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Nausea and Vomiting (PDQ®): Supportive care - Health Professional Information [NCI] - Prevention of Acute / Delayed Nausea and Vomiting (Emesis)

Antiemetic agents are the most common intervention in the management of treatment-related nausea and vomiting (N&V). The basis for antiemetic therapy is the neurochemical control of vomiting. Although the exact mechanism is not well understood, peripheral neuroreceptors and the chemoreceptor trigger zone (CTZ) are known to contain receptors for serotonin, histamine (H1 and H2), dopamine, acetylcholine, opioids, and numerous other endogenous neurotransmitters.[1,2] Many antiemetics act by competitively blocking receptors for these substances, thereby inhibiting stimulation of peripheral nerves at the CTZ and possibly at the vomiting center. Most drugs with proven antiemetic activity can be categorized into one of the following groups:

  • Competitive antagonists at dopaminergic (D2 subtype) receptors:
    • Phenothiazines.
    • Substituted benzamides.
    • Butyrophenones.
  • Competitive antagonists at serotonergic (5-hydroxytryptamine-3 or 5-HT3 subtype) receptors.
  • Substance P antagonists (NK-1 receptor antagonists).
  • Corticosteroids.
  • Cannabinoids.
  • Benzodiazepines.
  • Olanzapine.

Although all routes of administration are listed for each of the following drugs, the intramuscular (IM) route is used only when no other access is available. IM delivery is painful, is associated with erratic absorption of drug, and may lead to sterile abscess formation or fibrosis of the tissues. This is particularly important when more than one or two doses of a drug are to be given.

Phenothiazines

Phenothiazines act on dopaminergic receptors at the CTZ, possibly at other central nervous system (CNS) centers, and peripherally. With the exception of thioridazine, many phenothiazines possess antiemetic activity, including chlorpromazine given in the 10- to 50-mg dose range orally, IM, intravenously (IV), and rectally (pediatric dose for patients >12 years: 10 mg every 6-8 hours; for patients <12 years: 5 mg every 6-8 hours); thiethylperazine given in the 5- to 10-mg dose range orally, IM, and IV; and perphenazine. The primary consideration in selecting phenothiazines are differences in their adverse effect profiles, which substantially correlate with their structural classes. Generally, aliphatic phenothiazines (e.g., chlorpromazine, methotrimeprazine) produce sedation and anticholinergic effects, while piperazines (e.g., prochlorperazine, thiethylperazine, perphenazine, fluphenazine) are associated with less sedation but greater incidence of extrapyramidal reactions (EPRs).

Prochlorperazine

Prochlorperazine is perhaps the most frequently (and empirically) used antiemetic and, in low doses, is generally effective in preventing nausea associated with radiation therapy and in treating N&V attributed to very low to moderately emetogenic chemotherapeutic drugs. Prochlorperazine is a phenothiazine and can be given orally, IM, IV, and rectally. It is usually given in the 10- to 50-mg dose range (pediatric dose for children who weigh >10 kg or who are >2 years: orally or rectally, 0.4 mg/kg/dose tid-qid; or IM, 0.1-0.15 mg/kg/dose tid-qid, maximum 40 mg/d). Higher prochlorperazine doses (e.g., 0.2-0.6 mg/kg/dose) are also given IV for patients receiving chemotherapy with high emetogenic potential.[3];[4][Level of evidence: I] Phenothiazines may be of particular value in treating patients who experience delayed N&V (postacute phase symptoms) on cisplatin regimens.[5][Level of evidence: I]

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