The nausea and vomiting associated with cisplatin (see Chapter 51) has two components: an acute phase within 24 hours after chemotherapy that universally is experienced and a delayed phase on days 2-5 that affects only some patients. 5-HT receptor antagonists are not very effective against delayed emesis. Antagonists of the NK1 receptors for substance P, such as aprepitant (emend), have antiemetic effects in delayed nausea and improve the efficacy of standard antiemetic regimens in patients receiving multiple cycles of chemotherapy. Substance P belongs to the tachykinin family of neurotransmitters and is in vagal afferent fibers innervating the STN and area postrema.
After absorption, aprepitant is bound extensively to plasma proteins (>95%); it is extensively metabolized, primarily by hepatic CYP3A4, and is excreted in the stool; its t/2 is 9-13 hours. Aprepitant has the potential to interact with other substrates of CYP3A4, requiring adjustment of other drugs, including dexamethasone, methylprednisolone (whose dose may need to be reduced by 50%), and warfarin. Aprepitant is contraindicated in patients on cisapride (see above) or pimozide, in whom life-threatening ventricular tachyarrthmias has been reported.
Aprepitant is supplied in 80- and 125-mg capsules and is administered for 3 days in conjunction with highly emetogenic chemotherapy along with a 5-HT3-receptor antagonist and a glucocorticoid. The recommended adult dosage of aprepitant is 125 mg administered 1 hour before chemotherapy on day one, followed by 80 mg once daily in the morning on days 2 and 3 of the treatment regimen.
AGENTS USED FOR MISCELLANEOUS GASTROINTESTINAL DISORDERS Chronic Pancreatitis and Steatorrhea
PANCREATIC ENZYMES Chronic pancreatitis is a debilitating syndrome that results in symptoms from loss of glandular function (exocrine and endocrine) and inflammation (pain). The goals of pharmacological therapy are prevention of malabsorption and palliation of pain. The cornerstone of therapy for malabsorption is the use of pancreatic enzymes.
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