ATROPINE SULFATE

Chemistry - The prototype tertiary amine antimuscarinic agent, atropine sulfate is derived from thenaturally occurring atropine. It is a racemic mixture of d-hyoscyamine and l-hyoscyamine. The l-form of the drug is active, while the d- form has practically no antimuscarinic activity. Atropinesulfate occurs as colorless and odorless crystals, or white, crystalline powder. One gram of atropinesulfate is soluble in approximately 0.5 ml of water, 5 ml of alcohol, or 2.5 ml of glycerin. Aqueoussolutions are practically neutral or only slightly acidic. Commercially available injections may havethe pH adjusted to 3.0 - 6.5. Atropine may also be known as dl-hyoscyamine.

Storage, Stability, Compatibility

Atropine sulfate tablets or soluble tablets should be stored inwell-closed containers at room temperature (15-30°C). Atropine sulfate for injection should bestored at room temperature; avoid freezing.
Atropine sulfate for injection is reportedly compatible with the following agents: 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 24hours), perphenazine, prochlorperazine edisylate, promazine HCl, promethazine HCl (alsow/meperidine), and scopolamine HBr. Atropine sulfate is reported physically incompatible withnorepinephrine bitartrate, metaraminol bitartrate, methohexital sodium, and sodium bicarbonate.
Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents usedand it is suggested to consult specialized references for more specific information.

Pharmacology - ATROPINE SULFATE

Atropine, like other antimuscarinic agents, competitively inhibits acetylcholine orother cholinergic stimulants at postganglionic parasympathetic neuroeffector sites. High doses mayblock nicotinic receptors at the autonomic ganglia and at the neuromuscular junction.
Pharmacologic effects are dose related. At low doses salivation, bronchial secretions, and sweating(not horses) are inhibited. At moderate systemic doses, atropine dilates and inhibits accommodationof the pupil, and increases heart rate. High doses will decrease GI and urinary tract motility. Veryhigh doses will inhibit gastric secretion.
Uses, Indications - The principal veterinary indications for systemic atropine include:

1) Preanesthetic to prevent or reduce secretions of the respiratory tract

2) Treat sinus bradycardia, sinoatrial arrest, incomplete AV block

3) As an antidote for overdoses of cholinergic agents (e.g., physostigmine, etc.)

4) As an antidote for organophosphate or muscarinic mushroom intoxication

5) Hypersialism

6) Treatment of bronchoconstrictive disease

Pharmacokinetics - ATROPINE SULFATE

Atropine sulfate is well absorbed after oral administration, IM injection, inhalation, or endotracheal administration. After IV administration, peak effects in heart rates occur within 3-4 minutes.
Atropine is well distributed throughout the body and crosses into the CNS, across the placenta, and can distribute into the milk in small quantities.
Atropine is metabolized in the liver and excreted into the urine. Approximately 30-50% of a doseis excreted unchanged into the urine. The plasma half-life in humans has been reported to bebetween 2-3 hours.
Contraindications/Precautions - Atropine is contraindicated in patients with narrow-angleglaucoma, synchiae (adhesions) between the iris and lens, hypersensitivity to anticholinergic drugs, tachycardias secondary to thyrotoxicosis or cardiac insufficiency, myocardial ischemia, unstablecardiac status during acute hemorrhage, GI obstructive disease, paralytic ileus, severe ulcerativecolitis, obstructive uropathy, and myasthenia gravis (unless used to reverse adverse muscariniceffects secondary to therapy).
Antimuscarinic agents should be used with extreme caution in patients with known or suspected
GI infections. Atropine or other antimuscarinic agents can decrease GI motility and prolong retention of the causative agent(s) or toxin(s) resulting in prolonged symptoms. Antimuscarinicagents must also be used with extreme caution in patients with autonomic neuropathy.
Antimuscarinic agents should be used with caution in patients with hepatic or renal disease, geriatric or pediatric patients, hyperthyroidism, hypertension, CHF, tachyarrhythmias, prostatichypertrophy, or esophogeal reflux. Systemic atropine should be used cautiously in horses as it maydecrease gut motility and induce colic in susceptible animals. It may also reduce the arrhythmogenicdoses of epinephrine. Use of atropine in cat le may result in inappetance and rumen stasis whichmay persist for several days.

Adverse Effects, Warnings

Adverse effects are basically extensions of the drug's pharmacologiceffects and are generally dose related. At usual doses effects tend to mild in relatively healthypatients. The more severe effects listed tend to occur with high or toxic doses. GI effects caninclude dry mouth (xerostomia), dysphagia, constipation, vomiting, and thirst. GU effects mayinclude urinary retention or hesitancy. CNS effects may include stimulation, drowsiness, ataxia, seizures, respiratory depression, etc. Ophthalmic effects include blurred vision, pupil dilation, cycloplegia, and photophobia. Cardiovascular effects include sinus tachycardia (at higher doses), bradycardia (initially or at very low doses), hypertension, hypotension, arrhythmias (ectopiccomplexes), and circulatory failure.
Overdosage - For signs and symptoms of atropine toxicity see adverse effects above. If a recentoral ingestion, emptying of gut contents and administration of activated charcoal and salinecathartics may be warranted. Treat symptoms supportively and symptomatically. Do not usephenothiazines as they may contribute to the anticholinergic effects. Fluid therapy and standardtreatments for shock may be instituted.
The use of physostigmine is controversial and should probably be reserved for cases where thepatient exhibits either extreme agitation and is at risk for injuring themselves or others, or for caseswhere supraventricular tachycardias and sinus tachycardias are severe or life-threatening. The usualdose for physostigmine (human) is: 2 mg IV slowly (for average sized adult) If no response, mayrepeat every 20 minutes until reversal of toxic antimuscarinic effects or cholinergic effects takesplace. The human pediatric dose is 0.02 mg/kg slow IV (repeat q10 minutes as above) and may be areasonable choice for initial treatment of small animals. Physostigmine adverse effects(bronchoconstriction, bradycardia, seizures) may be treated with small doses of IV atropine.

Drug Interactions

The following drugs may enhance the activity of atropine and its derivatives:antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines.
The following drugs may potentiate the adverse effects of atropine and its derivatives: Primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocular pressure).
Atropine and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics.
Atropine and its derivatives may antagonize the actions of metoclopramide.