Nursing Pharmacology Chapter 22:  Serotonin Pharmacology

• Clinical Pharmacology

  • Serotonin Agonists

    • Buspirone (BuSpar):  5-HT_1A agonist, a nonbenzodiazepine anxiolytic

    • Sumatriptan (Imitrex):  5-HT_1D agonist: acute migraine and cluster headache.

  • Sumatriptan: (Imitrex)

    • Relief of migraine symptoms for most patients

    • Efficacy greater than or equal to other drug treatments (including parenteral agents or oral ergot alkaloids)

    • Multiple dosing may be required (headache lasts longer than single dose duration)

    •  Adverse Effects:  Sumatriptan

      •   Generally mild

      •   Altered sensations (tingling, warmth, etc.)

      •   Dizziness

      •   Muscle weakness

      •   Neck pain

      •   Chest pain (frequency: 5%)

    • Contraindications:

      • In patients with ischemic heart disease

      • In patients with Prinzmetal's angina (variant angina)

  • Serotonin Antagonists

    • Cyproheptadine (Periactin)

    • Ondansetron (Zofran)

    • Ketanserin

    • Granisetron (Kytril)

    • Ritanserin

    • Dolasetron

    • Tropisetron

    • Cyproheptadine (Periactin)

      • Overview

        • Blocks serotonergic and histaminergic affects on smooth muscle

        • No effect on histamine-stimulated gastric secretion

        • Significant antimuscarinic effects

        • Sedation

      • Clinical Use:  cyproheptadine

        • Major Use: cyproheptadine

          •  Reduces smooth muscle effects of carcinoid tumor

          •  Reduces postgastrectomy dumping syndrome

  • Ketanserin

    • Overview

      • Blocks 5-HT_1c and 5-HT₂ receptors (no activity another 5 HT or H₁ histamine receptors

      • Blocks a₁ adrenergic receptors

      • Blocks platelet 5-HT₂ receptors (inhibits serotonin-mediated platelet aggregation)

      • Effective antihypertensive drug (probably acting through a₁ adrenergic receptors

  • Ritanserin

    • Blocks 5-HT₂ receptors (no alpha blocking properties)

    • May alter platelet function

  • Ondansetron (Zofran)

    • 5-HT₃ receptor blocker

      • Minimal effects on dopamine, histamine, adrenergic or cholinergic receptor activity

    • Very effective for prevention of nausea and vomiting caused by chemotherapy or surgery. -- major role in management of severe nausea and vomiting due to anticancer drugs

    • Clinical Use:

      • Highly effective in reducing postoperative nausea/vomiting incidence -- particularly in susceptible patient groups:

        • Ambulatory gynecologic surgery

        • Middle ear surgery

      • Oral or IV reduces incidence of postoperative vomiting and preadolescent children undergoing:

        • Ambulatory surgery, e.g. tonsillectomy, strabismus surgery

      • Ondansetron (Zofran): effective both for prophylaxis and treatment of postoperative nausea/vomiting

        • Decreases incidents & intensity of postoperative nausea & vomiting -- but does not totally eliminate this problem

        • Major advance: reduced side effects compared to previously used antiemetic drugs such as:

          • Phenothiazines, antihistamines, butyrophenones

      • Propofol (Diprivan) for induction and maintenance of anesthesia may be as effective as ondansetron (Zofran) in reducing/preventing postoperative nausea & vomiting

    •   Side Effects:

      • Surgical patients:

        • 3% increased liver transaminase enzyme levels

        • 3% headache

      • No sedation, hypotension, dysphoria, extrapyramidal reactions; side effects associated with other antiemetic drugs

  • Tropisetron

    • 5-HT₃ receptor blocker

    • Effective in managing symptoms induced by carcinoid syndrome-- also some gastrokinetic characteristics

    • Effective in preventing chemotherapy/radio therapy-induced emesis

    • Effective in preventing postoperative nausea/vomiting when administered before general anesthetic induction

  • Granisetron (Kytril)

    • More selective 5-HT₃ receptor blocker compared to ondansetron

    • Clinical Use

      • Effective in the chemotherapy-induced emesis prevention

      • Effective in preventing postoperative nausea/vomiting

    • Elimination half-life: nine hours, compared to about three hours for ondansetron: suggesting less frequent dosing with granisetron.

    • Significantly higher cost may limit clinical use

  • Dolasetron

    • Highly potent/selective 5-HT₃ receptor blocker

    • Clinical Use:

      • Effective in preventing chemotherapy-induced nausea/vomiting

      • Effective in reducing likelihood of postoperative nausea & vomiting

      • Antiemetic effect due to long-acting, active metabolite (hydrodolasetron; elimination half-life = approximately 8 hours)

  Burkhalter, A, Julius, D.J. and Katzung, B. Histamine, Serotonin and the Ergot Alkaloids (Section IV. Drugs with Important Actions on Smooth Muscle), in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 261-286.