N/V tx

Question 1

receptors in area postrema

chemoreceptor trigger zone

Answer 1

D2
NK1
5HT3

Question 2

receptors in nucleus tractus solitarius

vomiting center

Answer 2

H1
M1
NK1
5-HT3

Question 3

receptors in stomach

Answer 3

chemoreceptors
mechanoreceptors
5-HT3
signals transmitted to vomiting center via IX or X

Question 4

receptors in vestibular system

Answer 4

M1

maybe H1

Question 5

5-HT3 receptor antagonists

Answer 5

Dolasetron
granisetron
ondansetron (Zofran)
palonosetron 
alosetron (only for IBS-D)
Block 5-HT3 receptor at vagal nerve

Question 6

Therapeutic use of 5-HT3 antagonists

Answer 6

CINV
RINV
post operative N/V
Pregnancy N/V

Question 7

adverse effects of 5-HT3 antagonists

Answer 7

QT prolongation and Torade’s
caution when used with antiarrhythmics
- dolasetron very high risk!
headache and constipation

Question 8

Pharmacokinetics of 5-HT3 antagonists

Answer 8

Palonosetron and Granisetron have long half-lives
effective for delayed CINV as single dose
all others have short half-lives

Question 9

Neurokinin (NK1) antagonists

Answer 9

aprepitant
fosaprepitant
netupitant (combo only with palonosetron)
rolapitant

Question 10

MOA of NK1 antagonists

Answer 10

block NK1 receptors in CTZ and vomitting center

Question 11

therapeutic use of NK1 antagonists

Answer 11

CINV in combo with glucocorticoids and 5-HT3 antagonists
prophylaxis of post operative N/V
- only aprepitant and fosaprepitant

Question 12

adverse effects of Nk1 antagonists

Answer 12

GI distress

CNS effects, fatigue

Question 13

pharmacokinetics of NK1 antagonists

Answer 13

netupitant/rolapitant have longer half lives and oral routes

inhibition of several CYP450 enzymes

Question 14

H1 antagonists

Answer 14

diphenhydramine (benadryl)
dimenhydrinate (dramamine)
hydroxyzine
promethazine
meclizine 
cyclizine

Question 15

H1 antagonists MOA

Answer 15

weak antiemetics
useful for post-operative N/V
block H1 receptors in vomiting center and vestibular system
also have central anticholinergic properties!!!

Question 16

Therapeurtic uses of H1 antagonists

Answer 16

mild N/V 
PONV
pregnancy N/V (doxylamine/B6)
motion sickness (meclizine and cyclizine) 
CINV
RINV

Question 17

adverse effects of H1 antagonists

Answer 17

anticholinergic effects!!!

Question 18

pharmacokinetics of H1 antagonists

Answer 18

hydroxyzine has long half life

interactions include other anticholinergic agents pt may be on

Question 19

D2 antagonists

Answer 19

Phenothiazine's 
- chlorpromazine
- perphenazine
- prochlorperazine 
metoclopramide

Question 20

D2 antagonists effects

Answer 20

weak to moderate antiemetic
block D2 in cortex
metoclopramide stimulates Ach actions in GI enhancing motility

Question 21

Therapeutic use of D2 antagonists

Answer 21

idiopathic, mild N/V (infections, opiates, migraines)
Metoclopramide for gastroparesis 
PONV
NVP 
CINV and RINV in combo with other agents

Question 22

Adverse effects of D2 antagonists

Answer 22

classic anticholinergic effects

arrhythmias possible with larger doses

Question 23

interactions of D2 antagonists

Answer 23

other anticholinergic agents
antiarrhythmics (QT prolongation)
anti-hypertensives

Question 24

M1 antagonists

Answer 24

scopolamine
weak antiemetic for motion sickness
block ach signaling from vestibular nuclei to VC
adverse effects include classic anticholinergic effects

Question 25

cannabinoid agonists

Answer 25

dronabinol (CIII) nabilone (CII) strong antiemetics for treatment resistant CINV stimulates central CB1 and peripheral CB2 receptors in VC and CTZ reduces 5-HT3 release from vagal afferents also increases appetite in anorexic cancer or AIDS pts short onset time and long duration of action

Question 26

adverse affects of cannabinoid agonists

Answer 26

``` irritability vertigo sedation impaired cognition xerostomia sympathomimetic ```

Question 27

interactions of cannabinoid agonists

Answer 27

caution with CNS depressants, CV agents, and sympathomimetics

Question 28

High emetogenic regimen for CINV

Answer 28

``` NK1 antagonist (aprepitant) 5-HT3 antagonist Dexamethasone give 1 day prior and 3 days after chemo add cannabinoid in treatment resistant ```

Question 29

Moderate emetogenic regimen for CINV

Answer 29

``` 5-HT3 antagonist (palonosetran/granisetran) dexamethasone give day before and 2 days after chemo add NK1 antagonist if necessary add cannabinoid in treatment resistant ```

Question 30

Low emetogenic regimen for CINV

Answer 30

``` Dexamethasone or 5-HT3 antagonist or metoclopramide or prochlorperazine give day prior to chemo ```

Question 31

Pregnancy induced N/V stepped therapy

Answer 31

B6 + doxylamine (H1) or 5-HT3 antagonist D1 antagonist Steroid or different D1 antagonist