KNOW ABOUT ONE DRUG EVERY DAY ATROPINE SULPHATE

KNOW ABOUT ONE DRUG EVERY DAY

ATROPINE SULPHATE

Names

Type                                       Antimuscarinic.

Alternative Names             DL-hyoscyamine; atrophine sulfate.

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.

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.

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

Pharmacokinetics and Drug Interactions

Absorption /Bioavailability

• Oral: well absorbed.
• Intramuscular injection, endotracheal administration or inhalation: well absorbed.
• Intravenous injection: peak effects on heart rate are seen within three to four minutes.

Distribution

Well distributed including into the CNS, across the placenta and (to a lesser extent) into milk.

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.  

Elimination half-life / Clearance Rate

In humans: plasma half life of 2 - 3 hours.  

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."
• 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.

Administration

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.

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.
• 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.
• 0.2 mg/kg intramuscularly or subcutaneously, with a quarter (fourth) of the dose intravenously suggested.
• In wild birds, a dose of 20 mg/kg may be required.
• 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.

Domestic rabbit:

• 50 micrograms/kg subcutaneously or intramuscularly.
• 0.04 - 1.0 mg/kg intramuscularly or subcutaneously. Due to endogenous atropinases, administration may need to be repeated every 10 - 15 minutes. 
• 0.05 mg/kg (5 µg/kg). As a premedicant, and in the treatment of organophosphate toxicity.  
• Note: about 40% of rabbits produce atropinesterase and rapidly metabolize atropine.
• 0.1 - 0.5 mg/kg subcutaneously or intramuscularly.
• 0.1 - 3.0 mg/kg subcutaneously.
• 0.8 - 1.0 mg/kg intramuscularly.

Primates: 0.05 - 0.10 mg/kg intravenously or intramuscularly.

Withdrawal period / Withholding time

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 our country MUST be consulted.

• Cattle: Following antimuscarinic dose, milk 3 days, slaughter 14 days. Following antidote use, milk 6 days, slaughter 28 days.
• Sheep and pigs: Following antimuscarinic dose, slaughter 14 days. Following antidote use, slaughter 28 days.

Toxic Information

Toxic effects of Pharmaceutical Products

Contraindications / Precautions

Contraindicated in individuals with:

• Glaucoma  - narrow-angle glaucoma;
• Adhesions between the iris and the lens (synchiae)
• Known hypersensitivity to anticholinergic drugs;
• Pre-existing tachycardia; Tachycardia secondary to thyrotoxicosis or cardiac insufficiency;
• 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).

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. 

In horses: 

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

In cattle: 

• May cause inappetance and ruminal stasis; this may be persistent (several days).

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.

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.

Treatment: 

• Following recent oral ingestion, consider emptying the gut contents and giving activated charcoal and saline cathartics to reduce further absorption.
• Symptomatic and supportive treatment, including fluids and standart treatment for shock if required.
• Do not use phenothiazines; these may contribute to the anticholinergic effects.
• "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."
• Small doses of of atropine, given intravenously, may be used to treat adverse effects of physostigmine (bronchoconstriction, bradycardia and seizures).