Medical Pharmacology Chapter 12:  Anxiolytics and Sedative-Hypnotics

• ¹Antiemetic drugs:

  • Overview and rationale:

    • Antiemetic agents are included in anesthetic premedication with the objective decreasing postoperative nausea and vomiting incidence.

  • Factors that tend to increase patients risk for developing postoperative nausea and vomiting:

    • Females

    • Previous history of postoperative nausea

    • History motion sickness

    • Use of general rather than regional anesthesia

    • Opioid (e.g. morphine, meperidine (Demerol)) administration

    • Opthalmological or gynecologic surgeries

    • Orthopedic shoulder surgery

  • Prophylactic use of antiemetic agents decrease the likelihood of postoperative nausea vomiting; however, little outcome difference has been documented based on whether the patient receives prophylactic medication or medication only if nausea and vomiting symptoms occur.

  • Drugs used for prophylaxis against postoperative nausea and vomiting:

    1. Serotonin antagonists such as: ondansetron (Zofran), tropisetron,  granisetron (Kytril), dolasetron (Anzemet)

    2. Butyrophenones class antipsychotic drugs: droperidol (Inapsine)

    3. Gastrointestinal prokinetic agents: metoclopramide (Reglan)

    4. Phenothiazine class antipsychotic drugs: perphenazine (Trilafon)

  • Administration protocols: often given near the end of the surgical procedure by IV Route of Administration

  • Arguments against prophylactic antiemetic use:

    • Increased cost -- at the present particularly for the serotonin antagonist drug class

    • Possibility of dysphoria/sedation should butyrophenones be used

    • Orthostatic hypotension (a side effect of phenothiazine-type agents because of their α-1 adrenergic receptor blocking properties)

    • A percentage of patients will vomit independent of whether antiemetic drug prophylaxis is used.

• ³More about metoclopramide (Reglan):

  • Dosage and Route of Administration:

    • Oral: 90-120 minutes preoperatively the dosage of 0.2 mg/kg

    • IV administration: onset occurs within 3  minutes (compared to a time to onset of about 20 minutes following oral dosage)

    • In emergent circumstances, oral dosing is still appropriate and clinically effective, since gastric contents will be decreased within 15 minutes

    • In the trauma setting, metoclopramide (Reglan) has been found more effective in emptying child's stomach compared to waiting 6-8 hours.

    • Contraindications to metoclopramide (Reglan) administration (note that metoclopramide is a dopamine antagonist)

      •  Metoclopramide (Reglan) not be given to patients who are taking dopamine antagonists, tricyclic antidepressants, sympathomimetic agents, or monoamine oxidase inhibitors (metoclopramide (Reglan) may cause hypertensive crises in patients with pheochromocytoma).

  • Complications/side effect associated with metoclopramide (Reglan)--

    • Extrapyramidal Neurological side effects: Frequency = 1%, more common in children and at those higher doses used to manage chemotherapy-induced vomiting. 

      • Diphenhydramine (Benadryl) may be effective in limiting these side effects.

        • Tremor

        • Torticollis (limited neck motion due to shortening of the sternocleidomastoid muscle; idiopathic spasmodic torticollis is classified as a focal dystonia and may be seen more commonly with neuroleptics and L-DOPA),

          •  

            Tortticollis

            "Picture 1. 69-year-old woman presenting with torticollis and fever"

            "Picture 2. Soft-tissue neck radiograph demonstrates retropharyngeal abscess appearing as torticollis."

        • Opisthotonus (abnormal postures and defined as rigidity with severe back arching what they had thrown backwards -- the extent of the syndrome can be visualized in that if a personal were layed on his/her back only the back of the head and heels would touch the  surface),

          • Opisthotonus

            Opisthotonus: image from Mount Allison University, used with permission

        • Oculogyric crisis (an acute dystonia:"A spasmodic movement of the eyeballs into a fixed position, usually upward, that persist for several minutes or hours")

  • ⁵From: " Torticollis" Authored by Michael Ross, MD, Staff Physician and Associate Director of EMS, Department of Emergency Medicine, Metrowest Medical Center Coauthored by Susan Dufel, MD, FACEP, Program Director, Associate Professor, Department of Traumatology and Emergency Medicine, Division of Emergency Medicine, University of Connecticut School of Medicine.

References

• ¹Preoperative Medication in Basis of Anesthesia, 4th Edition, Stoelting, R.K. and Miller, R., p 119- 130, 2000) 

• Hobbs, W.R, Rall, T.W., and Verdoorn, T.A., Hypnotics and Sedatives; Ethanol In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc., 1996, pp. 364-367.

• ³Sno E. White The Preoperative Visit and Premedication in Clinical Anesthesia Practice pp.  576-583 (Robert Kirby and Nikolaus Gravenstein, eds) W.B.  Saunders Co., Philadelphia, 1994

• ⁴John R. Moyers and Carla M. Vincent Preoperative Medication in Clinical Anethesia, 4th edition (Paul G. Barash, Bruce. F. Cullen, Robert K. Stoelting, eds) Lippincott Williams and Wilkins, Philadelphia, PA, pp 551-565, 2001

• ⁵Michael Ross and Susan Dufel "Torticollis" emedicine, http://www.emedicine.com/emerg/topic597.htm