McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 5 9 Antiemetic agents

with emetogenic chemotherapy. These are relatively new drugs, and the drug of choice depends on personal pref- erence and experience.

receptor antagonists aprepitant ( Emend ) and fosaprep- itant ( Emend IV ). Aprepitant is available in oral form while fosaprepitant is given intravenously. Therapeutic actions and indications These drugs act directly in the CNS to block receptors associated with nausea and vomiting with little to no effect on serotonin, dopamine or corticosteroid recep- tors. They are approved for use in treating the nausea and vomiting associated with highly emetogenic antineo- plastic chemotherapy, including cisplatin therapy. They are given orally, in combination with dexamethasone. Pharmacokinetics They are metabolised in the liver and excreted in urine and faeces, and are known to cross the placenta and to enter breast milk. Contraindications and cautions Aprepitant and fosaprepitant should not be used during pregnancy and breastfeeding because of the potential for adverse effects on the fetus or breastfeeding infant or with known allergy to any component of the drug to prevent hypersensitivity reactions. Adverse effects The adverse effects associated with aprepitant and fosa­ prepitant include GI effects of diarrhoea, constipation, gastritis, nausea; anorexia; headache; and fatigue. Clinically important drug–drug interactions There is a risk of serious increase in serum levels of pimozide if these drugs are used together; this Prototype summary: Aprepitant Indications: In combination with other agents for the prevention of acute and delayed nausea and vomiting associated with severely emetogenic cancer chemotherapy. Actions: Selectively blocks human substance P/neurokinin 1 (NK1) receptors in the CNS, blocking the nausea and vomiting caused by highly emetogenic chemotherapeutic agents. Pharmacokinetics: Route Onset Peak Oral Rapid 4 hours T 1/2 : 9 to 13 hours; metabolised in the liver and excreted in urine and faeces. Adverse effects: Anorexia, fatigue, constipation, diarrhoea, liver enzyme elevations, dehydration.

Pharmacokinetics The 5-HT 3

receptor blockers are rapidly absorbed, reaching peak levels within 1 hour. They are metabo- lised in the liver and excreted in urine. Ondansetron, dolasetron, granisetron and tropisetron are available in oral and IV forms; palonosetron is only available in an IV form. Contraindications and cautions These drugs are contraindicated with known allergy to any component of the drug to prevent hypersensitivity reactions. Caution should be used during pregnancy and breastfeeding because of the potential for adverse effects on the fetus or nursing baby. Adverse effects The adverse effects most frequently seen with these drugs are headache, dizziness and myalgia related to their CNS effects. Pain at the injection site, rash, con- stipation, hypotension and urinary retention have also been reported. Prototype summary: Ondansetron Indications: Control of severe nausea and vomiting associated with emetogenic cancer chemotherapy, radiation therapy; treatment of postoperative nausea and vomiting. Actions: Blocks specific receptor sites associated with nausea and vomiting, peripherally and in the CTZ. Pharmacokinetics: Route Onset Peak Duration Oral 30–60 mins 60–90 mins 1.7–2.2 hours IV Immediate 60–90 mins Duration of infusion T 1/2 : 3.5–6 hours; metabolised in the liver and excreted in urine. Adverse effects: Headache, dizziness, drowsiness, myalgia, urinary retention, constipation, pain at injection site.

S ubstance P/ neurokinin 1 receptor antagonists

Two drugs in the newest class of drugs for treating nausea and vomiting are the substance P/neurokinin 1