Meprosetil

Uses

Meprosetil is used for Psychoses, Nausea and vomiting, Psychoses, Intractable hiccup, Psychoses.

Meprosetil is also used to associated treatment for these conditions: Acute Intermittent Porphyria (AIP), Apprehension, Mania, Nausea and vomiting, Oppositional Defiant Disorder, Restlessness, Schizophrenia, Tetanus, Intractable singultus, Severe behavioural problems, Short term Hyperactivity

How Meprosetil works

Meprosetil acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Meprosetil is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).

Dosage

Meprosetil dosage

Oral: Psychoses:

• Adult: 25 mg tid; may be given as a single 75 mg dose at night. Maintenance: 25-100 mg tid increased to ≥1 g daily as required in psychotic patients.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Oral: Intractable hiccup:

• Adult: Initially, 25-50 mg 3-4 times daily for 2-3 days; if unresponsive, may admin 25-50 mg via IM inj. If still necessary, 25-50 mg in 500-1000 ml of normal saline may be given via slow IV infusion.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Intramuscular: Psychoses:

• Adult: 25-50 mg repeated every 6-8 hr. Substitute with oral therapy as soon as possible.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

Intramuscular: Nausea and vomiting:

• Adult: Initially, 25 mg via IM inj, followed by 25-50 mg every 3-4 hr until vomiting stops.
• Child: 1-12 yr: 500 mcg/kg every 4-6 hr. Max: >5 yr: 75 mg daily; 1-5 yr: 40 mg daily.
• Elderly: Initially, ⅓-½ the normal adult dose.

May be taken with or without food. May be taken with meals to reduce GI discomfort.

Side Effects

Tardive dyskinesia (on long-term therapy). Involuntary movements of extremities may also occur. Dry mouth, constipation, urinary retention, mydriasis, agitation, insomnia, depression and convulsions; postural hypotension, ECG changes. Allergic skin reaction, amenorrhoea, gynaecomastia, weight gain. Hyperglycaemia and raised serum cholesterol.

Toxicity

Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness

Precaution

Parkinson's disease; CV disease; renal or hepatic impairment; cerebrovascular and respiratoty disease; jaundice; DM; hypothyroidism; paralytic ileus; prostatic hyperplasia or urinary retention; epilepsy or history of seizures; myasthenia gravis; pregnancy; elderly (especially with dementia), and debilitated patients. Avoid direct sunlight.

Interaction

Potentiation of anticholinergic effects of antiparkinson agents and TCAs may lead to an anticholinergic crisis. Additive orthostatic hypotensive effect in combination with MAOIs. Reverses antihypertensive effect of guanethidine, methyldopa and clonidine.

Food Interaction

• Avoid alcohol.
• Take with food. Food reduces irritation.

Meprosetil Alcohol interaction

[Moderate] GENERALLY AVOID:

Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment.

Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines.

The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

Patients should be advised to avoid alcohol during phenothiazine therapy.

Meprosetil Drug Interaction

Moderate: aripiprazole, aripiprazole, lamotrigine, lamotrigine, lithium, lithium, pregabalin, pregabalin, quetiapine, quetiapine, alprazolam, alprazolam, sertraline, sertralineUnknown: esomeprazole, esomeprazole, acetaminophen, acetaminophen, cholecalciferol, cholecalciferol

Meprosetil Disease Interaction

Major: dementia, acute alcohol intoxication, cardiovascular disease, CNS depression, head injuryModerate: anticholinergic effects, breast cancer, dystonic reactions, hematologic toxicity, liver disease, NMS, parkinsonism, renal dysfunction, respiratory disorders, seizure disorders, tardive dyskinesia

Volume of Distribution

• 20 L/kg

Elimination Route

Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.

Half Life

~ 30 hours

Elimination Route

Kidneys, ~ 37% excreted in urine

Pregnancy & Breastfeeding use

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity; preexisting CNS depression, coma, bone-marrow supression; phaeochromocytoma; lactation

Acute Overdose

Symptoms include somnolence, coma, hypotension and extrapyramidal symptoms. Other possible manifestations include agitation and restlessness, convulsions, fever, autonomic reactions such as dry mouth and ileus, EKG changes and cardiac arrhythmias.

Treatment is symptomatic and supportive. Early gastric lavage may be helpful. Observe patient and maintain an open airway.

Storage Condition

Store at 15-30°C.

Innovators Monograph

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