A-32. Antiemetic drugs. Prokinetic agents. Drugs for irritable bowel disease (IBS)

Question 1

What are the main groups of Antiemetic drugs?

Answer 1

H1 antagonists
Antimuscarinics
D2 antagonists
5HT3 antagonists
Neurokinin-1 receptor antagonists:
CB1 agonists
Others
(Dexamethasone, Benzodiazepines)
Vomit Inducers
(Ipecacuana + Apomorphine)

Question 2

Brief physiology of vomiting?

Answer 2

● Vestibular system - responsible for motion sickness; H1 and M1
● Chemoreceptor Trigger Zone - in area postrema (IV ventricle); D2, NK1 and chemoreceptors; fenestrated capillaries allow noxious stimuli through BBB for detection
● Vomiting Center - solitary tract nucleus (medulla); H1, NK1 and NK1
● GI tract / Heart - mechano-/chemoreceptors and 5HT3
● Higher CNS input to the CTZ and VC can induce / inhibit vomiting

Question 3

H1 antagonists drugs, names?

Answer 3

Diphenhydramine, Dimenhydrinate and Promethazine

Question 4

H1 antagonists drugs, MOA?

Answer 4

H1 blockade in vestibular system and vomiting center (solitary nucleus) → for motion sickness
○ as 1st gen. antihistamines, these drugs cross the BBB; also block M1

Question 5

H1 antagonists drugs, side effects?

Answer 5

drowsiness, cognitive dysfunction and antimuscarinic effects

Question 6

Muscarinic agonist. Drug and MOA?

Answer 6

● Scopolamine - short DOA → extended-release transdermal patch for motion sickness prophylaxis

muscarinic blockade (M1) in the vestibular system → motion sickness only

Question 7

D2 antagonists, MOA and drugs?

Answer 7

D2 blockade in the area postrema (CTZ)

Chloropromazine, Thiethylperazine, Metoclopramide, Domperidone, Haloperidol

Question 8

Metoclopramide, Side effect and uses?

Answer 8

also a 5-HT3 atg and 5-HT4 ag (pro-kinetic effect)
● weak central D2 atg side effects; also available as suppository
● also useful for post-surgical delayed gastric emptying + diabetic gastroparesis
● CI in small bowel obstruction
● may cause diarrhea, drowsiness, depression, EPS, NMS, ↑ PRL and long QT

Question 9

5HT-3 Antagonists. Drugs, MOA and Side effects?

Answer 9

Ondansetron, Granisetron and Palonosetron

5-HT3 blockade in GI tract → good for chemo-induced or post-op vomiting

Side effects: constipation, HA / dizziness, long QT and serotonin syndrome

Question 10

Neurokinin 1 receptor antagonists. Drugs, MOA?

Answer 10

Aprepitant and Fosaprepitant

NK1 blockade in the area postrema (CTZ) and solitary nucleus (VC) → for chemo-induced vomiting
○ NK1-R is activated by substance P
○ often combined with 5-HT3 atg

Question 11

CB1 antagonists. Drugs, MOA, Side effects?

Answer 11

○ Nabilone - for chemo nausea + neuropathic pain
○ Dronabinol (synthetic THC) - for nausea in chemo + AIDS patients

CB1 agonism → unclear mechanisms leading to ↓ nausea and ↑ appetite

Side effects: euphoria, hallucinations, tachycardia

Question 12

3 anti obesity drugs, plus short info about them?

Answer 12

Orlistat - inhibits pancreatic lipase → ↓ lipid absorption; only drug still used

Sibutramine - amphetamine derivative; used to ↓ appetite; withdrawn due to sfx

Rimonabant - cannabinoid receptor atg → ↓ appetite; withdrawn due to depression / suicidality sfx

Question 13

Prokinetic agents. Main drugs and their MOA?

Answer 13

Neostigmine (ACh-ase inhibitor)
Bethanechol (M-selective agonist)
(Indications:
○ Post-op - for ileus; CI in obstructive ileus!)

Metoclopramide / Domperidone - modulate cholinergic neuron function in GI tract → ↑ motility; 5-HT4 agonism of metoclopramide is prokinetic

Prucalopride - 5-HT4 agonist for ↑ motility

Cisapride / Tegaserod - withdrawn due to cardiotoxicity; 5-HT4 agonists

Erythromycin - has motilin-like metabolite which increases motility