloride is also used for gastrointestinal disorders.

Poisoning.

Atropine is used in the management of overdosage or poisoning due to anticholinesterase compounds including organophosphorus pesticides,1,2 chemical warfare nerve gases,3and parasympathomimetics such as neostigmine. It is also used to antagonise the effects of cholinomimetic substances in the treatment of overdosage with parasympathomimetics such as bethanechol, and in the treatment of poisoning with mushrooms that contain muscarine. Atropine blocks the action of these compounds at muscarinic receptors, reversing bradycardia and decreasing tracheobronchial secretions, bronchoconstriction, intestinal secretions, and intestinal motility.
In the treatment of poisoning with organophosphorus pesticides or chemical warfare nerve gases atropine sulfate may be given to adults in an initial dose of 2 mg intramuscularly or intravenously every 10 to 30 minutes until muscarinic effects disappear or signs of atropine toxicity are seen. In severe cases injections have been given as often as every 5 minutes in some centres. Continuous infusion has also been used.4,5 A dose of at least 50 micrograms/kg has been suggested for children by some;6 the BNF includes a dose of 20 micrograms/kg given every 5 to 10 minutes.
In moderate to severe poisoning a state of atropinisation is usually maintained for at least 2 days and continued for as long as symptoms are evident. In severely poisoned patients this may entail prolonged treatment.7,8 As large amounts of atropine may be required it is important to use a preservativefree preparation to avoid the potential toxicity associated with use of excess quantities of preservatives such as benzyl alcohol or chlorobutanol.
Since atropine is ineffective against any nicotinic effects of these compounds a cholinesterase reactivator such as pralidoxime may be used as an adjunct. The use of atropine in poisoning or overdosage with other compounds having muscarinic actions is similar to that for organophosphorus pesticides but the duration of treatment necessary is usually shorter. An initial dose of 0.6 to 1 mg given subcutaneously, intramuscularly, or intravenously and repeated every 2 hours may be adequate for overdosage with cholinomimetics such as bethanechol.
1. Singh S, et al. Is atropine alone sufficient in acute severe organophosphorus poisoning: experience of a North West Indian hospital. Int J Clin Pharmacol Ther 1995; 33: 628–30
2. Eddleston M, et al. Management of severe organophosphorus pesticide poisoning. Crit Care 2002; 6: 259
3. Anonymous. Treatment of nerve gas poisoning. Med Lett Drugs Ther 1995; 37: 43–4
4. Ram JS, et al. Continuous infusion of high doses of atropine in the management of organophosphorus compound poisoning. J Assoc Physicians India 1991; 39: 190–3
5. Sungur M, Güven M. Intensive care management of organophosphate insecticide poisoning. Crit Care 2001; 5: 211–15
6. Rotenberg JS, Newmark J. Nerve agent attacks on children: diagnosis and management. Pediatrics 2003; 112: 648–58
7. Golsousidis H, Kokkas V. Use of 19 590 mg of atropine during 24 days of treatment, after a case of unusually severe parathion poisoning. Hum Toxicol 1985; 4: 339–40
8. Afzaal S, et al. High dose atropine in organophosphorus poisoning. Postgrad Med J 1990; 66: 70–1.

Respiratory-tract disorders.

Although atropine is a potent bronchodilator its use in the management of reversible airways obstruction has largely been replaced by other antimuscarinics such as ipratropium. Atropine is sometimes used in combination preparations with antihistamines and decongestants for the symptomatic relief of symptoms of the common cold.
1. Sur S, et al. A random double-blind trial of the combination of nebulized atropine methylnitrate and albuterol in nocturnal asthma. Ann Allergy 1990; 65: 384–8
2. Vichyanond P, et al. Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma. Chest 1990; 98: 637–42.

