Prokinetic Drugs - Antiemetics and Prokinetic Drug

Prokinetic Drugs

Classification

·              Benzamides: metoclopramide, trimethobenzamide, cisap- ride.

·              Benzimidazole derivatives: domperidone.

·              Motilin, erythromycin, and other macrolide antibiotics.

Metoclopramide

Metoclopramide is a benzamide analogue, and is structur-ally related to procainamide, but lacks local anaesthetic and antiarrhythmic actions. It is a central and peripheral acting dopamine antagonist. Because of dopaminergic blockade, it can cause significant CNS effects and hyperprolactinaemia. As a cholinergic agonist, it enhances the action of acetylcholine at muscarinic receptors. Metoclopramide also possesses oxidant activity. Bromopride is the bromo-analogue of metoclopramide.

Metoclopramide enhances the motility of smooth muscle of oesophagus, stomach, and upper small intestine, leading to an acceleration of gastric emptying and intestinal transit. Lower oesophageal sphincter pressure is increased preventing oesophageal reflux. Central dopamine inhibition leads to aboli-tion of nausea and vomiting.

Metoclopramide is used in the treatment of gastroesophageal reflux, gastric stasis, vascular headache (adjunct treatment) and persistent hiccups. It is also useful for managing diabetic gastro-paresis, oesophageal reflux, and vomiting, including that due to postoperative- and cancer chemotherapy-related. Bromopride is used as an antiemetic, and for the treatment of various gastroin-testinal disorders, similar to metoclopramide.

Adverse effects include drowsiness, vertigo, anxiety, extra-pyramidal effects (tremors, agitation, parkinsonian syndrome). Hyperaldosteronism and hyperprolactinaemia with amenor-rhoea may occur. Neuroleptic malignant syndrome has been reported.

Overdose results in increased muscle tone, opisthotonus, torticollis, trismus, cog-wheel rigidity, grimacing, extrapyram-idal reactions, confusion, irritability, panic-like reactions, agita-tion, nystagmus, strabismus, conjugate deviation of eyes, and convulsions. Bradycardia and heart block have been reported. Methaemoglobinaemia has also been reported, as well as rare reports of sulfhaemoglobinaemia. Acute dystonic reactions are more common in children and young adults, whereas prolonged reactions such as tardive dyskinesia, and parkinsonism are more common in elderly patients.

Treatment

·      Stabilisation—maintenance of airway, cardiovascular and respiratory function, intravenous line, cardiac monitoring, brain scan, and EEG.

·      Consider administration of activated charcoal after a poten-tially toxic ingestion. Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

·      Treatment of convulsions with diazepam.

·      Treatment of hypokalaemia.

·      Diphenhydramine (25 to 50 mg IV over 2 min) or benztro-pine (1 to 4 mg IV or IM) for extrapyramidal effects. If the patient does not respond administer diazepam.

·      For bradycardia: Give 1 mg IV, and repeat in 3 to 5 minutes if asystolic cardiac arrest persists. 3 mg (0.04 mg/kg) IV is a fully vagolytic dose in most adults.

·      Methylene blue (1 to 2 mg/kg of a 1% solution given IV over 5 minutes) has been used successfully to reverse methae-moglobinaemia in premature and full term infants who had received metoclopramide.

·              Haemodialysis or peritoneal dialysis are reported to be inef-fective in removing metoclopramide, probably due to the drug’s high volume of distribution.