Chemicals / Complex Chemical Agents/ Chemical:

Atropine Sulphate

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 

Antimuscarinic agent used as a preanaesthetic medication and in the treatment of anticholinesterase toxicity.

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Names and Formulae

Type Antimuscarinic.
Alternative Names DL-hyoscyamine; atrophine sulfate.
Chemical Formula D-hyoscyamine and L-hyoscyamine in a racemic mixture; the L form is the active form; the D-form is practically lacking in antimuscarinic activity. (B263)
Chemical Structure --
Molecular Weight --
Related Chemicals --

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Physical Properties / Chemistry

Appearance

A white, crystalline powder or colourless, odourless crystals. (B263)

Melting point --
Boiling point --
Density --
Water solubility Soluble in water: one gram is soluble in about 0.5 mL water. 
sulfate is soluble in approximately 0.5 ml of water, 5 ml of 
Other solubility
  • One gram is soluble in about 5 mL of alcohol. (B263)
  • One gram is soluble in about 2.5 mL of glycerin. (B263)
Acid/Base In aqueous solution, neutral or just slightly acidic. However, commercially-available solutions may have been pH adjusted to between pH 3.0 - 6.5. (B263)

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Pharmacology & General Information

Pharmacology Competitively inhibits acetylcholine (and other cholinergic stimulants) at postganglionic parasympathetic neuroeffector sites. Additionally, with high doses, nicotinic receptors may be blocked at neuromuscular junctions and autonomic ganglia.
Storage / Stability
  • Store at room temperature (15 - 30 C) and avoid freezing. (B263)
  • Tablets should be stored in a well-closed container. (B263)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referees Nikki Fox BVSc MRCVS (V.w103)

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Therapeutic Information

Uses/Indications

Activity
  • Low systemic dose: inhibition of salivation, bronchial secretions and sweating
  • Moderate systemic dose: pupil dilated and accommodation of the pupil inhibited; heart rate increased. 
  • High dose: gastro-intestinal and urinary tract motility decreased.
  • Very high dose: gastric secretion inhibited.

(B263)

Appropriate Use
  • Preanesthetic medication, to reduce respiratory tract secretions
  • Treatment of vagally-mediated cardiac arrhythmias (sinus bradycardia, sinoatrial arrest or incomplete atrio-ventricular block)
  • Adjunct in the treatment of GIT disorders involving spasm of smooth muscle.
  • Antidote to overdoses of cholinergic agents such as physostigmine
  • Antidote to organophosphorus compound (organophosphate) poisoning
  • Antidote to muscarinic mushroom toxicity
  • Treatment of hypersyalism (excessive salivation)
  • Treatment of bronchoconstrictive disease

(B263, B340.6.w6)

Limitations --
Notes --

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Pharmacokinetics and Drug Interactions

Absorption /Bioavailability
  • Oral: well absorbed. (B263)
  • Intramuscular injection, endotracheal administration or inhalation: well absorbed. (B263)
  • Intravenous injection: peak effects on heart rate are seen within three to four minutes. (B263)
Distribution Well distributed including into the CNS, across the placenta and (to a lesser extent) into milk. (B263)
Plasma Protein binding / Storage --
Elimination Route Both metabolised in the liver and excreted in urine; about 30 - 50% of the drug is excreted in urine unchanged. (B263)
Elimination half-life / Clearance Rate In humans: plasma half life of 2 - 3 hours. (B263)
Drug Interactions
  • The effects of atropine may be enhanced by: "antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines."
  • The adverse effects of atropine may be potentiated by: "primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocular pressure)."
  • Atropine may enhance the actions of: "nitrofurantoin, thiazide diuretics, sympathomimetics.
  • Atropine may antagonize the action of: "metoclopramide".
Physical interactions
  • Atropine sulphate is reported to be physically incompatible with: "norepinephrine bitartrate, metaraminol bitartrate, methohexital sodium, and sodium bicarbonate." (B263)
  • Atropine sulphate for injection is reported to be physically compatible with: "benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, cimetidine HCl (not with pentobarbital), dimenhydrinate, diphenhydramine HCl, dobutamine HCl, droperidol, fentanyl citrate, glycopyrrolate, hydromorphone HCl, hydroxyzine HCl (also w/meperidine), meperidine HCl, morphine sulfate, nalbuphine HCl, pentazocine lactate, pentobarbital sodium (OK for 5 minutes, not 24 hours), perphenazine, prochlorperazine edisylate, promazine HCl, promethazine HCl (also w/meperidine), and scopolamine HBr.
  • Note: Physical compatibility is affected by factors such as concentration, pH, temperature and diluents; specialized references should be consulted for more specific information. (B263)

