Lower GI Pharm

Question 1

Serotonin (5-Hydroxytryptamine) Receptor Antagonists

Answer 1

Ondansetron (Zofran)

Block of serotonin (5-HT3) receptors at chemoreceptor trigger zone (CTZ in CNS), solitary tract nucleus, and on visceral afferents (GI tract)

Side effects: CONSTIPATION, QT prolongation so caution if underlying heart condition-hypomagnesemia-hypokalemia

Question 2

Dopamine Receptor Antagonists

Answer 2

Metoclopramide, Prochlorperazine

Blockade of dopamine receptors in CTZ

Side effects: Extrapyramidal symptoms

Question 3

Metoclopramide

Answer 3

D2 antagonist

used for n/v of chemotherapy

Question 4

Prochlorperazine

Answer 4

D2 antagonist

less effective against emetic stimuli in gut, but block of M and H1 receptors increases utility in nausea with motion sickness

Blocking alpha 1 receptors can cause hypotension

Question 5

Antihistamines

Answer 5

meclizine, promethazine, diphenhydramine

First generation agents with good CNS penetration and additional muscarinic receptor blocking actions

Used for motion sickness and less-severe post-op n/v

Question 6

Anticholinergic agents

Answer 6

scopolamine

Usually transdermal

Primary use is prevention and treatment of motion sickness; some efficacy in post-operative nausea and vomiting

Question 7

Dronabinol

Answer 7

Mechanism of action: Unknown, probably related to stimulation of CB1 cannabinoid receptors on neurons in and around area postrema.

Question 8

Substance P Receptor Antagonists

Answer 8

Block the actions of the neurotransmitter substance P at the neurokinin 1 (NK1) receptor that are mediated via vagal afferent fibers to the solitary tract nucleus and the area postrema.

Question 9

Anti-inflammatory glucocorticoids

Answer 9

Possible anti-emetic action via mechanism to suppress peritumoral inflammation and prostaglandin production

Question 10

Benzodiazepines

Answer 10

Sedative, anti-anxiety, and amnestic properties can reduce the anticipatory component of nausea and vomiting

Question 11

Treatment of Nausea and Vomiting of Pregnancy

Answer 11

Ginger (improved nausea compared to placebo but did not decrease episodes of vomiting)

Pyridoxine (Reasonable first-line treatment that is effective in mild to moderate nausea, but no effect on vomiting); Most often used in combination with doxylamine

H1 antagonists (Doxylamine, diphenhydramine, dimenhydrinate, and meclizine): . Acts on the vestibular system to decrease stimulation of the vomiting center

Dopamine antagonists (Second line: Prochlorperazine, Metoclopramide for hyperemesis, Promethazine)

5HT3 antagonists. Oral-IV routes Ondansetron most commonly used agent - greater efficacy in reducing both nausea and vomiting than pyridoxine-doxylamine

Question 12

Side effects of Metoclopramide

Answer 12

movement disorders

Question 13

Side effects of Promethazine

Answer 13

Sedation and dystonic reactions