Serotonin Antagonists

Question 1

What is the most common use for serotonin

antagonists?

Answer 1

They are most commonly used as prophylactic antiemetics.
Depending upon the specific serotonin receptor they
antagonize, however, serotonin antagonists can be used to
treat nausea and vomiting, carcinoid syndrome,
gastroesophageal reflux, and irritable bowel syndrome.
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1278-
1279.

Question 2

How is serotonin metabolized?

Answer 2

Serotonin is metabolized by monoamine oxidase into 5-
hydroxyindoleacetic acid
Katzung BG, Masters, SB, & Trevor AJ. Basic and Clinical
Pharmacology. 12th ed. New York: McGraw-Hill; 2012: 282.

Question 3

What is the principal use for the serotonin

antagonist, cyproheptadine?

Answer 3

Cyproheptadine is a 5-HT2 receptor antagonist that also has
Histamine-1 receptor antagonist properties. It is used to treat
the smooth muscle dysfunction associated with carcinoid
syndrome.
Katzung BG, Masters, SB, & Trevor AJ. Basic and Clinical
Pharmacology. 12th ed. New York: McGraw-Hill; 2012: 286.

Question 4

What is the prototypical 5-HT3 serotonin antagonist?

Answer 4

Ondansetron
Katzung BG, Masters, SB, & Trevor AJ. Basic and Clinical
Pharmacology. 12th ed. New York: McGraw-Hill; 2012: 287.

Question 5

How do 5-HT3 receptor antagonists prevent nausea?

Answer 5

5-HT3 receptor antagonists exert their antiemetic effects by
blocking 5-HT3 receptors centrally in the vomiting and
chemoreceptor trigger zone as well as peripherally in the
intestinal vagal and spinal afferent nerves.
Katzung BG, Masters, SB, & Trevor AJ. Basic and Clinical
Pharmacology. 12th ed. New York: McGraw-Hill; 2012: 1098.

Question 6

What is the dose of ondansetron in pediatric patients
for the treatment and prophylaxis of postoperative
vomiting?

Answer 6

0.1 mg/kg
Longnecker DE, Newman MF, Brown DL, Zapol WM.
Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012: 1192.

Question 7

How is ondansetron metabolized?

Answer 7

Ondansetron undergoes extensive metabolism by the liver via
hydroxylation and conjugation by the cytochrome P-450
pathway. As a result, the elimination half-life is prolonged in
patients with liver failure and the dosage may need to be
reduced.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 285.

Question 8

What are the side effects of 5-HT3 receptor

antagonists?

Answer 8

5-HT3 receptor antagonists exhibit no serious side effects, even
in large doses. The most common side effects are headache
and a slight prolongation of the QT interval in some
circumstances.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 285.

Question 9

Are the serotonin receptors coupled to G-proteins or

are they ion channels?

Answer 9

All of the serotonin receptors are G-protein-coupled and affect
either adenylyl cyclase or phospholipase C with the exception of
the 5-HT3 receptor which is an ion channel.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 284.