Continuing Education Activity
Bethanechol is FDA approved to treat postoperative urinary retention, postpartum urinary retention, and overflow incontinence caused by neurogenic atony of the bladder. It is in the parasympathomimetic class of drugs. This activity reviews the indications, action, and contraindications for bethanechol as a valuable agent in managing nonobstructive urinary retention-related disorders when applicable. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to members of the interprofessional team in the management of patients with nonobstructive urinary retention and related conditions.
Objectives:
- Identify the mechanism of action of bethanechol.
- Describe the adverse effects of bethanechol.
- Review the appropriate monitoring of bethanechol.
- Summarize some interprofessional team strategies for improving care coordination and communication to advance bethanechol use in the care of nonobstructive urinary retention and improve outcomes.
Indications
Bethanechol was first synthesized in 1935, and it is a direct-acting parasympathomimetic agent that acts on postganglionic parasympathetic receptors.[1] The pharmacological agent is FDA-approved for the treatment of postoperative urinary retention, postpartum urinary retention, and overflow incontinence caused by neurogenic atony of the bladder.[2][3][4]
Bethanechol may be utilized in spinal shock subjects who have recovered to the point of voluntary control of the urethra and in patients with a sensory and motor paralytic bladder.[4] Bethanechol's actions are similar to those of acetylcholine(Ach), but the agent is not broken down via cholinesterase, making its therapeutic effects more lengthened when compared to acetylcholine. Bethanechol's moieties as a quaternary amine do not allow it to cross the blood-brain barrier and cause depressive actions. It is one of the most readily utilized agents to promote bladder emptying.[1] The prescribed course of bethanechol varies following the character of the bladder dysfunction treated.[4]
FDA Approved Uses
- Postoperative urinary retention
- Postpartum nonobstructive urinary retention
- Neurogenic atony of the bladder
Mechanism of Action
Bethanechol exerts its effects via directly stimulating the muscarinic receptors(M1, M2, M3, M4, M5) of the parasympathetic nervous system, further increasing the tone of the detrusor urinae muscle of the bladder, giving a contraction adequately effective to initiate micturition and void the bladder.[5][3][6] The M3 receptors are where the agent acts in the bladder and are also present in smooth muscles and exocrine glands.[3][6]
Bethanechol also acts on the M1 parasympathetic receptors of the gastric parietal cells found in the gastrointestinal tract inciting gastric motility, increasing gastric tone, and may reestablish diminished rhythmic peristalsis.[3] Bethanechol's effects are selective to muscarinic receptor stimulation, and its effects on nicotinic receptors are absent or very minimal, producing no effects.
Administration
Bethanechol is available in oral and subcutaneous preparations. Tablets are available in 5 mg, 10 mg, 25 mg, and 50 mg dosages.[7]
Postoperative Urinary Retention
- 10 to 50 mg three or four times daily.
Postpartum Nonobstructive Urinary Retention
- 10 to 50 mg three or four times daily.
Neurogenic Bladder
- 10 to 50 mg three or four times daily.
The dosage for bethanechol is decided on a case-by-case basis, which is dependent on the type and severity of the urinary retention. Patients are initiated on a 5 to 10 mg dosage to ascertain the minimum effective dosage and are repeated in hourly intervals until an adequate response transpires. Patients should not consume greater than 50 mg per single dose as adverse effects may occur. The agent is preferred to be administered on an empty stomach as nausea and vomiting can incite.
Adverse Effects
The adverse effects of bethanechol include[8][9]:
Gastrointestinal
- Abdominal cramps
- Abdominal discomfort
- Colicky pain
- Nausea
- Vomiting
- Diarrhea,
- Borborygmi
- Salivation
Nervous System
- Headache
- Lacrimation
- Miosis
Cardiovascular
- Decreased blood pressure
- Reflex tachycardia
- vasomotor response
Skin
- Flushing producing a feeling of warmth,
- The sensation of heat around the face
- Diaphoresis
Respiratory
- Bronchial constriction
- Asthmatic attacks
Renal
The agent may cause nausea and vomiting if taken immediately after eating and is advised to be administered 2 hours post-meal or one hour before eating. Bethanechol parasympathetic effects of the M2 receptors located in the heart stimulate the SA node and AV node resulting in a decreased heart rate (bradycardia) and decreased electrical conduction rate. This activity may lead to more severe conditions such as heart blocks, cardiac arrest, and arrhythmias.[3]
The parasympathetic actions on the M3 receptors present in vasculature cause vasodilation, further decreasing blood pressure.[10] This vasodilation can precipitate postural hypotension, causing dizziness and lightheadedness when standing from a supine or prone position.[3][10] Adverse effects are observed more frequently with an increased dose and with subcutaneous injections rather than oral administration.
