Promethazine (Phenergan)
Promethazine
Brand Name(s): Phenergan® | Anergan™ | Antinaus® | Pentazine® | Phenadoz™ | Phenergan® Fortis | Progan™ | Promacot™ | Prometh® | Promethegan®
Classification:
Antihistamines
» H1-blockers
» Sedating H1-blockers
Gastrointestinal Agents
» Antiemetics
» Phenothiazines
Description: Promethazine is a phenothiazine; however, it is not used clinically as a neuroleptic. It is an H1-antagonist with considerable anticholinergic, sedative, and antiemetic effects and some local anesthetic properties. Promethazine is commonly used as an antihistamine in combination cough and cold products. Promethazine is also used as an antiemetic or to prevent motion sickness. In November 2004 the FDA directed manufacturers of promethazine to include a Black Box warning contraindicating its use in children < 2 years of age. Promethazine should be used with extreme caution in young children due to an increased risk for fatal respiratory depression. Promethazine was approved by the FDA in 1951.
Mechanism of Action: The predominant action of promethazine is antagonism of H1-receptors. Although promethazine is classified as a phenothiazine, its ability to antagonize dopamine is approximately one-tenth that of chlorpromazine. For this reason, promethazine is not used as a neuroleptic.
Like other H1-antagonists, promethazine does not prevent the release of histamine, as do cromolyn and nedocromil, but competes with free histamine for binding at H1-receptor sites. Histamine receptors in the GI tract, uterus, large blood vessels, and bronchial muscle are blocked. The relief of motion sickness and nausea/vomiting appear to be related to central anticholinergic actions and may implicate activity on the medullary chemoreceptor trigger zone. Other CNS receptor sites can also be affected, since promethazine is believed to indirectly reduce stimuli to the brain stem reticular system. Sedation is significant at concentrations achieved from therapeutic dosages. Mild antitussive activity has been attributed to promethazine, but this effect probably results from anticholinergic and sedative actions. Local anesthetic activity requires higher concentrations than those required to antagonize histamine receptors.
Pharmacokinetics: Promethazine is administered orally, rectally, intramuscularly, and intravenously. Onset of action occurs within 15 - 60 minutes after oral or rectal administration and within 20 minutes after intramuscular administration. Following intravenous administration, onset of action occurs within 3 - 5 minutes. Antihistaminic and sedative effects are sustained for 4 - 6 hours and 2 - 8 hours, respectively. Promethazine is highly protein-bound (80 - 93%). It is widely distributed in body tissues and fluids, and it crosses the placenta and is excreted into breast milk. Metabolism occurs in the liver, producing inactive metabolites such as promethazine sulfoxide and other glucuronides. The elimination half-life is 10 - 14 hours, with excretion of metabolites in the urine and the feces.
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[ Revised 6/30/2006 12:44:00 PM ]
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