1. Anti-Emetic Drugs

2. Anti-emetics are used in treatment of nausea and
vomiting which may be caused by:
1. GIT diseases.
2. Pregnancy.
3. Motion sickness, labyrinthitis, Meniere's disease.
4. Severe pain as acute myocardial infarction and renal colic.
5. Stress and psychological disorders.
6. Drugs

3. Drugs that cause emesis.
➢Opioid analgesics: morphine, fentanyl, methadone…
➢Cardiac glycosides.
➢Theophylline and Aminophylline.
➢Estrogen (oral contraceptives).
➢D2-Agonists as L-dopa and Bromocriptine (antiparkinsonian drugs).
➢Cancer chemotherapy and radiotherapy

4. Classification of Anti-emetic Drugs:
1.D2-Antagonists.
2.5-HT3-Antagonists e.g. Ondansetron and Granisetron.
3.Anti-muscarinic drugs(Anti-cholinergic): Hyoscine.
4.Antihistaminics: only sedating (1st generation) antihistaminics
have antiemetic action.
5. Other Anti-emetics.

5. Other Anti-emetics
1- Pyridoxine (vitamin B6): useful in vomiting of pregnancy.
2- Glucocorticoids: as dexamethasone in vomiting due to cancer chemotherapy.
(It may be combined with B6 =Cortigen B6®).
3- Neurokinin receptor blockers: e.g. Aprepitant used to inhibit cancer
chemotherapy-induced vomiting (it blocks neurokinin receptors in vomiting
center which are stimulated by substance P causing vomiting).

6. D2- Antagonists:
1. Metoclopramide (Primperan):
Mechanism of action:
Central action: Blocks D2-receptors in CTZ → anti-emetic except in motion sickness.
Peripheral action: Stimulates (modulates) 5-HT4 receptors in GIT → release of acetylcholine from
cholinergic neurons → Prokinetic action: stimulates gastric motility and emptying, increases tone of
lower esophageal sphincter (LES), and stimulates peristalsis, This action is blocked by atropine.

7. Pharmacological actions:
1. Anti-emetic except in motion sickness.
2. Prokinetic action.
3. Blocks D2-receptors in basal ganglia → extrapyramidal effects and Parkinsonism.
4. Blocks D2-receptors in hypothalamus → Hyperprolactinemia.
Metoclopramide has no action on GIT secretions (no atropine-like action)

8. Uses:
1) Anti-emetic in cancer chemotherapy and radiotherapy, post-operative vomiting, hiccup but
not effective in motion sickness.
2) Prokinetic in:
➢GERD.
➢Gastric hypomotility as in diabetic gastroparesis.
➢Before emergency operations (anaesthesia may cause vomiting and aspiration pneumonia).
3) Treatment of hiccough (hiccup).

9. Adverse effects:
1. Extrapyramidal manifestations as akathisia- dystonia- tremors-and Parkinsonism.
2. Hyperprolactinemia (gynecomastia, impotence, and loss of libido in males, galactorrhea-
amenorrhea and menstrual disturbances in females).
3. Dizziness, restlessness, insomnia, anxiety, ataxia.
4. Increases absorption of concomitantly administered drugs except digoxin (being slowly
disintegrated in the stomach).

10. 2. Domperidone (Motilium – Motinorm):
Mechanism of action:
Central action:As metoclopramide; it blocks D2 receptors in CTZ, but poorly penetrates
BBB and does not markedly block D2-receptors in basal ganglia, so it is much less liable to
cause extrapyramidal manifestations but still can cause hyperprolactinemia.
Peripheral action: blocks α1 receptors in the stomach leading to stimulation of gastric
motility and emptying (prokinetic action).
This action is not blocked by atropine.

11. 5-HT3-Antagonists
e.g. Ondansetron and Granisetron given orally or IV to treat nausea and vomiting induced by cancer
chemotherapy.
3. Anti-muscarinic drugs(Anti-cholinergic):
Hyoscine (drug of choice in prophylaxis of motion sickness-especially air sickness due to short duration-
given as transdermal patch).
Adverse effects: tachycardia-dry mouth-constipation-urine retention-blurred vision, xerophthalmia, and
elevation of IOP.
Contraindications: Glaucoma- Benign Prostatic Hyperplasia (BPH).

12. 4. Antihistaminics:
only sedating (1st generation) antihistaminics have antiemetic action by blocking H1 and muscarinic
receptors in vomiting centre and vestibular system, and are accordingly useful in motion sickness -
especially sea sickness due to their long duration-, e.g. Diphenhydramine, Dimenhydrinate, Promethazine
Cyclizine, and Meclizine.
Adverse effects:
atropine-like + sedation and drowsiness.
Contraindications:
as atropine + car drivers.

13. Prokinetic Drugs
1. Metoclopramide (Primperan) and Domperidone (Motilium –Motinorm).
2. Itopride and Mosapride:
➢Prokinetic by activation of 5-HT4 receptors leading to release of acetylcholine
and stimulation of gastric motility and emptying.
No D2 blocking action and accordingly it is not an antiemetic.
➢Used in treatment of GERD in addition to PPIs.
4. Muscarinic agonists (parasympathomimetics): as bethanechol used in non-
obstructive paralytic ileus.
➢Unlike metoclopramide; bethanechol increases GIT secretions as well as
motility.
5. Erythromycin: has "motilin-like action" as it stimulates motilin receptors in
GIT. It is used in diabetic gastroparesis.

14. Special populations
• Meclizine + vitamin B6 ---------- Drug of choice for management of
nausea and vomiting during pregnancy.
• Infants < 6 months : vitamin B6+corticosteroids (Cortigen B6).
• Infants > 6 months : Ondansetron.