PROPANTHELINE BROMIDE

Chemistry - A quaternary ammonium antimuscarinic agent, propantheline bromide occurs asbitter-tasting, odorless, white or practically white crystals, with a melting range of 156-162° (withdecomposition). It is very soluble in both water and alcohol.

Storage, Stability, Compatibility

Propantheline bromide tablets should be stored at room temperature in tight containers.

Pharmacology - PROPANTHELINE BROMIDE

An antimuscarinic with similar actions as atropine, propantheline is a quaternaryammonium compound, however, and does not cross appreciably into the CNS. It, therefore, shouldnot exhibit the same extent of CNS adverse effects that atropine possesses. For further information, refer to the atropine monograph.
Uses, Indications - In small animal medicine propantheline bromide has been used for its antispasmodic/antisecretory effects in the treatment of diarrhea. It is also employed in the treatment ofhyperreflexic detrusor or urge incontinence and as oral treatment in anticholinergic responsivebradycardias. In horses, propantheline has been used intravenously to reduce colonic peristalsis andto relax the rectum to allow easier rectal examination and perform surgical procedures to the rectum.

Pharmacokinetics - PROPANTHELINE BROMIDE

Quaternary anticholinergic agents are not completely absorbed after oraladministration because it is completely ionized. In humans, peak levels occur about 2 hours afteroral administration. Food apparently decreases the amount of drug absorbed.
The distribution of propantheline has not been extensively studied, but like other quaternaryantimuscarinics, propantheline is poorly lipid soluble and does not extensively penetrate into the
CNS or eye.
Propantheline is believed to be prevalently metabolized in the GI and/or liver; less than 5% of anoral dose is excreted unchanged in the urine.
Contraindications/Precautions - Use of propantheline should be considered contraindicated ifthe patient has a history of hypersensitivity to anticholinergic drugs, tachycardias secondary tothyrotoxicosis or cardiac insufficiency, myocardial ischemia, unstable cardiac status during acutehemorrhage, GI obstructive disease, paralytic ileus, severe ulcerative colitis, obstructive uropathy ormyasthenia gravis (unless used to reverse adverse muscarinic effects secondary to therapy).
Antimuscarinic agents should be used with extreme caution in patients with known or suspected
GI infections. Propantheline or other antimuscarinic agents can decrease GI motility and prolongretention 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 disease, renal disease, hyperthyroidism, hypertension, CHF, tachyarrhythmias, prostatic hypertrophy, esophogeal reflux, and geriatric or pediatric patients.

Adverse Effects, Warnings

With the exception of fewer effects on the eye and the CNS, propantheline can be expected to have a similar adverse reaction profile as atropine (dry mouth, dryeyes, urinary hesitancy, tachycardia, constipation, etc.). High doses may lead to the development ofileus with resultant bacterial overgrowth in susceptible animals. For more information refer to theatropine monograph.
Overdosage - Because of its quaternary structure, it would be expected that minimal CNS effectswould occur after an overdose of propantheline when compared to atropine. See the informationlisted in the atropine monograph for more information on the symptoms and signs that may be seefollowing an overdose.
If a recent oral ingestion, emptying of gut contents and administration of activated charcoal andsaline cathartics 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 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 propantheline and itsderivatives: antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines.
The following drugs may potentiate the adverse effects of propantheline and its derivatives:primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocularpressure).
Propantheline and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics.
Propantheline delays the absorption, but increases the peak serum level of ranitidine. The relativebioavailability of ranitidine may be increased by 23% when propantheline is administeredconcomitantly with ranitidine.
Propantheline may decrease the absorption of cimetidine.