Medical Pharmacology Chapter 22:  Serotonin Pharmacology

• Clinical Pharmacology

  • "The Different Medications Used to Treat Migranes"

    Attribution:  Newman LC "The Different Medications Used to Treat Migranes" https://www.youtube.com/watch?v=sY4k21ZFDW0 (7/2010) Best Doctors YouTube Channel:   https://www.youtube.com/channel/UCqvEALGXtBCFxCVe20e2yaA "Lawrence C. Newman, MD: There are many different approaches that we used to treat people who suffer from migraine. In general, we divide the therapies into acute medications and preventative medications.  The acute medications are medications that taken at the onset of the headache to shorten the attack of pain, and hopefully to get rid of the associated symptoms, the nausea and vomiting for instance. We divide the acute medications into two broad categories, symptomatic medications and specific medications. A symptomatic medication is not just for migraine.  It can be used for pain or for nausea and vomiting for any reason. It can include over the counter medications like Aspirin or Tylenol or medications combined like with caffeine like Excedrin for instance or certain prescription medications.  The prescription forms of antiinflammatory medications as well. Specific agents on the other hand worked just for migraine and the beauty of these agents is that they target not only the head pain, but the associated features, the nausea, the vomiting, the lightness, the sound and the smell sensitivity.  They work quickly. They do not cause sedation in general, and they are not addicted. Agents like those include the Triptans, Sumatriptan or Imitrex, Rizatriptan or Maxalt were various forms, those medications, Ergotamines and Dihydroergotamine like Migranal nasal spray and several others.  Again, these agents target the headaches specifically not generally. For people who had very frequent attacks of migraine, frequent is defined as more than one headache per month will often use preventative agents.  Preventative agents fall in several different categories. High blood pressure medications, antidepressant medications, and antiseizure medications. These agents have been shown to decrease both the frequency and severity of attacks of migraine letting patients go on to live a normal life."

   

  • Serotonin Agonists

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

      • Buspirone (BuSpar)

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

    • "Migrane Mechanism"

      Attribution:  Blackwell C "Migrane Mechanism" https://www.youtube.com/watch?v=dFsfzLV8ZEw (12/2010) Craig Blackwell YouTube Channel:  https://www.youtube.com/channel/UCn6gcfNSZvBUeccmqsn1LXg

  • Sumatriptan: (Imitrex)

    •  

      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)

      • Ondansetron

    • 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 apparent activity on other 5 HT or H₁ histamine receptors)

      • Blocks α₁ adrenergic receptors

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

      • Effective antihypertensive drug (probably acting through α₁ adrenergic receptors.

  • Ritanserin

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

    • May alter platelet function.

  • Ondansetron (Zofran)

    • "Anti-emetics"

      Attribution:  Wallitt E "Anti-Emetics"  https://www.youtube.com/watch?v=vRL3OBJgv00 Podmedics YouTube Channel:  Podcast (Podmedics Videos on various subjects: https://www.youtube.com/channel/UCs6QcH-PR_mvl3KXh-InzKg

     

    • 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.

      • This agent has a major role in management of severe nausea and vomiting due to anticancer drugs

    • Clinical Use:

      • Dosage: 4-8 mg IV (administered over 2-5 minutes just before anesthesia induction).

      • 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 and 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 and 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-- could 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.