Pharm: Tx of Nausea and Vomiting

Question 1

what causes N/V?

Answer 1

• chemo/radiation (CINV, RINV)
• postoperative (PONV)
• pregnancy (NVP)
• vestibular dysfunction
• GI obstruction/dysmotility

Question 2

where are N/V receptors in the body?

what are they?

Answer 2

-in GI tract and the brain
5-HT3 (serotonin type 3)
H1 (histamine type 1)
M1 (muscarinic type 1)
D2 (dopamine type 2)
NK1 (neurokinin 1/substance P)

Question 3

5HT3 receptor antagonists

Answer 3

• dolasetron
• granisetron
• ondansetron
• palonosetron
• alosetron (IBS)

MOA: strong antiemetic for CINV, blocks 5HT3 receptors at vagal nerve terminals, blocks serotonin receptor activation after release of serotonin

Question 4

Other 5HT3 Info

Answer 4

AE: Headache, constipation, diarrhea (serotonin syndrome)

• dose dependent risk of QT prolongation/torsades (dont take with anytiarrhythmics)
• most have short 1/2 lives, except palonosetron and granisetron

Question 5

NK1 receptor antagonists

Answer 5

-aprepitant
-fosaprepitant
-netupitant
-fosnetupitant
-rolapitant
MOA: moderate antiemetic, peripheral blockade of NK1 receptors located on vagal terminals ingut
-used for CONV (used in combo with glucocorticoid and 5HT3
-aprepitant given 3 hours before surgery to prevent PONV

Question 6

Other NK1 info

Answer 6

AE: dizzy, fatigue, dyspepsia, constipation, diarrhea

• are mild inhibitors of some CYP450
• netupitant/rolapitant have moderate major metabolites, longer half life

Question 7

H1 receptor antagonist

Answer 7

-diphenhydramine
-dimenhydrinate
-hydroxyzine
-promethazine
-meclizine
-cyclizone
-doxylamine (initial therapy for NVP)
MOA: weak antiemetic, originally made for other uses, blocks H1 receptors in VC and vestibular systems, used for motion sickness, idiopathic mild NV, PONV, NVP, CINV, RINV

Question 8

Other H1 info

Answer 8

AE: (classic anticholinergic effects) drowsy, dry mouth, constipation, urinary retention, blurred vision, decrease BP

Question 9

D2 receptor antagonist

Answer 9

-phenothiazines (chlorpromazine, perphenazine, prochlorperazine), and metoclopramide
MOA: weak antiemetic, metoclopramide stimulates ACh actions in GI and enhances GI motility and increases LES tone (used for gastroparesis/dysmotility), others used for mild idiopathic NV, PONV, NVP, RINV, CINV
**originally used as antipsychotics

Question 10

Other D2 info

Answer 10

AE: anticholinergic effects, with larger psych doses, arrhythmias possible

Question 11

M1 Receptor Blocker

Answer 11

-scopolamine (transdermal patch placed behind ear)
MOA: weak antiemetic, mainly used for motion sickness, blockade of ACh stimulated muscarinic receptors, significant anticholinergic effects

Question 12

Cannabinoid Receptor Antagonist

Answer 12

-dronabinol (class 3)- 1st pass metabolism into 1 active metabolite
-nabilone (class 2)- metabolized into several active metabolites
*are synthetic
MOA: strong antiemetic agents, used for tx resistance with CINV (also stimulates appetite), leads to decreased excitability of neurons, short onset and long lasting
AE:euphoria, irritability, vertigo, sedation, dry mouth, impaired cognition, dont take with other CNS depressants

Question 13

High-Emetic Regimen

Answer 13

(3 drug regimen, 1 day prior to chemo and 3 days after)

1. NK1 receptor antagonist
2. 5-HT3 receptor antagonist
3. corticosteroid (dexomethasone)

Question 14

Moderate-Emetic Regimen

Answer 14

(2 drug regimen, 1 day prior to chemo and 2 days after)\

1. 5-HT3 receptor antagonist
2. corticosteroid (dexomethasone)

Question 15

Low-Emetic Regimen

Answer 15

(1 drug regimen, given day of, prior to treatment)
1. corticosteroid (dexomethasone) or 5-HT3 receptor antagonist or metoclopramide or prochlorperazine (give one of these!)

Question 16

how to treat breakthrough/anticipatory N/V

Answer 16

• focus on prevention
• give a drug from a different class to see if it will work better
• multiclass/combination therapy is best for moderate/high emetics