Cyproheptadine (Periactin®)
Classification:
Antihistamines
» H1-blockers
» Sedating H1-blockers
Description: Cyproheptadine is a piperidine H1-antagonist. Unlike other H1-antagonists, this drug also antagonizes serotonin receptors. This action makes cyproheptadine useful in conditions such as Cushing’s syndrome, vascular headache and anorexia. Cyproheptadine has also been used for the management of anorgasmy caused by antidepressants such as SSRIs; however, it must be monitored closely when used for this purpose since the antidepressant effects of the SSRI may also be reversed. In a small study, patients with chronic urticaria ranked cyproheptadine higher than five other H1-antagonists in efficacy and freedom from side effects. Cyproheptadine was approved by the FDA in 1961.
Mechanism of Action: Cyproheptadine does not prevent the release of histamine, as do cromolyn and nedocromil, but rather competes with free histamine for binding at H1-receptor sites. Cyproheptadine competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. H1-antagonists also possess anticholinergic properties in varying degrees. The anticholinergic activity of piperidine derivatives such as cyproheptadine is moderate.
Sedative effects from cyproheptadine are a result of antagonism at central histaminergic receptors, although sedation is not as pronounced as with other H1-antagonists such as diphenhydramine. Following prolonged administration, tolerance may occur, but this may be beneficial because sedative effects may be reduced. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine’s ability to stimulate appetite. Cyproheptadine also has been used to counter vascular headaches, which many believe are caused by changes in serotonin activity. It is unclear how cyproheptadine, a serotonin-receptor antagonist, exerts a beneficial effect on this condition, since sumatriptan, an agent specifically indicated for treating migraine, acts as an agonist at serotonin receptors.
Pharmacokinetics: Cyproheptadine is administered orally. In general, H1-blockers are well absorbed from the GI tract, but they vary in solubility, which ultimately affects the onset of action. Less soluble H1-antagonists have a slower onset of action and are less likely to cause toxicity; cyproheptadine has moderate solubility. Peak concentration of cyproheptadine occurs in about 6 - 9 hours, and the duration of action is about 8 hours. Distribution of cyproheptadine has not been elucidated and it is unknown if the drug is distributed into milk. The parent compound is extensively metabolized in the liver to a number of conjugated metabolites. Plasma half-life ranges from 1 - 4 hours. Excretion is mainly renal, with no apparent excretion of unchanged drug. Some unchanged drug and metabolites are excreted in feces.
Cyproheptadine Tablets (Tab 4 mg)
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References
. Coutts A, Greaves MW. Evaluation of six antihistamines in vitro and in patients with urticaria. Clin Exp Dermatol 1982;7:529 - 36.
[ Revised 6/21/2006 3:19:00 PM ]
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