Urecholine Pharmacology, Pharmacokinetics, Studies, Metabolism - Bethanechol

Urecholine Pharmacology, Pharmacokinetics, Studies, Metabolism - Bethanechol

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 acetytcholine.

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 study¹ 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.