2- Drugs Used for Nausea and Vomiting

  • Classifications of Antiemetic Drugs

    • 5HT3 antagonists

    • DA antagonists

    • NK1-receptor antagonist

    • Corticosteroids

    • H1 antagonists

    • Muscarinic antagonists

    • Cannabinoids

    • Benzodiazepines

  • Serotonin 5HT3 Antagonists

    • Examples: Ondansetron, Granisetron, Dolasetron, Palonosetron

    • Key Indications: Highly effective for Chemotherapy-Induced Nausea and Vomiting (CINV) across all grades. Postoperative Nausea and Vomiting (PONV) management.

    • Administration: Can be used alone or in combination therapy before chemotherapy to prevent nausea and vomiting.

  • Safety Considerations: QT prolongation may occur, particularly with higher doses of Ondansetron and Dolasetron. Palonosetron has a longer half-life and is less likely to cause QT prolongation, making it suitable for delayed-phase CINV.

  • DA Antagonists

      1. Phenothiazines

      • Example: Prochlorperazine

      • Clinical Use: Effective for low to moderately emetogenic chemotherapy agents. Commonly used for agents like fluorouracil and doxorubicin.

      • Mechanism: Acts as a dopamine (D2) receptor antagonist in the chemoreceptor trigger zone (CTZ).

      • Key Benefits: Useful in preventing chemotherapy-induced nausea and vomiting (CINV).

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    1. Butyrophenones

    • Examples: Haloperidol, Droperidol

      Clinical Use:

      • Haloperidol: Moderately effective as an antiemetic, often used in refractory cases.

      • Droperidol: Primarily used for sedation during endoscopy and surgery. Often combined with opioids or benzodiazepines.

      • Key Considerations: Droperidol may prolong the QT interval, requiring monitoring in at-risk patients. Best used in patients with an inadequate response to other antiemetic agents.

    1. Substituted Benzamides

    • Metoclopramide: A substituted benzamide with notable antiemetic properties.

    • Mechanism: Acts as a dopamine (D2) receptor antagonist, and enhances gastric motility by promoting acetylcholine release in the GI tract.

    • Clinical Use: Effective against highly emetogenic chemotherapy, such as cisplatin. Beneficial in managing gastroparesis due to its prokinetic effects.

  • Adverse Effects:

    • Antidopaminergic effects may cause extrapyramidal symptoms (e.g., dystonia, tardive dyskinesia), especially with long-term or high-dose use.

    • Caution is advised in prolonged therapy due to the risk of neurological side effects.

  • Substance P/Neurokinin-1 Receptor Antagonists

    • Aprepitant, Netupitant, and Rolapitant are examples.

    • Clinical Use: Effective for highly or moderately emetogenic chemotherapy. Effective for the delayed phase of CINV, which occurs 24 hours or more. Can also be prescribed in the acute phase of CINV.

    • Drug Interaction: They may affect the metabolism of other drugs.

  • Corticosteroids

    Dexamethasone and Methylprednisolone are examples.

    • Clinical Use: Effective against mildly to moderately emetogenic chemotherapy. Most frequently used in combination with other agents. Used for delayed vomiting and early phase (in case of CINV).

    • Mechanism: Their antiemetic mechanism is not known, but it may involve blockade of prostaglandins.

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  • Benzodiazepines

    Lorazepam and Alprazolam have low antiemetic potency.

    • Benefits: Useful for their sedative, anxiolytic, and amnestic properties, especially for anticipatory vomiting.

  • Other Antiemetic Classes:

    • H1 Antagonists: Diphenhydramine, Meclizine, Promethazine

    • Muscarinic Antagonists: Scopolamine

    • Cannabinoids:

      Dronabinol: Used for chemotherapy-induced emesis and as an appetite stimulant for anorexic patients.

  • Combined Treatment

    Antiemetic drugs are often combined to increase efficacy or reduce toxicity. Corticosteroids enhance antiemetic activity when combined with various agents. Antihistamines (like Diphenhydramine) can reduce extrapyramidal reactions or diarrhea when combined with specific drugs. Combining substance P/neurokinin-1 receptor antagonists with 5-HT3 antagonists and Dexamethasone is beneficial for highly emetogenic regimens with delayed CINV.

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  • Conditions and Preferred Drugs

    • Neurology: Motion sickness

      • Preferred Drugs: Dimenhydrinate, Scopolamine, Cyclizine, Meclizine, Promethazine

      • Oncology: Vomiting due to cytotoxic drugs

        • Preferred Drugs: Metoclopramide, Ondansetron (acute phase), Dexamethasone, Aprepitant (acute and delayed phase)

      • Surgery: POV

        • Preferred Drugs: Ondansetron, Metoclopramide

      • Gynecology: Morning sickness

        • Preferred Drugs: Pyridoxine, Meclizine + Pyridoxine, Doxylamine + Pyridoxine, Meclizine, Cyclizine

      • GIT: Gastroparesis

        • Preferred Drug: Metoclopramide