Usage
This combination medication is primarily indicated for the symptomatic relief of irritable bowel syndrome (IBS). It targets the abdominal pain, cramping, bloating, and altered bowel habits commonly associated with IBS.
Pharmacological Classification: This is a combination product comprising a benzodiazepine (diazepam), an antacid (aluminium hydroxide), and an anticholinergic agent (propantheline).
Mechanism of Action: Diazepam acts as an anxiolytic and skeletal muscle relaxant by potentiating the effect of GABA, an inhibitory neurotransmitter, leading to decreased neuronal excitability. Aluminium hydroxide neutralizes gastric acid, offering relief from heartburn and dyspepsia, frequent IBS symptoms. Propantheline bromide competitively blocks muscarinic receptors in the parasympathetic nervous system, leading to smooth muscle relaxation, thereby reducing gastrointestinal motility and spasms.
Alternate Names
This combination medication, while marketed under various brand names like Ulsedin, doesn’t possess a universally recognized International Nonproprietary Name (INN).
How It Works
Pharmacodynamics: Diazepam’s action enhances GABA’s inhibitory effects, reducing neuronal excitability within the central nervous system. Aluminium hydroxide, through chemical neutralization, decreases gastric acidity. Propantheline bromide’s anticholinergic properties stem from competitive inhibition of muscarinic receptors, thus reducing gastrointestinal motility and spasm.
Pharmacokinetics: Diazepam is well-absorbed after oral administration, undergoes extensive hepatic metabolism via CYP enzymes, and is primarily renally excreted. Aluminium hydroxide experiences minimal systemic absorption. Propantheline bromide undergoes partial hepatic metabolism and subsequent urinary excretion.
Mode of Action (Cellular/Molecular): Diazepam binds to the benzodiazepine site on GABA-A receptors, allosterically modulating the receptor to increase the frequency of chloride channel opening, resulting in neuronal hyperpolarization. Aluminium hydroxide chemically neutralizes gastric acid through an acid-base reaction. Propantheline bromide blocks the action of acetylcholine at muscarinic receptors.
Elimination Pathways: Diazepam is primarily eliminated through hepatic metabolism followed by renal excretion. Aluminium hydroxide is mainly eliminated in the feces. Propantheline bromide undergoes both hepatic metabolism and renal excretion.
Dosage
Standard Dosage
Adults: One tablet three times a day, preferably before meals, or as directed by a physician.
Children: This combination is generally not recommended for pediatric use due to the inclusion of diazepam and propantheline. Consider safer alternative therapies.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate upwards based on individual tolerance and response due to increased sensitivity to both diazepam and propantheline.
- Patients with Renal Impairment: Administer cautiously. Aluminium hydroxide may accumulate, necessitating dose adjustments based on the degree of impairment. Diazepam and its metabolites can also accumulate, requiring careful monitoring and potential dose reduction.
- Patients with Hepatic Dysfunction: Reduce the diazepam component due to potentially impaired metabolism. Exercise caution with aluminium hydroxide. Propantheline’s effects may be prolonged.
- Patients with Comorbid Conditions: Administer with caution in patients with glaucoma, prostatic hypertrophy, myasthenia gravis, urinary retention, or cardiovascular disease. Individualized dosing and close monitoring are crucial.
Clinical Use Cases
This combination is not typically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is specifically directed towards IBS symptom management.
Dosage Adjustments
Adjustments should be based on patient-specific factors such as age, renal and hepatic function, coexisting medical conditions, and individual response. Therapeutic drug monitoring of diazepam levels may be beneficial in certain scenarios.
