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  1. Pharmacology. Bromocriptine mesylate is a semisynthetic derivative of the ergopeptide group of ergot alkaloids with dopaminergic agonist effects. It also has minor alpha-adrenergic antagonist properties. The dopaminergic effects account for its inhibition of prolactin secretion and its beneficial effects in the treatment of parkinsonism, acromegaly, neuroleptic malignant syndrome (NMS), and cocaine craving as well as its adverse effect profile and drug interactions. A key limitation is the inability to administer bromocriptine by the parenteral route coupled with poor bioavailability (only about 6% of an oral dose is absorbed). In addition, the onset of therapeutic effects (eg, alleviation of muscle rigidity, hypertension, and hyperthermia) in the treatment of NMS may take several hours to days.

  2. Indications

    1. Treatment of NMS caused by neuroleptic drugs (eg, haloperidol and other antipsychotics) or levodopa withdrawal. Note: If the patient has significant hyperthermia (eg, rectal or core temperature ≥40°C [104°F]), bromocriptine should be considered secondary and adjunctive therapy to immediate measures such as neuromuscular paralysis and aggressive external cooling. Its efficacy to treat NMS is uncertain, and there is concern that it could worsen other types of hyperthermia (eg, malignant hyperthermia, heat stroke) owing to activation of dopamine and 5-HT2A receptors.

    2. Bromocriptine has been used experimentally to alleviate craving for cocaine. However, a Cochrane database review (2003) concluded that current research does not support the use of dopamine agonists for the treatment of cocaine dependence. Caution: There is one case report of a severe adverse reaction (hypertension, seizures, and blindness) when bromocriptine was used in a cocaine abuser during the postpartum period.

    3. Note: Bromocriptine is not considered appropriate first-line therapy for acute drug-induced extrapyramidal or parkinsonian symptoms (Other Complications).

  3. Contraindications

    1. Uncontrolled hypertension or toxemia of pregnancy.

    2. Known hypersensitivity to the drug.

    3. A relative contraindication is a history of angina, myocardial infarction, stroke, vasospastic disorders (eg, Raynaud disease), or bipolar affective disorder. In addition, there is no published experience in children younger than 7 years. Children may achieve higher blood levels and require lower doses.

  4. Adverse effects. Most adverse effects are dose-related and of minor clinical consequence; some are unpredictable.

    1. The most common side effect is nausea. Epigastric pain, dyspepsia, and diarrhea also have been reported.

    2. Hypotension (usually transient) and syncope may occur at the initiation of treatment, and hypertension may occur later. Other cardiovascular effects include dysrhythmias (with high doses), exacerbation of angina and vasospastic disorders such as Raynaud disease, and intravascular thrombosis resulting in acute myocardial infarction (one case report).

    3. Nervous system side effects vary considerably and include headache, drowsiness, fatigue, hallucinations, mania, psychosis, agitation, seizures, and cerebrovascular accident. Multiple interrelated risk factors include dose, concurrent drug therapy, and preexisting medical and psychiatric disorders.

    4. Rare effects include pulmonary toxicity (infiltrates, pleural effusion, and thickening) and myopia with long-term, high-dose treatment (months). There has been one case of retroperitoneal fibrosis.

    5. Use in pregnancy. FDA Category B (Introduction). This drug has been used therapeutically during the last trimester of pregnancy for the treatment ...

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