VPT 311: General and Systemic Veterinary Pharmacology (2+1)

ANTIEMETICS

• Antiemetics are agents that are used to control emesis
• Species like the horses, rabbits and rodents are unable to vomit.
• Protracted vomiting is undesirable in dogs, cats and other species.
• Vomiting usually occurs secondary to another disease process. If the primary cause is treated then vomiting disappears.
• Antiemetics are useful in motion sickness, uremia, liver disease, endotoxemia, canine parvovial gastroenteritis and in cancer chemotherapy.
• Use of antiemetics may mask the primary disease.
• Prolonged vomiting leads to electrolyte and acid base imbalances and dehydration. Antiemetics may also be locally acting or centrally acting.

Centrally acting antiemetics

Phenothiazine derivatives

• A number of phenothiazine derivatives (chlorpromazine, promethazine, prochlorperazine, trifluopromazine etc.) are classified as broadspectrum antiemetics.
• They act by blocking the chemoreceptor trigger zone at low doses and the emetic centre in the brain at higher doses.
• Promethazine is a H₁ antagonist (classical antihistaminic) which also has antimuscarinic actions. It is very effective at preventing motion sickness (since the vestibular afferents input in the vomiting center which has H₁ and muscarinic receptors).
• Prochlorperazine is a D₂ antagonist and has no antipsychotic effects. It is useful as an antiemetic as well as for dizziness. It has minor anticholinergic effects. Since it blocks D₂ receptors elsewhere (e.g. substantia nigra), it may cause extrapyramidal effects.
• Chlorpromazine, another phenothiazine, can also be used as an antiemetic, although it tends to be sedative. It also has antipsychotic effects.
• Hyoscine (scopolamine) is a muscarinic antagonist (M₂). It is used as a patch behind the ear for controlling CTZ mediated vomiting.
• Metoclopromide is a D₂ antagonist which is also a weak 5HT₃ antagonist. It increases the motility of the gut in the upper regions (does not cause diarrhoea - only facilitates gastric emptying). It is useful in gastric stasis in a number of species including the cattle and horses. Metoclopromide will help the absorption of drugs because it stimulates gastric emptying. This drug is useful in vomiting associated with vagal afferents (gut disorders, heart, testes, gut irritants - all stimulate the 5HT3 receptor on the vagal afferents) .
• Ondansetron is a 5HT₃ antagonist and is a potent antiemetic. It is very effective in patients receiving cancer chemotherapy. It can also be used for CTZ nausea.

 Locally acting antiemetics

• H₂ antagonists like cimetidine, ranitidine etc. These drugs reduce the acid output and hence decrease the irritating effects on acid stomach lining. As a consequence, afferent signals to vomiting centres are decreased. Antacids like sodium bicarbonate are also useful.