Bromocriptine - Antiparkinsonian Drug

Bromocriptine

Bromocriptine is an ergot derivative with potent dopaminergic agonist action (high affinity for the D₂ receptor site). 

Uses

·              Bromocriptine is indicated for treatment of dysfunctions associated with hyperprolactinaemia, acromegaly to reduce serum growth hormone, and for idiopathic or postencepha-litic Parkinson’s disease.

·              It is no longer indicated for the treatment of suppression of physiological post-partum lactation; the FDA (USA) is of the opinion that bromocriptine may cause a serious adverse effect in post-partum women.

Toxicokinetics

The drug is well absorbed on oral administration and peak plasma levels are reached in about 2 hours. The plasma half-life of bromocriptine is approximately 6 to 8 hours. The volume of distribution is 1 to 4 L/kg, and plasma protein binding is to the extent of 96%. Liver is the main site of metabolism and the main route of excretion is biliary. Less than 0.1% is excreted unchanged.

Mode of Action

Bromocriptine is a synthetic ergoline and a direct dopamine D₂ agonist stimulant. Some of its activity includes inhibi-tion of the release of prolactin by the pituitary, resulting in decreased plasma prolactin concentrations. Bromocriptine, as a dopamine agonist, occupies dopaminergic receptors in the pituitary gland to inhibit prolactin secretion. The D₂ receptor sites show properties related to dopaminergic behavioural and endocrine responses.

Adverse Effects

·              Nausea, vomiting, vertigo, postural hypotension, nasal congestion, constipation, and mood disturbances.

·              Less common problems include headache, dryness of mouth, mydriasis, hallucinations, digital vasospasm, eryth- romelalgia,* and bladder disturbances.

·              Diplopia, dyskinesia, anginal pain, and ergotism have also been reported.

·              Long-term therapy may result in pleural effusion, pleural and pulmonary fibrosis, retroperitoneal fibrosis, and pleu- ritic chest pain.

·              Hypothermia, hypertension, myocardial infarction, stroke, and seizures have been reported in postpartum women who were given bromocriptine for lactation suppression.

·              Sudden discontinuation can result in hyperpyrexia.

Drug Interactions

·              Bioavailability of bromocriptine is increased if it is given along with erythromycin.

·              Alcohol reduces tolerance to bromocriptine and vice versa.

·              Bromocriptine has been reported to sensitise patients to acute dystonic crisis following administration of a neuro- leptic. Dopamine antagonists, such as the neuroleptics or leptic. Dopamine antagonists, such as the neuroleptics or C

·              dopamine agonists when given concurrently. Life-threatening symptoms of seizures, cerebral vasospasm, ventricular tachycardia and cardiac dysfunction have been reported when bromocriptine was combined with sympa- thomimetics.

Clinical (Toxic) Features

·              Drowsiness, vertigo, postural hypotension, sweating, hallucina-tions, agitation, convulsions, nausea, and vomiting. Dyskinesias may occur.

Treatment

·      Gastric lavage can be done if the patient is seen within a short time post-ingestion (upto 2 to 3 hours). Activated charcoal may not be beneficial.

·      Rest of the treatment involves supportive and symptomatic measures. Most cases of overdose with bromocriptine appear minimal and treatable with supportive care.

·      Monitor CNS changes for possible dyskinesias or seizures. Specific treatment for dyskinesias primarily includes reduc-tion of dosage and supportive care.

·      If the patient is hyperactive, administer diazepam 10 to 20 mg orally to adults, (no more than 0.1 mg/kg in children).

·      Blood pressure and ECG must be followed up in sympto-matic patients.

·      Because of the significant protein binding of bromocriptine, haemodialysis is not expected to be of benefit.