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Mohammad Shariful Alam (Shohan)

ANTI-EMETIC DRUGS
Vomiting: Def. : Vomiting is a forceful expulsion through the mouth. Physiology: The act of emesis is controlled by the vomiting center in the medulla and close to it lie other vomiting centers, ex- center for respiration, salivation, and vascular control which gives rise to the sensation of vomiting. **The vomiting center does not initiate but rather it co-ordinates the act of emesis on receiving stimuli from various sources1. The chemoreceptor trigger zone (CTZ) 2. The vestibular system 3. The periphery, ex- distention or irritation of the gut, myocardial infarction, billiary and renal stone. 4. Cortical centers. The vomiting center and the nucleus tractus solitarius contain many muscarinic cholinergic and histamine H1 receptors, and the CTZ is rich in dopamine D2 receptors. Drugs that block these receptors are effective antiemetic. Conditions where nausea, vomiting are the common clinical symptoms: o o o o o o o Pregnancy, motion sickness Gastrointestinal obstruction Renal failure Peptic ulcer Hepatitis Drug toxicity Myocardial infarction

Drugs causing vomiting: - Cytotoxic drugs (cisplatin) - Opioid analgesics (apomorphine) - CuSo4 - Estrogen (endogenous, during pregnancy) Classification of antiemetic drugs: Drugs Site of action CTZ and gut CTZ and gut CTZ Vomiting center and CTZ

a)

Dopamine D2-receptor antagonists: Domperidone Metoclopramide Haloperidol Phenothiazine, ex- Chlorpromazine

Mohammad Shariful Alam (Shohan)

b)

- Prochlorperazine Serotonin 5HT3- receptor antagonists: Granisetron Ondansetron Tropisetron Dolasetron Antimuscarinics: Hyoscine H1- receptor antagonist: Cyclizine Dimenhydrinate Promethazine Neurokinin receptor antagonist: Aprepitant Other agents: Cisapride Corticosteroids - Dexamethasone - Methylprednisolone Benzodiazipines - Lorazepam

CTZ and gut

c)

d)

Vomiting center and gut

e) f)

Gut

Metoclopramide (Motilon)

Mechanism of action: Metoclopramide exerts its antiemetic effects via 3 mechanisms. At low doses, by blocking dopamine D2- receptors it inhibits dopaminergic transmission in the CNS, while at high doses, it inhibits serotonin receptors in the CTZ. Peripherally, by enhancing the action of Ach at muscarinic nerve endings in the gut, it raises the tone of the lower esophageal sphincter, relaxes the pyloric antrum, and duodenal cap and increases peristalsis and emptying of the upper gut. Indication: For nausea vomiting associated with Gastrointestinal disorder e.g., delayed gastric emptying, reflux gastritis, viral enteritis. Post surgical condition With cytotoxic drug and radiotherapy. Adverse effects:

tenismus, oculogyric crisis)

Extra-pyramidal dystonia

(torticollis,

facial

spasm,

It occurs most commonly in children and young adults and in other dopamine receptor antagonists, ex- Phenothiazine.

Mohammad Shariful Alam (Shohan) those receiving

lactation.

[This effect is abolished with an anti-muscarinic drug- benzodiazepine] Long term use cause- Tardive dyskinesia As it stimulates prolactin release it causes- Gynaecomastia and Motor restlessness Diarrhea.

Dose: Metoclopramide may be given in the relatively high dosage of 10-20mg orally or intravenously every 6 hours.

Domperidone (Omidon)

Mechanism of action: It acts by blocking dopamine D2- receptor in CTZ and peripherally in the upper gut where it increases the tone in the lower esophageal sphincter, enhances contraction of the gastric antrum and relaxes the pyloric sphincter. Indication: For nausea vomiting associated with Cancer chemotherapy and radiotherapy Surgical procedures Migraine Head injury Gastrointestinal disorders e.g., dyspepsia, reflux oesophagitis. Dose: 10-20mg every 4-8 hrs, orally 15-30 minutes before

meals.
Onset: Oral: 30mins 1hr. Duration: Oral: 6-8 hrs. **Advantage over Metoclopramide:

It crosses the BBB poorly. This does not limit the therapeutic efficacy, for the CTZ is functionally out with the barrier but there is less risk of adverse effect in the CNS.