Antiemetic drugs

1. Muscarinic blockers Atropine , Hyoscine Antiemetic mechanism: They block M1 receptors in the vestibulocerebellar pathway and CTZ. Uses as antiemetic : Prevention (and less effectively to treat) vomiting due to motion sickness Adverse effects; antimuscarinic side effects

2. H1-blockers Diphenhydramine, Cyclizine, Meclizine Antiemetic mechanism: They block H1 (also M1) receptors in the vestibulocerebellar pathway and CTZ. Uses as antiemetic Vomiting due to motion sickness Vomiting of pregnancy Vertigo Adverse effects: Sedation (excitation may occur in children). Atropine-like actions Hypotension (block alpha1)

3. 5-HT3 blockers Ondansetron Antiemetic mechanism: Competitively block 5HT3 receptors in the GIT and CTZ. Uses as antiemetic: Vomiting due to cancer chemotherapy or radiotherapy. Postoperative nausea and vomiting. Not effective against motion sickness

Adverse effects: Generally are well tolerated Dizziness, headache, and constipation. Prolong QT interval, torsade de points is reported especially if co-administered with another drug that prolong the QT interval

4. Dopamine blockers Benzamides; (Metoclopramide, Domperidone) Phenothiazines (e.g.  Prochlorperazine, chlorpromazine) Antiemetic mechanism: Benzamide Metoclopramide causes central and peripheral dopamine D2 antagonism Domperidone is a D2-blocker with selective peripheral activity in the upper gastrointestinal tract. Phenothiazines Antagonizing D2-dopamine receptors in the area postrema of the midbrain, also block M, H1

Uses: Vomiting due to drugs or febrile illness Vomiting due to cancer chemotherapy. Postoperative nausea and vomiting.

Adverse effects: Benzamides;   Metoclopramide; (anxiety, restlessness, and depression, hyperprolactinemia, irreversible tardive dyskinesia and QT interval prolongation Domperidone; it does not cross the blood-brain barrier and therefore lacks the neurologic side effects of metoclopramide Phenothiazine Sedation, Hyperprolactinemia, Postural hypotension Extrapyramidal effects e.g. dystonia and dyskinesia

5. Cannabinoids Dronabinol Antiemetic mechanism: It is a cannabinoid receptor agonist. the drug likely activates specific cannabinoid receptors in the vomiting center, which results in decreased excitability of target neurons Uses as antiemetic: Vomiting due to cancer chemotherapy Patients refractory to other antiemetics.

Adverse effects: Sedation Paranoia Dysphoria Hypotension Drug abuse. NB; The modest antiemetic activity of this and their relatively unfavorable side effect profile, especially in older patients, has limited their clinical use.

6. Vitamin B6 Pyridoxine is a water-soluble vitamin Antiemetic mechanism: Is unknown Uses as antiemetic: Vomiting in pregnancy. Pyridoxine has a good safety profile with minimal side effects  Vomiting in children

7. Corticosteroids Dexamethasone the commonest steroid used Antiemetic mechanism; The exact mechanism is unclear. Uses as antiemetic: Effective and well-tolerated antiemetic for chemotherapy induced emesis

8. Neurokinin-1 receptor blockers Aprepitant Antiemetic mechanism Neurokinin 1 (NK1) receptor antagonist on nucleus of tractus solitaries and Visceral afferent nerves So it prevent both peripheral and central stimulation of the vomiting center Uses as antiemetic: In combination with 5-HT3 blockers to treat vomiting due to cancer chemotherapy Adverse effects: Diarrhea and fatigue Inhibit CYP3A4 so increase the level of many drugs Neurokinin-1 receptors mediate most of central and peripheral effects of substance P.

Prokinetic Drugs A gastroprokinetic agent, gastrokinetic, or prokinetic, is a type of drug which enhances gastrointestinal motility by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm. They are used to treat irritable bowel syndrome, gastritis, acid reflux disease, gastroparesis, and functional dyspepsia.

1. Cholinomimetic agents Not commonly used Cholinomimetic agonists; Bethanechol stimulate muscarinic M3 receptors on smooth muscle cells and at myenteric plexus synapses. Due to multiple cholinergic effects and the advent of less toxic agents, it is now seldom used. The acetylcholinesterase inhibitor: Intravenous neostigmine can be used in the treatment of acute large bowel distention . Cholinergic effects include excessive salivation, nausea, vomiting, diarrhea, and bradycardia.

2. D2 receptor antagonists. Mechanism of action Metoclopramide and domperidone are dopamine D2 receptor antagonists. Pharmacological action Increase esophageal peristaltic amplitude Increase lower esophageal sphincter pressure Enhance gastric emptying Have no effect on small intestine or colonic motility. Antinausea and antiemetic action.

Therapeutic Uses Impaired Gastric Emptying due to postsurgical disorders (vagotomy, antrectomy) and diabetic gastroparesis. Prevention and treatment of emesis. Gastroesophageal Reflux Disease (GERD): Metoclopramide is used mainly in combination with acid suppressors in patients with regurgitation or refractory heartburn.

3. Macrolides Macrolide antibiotics such as erythromycin directly stimulate motilin receptors on gastrointestinal smooth muscle and promote gastric peristalsis, however, tolerance rapidly develops. It may be used in patients with acute upper gastrointestinal hemorrhage to promote gastric emptying of blood prior to endoscopy.

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