Action And Clinical Pharmacology: Bethanechol acts principally by producing the effects of stimulation of the parasympathetic nervous system. It increases the tone of the detrusor urinae muscle, usually producing a contraction sufficiently strong to initiate micturition and empty the bladder. It stimulates gastric motility, increases gastric tone, and often restores rhythmic peristalsis.
Stimulation of the parasympathetic nervous system releases acetylcholine at the nerve endings. When spontaneous stimulation is reduced and therapeutic intervention is required, acetylcholine can be given, but it is rapidly hydrolyzed by cholinesterase, and its effects are transient. Bethanechol is not destroyed by cholinesterase and its effects are more prolonged and predictable than those of acetylcholine.
It has predominant muscarinic action and only feeble nicotinic action. Doses that stimulate micturition and defecation and increase peristalsis do not ordinarily stimulate ganglia or voluntary muscles. Therapeutic test doses in normal human subjects have little effect on heart rate, blood pressure, or peripheral circulation.
Indications And Clinical Uses: The treatment of acute postoperative and postpartum nonobstructive (functional) urinary retention and for neurogenic atony of the urinary bladder with retention.
As adjunctive therapy in the treatment of gastroesophageal reflux with pyrosis unresponsive to conventional therapy.
Contra-Indications: Hypersensitivity to bethanechol or to any component of the injection. Hyperthyroidism, pregnancy, lactation, peptic ulcer, latent or active bronchial asthma, pronounced bradycardia or hypotension, vasomotor instability, coronary artery disease, epilepsy, and parkinsonism.
Should not be employed when the strength or integrity of the gastrointestinal or bladder wall is in question, or in the presence of mechanical obstruction; when increased muscular activity of the gastrointestinal tract or urinary bladder might prove harmful, as following recent urinary bladder surgery, gastrointestinal resection and anastomosis, or when there is possible gastrointestinal obstruction; in bladder neck obstruction, spastic gastrointestinal disturbances, acute inflammatory lesions of the gastrointestinal tract, or peritonitis; or in marked vagotonia.
Precautions: The sterile solution is for s.c. use only. It should never be given i.m. or i.v. Violent symptoms of cholinergic over-stimulation, such as circulatory collapse, fall in blood pressure, abdominal cramps, bloody diarrhea, shock, or sudden cardiac arrest are likely to occur if the drug is given by either of these routes. Although rare, these same symptoms have occurred after s.c. injection, and may occur in cases of hypersensitivity or overdosage.
Special care is required when bethanechol is given to patients receiving ganglion blocking compounds because a critical fall in blood pressure may occur. Usually, severe abdominal symptoms appear before there is such a fall in the blood pressure.
In urinary retention, if the sphincter fails to relax as bethanechol contracts the bladder, urine may be forced up the ureter into the kidney pelvis. If there is bacteriuria, this may cause reflux infection.
Adverse Reactions: Abdominal discomfort, salivation, flushing of the skin (“hot feeling”), sweating.
Large doses more commonly result in effects of parasympathetic stimulation, such as malaise, headache, sensation of heat about the face, flushing, colicky pain, diarrhea, nausea and belching, abdominal cramps, borborygmi, asthmatic attacks, and fall in blood pressure.
Atropine is a specific antidote. A syringe containing a dose, for adults, of 0.6 mg of atropine sulfate should always be available to treat symptoms of toxicity. Use proportionately smaller amounts for children. S.C. injection is preferred except in emergencies when the i.v. route may be employed.
Symptoms And Treatment Of Overdose: Symptoms: Overdosage, i.v., i.m. administration and hypersensitivity to the drug can cause violent symptoms of cholinergic over-stimulation including fall in blood pressure, circulatory collapse, cardiac arrest, shock, severe abdominal cramps with bloody diarrhea and possibly severe bronchospasm.
Treatment: Atropine is a specific antidote. Use a dose of 0.6 mg for adults and proportionately smaller doses for children. S.C. injection is the preferred route of administration, except in emergencies when the i.v. route may be used.
Administer the atropine first followed by standard treatment for cardiac arrest, circulatory collapse, shock and/or bronchospasm. Bloody diarrhea and other symptoms of violent cholinergic over-stimulation rarely require any additional treatment following adequate doses of atropine.
Dosage And Administration: Dosage and route of administration must be individualized, depending on the type and severity of the condition to be treated. Preferably give the drug when the stomach is empty. If taken soon after eating, nausea and vomiting may occur.
If necessary, the effects of the drug can be abolished promptly by atropine (see Adverse Effects).
Urinary Retention: Oral: The usual adult dosage is 10 to 50 mg 3 or 4 times a day. The minimum effective dose is determined by giving 5 to 10 mg initially and repeating the same amount at hourly intervals until a satisfactory response occurs or a maximum of 50 mg has been given. The effects of the drug sometimes appear within 30 minutes and usually within 60 to 90 minutes. They persist for about an hour.
S.C.: The usual dose is 5 mg, although some patients respond satisfactorily to as little as 2.5 mg. The minimum effective dose is determined by injecting 2.5 mg initially and repeating the same dose at 15 to 30 minute intervals to a maximum of 4 doses until satisfactory response is obtained, unless disturbing reactions appear. The minimum effective dose may be repeated thereafter 3 or 4 times a day as required. Rarely, single doses up to 10 mg may be required. Such large doses may cause severe reactions and should be used only after adequate trial of single doses of 2.5 to 5 mg has established that smaller doses are not sufficient.
Bethanechol is usually effective in 5 to 15 minutes after s.c. injection.
Gastroesophageal reflux with pyrosis: 25 mg 4 times a day, orally, one half hour before meals and at bedtime.
Availability And Storage: Injection: Each mL of clear, colorless sterile solution contains: bethanechol chloride 5 mg. May be autoclaved at 120°C for 20 minutes without discoloration or loss of potency. Ampuls of 1 mL, boxes of 6.
Tablets: 10 mg: Each white, discoid, compressed tablet, with a beveled edge quadrisected on one side and engraved “FROSST 412” on the other, contains: bethanechol chloride 10 mg. Also contains lactose. Bottles of 100.
25 mg: Each yellow, discoid, compressed tablet, with a beveled edge, scored on one side, contains: bethanechol chloride 25 mg. Also contains lactose. Bottles of 50.
Both strengths gluten- and tartrazine-free. (Shown in Product Recognition Section)
URECHOLINE® Frosst Bethanechol Chloride Parasympathomimetic Agent