Contraindications
- Hypersensitivity
- Hyperthyroidism
- Peptic ulcer
- Latent bronchial asthma
- Active bronchial asthma
- Bradycardia
- Orthostatic hypotension
- Vasomotor instability
- Coronary artery disease
- Epilepsy/seizures
- Parkinsonism
- Arrhythmias
- Angle-closure glaucoma
- Intestinal resection or anastomosis
- Urinary obstruction
- Severe miosis
Bethanechol should not be administered to subjects with compromised durability of the urinary bladder wall and GI tract. The agent is also contraindicated if a mechanical obstruction is present or suspected, as the therapeutic effects on the muscular tone of the GI tract and bladder may cause harm as retained urine may reflux back into the kidneys.[3]
Monitoring
Therapeutic effects of bethanechol develop within thirty minutes following oral administration. The maximum effectiveness often ensues between 60 to 90 minutes. Therapeutic effects usually last for one hour. Subcutaneous injection administration delivers a more powerful effect on the detrusor urinae muscle when compared to the oral administration of the agent. Its effects on muscarinic receptors customarily occur within 5 to 15 minutes post subcutaneous administration and arrive at a maximum therapeutic efficacy in 15 to 30 minutes, persisting for approximately two hours.[3]
Pregnancy Category C: Bethanechol use during pregnancy has not been studied, and it is not known if it causes fetal harm. Use during pregnancy should be carefully assessed and administered if needed.
Toxicity
Reversal Agent
Atropine sulfate competes with bethanechol at the muscarinic receptor junction, competitively blocking its binding at the postganglionic arch receptors and preventing parasympathetic cholinergic activation.[3][11] A 0.6 mg dosage of atropine is recommended for adults and is repeatable every two hours as needed, depending on therapeutic responses. 0.01 mg/kg to 0.4mg can be administered in the pediatric population(infant/children) and should be repeated every two hours as needed, depending on therapeutic responses. The subcutaneous route via injection is also an option. An emergency indicates the use of the intravenous administration route.
This diagnosis of overdose and toxicity is based on clinical manifestations, as there are no definite lab examinations or radiographic imaging that will affirm the determination.[12][9] The excessive parasympathetic action at M2 and M3 muscarinic receptors in the heart, GI tract, vasculature, and bronchial muscles generate an increased response resulting in bronchorrhea, salivation, lacrimation, diaphoresis, bronchoconstriction, chest tightness, decreased heart rate, decreased blood pressure, vomiting, increased gastrointestinal motility, abdominal tightness, diarrhea, and cramps.[12][9][10] The disproportionate effects of muscarinic receptors in the eyes will cause miosis and blurring of vision.[12][9]
Enhancing Healthcare Team Outcomes
Bethanechol is a direct-acting parasympathomimetic agent that is FDA approved for the treatment of postoperative urinary retention, postpartum urinary retention, and overflow incontinence caused by neurogenic atony of the bladder. The care for patients suffering from urologic conditions requires critical care from an interprofessional team of healthcare professionals. Pharmacologic management can lead to a better quality of life for patients. These healthcare professionals include family or primary care clinicians (MDs, DOs, NPs, PAs), urologists, gynecologists, nurses, and pharmacists.
The primary care clinicians and specialists should be up to date with the latest guidelines on dosage and indications using bethanechol. Prescribing clinicians should determine the minimum effective dosage via 5 to 10 mg repeated in hourly intervals until the desired therapeutic result. The primary care physician should routinely monitor patients taking this medication for therapeutic efficacy, as dosing modifications may be necessary. The prescriber should also be aware of any underlying contraindications such as epilepsy, glaucoma, and COPD before administration, as these conditions can occur upon using the parasympathomimetic agent.
Patients should fully understand the multisystemic adverse events that may occur with bethanechol use. In the event of toxicity and overdose causing systemic effects, atropine should be administered at a dose of 0.6 mg and repeated every two hours as needed until the effects subside. Counseling and careful monitoring are necessary during pregnancy, as clinical studies during its use in pregnancy are limited, and bethanechol is FDA pregnancy category C. This is where the nursing staff and pharmacists can contribute to therapy, with patient counseling on dosing and possible adverse events and helping to monitor therapeutic progress.
Interprofessional teamwork and communication are key to building patient rapport and developing a therapeutic alliance, so the patients comply with therapy competently. Continued teamwork between healthcare professionals will improve patient outcomes and quality of life while mitigating potential adverse events. [Level 5]
Bethanechol