Side Effects
Common Side Effects:
- Drowsiness
- Confusion
- Dry mouth
- Blurred vision
- Constipation
- Urinary retention
- Dizziness
- Fatigue
- Memory Impairment
- Abnormality of voluntary movements
- Depression
Rare but Serious Side Effects:
- Paradoxical excitement or agitation
- Worsening of glaucoma
- Allergic reactions (rash, itching, swelling)
- Respiratory depression (with higher doses of diazepam)
- Angioedema; Stevens-Johnson syndrome; Toxic epidermal necrolysis
Long-Term Effects:
- Dependence on diazepam (with prolonged use)
- Cognitive impairment (with chronic diazepam use)
- Osteomalacia (with chronic aluminium hydroxide use)
Contraindications
- Hypersensitivity to any of the medication’s components
- Glaucoma (especially angle-closure glaucoma)
- Prostatic hypertrophy
- Urinary retention
- Myasthenia gravis
- Severe ulcerative colitis
- Megacolon
- Obstructive gastrointestinal disorders
Drug Interactions
- Alcohol (increases CNS depression)
- CNS depressants (additive effects)
- Antacids containing magnesium (may reduce aluminium hydroxide absorption)
- Anticholinergic agents (additive anticholinergic effects)
- Ketoconazole and itraconazole (inhibit diazepam metabolism)
- Phenytoin and carbamazepine (induce diazepam metabolism)
Pregnancy and Breastfeeding
Pregnancy Safety Category: Not definitively established. Use only if the potential benefit outweighs the risk. Diazepam is a known teratogen and should be avoided, especially during the first trimester. Diazepam is excreted in breast milk, and propantheline bromide may suppress lactation. This combination is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Enhances GABAergic transmission (diazepam), neutralizes gastric acid (aluminium hydroxide), inhibits muscarinic receptors (propantheline).
- Side Effects: Drowsiness, confusion, dry mouth, blurred vision, constipation, urinary retention. Serious side effects: Paradoxical reactions, respiratory depression, allergic reactions.
- Contraindications: Glaucoma, prostatic hypertrophy, urinary retention, myasthenia gravis, megacolon, obstructive GI disorders.
- Drug Interactions: Alcohol, CNS depressants, antacids with magnesium, anticholinergics, azole antifungals, phenytoin, carbamazepine.
- Pregnancy & Breastfeeding: Not recommended. Diazepam is a teratogen.
- Dosage: Adults: One tablet three times daily before meals. Not recommended for children.
- Monitoring Parameters: Liver function tests, renal function tests, complete blood count (CBC), electrolyte levels.
Popular Combinations
This specific combination is not generally combined with other drugs. Treatment for IBS may involve additional medications administered separately, including antispasmodics, antidepressants, and probiotics. This will depend on the patient’s individual needs and symptoms.
Precautions
- General Precautions: Evaluate renal and hepatic function before initiating therapy. Monitor for CNS depression, anticholinergic effects, paradoxical reactions, and drug interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aluminium Hydroxide + Diazepam + Propantheline?
A: The standard adult dose is one tablet three times daily, before meals or as directed by a physician. Dosage adjustments may be necessary.
Q2: Is this combination safe for use in children?
A: No, it is generally not recommended for pediatric use.
Q3: What are the most common side effects?
A: Common side effects include drowsiness, confusion, dry mouth, blurred vision, constipation, and urinary retention.
Q4: What are the contraindications for this medication?
A: Contraindications include glaucoma, prostatic hypertrophy, urinary retention, myasthenia gravis, severe ulcerative colitis, megacolon, and obstructive gastrointestinal disorders.
Q5: Does this medication interact with alcohol?
A: Yes, concurrent alcohol use can increase the risk of CNS depression. Patients should avoid alcohol while taking this medication.
Q6: What should patients be advised regarding activities requiring mental alertness?
A: Due to the potential for drowsiness and dizziness, caution patients against driving or operating machinery until they understand how the medication affects them.
Q7: Are there any long-term risks associated with this combination?
A: Long-term use of diazepam carries a risk of dependence. Chronic use of aluminum hydroxide can lead to osteomalacia.
Q8: What monitoring parameters should be considered during treatment?
A: Monitoring parameters should include periodic liver function tests, renal function tests, complete blood counts (CBCs), and electrolyte levels.
Q9: Is there a pregnancy safety category assigned to this combination product?
A: No, a definitive Pregnancy Safety Category has not been established for this combination. Its use during pregnancy is generally discouraged, especially in the first trimester, due to the teratogenic potential of diazepam.
Q10: Can this medication be used during breastfeeding?
A: It is generally not recommended during breastfeeding. Diazepam is excreted in breast milk, and propantheline bromide might decrease milk production.
