Anti-nausea and anti-emetic drugs

Question 1

What are the six different families of anti-nausea and anti-emetic drugs?

Answer 1

serotonin receptor antagonists, neurokinin receptor antagonists, histamine receptor antagonists, dopamine receptor antagonists, muscarinic receptor antagonists, and cannabinoid receptor agonist

Question 2

what are the 4 drugs in the serotonin receptor antagonist family?

Answer 2

Dolasetron, Granisetron, Ondansetron, and Palonosetron

Question 3

what are the 5 drugs in the Neurokinin receptor antagonist family?

Answer 3

Aprepitant, fosaprepitant, netupitant, fosnetupitant, rolapitant

Question 4

what are the 6 drugs in the histamine receptor antagonist family?

Answer 4

Diphenhydramine, dimenhydrinate, hydroxyzine, promethazine, meclizine, and cyclizine

Question 5

what are the 4 drugs in the dopamine receptor antagonist family?

Answer 5

prochlorperazine, olanzapine, metoclopramide, amisulpride

Question 6

what is the drug in the muscarinic receptor antagonist family?

Answer 6

scopolamine

Question 7

what are the 2 drugs in the cannabinoid (CB) receptor agonist family?

Answer 7

dronabinol and nabilone

Question 8

what is the MOA of the serotonin (5-HT3) receptor antagonists?

Answer 8

they block serotonin type-3 receptors at vagal nerve terminals and block signal transmission to CTZ

Question 9

what are the therapeutic uses of serotonin (5-HT3) receptor antagonists?

Answer 9

there are multiple- this is our go to first line agent

Question 10

what are the common adverse effects associated with serotonin (5-HT3) receptor antagonists?

Answer 10

a few mild to moderate CNS and GI effects

Question 11

what is the more worrisome adverse effect associated with serotonin (5-HT3) receptor antagonists?

Answer 11

dose-dependent QT prolongation (Torsade’s)

Question 12

which serotonin receptor antagonist has the highest risk of dose dependent QT prolongation and is therefore the most deadly?

Answer 12

Dolasetron

Question 13

what are the pharmacokinetics like of the serotonin receptor antagonists?

Answer 13

all agents have short half lives except 2

Question 14

what 2 serotonin receptor antagonists have longer half lives?

Answer 14

Palonosetron and sustained-release formulation of Granisetron

Question 15

the long half life of Palonosetron and sustained-release formulation of Granisetron make them effective for what?

Answer 15

delayed chemotherapy induced nausea and vomiting (CINV) as a single dose

Question 16

what are the drug interactions associated with serotonin receptor antagonists?

Answer 16

interact with antiarrhythmics/ QT- prolonging agents

Question 17

what is the MOA of neurokinin-1 receptor (substance P) antagonists?

Answer 17

blockade of neurokinin (substance P) receptors in CTZ/ VC; peripheral blockade of NK1 receptors located on vagal terminals in gut possibly

Question 18

what are the therapeutic uses of the neurokinin-1 receptor (substance P) antagonists?

Answer 18

chemotherapy-induced N/V; most effective when used in combination with other anti-emetic agents–> so not alone

Question 19

what are the adverse effects associated with the neurokinin-1 receptor (substance P) antagonists?

Answer 19

a few mild to moderate CNS and GI effects

Question 20

which two drugs in the neurokinin-1 receptor (substance P) antagonist family hace moderate to major active metabolites? and what does this mean?

Answer 20

Netupitant/ Rolapitant; they have longer half lives; so your patients feel a prolonged duration of action

Question 21

if a patient presents with pregnancy, nausea, and vomiting, what is a great first line drug?

Answer 21

Doxylamine with pyridoxine (vitamin B6)

Question 22

what is doxylamine?

Answer 22

an antihistamine

Question 23

what is the MOA of the histamine receptor antagonists?

Answer 23

blockade of histamine 1 receptors in VC and vestibular system

Question 24

what are the adverse effects associated with histamine receptor antagonists?

Answer 24

classic cholinergic effects

Question 25

what are the classic cholinergic effects? (6)

Answer 25

drowsiness(CNS depression), dry mouth, constipation, urinary retention, blurred vision, decreased BP

Question 26

what are the 2 drugs in the histamine receptor antagonist family that are used for motion sickness/vertigo?

Answer 26

meclizine and cyclizine

Question 27

what is the MOA of Dopamine receptor antagonists?

Answer 27

blockade of dopamine 2 receptors in CTZ

Question 28

what are the MOAs of metoclopramide?

