BETHANECHOL CHLORIDE
DESCRIPTION:
Bethanechol Chloride, a cholinergic agent, is a synthetic ester
which is structurally and pharmacologically related to acetylcholine.
It is designated chemically as 2-((aminocarbonyl)oxy)-N,N,N-trimethyl- 1-
propanaminium chloride. Its empirical formula is C7H17ClN2O2.
It is a white, hygroscopic crystalline compound having a slight amine-like odor,
freely soluble in water, and has a molecular weight of 196.68.
ACTIONS/CLINICAL PHARMACOLOGY:
Bethanechol chloride 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 impaired 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
chloride is not destroyed by cholinesterase and its effects are more prolonged
than those of acetylcholine.
Effects on the GI and urinary tracts sometimes appear within 30 minutes after
oral administration of bethanechol chloride, but more often 60-90 minutes are
required to reach maximum effectiveness. Following oral administration, the
usual duration of action of bethanechol is one hour, although large doses (300-
400 mg) have been reported to produce effects for up to six hours. Subcutaneous
injection produces a more intense action on bladder muscle than does oral
administration of the drug.
Because of the selective action of bethanechol, nicotinic symptoms of
cholinergic stimulation are usually absent or minimal when orally or
subcutaneously administered in therapeutic doses, while muscarinic effects are
prominent. Muscarinic effects usually occur within 5-15 minutes after
subcutaneous injection, reach a maximum in 15-30 minutes, and disappear within
two hours. 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.
Bethanechol chloride does not cross the blood- brain barrier because of its
charged quaternary amine moiety. The metabolic fate and mode of excretion of the
drug have not been elucidated.
A clinical study* was conducted on the relative effectiveness of oral and
subcutaneous doses of bethanechol chloride on the stretch response of bladder
muscle in patients with urinary retention. Results showed that 5 mg of the drug
given subcutaneously stimulated a response that was more rapid in onset and of
larger magnitude than an oral dose of 50 mg, 100 mg, or 200 mg. All the oral
doses, however, had a longer duration of effect than the subcutaneous dose.
Although the 50 mg oral dose caused little change in intravesical pressure in
this study, this dose has been found in other studies to be clinically effective
in the rehabilitation of patients with decompensated bladders.
INDICATIONS AND USAGE:
For the treatment of acute postoperative and postpartum nonobstructive
(functional) urinary retention and for neurogenic atony of the urinary bladder
with retention.
CONTRAINDICATIONS:
Hypersensitivity to BETHANECHOL CHLORIDE tablets or to any component of BETHANECHOL CHLORIDE
injection, hyperthyroidism, peptic ulcer, latent or active bronchial asthma,
pronounced bradycardia or hypotension, vasomotor instability, coronary artery
disease, epilepsy, and parkinsonism.
BETHANECHOL CHLORIDE 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.
WARNINGS:
THE STERILE SOLUTION IS FOR SUBCUTANEOUS USE ONLY. IT SHOULD NEVER BE GIVEN
INTRAMUSCULARLY OR INTRAVENOUSLY. 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 subcutaneous injection, and may occur in cases of
hypersensitivity or overdosage.
PRECAUTIONS:
General
In urinary retention, if the sphincter fails to relax as BETHANECHOL CHLORIDE contracts
the bladder, urine may be forced up the ureter into the kidney pelvis. If there
is bacteriuria, this may cause reflux infection.
Information For Patients
BETHANECHOL CHLORIDE tablets should preferably be taken one hour before or two hours after
meals to avoid nausea or vomiting. Dizziness, lightheadedness or fainting may
occur, especially when getting up from a lying or sitting position.
Drug Interactions
Special care is required if this drug 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.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals have not been performed to evaluate the effects
upon fertility, mutagenic or carcinogenic potential of BETHANECHOL CHLORIDE.
Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with
BETHANECHOL CHLORIDE. It is also not known whether BETHANECHOL CHLORIDE can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity. BETHANECHOL CHLORIDE
should be given to a pregnant woman only if clearly needed.
Nursing Mothers
It is not known whether this drug is secreted in human milk. Because many drugs
are secreted in human milk and because of the potential for serious adverse
reactions from BETHANECHOL CHLORIDE in nursing infants, a decision should be made whether
to discontinue nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
DRUG INTERACTIONS:
Special care is required if this drug 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.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Adverse reactions are rare following oral administration of bethanechol, but are
more common following subcutaneous injection. Adverse reactions are more likely
to occur when dosage is increased.
The following adverse reactions have been observed: Body As A Whole: malaise;
Digestive: abdominal cramps or discomfort, colicky pain, nausea and belching,
diarrhea, borborygmi, salivation; Renal: urinary urgency; Nervous System:
headache; Cardiovascular: a fall in blood pressure with reflex tachycardia,
vasomotor response; Skin: flushing producing a feeling of warmth, sensation of
heat about the face, sweating; Respiratory: bronchial constriction, asthmatic
attacks; Special Senses: lacrimation, miosis.
Causal Relationship Unknown: The following adverse reactions have been reported,
and a causal relationship to therapy with BETHANECHOL CHLORIDE has not been established:
Body As A Whole: hypothermia; Nervous System: seizures.
OVERDOSAGE:
Early signs of overdosage are abdominal discomfort, salivation, flushing of the
skin ("hot feeling"), sweating, nausea and vomiting.
Atropine Is A Specific Antidote. The recommended dose for adults is 0.6 mg
(1/100 grain). Repeat doses can be given every two hours, according to clinical
response. The recommended dosage in infants and children up to 12 years of age
is 0.01 mg/kg (to a maximum single dose of 0.4 mg) repeated every two hours as
needed until the desired effect is obtained, or adverse effects of atropine
preclude further usage. Subcutaneous injection of atropine is preferred except
in emergencies when the intravenous route may be employed.
When BETHANECHOL CHLORIDE is administered subcutaneously, a syringe containing a dose of
atropine sulfate should always be available to treat symptoms of toxicity.
The oral LD50 of bethanechol chloride is 1510 mg/kg in the mouse.
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.
Oral--The usual adult dosage is 10 to 50 mg three or four times a day. The
minimum effective dose is determined by giving 5 or 10 mg initially and
repeating the same amount at hourly intervals until satisfactory response occurs
or until 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.
Subcutaneous--The usual dose is 1 mL (5.15 mg), although some patients respond
satisfactorily to as little as 0.5 mL (2.575 mg). The minimum effective dose is
determined by injecting 0.5 mL (2.5 mg) initially and repeating the same amount
at 15 to 30 minute intervals to a maximum of four doses until satisfactory
response is obtained, unless disturbing reactions appear. The minimum effective
dose may be repeated thereafter three or four times a day as required.
Rarely, single doses up to 2 mL (10.30 mg) may be required. Such large doses may
cause severe reactions and should be used only after adequate trial of single
doses of 0.5 to 1 mL (2.575 to 5.15 mg) has established that smaller doses are
not sufficient.
BETHANECHOL CHLORIDE is usually effective in 5 to 15 minutes after subcutaneous injection.
If necessary, the effects of the drug can be abolished promptly by atropine (see
OVERDOSAGE).
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration, whenever solution and container permit.
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