B.24

Question 1

Antiemetic drugs. Prokinetic agents

Answer 1

1. DA-antagonists: Droperidol, Metoclopramide
2. Antihistamine: Dimenhydrinate
3. Serotonine antagonists: Ondansetron, Palonosetron
4. NK1-R antagonist: (fos)aprepitant
5. Some cannabinoids: Nabilone, Dronabinole
6. TCA and SSRIs: TCAs: Clomipramin, Amitriptyline; SSRIs: Fluoxetine, (es)Citalopram, Sertraline

Question 2

Dimenhydrinate

Answer 2

MOA: 1st generation antihistamine, H1-R antagonist; IND: Vestibular system related nausea/vomiting;
SEs: sedation

Question 3

Droperidol

Answer 3

MOA: Dopamin receptor antagonist (D2R ant.), and α1-R antagonist;
IND: not widely used antiemetic;
SEs: QT prolongation (→TdP), extrapyramidal motor symptoms (with chronic use), hyperprolacinemia (with chronic use)

Question 4

Metoclopramide

Answer 4

MOA: D2-R antagonist, 5HT3-R antagonist (↑gastric emptying-most important effect!, central antiemetic mechanism of D2 via the area postrema);
Kinetics: p.o/i.v adm.;
SEs: QT prolongation, hyperprolactinemia and extrapyramidal symptoms (if therapy is longer than 12 weeks);
IND: Enhances gastric emptying (→gastroparesis in DM OR in abdominal cause of vomiting and nausea), Upper GI bleeding (to make it more visible in endoscopy)

Question 5

Ondansetron, Palonosetron

Answer 5

MOA: 5HT3-R antagonists (Ondansetron- 1st generation, Palonosetron- 2nd generation);
Kinetics: p.o/i.v adm., Hepatic metabolism (CYP3A4, CYP2D6, CYP1A2),
-Palonosetron T1/2:40h;
IND: chemo/radiotherapy induced emesis/nausea, GI neuroendocrine tumors/carcinoid tumors causing nausea, Severe nausea/vomiting by any other reason; SEs: QT prolongation, headache, constipation, serotonin syndrome

Question 6

(fos)aprepitant

Answer 6

MOA: NK1-R antagonist (competitive inhibitor of substance P);
Kinetics: aprepitant p.o adm, fosaprepitant i.v adm., Hepatic metabolism (CYP3A4), weak CYP inhibition; IND: oncotherapy-induced nausea/vomiting (severe)→usually in combination with 5HT antagonists and Glucocorticoids;
SEs: Dizziness, constipation, QT prolongation

Question 7

some cannabinoids

Answer 7

NAMES: Nabilone, Dronabilone;
MOA: CB1/2-R agonists;
SEs: Dizziness, xerosthomia, sedation (weed-like sedation), euphoria (weed-like), increased apetite;
IND: as adjunctive antiemetic during chemo/radiotherapy

Question 8

Emetins

Answer 8

Ipechachuana derivatives, can be cardiotoxic in high doses

Question 9

Apoomorphine

Answer 9

MOA: strong and potent D2-R agonist; SEs: intense nausea & vomiting

Question 10

Not a drug but used for emesis

Answer 10

warm salty tap water→they are more emetogenic

Question 11

On which area does antiemetic drugs work

Answer 11

Area postrema (anatomical location) / CTZ (functional terminology)