Answer 28

it acts as a blockade of dopamine 2 receptors in the CTZ but also stimulates ACh actions in the GI, enhancing GI motility and increases LES tone

Question 29

what is metoclopramide used for?

Answer 29

dysmotility use; so in a diabetic patient who isn't moving their GI things along fast enough

Question 30

what is amisulpride used for?

Answer 30

it is newer; it is ONLY used for prevention/treatment of post operative n/v when all other therapies have failed

Question 31

what are the adverse effects for all of the dopamine receptor antagonists?

Answer 31

drowsiness

Question 32

what are the adverse effects for prochlorperazine?

Answer 32

Dry mouth, constipation, urinary retention, blurred vision

Question 33

what are the adverse effects for amisulpride?

Answer 33

hypokalemia, hyperprolactinemia, chills

Question 34

what is scopolamine?

Answer 34

A transderm Scop (patch; worn for 72 hours)

Question 35

when is scopolamine most commonly used?

Answer 35

for motion sickness; also used in end-of-life care for excessive secretions

Question 36

what is the MOA of muscarinic receptor antagonists?

Answer 36

block acetylcholine-stimulated muscarinic receptors in neural pathways from the vestibular nuclei in inner ear to brain stem and from reticular formation to VC; significant anticholinergic properties

Question 37

what are the adverse effects associated with the muscarinic receptor antagonists?

Answer 37

the classic anticholinergic effects

Question 38

what are cannabinoids?

Answer 38

synthetic preparations of cannabinol (THC in marijuana); synthetic cannabinoids are FDA-scheduled (controlled) medications (abuse potential)

Question 39

what is the MOA of cannabinoids?

Answer 39

stimulation of cannabinoid receptors; exert signal transduction effects through G-protein coupled receptors resulting in decreased excitability of neurons- minimizing serotonin release from vagal afferent terminals

Question 40

what are the therapeutic uses of cannabinoids?

Answer 40

chemotherapy-induced n/v; due to FDA scheduling, these agents are often reserved for treatment-resistant clinical scenarios; appetite stimulation in select (anorexic) patients due to severe disease (eg cancer or AIDS)

Question 41

chemotherapy-induced n/v: acute n/v timing?

Answer 41

occurring less than 24 hours after chemo given

Question 42

chemotherapy-induced n/v: chronic n/v timing?

Answer 42

occurring more than 24 hours after chemo is given

Question 43

chemotherapy-induced n/v: anticipatory n/v timing?

Answer 43

occurring before chemo given, customarily in non-treatment naive patients

Question 44

a high-emetogenic regimen is how many drugs?

Answer 44

4

Question 45

what anti-nausea and anti-emetic drugs are involved in a high-emetogenic regimen?

Answer 45

1. D2 antagonist (olanzapine) 2. NK1 receptor antagonist 3. 5-HT3 receptor antagonist 4. Corticosteroid (dexamethasone)

Question 46

how do you treat a high-emetogenic regimen?

Answer 46

give treatment day of (prior to) chemotherapy, then a 3-drug treatment for 3 days after chemotherapy

Question 47

what happens if your treatment for a high-emetogenic regimen is resistant?

Answer 47

you can add a cannabinoid (so now 5 drugs)

Question 48

a moderate-emetogenic regimen has how many drugs?

Answer 48

3

Question 49

what anti-nausea and anti-emetic drugs are involved in a moderate-emetogenic regimen?

Answer 49

1. NK1 receptor antagonist 2. 5-HT3 receptor antagonist 3. Corticosteroid (dexamethasone)

Question 50

how do you treat a moderate-emetogenic regimen?

Answer 50

give treatment regimen day of (prior to) chemotherapy, then 2-drug treatment for 2 days after chemotherapy

Question 51

what happens if your treatment for a moderate-emetogenic regimen is resistant?

Answer 51

you can add D2 antagonist (olansapine) (so now 4 drugs)

Question 52

a low-emetogenic regimen has how many drugs?

Answer 52

1

Question 53

how do you treat a low-emetogenic regimen?

Answer 53

give treatment regimen day of (prior to) chemotherapy; may repeat daily for multi-day anticancer therapy

Question 54

a minimal-emetogenic regimen has how many drugs?

Answer 54

0-drug regimen; no routine prophylaxis therapy recommended

Question 55

what 3 drugs can treat motion sickness?

Answer 55

scopolamine (patch), dimenhydrinate, or meclizine

Question 56

what 2 drugs can treat vertigo?

Answer 56

meclizine or cyclizine

Question 57

what drug can treat diabetic gastroparesis?

Answer 57

metoclopramide