Prochlorperazine is an antipsychotic drug that belongs to phenothiazine group. It acts by inhibiting the effects of a chemical in the brain called dopamine by blocking the D2 dopamine receptors. Though it is antipsychotic drug, it is also used in nonpsychotic disorders such as vertigo (spinning sensation), vomiting and anxiety.
General pharmacology of prochlorperazine:
The chemical name of prochlorperazine is 2-chloro-10-[3-(4-methyl-1-piperazinyl)-prophyl] phenothiazine and molecular formula is C20H24CIN3S. It is well absorbed from the gastrointestinal tract after oral administration and distribute widely. Onset of action is 30 to 40 minutes after oral administration, 60 minutes for suppository and 10 to 20 minutes after intramuscular injection. Duration of action is 3 to 4 hours. Prochlorperazine is metabolized mainly in the liver and is excreted through the feces. Learn more.
Mechanism of action of prochlorperazine:
► Prochlorperazine acts on chemoreceptor trigger zone. It is an area located on the lateral walls of the fourth ventricle in the brain. Chemoreceptor trigger zone initiates vomiting in abnormal situations. Prochlorperazine blocks the dopamine receptors in the chemoreceptor trigger zone and stops vomiting.
► Another action of prochlorperazine on vestibular apparatus. It is a part of the inner ear that maintains equilibrium of our body by sending signals to the brain via vestibular nerve. It is excessively stimulated in vestibular disorders and producing a spinning sensation called vertigo. Prochlorperazine suppress this vestibular apparatus and stops vertigo.
► Prochlorperazine also act on mesolimbic system in the brain. This system contains a group of neuron that release dopamine. Schizophrenia develops from excessive functioning of this group of neuron. Prochlorperazine blocks the dopamine receptors in the mesolimbic system and exerts its antipsychotic effect.
Indications of prochlorperazine:
► Prochlorperazine is highly effective in vertigo due to vestibular disorders such as labyrinthitis and Meniere’s disease.
► It is used for the control of nausea and vomiting caused by migraine, cancer chemotherapy, radiotherapy, surgery and other conditions.
► It is used for the treatment of psychotic disorders such as schizophrenia and acute mania.
► Prochlorperazine may be helpful for short term relief of anxiety.
Contraindications of prochlorperazine:
Prochlorperazine should be avoided in the following conditions:
► In patients with reduced consciousness level particularly when these conditions are due to intoxication of alcohol, hypnotics, narcotics or others central depressant drugs.
► In severely depressed patients.
► In patients with blood dyscrasias, kidney dysfunction, liver dysfunction, Parkinson’s disease, pheochromocytoma, severe cardiovascular diseases or a history of hypersensitivity to prochlorperazine.
Use of prochlorperazine in pregnancy and lactation:
Safety of use of prochlorperazine during pregnancy has not been established. So, it should be avoided during pregnancy. Prochlorperazine may be excreted into the breast milk. Therefore, breast feeding should be suspended during therapy or drug should be avoided during lactation.
Preparations of prochlorperazine:
Prochlorperazine is available as tablet, capsule, syrup, suppository and injectable (intramuscular and intravenous) form.
► Tablet forms: Each tablet contains 5 or 10 mg prochlorperazine maleate.
► Sustain release capsule form: Each capsule contains 10 or 15 mg prochlorperazine maleate.
► Liquid form: Each 5 ml syrup contains 5 mg prochlorperazine mesylate or edisylate.
► Injectable form: Each ml injection contains 5 mg prochlorperazine mesylate or edisylate.
► Suppository form: Each suppository contains 2.5, 5, 10 or 25 mg prochlorperazine base.
Dosage of prochlorperazine:
Prochlorperazine should be started with lower dosage, then increase the dose gradually until an optimal response is achieved. It may be given in both children and adult but children below two years of age are not recommended.
► To control vertigo and vomiting, the usual dose of prochlorperazine is 5 to 10 mg three or four times a day in adult and 2.5 to 5 mg two or three times a day in children.
► In psychotic disorders, the usual starting dose is 10 mg three or four times a day in adult and 5 mg two or three times a day in children. In severe cases, the doses may reach up to 100 to 150 mg per day in adult and 20 to 25 mg in children. For maintenance therapy, the doses should be reduced to the minimum effective level.
► In anxiety, the usual dosage is 5 mg three or four times a day in adult. Do not intake in doses more than 20 mg per day and for longer than 12 weeks.
Click here to learn more about dosage guideline of prochlorperazine.
Side effects of prochlorperazine:
(A) Extrapyramidal side effects:
It is the most important side effects of prochlorperazine. These side effects usually occur with high doses, particularly in children and elderly persons. The extrapyramidal side effects are –
► Parkinsonism – It may occur between 1 to 4 weeks of therapy. Prochlorperazine blocks the dopamine receptors in the brain. This leads to reduce dopaminergic output from the brain and produces the manifestations of Parkinsonism like rigidity (increased muscle resistance), tremor, hypokinesia (slowness of movement), mask like faces and festinating gait. Usually, it disappears after reducing the dose of prochlorperazine.
► Acute muscular dystonia – It may appear within a few hours of a single dose or at the most in the first week of therapy. Bizarre spasms of the facial, tongue and neck muscles occur in this condition and producing grimacing, torticollis and locked jaw. It is more common in children below ten years, particularly after intramuscular (IM) or intravenous (IV) injection. This effect is treated with procyclidine or orphenadrine.
► Tardive dyskinesia – It may occur late in therapy or sometimes observed after withdrawal of drug therapy. It is more common in elderly persons on high doses, especially females. The dyskinesia may subside months or years after withdrawal of drug therapy or may be persists lifelong. The symptoms of dyskinesia are rhythmical involuntary movements of the face, mouth, tongue, jaw or limb (e.g. constant chewing, puckering of mouth, protrusion of tongue, puffing of cheeks). There is no satisfactory solution for tardive dyskinesia.
► Akathisia – It may be seen in some persons between 1 to 8 weeks of therapy. Features of akathisia are restlessness, feeling of discomfort and apparent agitation. A central anticholinergic drug like procyclidine may reduce the intensity, but most cases require reduction of doses of prochlorperazine.
(B) Central nervous system side effects:
Lethargy, drowsiness, mental confusion, aggravation of seizures in epilepsy.
(C) Cardiovascular side effects:
Postural hypotension, ventricular tachycardia, atrio-ventricular block, prolongation of QT interval.
(D) Anticholinergic side effects:
Dry mouth, constipation, urinary hesitancy in elderly males, blurring of vision.
(E) Skin side effects:
Mild photosensitivity, skin rash and urticaria.
Blood dyscrasias, cholestatic jaundice.
Precautions of prochlorperazine:
Patients should be warned about drowsiness effect of prochlorperazine and advised not to drive or operate machinery during therapy. This drug may increase sensitivity to sunlight. Prolonged exposure to sunlight should be avoided, and a sunscreen and protective clothing should be used when body is exposed to sun. Prochlorperazine may interfere the thermoregulatory mechanisms and making more susceptible to heat stroke. Therefore, patients should be advised to avoid heat exposure. Learn more.
Overdose of prochorperazine:
Prochlorperazine overdose may cause different toxic manifestations including cardiac arrhythmias, hypotension, hypothermia, severe extra pyramidal muscular dystonic reactions, drowsiness, loss of consciousness. If the patient is seen within 6 hours after ingestion of drug, gastric lavage may be attempted. Treatment is supportive. Activated charcoal may be given. There is no specific antidote of prochlorperazine. Learn more.