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Administration

Formulations available UK: Atrocare Injection (Animalcare Limited).
Doses / Administration Routes / Frequencies Antimuscarinic:
  • By subcutaneous injection. 
    • Horses and cattle 30 - 60 micrograms per kg.
    • Sheep 80 - 160 micrograms per kg.
    • Pigs 20-40 micrograms per kg.
    • Dogs and cats 30-100 micrograms per kg.

    (B340.6.w6)

For treatment of organophosphorus compound (organophosphate) toxicity:

  • 25-300 micrograms per kg bodyweight, subcutaneously about every three to four hours until signs of toxicity are relieved. (B340.6.w6)
    • In severe poisoning, 25% of the dose may be given intramuscularly or by slow intravenous injection, with the remaining 75% of the dose given subcutaneously. (B340.6.w6)
  • 0.2 mg/kg intramuscularly or subcutaneously, with a quarter (fourth) of the dose intravenously suggested. (B20.5.w3)
  • In wild birds, a dose of 20 mg/kg may be required. (B20.5.w3)
  • Note: atropine does not affect the binding of cholinesterase-inhibiting pesticides to the cholinesterase enzyme, but blocks the muscarinic peripheral nerve receptors and some of the CNS effects. High atropine doses are toxic. It is suggested that a dose of atropine should be given and the patient observed for 10-15 minutes, with a repeat dose of atropine given if signs of the anticholinesterase toxicity have not reduced. (B20.5.w3)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 50 micrograms/kg subcutaneously or intramuscularly. (B373.Guide.w41)
  • 0.04 - 1.0 mg/kg intramuscularly or subcutaneously. Due to endogenous atropinases, administration may need to be repeated every 10 - 15 minutes. (B546
  • 0.05 mg/kg (5 g/kg). As a premedicant, and in the treatment of organophosphate toxicity. (B600.4.w4, B601.15.w15)
    • Note: about 40% of rabbits produce atropinesterase and rapidly metabolize atropine. (B600.4.w4)
  • 0.1 - 0.5 mg/kg subcutaneously or intramuscularly. (B602.41.w41, B548.w8)
  • 0.1 - 3.0 mg/kg subcutaneously. (B548.w8)
  • 0.8 - 1.0 mg/kg intramuscularly (B548.w8)

Ferrets - Mustela putorius furo - Ferret:

  • 0.04 mg/kg subcutaneously, intramuscularly or intravenously. (B602.41.w41)
  • 0.04 mg/kg intramuscularly subcutaneously or intravenously. Used particularly with Isoflurane. Note: gives prolonged dilated pupils. (B626.App.w22)
  • In the treatment of organophosphate poisoning: 5 -10 mg/kg subcutaneously or intramuscularly. (B626.App.w22, B631.21.w21)
  • 0.02 - 0.04 mg/kg intravenously or subcutaneously or 0.1 mg/kg intratracheally. In the treatment of bradycardia. (B631.21.w21)
  • 0.05 mg/kg subcutaneously, intramuscularly or intravenously once as a pre-anaesthetic drug to reduce salivation and bradycardia. (B631.22.w22)
  • 0.05 mg/kg intramuscularly or subcutaneously. For the treatment of bradycardia or to control salivation. (J213.3.w1)

Great Apes

  • Adult Pan troglodytes - Chimpanzee: 0.02 - 0.05 mg/kg intravenously, intramuscularly or subcutaneously. (W768.Jun2012.w1)
  • Primates: 0.05 - 0.10 mg/kg intravenously or intramuscularly. (D425.3.15.w3o)
Monitoring parameters --

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Withdrawal period / Withholding time

Notes NOTE: the required withdrawal period / withholding time may vary between countries and over time. The following information is provided as a guide only. Current regulations for your country MUST be consulted.
  • Cattle: Following antimuscarinic dose, milk 3 days, slaughter 14 days. Following antidote use, milk 6 days, slaughter 28 days. (B340.6.w6)
  • Sheep and pigs: Following antimuscarinic dose, slaughter 14 days. Following antidote use, slaughter 28 days. (B340.6.w6)

