BETHANECHOL CHLORIDE
Chemistry - A synthetic cholinergic ester, bethanechol occurs as a slightly hygroscopic, white orcolorless crystalline powder with a slight, amine-like or "fishy" odor. It exhibits polymorphism, with one form melting at 211° and the other form at 219°. One gram of the drug is soluble in approximately 1 ml of water or 10 ml of alcohol. The commercially available injection has a pH from5.5 - 7.5.
Pharmacologic effects include increased esophageal peristalsis and lower esophageal sphinctertone, increased tone and peristaltic activity of the stomach and intestines, increased gastric andpancreatic secretions, increased tone of the detrusor muscle of the bladder, and decreased bladdercapacity. At high doses after parenteral administration, effects such as increased bronchial secretions and constriction, miosis, lacrimation, and salivation can be seen. When administered SQ ororally, effects are predominantly on the GI and urinary tracts.
Uses, Indications - In veterinary medicine, bethanechol is used primarily to stimulate bladdercontractions in small animals. It also can be used as an esophageal or general GI stimulant, butmetoclopramide and/or neostigmine have largely supplanted it for these uses.
Bethanechol does not enter the CNS after usual doses; other distribution aspects of the drug arenot known. The metabolic or excretory fate of bethanechol have not been described.
Contraindications/Precautions - Contraindications to bethanechol therapy include: bladder neckor other urinary outflow obstruction, when the integrity of the bladder wall is in question (e.g., asafter recent bladder surgery), hyperthyroidism, peptic ulcer disease or when other inflammatory GIlesions are present, recent GI surgery with resections/anastomoses, GI obstruction or peritonitis, hypersensitivity to the drug, epilepsy, asthma, coronary artery disease or occlusion, hypotension, severe bradycardia or vagotonia or vasomotor instability. If urinary outflow resistance is increaseddue to enhanced urethral tone (not mechanical obstruction!), bethanechol should only be used inconjunction with another agent that will sufficiently reduce outflow resistance (e.g., diazepam, dantrolene (striated muscle) or phenoxybenzamine (smooth muscle)).
Cardiovascular (arrhythmias, hypotension) and respiratory effects (asthma) are most likely onlyseen after overdosage situations or with high dose SQ therapy.
IM or IV use is not recommended, except in emergency situations when the IV route may be used.
Severe cholinergic reactions are likely if given IV. If injecting the drug (SQ or IV), it isrecommended that atropine be immediately available.
Overdosage - Symptoms of overdosage are basically cholinergic in nature. Muscarinic effects(salivation, urination, defecation, etc.) are usually seen with oral or SQ administration. If given IMor IV, a full-blown cholinergic crisis can occur with circulatory collapse, bloody diarrhea, shock andcardiac arrest possible.
Treatment for bethanechol toxicity is atropine. Refer to the atropine monograph for more information on its use. Epinephrine may also be employed to treat symptoms of bronchospasm.
Quinidine, procainamide, epinephrine (or sympathomimetic amines) or atropine can antagonize the effects of bethanechol.
Bethanechol used in combination with ganglionic blocking drugs (e.g., mecamylamine) canproduce severe GI and hypotensive effects.
Storage, Stability, Compatibility
Bethanechol tablets should be stored at room temperature intight containers. The injectable form should be stored at room temperature; avoid freezing. It maybe autoclaved at 120°C for 20 minutes without any loss of potency.Pharmacology - BETHANECHOL CHLORIDE
Bethanechol directly stimulates cholinergic receptors. Its effects are principallymuscarinic and at usual doses has negligible nicotinic activity. It is more resistant to hydrolysis thanacetylcholine by cholinesterase and, therefore, has an increased duration of activity.Pharmacologic effects include increased esophageal peristalsis and lower esophageal sphinctertone, increased tone and peristaltic activity of the stomach and intestines, increased gastric andpancreatic secretions, increased tone of the detrusor muscle of the bladder, and decreased bladdercapacity. At high doses after parenteral administration, effects such as increased bronchial secretions and constriction, miosis, lacrimation, and salivation can be seen. When administered SQ ororally, effects are predominantly on the GI and urinary tracts.
Uses, Indications - In veterinary medicine, bethanechol is used primarily to stimulate bladdercontractions in small animals. It also can be used as an esophageal or general GI stimulant, butmetoclopramide and/or neostigmine have largely supplanted it for these uses.
Pharmacokinetics - BETHANECHOL CHLORIDE
No information was located on the pharmacokinetics of this agent in veterinary species. In humans, bethanechol is poorly absorbed from the GI tract, and the onset of actionis usually within 30-90 minutes after oral dosing. After subcutaneous administration, effects beginwithin 5-15 minutes and usually peak within 30 minutes. The duration of action after oral dosingmay persist for up to 6 hours after large doses and 2 hours after SQ dosing. Subcutaneousadministration yields a more enhanced effect on urinary tract stimulation than does oral administration.Bethanechol does not enter the CNS after usual doses; other distribution aspects of the drug arenot known. The metabolic or excretory fate of bethanechol have not been described.
Contraindications/Precautions - Contraindications to bethanechol therapy include: bladder neckor other urinary outflow obstruction, when the integrity of the bladder wall is in question (e.g., asafter recent bladder surgery), hyperthyroidism, peptic ulcer disease or when other inflammatory GIlesions are present, recent GI surgery with resections/anastomoses, GI obstruction or peritonitis, hypersensitivity to the drug, epilepsy, asthma, coronary artery disease or occlusion, hypotension, severe bradycardia or vagotonia or vasomotor instability. If urinary outflow resistance is increaseddue to enhanced urethral tone (not mechanical obstruction!), bethanechol should only be used inconjunction with another agent that will sufficiently reduce outflow resistance (e.g., diazepam, dantrolene (striated muscle) or phenoxybenzamine (smooth muscle)).
Adverse Effects, Warnings
When administered orally to small animals, adverse effects areusually mild, with vomiting, diarrhea, salivation, and anorexia being the most likely to occur.Cardiovascular (arrhythmias, hypotension) and respiratory effects (asthma) are most likely onlyseen after overdosage situations or with high dose SQ therapy.
IM or IV use is not recommended, except in emergency situations when the IV route may be used.
Severe cholinergic reactions are likely if given IV. If injecting the drug (SQ or IV), it isrecommended that atropine be immediately available.
Overdosage - Symptoms of overdosage are basically cholinergic in nature. Muscarinic effects(salivation, urination, defecation, etc.) are usually seen with oral or SQ administration. If given IMor IV, a full-blown cholinergic crisis can occur with circulatory collapse, bloody diarrhea, shock andcardiac arrest possible.
Treatment for bethanechol toxicity is atropine. Refer to the atropine monograph for more information on its use. Epinephrine may also be employed to treat symptoms of bronchospasm.
Drug Interactions
Bethanechol should not be used concomitantly with other cholinergic (e.g., carbachol) or anticholinesterase (e.g., neostigmine) agents because of additive effects and increased likelihood of toxicity developing.Quinidine, procainamide, epinephrine (or sympathomimetic amines) or atropine can antagonize the effects of bethanechol.
Bethanechol used in combination with ganglionic blocking drugs (e.g., mecamylamine) canproduce severe GI and hypotensive effects.