💊 Preparations

BP 2008: Atropine Eye Drops; Atropine Eye Ointment; Atropine Injection; Atropine Tablets; Morphine and Atropine Injection; USP 31: Atropine Sulfate Injection; Atropine Sulfate Ophthalmic Ointment; Atropine Sulfate Ophthalmic Solution; Atropine Sulfate Tablets; Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution; Diphenoxylate Hydrochloride and Atropine Sulfate Tablets.

Proprietary Preparations

Arg.: Endotropina; Klonatropina; Austral.: Atropt; Belg.: Stellatropine; Braz.: Atropion; Sulfatina†; Canad.: Atropisol†; Fin.: Oftan Atropin†; Ger.: Atropinol†; Dysurgal; India: Bell Pino-Atrin; Indon.: Isotic Cycloma; Israel: Atrospan; Malaysia: Atrop†; Mex.: Atro Grin†; Atro Ofteno; Atropisa; Tropyn; NZ: Atropt; Port.: Atropocil; Switz.: Bellafit N; Skiatropine†; Turk.: Atrosol; USA: AtroPen; Ocu-Tropine; Sal-Tropine; Venez.: Atropicel†. Multi-ingredient: Arg.: Asmopul†; Otorinazol†; Saldeva†; Trixol†; Yanal; Austral.: Donnagel; Donnalix; Donnatab; Neo-Diophen†; Austria: Causat; Ichtho-Bellol; Lactolavol; Myocardon; Braz.: Espasmocron; Neogrein; Ormigrein; Sedabel†; Tonaton; Vagostesyl; Chile: Buton; Dipatropin; Dispasmol†; Dolospam; Papatropin†; Cz.: Spasmoveralgin Neo†; Ger.: IchthoBellol compositum S†; Ichtho-Bellol†; Mydrial-Atropin†; Hong Kong: Virulex Forte; Hung.: Meristin†; India: Atrisolon; Brovon; Pino-Cort; Indon.: Aludonna; Israel: Patropin; Spasmalgin; Ital.: Cardiostenol; Deltamidrina; Genatrop; Mex.: Paliatil; Redotex; Redotex NF; Pol.: Tolargin; Port.: Cosmaxil†; S.Afr.: Colstat; Donnatal; Famucaps; Millerspas; Virobis†; Spain: Abdominol; Midriati; Sulmetin Papaver; Sulmetin Papaverina†; Tabletas Quimpe; Swed.: Dilaudid-Atropin; Switz.: Dilaudid-Atropin†; Dolopyrine†; Nardyl; Spasmosol; Thai.: Alkamine; Alumag; Alupep; Donnatal†; Droximag†; Stomac; UK: Actonorm; Brovon; Nerve Agent Antidote L4A1; Valonorm; USA: Accuhist LA†; Alkabel; Antispasmodic Elixir; Atrosept; Barbidonna†; Bellahist-D; Bellatal; Dolsed†; Donnatal; DuoDote; EmergentEz; Hyosophen; MHP-A; Prosed/DS; Stahist; Susano; Trac Tabs 2X†; UAA; Uridon Modified†; Urised; Uriseptic; Uritact; Venez.: Butropina; Carbargal con Atropina; Eumidral; Fenopol†. Used as an adjunct in: Austral.: Lofenoxal; Lomotil; Braz.: Colestase; Lomotil; Canad.: Lomotil; Cz.: Reasec; Fr.: Diarsed; Hong Kong: Dhamotil; Dimotil; Lomotil; Hung.: Reasec; India: Lomofen; Lomotil; Irl.: Lomotil; Malaysia: Atrotil†; Beamotil; Dhamotil; Lomotil†; Setmotil†; NZ: Diastop; Lomotil†; Pol.: Reasec; Port.: Lomotil†; S.Afr.: Lomotil; Singapore: Beamotil; Dhamotil; Lomotil; Remodil†; Thai.: Dilomil†; Lomotil; Turk.: Lomotil; UAE: Intard; UK: Dymotil; Lomotil; USA: Enlon-Plus†; Logen; Lomotil; Lonox; Motofen; Neostigmine Min-I-Mix; Venez.: Lomotil†.
Published December 08, 2018.