UNDER REVIEW (September 2016)
Mechanism of Action:
A member of the phenothiazine group of “typical” antipsychotic drugs. Predominant action is as a dopamine D2-receptor antagonist which provides a centrally mediated anti-emetic effect.
Drug specifics
| Alternative drug name | not specified |
| Effects | Indicated for the treatment of severe nausea, vomiting, vertigo, labyrinthine disorders. The phenothiazines are dopamine antagonists and act centrally by blocking the chemoreceptor trigger zone. They are of considerable value for the prophylaxis and treatment of nausea and vomiting associated with diffuse neoplastic disease, radiation sickness, and the emesis caused by drugs such as opioids, general anaesthetics, and cytotoxics. Anti-emetics should be prescribed only when the cause of vomiting is known because otherwise they may delay diagnosis, particularly in children. Anti-emetics are unnecessary and sometimes harmful when the cause can be treated, such as in diabetic ketoacidosis, or in digoxin or antiepileptic overdose. |
| Adverse actions | Similar to other related antipsychotic drugs. Extrapyramidal symptoms consist of: (a) Parkinsonian symptoms (including tremor), (b) dystonia (abnormal face and body movements) and dyskinesia, (c) akathisia (restlessness), and (d) tardive dyskinesia (rhythmic, involuntary movements of tongue, face, and jaw), which usually develops on long-term therapy or with high dosage, but it may develop on short-term treatment with low doses—short-lived tardive dyskinesia may occur after withdrawal of the drug. Parkinsonian symptoms remit if the drug is withdrawn and may be suppressed by the administration of antimuscarinic drugs. Hypotension and interference with temperature regulation are dose-related side-effects and are liable to cause dangerous falls and hypothermia or hyperthermia in the elderly. Neuroleptic malignant syndrome (hyperthermia, fluctuating level of consciousness, muscular rigidity, and autonomic dysfunction with pallor, tachycardia, labile blood pressure, sweating, and urinary incontinence) is a rare but potentially fatal side-effect. Other side-effects are numerous but include antimuscarinic symptoms (such as dry mouth, constipation, difficulty with micturition, and blurred vision); cardiovascular symptoms (such as hypotension, tachycardia, and arrhythmias); ECG changes (cases of sudden death have occurred); endocrine effects such as menstrual disturbances, galactorrhoea, gynaecomastia, impotence, and weight gain; blood dyscrasias (such as agranulocytosis and leucopenia), photosensitisation, contact sensitisation and rashes, and jaundice (including cholestatic). |
| Dose | Given by mouth, by deep intramuscular injection, or by rectum in suppositories. |
| Interactions | See BNF. |
| Contraindications | not specified |
| Comments | The phenothiazines are all dopamine antagonists and act centrally by blocking the chemoreceptor trigger zone. They are of considerable value for the prophylaxis and treatment of nausea and vomiting associated with diffuse neoplastic disease, radiation sickness, and the emesis caused by drugs such as opioids, general anaesthetics, and cytotoxics. Prochlorperazine, perphenazine, and trifluoperazine are less sedating than chlorpromazine; severe dystonic reactions sometimes occur with phenothiazines, especially in children. Other antipsychotic drugs including haloperidol and levomepromazine (methotrimeprazine) are also used for the relief of nausea. Some phenothiazines are available as rectal suppositories, which can be useful in patients with persistent vomiting or with severe nausea; prochlorperazine can also be administered as a buccal tablet which is placed between the upper lip and the gum. OTHER ANTI-EMETIC DRUGS. Domperidone and metoclopramide act at D2 receptors at the chemoreceptor trigger zone; it is used for the relief of nausea and vomiting, especially when associated with cytotoxic therapy. Domperidone has the advantage over metoclopramide and the phenothiazines of being less likely to cause central effects such as sedation and dystonic reactions because it does not readily cross the blood-brain barrier. 5HT3 antagonists (see granisetron). Dexamethasone is a powerful corticosteroid (glucocorticoid) that has anti-emetic effects and it is used in vomiting associated with cancer chemotherapy. Nabilone is a synthetic cannabinoid with anti-emetic properties. It may be used for nausea and vomiting caused by cytotoxic chemotherapy that is unresponsive to conventional anti-emetics. Antihistamines (eg. promethazine, cyclizine and cinnarizine) are used as anti-emetics, particularly in the setting of motion sickness (generally better tolerated than hyoscine). If a sedative effect is desired promethazine is useful, but generally a slightly less sedating antihistamine such as cyclizine or cinnarizine is preferred. OTHER DRUGS FOR VESTIBULAR DISORDERS. Betahistine (Serc) is commonly prescribed for vertigo, tinnitus and hearing loss associated with Ménière's disease. It is taken as a tablet 3 times daily. |
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