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Toxic Information

Toxic effects of Pharmaceutical Products

Contraindications / Precautions Contraindicated in individuals with:
  • Glaucoma (B340.6.w6) narrow-angle glaucoma (B263);
  • Adhesions between the iris and the lens (synchiae)
  • Known hypersensitivity to anticholinergic drugs;
  • Pre-existing tachycardia (B340.6.w6) Tachycardia secondary to thyrotoxicosis or cardiac insufficiency; (B263)
  • Myocardial ischemia;
  • Unstable cardiac status associated with acute haemorrhage;
  • Gastro-intestinal obstructive disease, paralytic ileus or severe ulcerative colitis
  • Obstructive uropathy,
  • Myasthenia gravis (unless used to reverse adverse muscarinic effects secondary to therapy).

(B263, B340.6.w6)

Use with extreme caution in individuals with:

  • Known or suspected gastrointestinal infection, since reduced GIT motility may prolong retention of the infectious agent and thereby prolong signs of infection.
  • In with autonomic neuropathy.
  • Hepatic or renal disease,
  • The very young or very old; 
  • Hyperthyroidism
  • Hypertension
  • Congestive heart failure
  • Tachyarrhythmias
  • Prostatic hypertrophy
  • Oesophogeal reflux. 

(B263)

In horses: 

  • Use systemic atropine with caution due to the risk of decreased gut motility and induction of colic in susceptible animals. (B263)
  • "May also reduce the arrhythmogenic doses of epinephrine." (B263)

In cattle: 

  • May cause inappetance and ruminal stasis; this may be persistent (several days). (B263)
Adverse Effects / Side Effects / Warnings These are generally dose related and are extensions of the expected pharmacological effects of this drug. 
  • In healthy patients, effects are usually mild with normal doses, but may be more severe with high doses
  • GIT and urinary: dry mouth, dysphagia, vomiting, constipation, thirst, and urinary retention or hesitancy.
  • CNS effects: stimulation, drowsiness, ataxia, seizures, and respiratory depression, etc. 
  • Ophthalmic effects: dilation of the pupil, photophobia, blurred vision and cycloplegia
  • Cardiovascular effects: initially or with very low doses, bradycardia; with higher doses, sinus tachycardia; hypertension, hypotension, arrhythmias (ectopic complexes); circulatory failure.

(B263)

Operator Warnings --
Overdose / Acute Toxicity
  • GIT and urinary: dry mouth, dysphagia, vomiting, constipation, thirst, and urinary retention or hesitancy.
  • CNS effects: stimulation, drowsiness, ataxia, seizures, and respiratory depression, etc. 
  • Ophthalmic effects: blurred vision, dilatation of the pupil, cycloplegia, and photophobia. 
  • Cardiovascular effects: initially or with very low doses, bradycardia; with higher doses, sinus tachycardia; hypertension, hypotension, arrhythmias (ectopic complexes); circulatory failure.

(B263)

Treatment: 

  • Following recent oral ingestion, consider emptying the gut contents and giving activated charcoal and saline cathartics to reduce further absorption. (B263)
  • Symptomatic and supportive treatment, including fluids and standart treatment for shock if required. (B263)
  • Do not use phenothiazines; these may contribute to the anticholinergic effects. (B263)
  • "The use of physostigmine is controversial and should probably be reserved for cases where the patient exhibits either extreme agitation and is at risk for injuring themselves or others, or for cases where supraventricular tachycardias and sinus tachycardias are severe or life-threatening. The usual dose for physostigmine (human) is: 2 mg IV slowly (for average sized adult) If no response, may repeat every 20 minutes until reversal of toxic antimuscarinic effects or cholinergic effects takes place. The human pediatric dose is 0.02 mg/kg slow IV (repeat q10 minutes as above) and may be a reasonable choice for initial treatment of small animals." (B263)
    • Small doses of of atropine, given intravenously, may be used to treat adverse effects of physostigmine (bronchoconstriction, bradycardia and seizures). (B263)

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Detailed Toxicological Information

Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data

Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses

Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment

Natural sources --
Human-associated sources

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Effects on the Environment

Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment

Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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