A/36. Antiemetic drugs. Prokinetic agents. Drugs for irritable bowel disease (IBS).

Question 1

drugs need to know in this topic

Answer 1

dimenhydrinate

droperidol

metoclopramide

ondansetron

palonosetron

aprepitant

some cannabinoids

Question 2

Emetic mechanism

Answer 2

Emetic pathways represent a complex mechanism with a final effect on the vomiting center.
Involve interaction with multiple mediators, including Ach, dopamine, 5-HT, histamine, endogenous opioids, endogenous cannabinoids, and neurokinins.

1. Anti-cholinergics

2. H1 anti histamin

3. D3 blockers

4. 5HT3 antagonists

5. Prokinetic drugs

6. NK1 receptors

7. Adjuvant antiemetics

Question 3

Scopolamine

Answer 3

Antimuscarinic agents: Inhibit muscarinic receptors in the vomiting center → inhibitory effect on emetic pathways

Transdermal patch

1. Motion sickness (vestibular nausea)

Question 4

Dimenhydrinate

Answer 4

• *H1 histamine blockers**
  1. In addition to their central and peripheral H1 blockade effect, exert muscarinic blockade
  2. Inhibition of muscarinic receptors in the vomiting center → inhibitory effect on emetic pathways

Combination drug of diphenhydramine and theophylline derivative

• *(intend to reduce sedative effect and abuse liability due to H1 blockade**)
  1. Oral, parenteral
  2. Metabolism by hepatic P450 enzymes

1. Motion sickness, Meniere’s disease (vestibular nausea)
2. Antiemetic (chemotherapy-induced vomiting)
   * *Side effects:**
3. CNS effects
4. Atropine-like effects
5. α-blockade (orthostatic hypotension)
6. Abuse liability

Question 5

Metoclopramide

Answer 5

• *D2 dopamine receptor blockers**
  1. Central effects → inhibition of dopamine D2-receptor in the chemoreceptor trigger zone (area postrema) results in potent anti-nausea and antiemetic action
  2. Peripheral effects → in the GI, dopamine acts as an inhibitor of Ach release; reducing this inhibitory effect results in prokinetic effect (mediated by Ach)

Oral, parenteral

1. Prokinetic effect (gastric paresis) at low doses
2. Anti-emetic effect (achieved only at high doses)

Side effects:
1. CNS effects: restlessness, drowsiness, insomnia, anxiety
2. Extrapyramidal symptoms (drug-induced parkinsonism)
3. Hyperprolactinemia (PRL ↑) – galactorrhea, gynecomastia,
impotence, menstrual disorders

Question 6

Droperidol

Answer 6

Antipsychotic agent with general properties similar to those of

• *D2 dopamine receptor blockers**
  1. Central effects → inhibition of dopamine D2-receptor in the chemoreceptor trigger zone (area postrema) results in potent anti-nausea and antiemetic action
  2. Peripheral effects → in the GI, dopamine acts as an inhibitor of Ach release; reducing this inhibitory effect results in prokinetic effect (mediated by Ach)

haloperidol (management of acute psychosis)
1. Oral, parenteral
2. Metabolism by hepatic P450 enzymes

1. Antiemetic (used in surgical and diagnostic procedures)
   * *Side effects:**
2. CNS depression (additive effect)
3. α-blockade (orthostatic hypotension)

Question 7

Ondansetron (oral, IV)
Palonosetron (IV)

Answer 7

5-HT3 receptor blockers

Block serotonin receptors (excitatory) in the chemoreceptor trigger zone and enteric nervous system

1. Highly-potent antiemetic effect
2. Duration of action 3-6 h’
3. Metabolism by hepatic P450 enzymes
   (consider dose reduction in patients with hepatic insufficiency)
4. Chemotherapy-induced nausea and vomiting
5. Post-operative nausea and vomiting
   * *Side effects:**
6. Constipation
7. QT prolongation, arrhythmias
8. Serotonin syn. (milder risk compared to SSRI’s or TCA’s)

Question 8

Aprepitant

Answer 8

• *NK1 receptor antagonists**
  1. Neurokinin receptors in the spinal cord and area postrema – play a role in pain transmission; ligands include neurokinin, substance-P, substance-A, bradykinins
  2. Inhibition of NK1 receptors → reduce pain-induced vomiting

1. Oral
2. Metabolism by hepatic P450 enzymes
3. Inhibitor of cytochrome P450
   (reduces serum half-life of warfarin)
4. Chemotherapy-induced nausea and vomiting
5. Post-operative nausea and vomiting
6. Usually given in combination with
   dexamethasone and palonosetron
   Side effects:
7. Fatigue, dizziness
8. Diarrhea

Question 9

Dronabinol

Answer 9

CB1 cannabinoid agonist

Inhibitory CB receptors, act to inhibit presynaptic release of conventional transmitters, including dopamine

1. Oral
2. Biliary elimination
3. Peak effect in 2-4 h’, psychoactive effects may last up to 6 h’, appetite stimulant
   effects may persist for 24 h’
4. Chemotherapy-induced nausea and vomiting
5. AIDS wasting syndrome (appetite stimulant)
   * *Side effects:**
6. Tachycardia, hypotension
7. Hallucination
8. Reddening of the conjunctiva