Antiemetics by dr. pavulraj.s angels presentation

Dr. Pavulraj.S

M.V.Sc., (Veterinary Pathologist)

Research fellow

National Research Centre of Equines, India

2/15/2015

Dr. Pavulraj.S., M.V.Sc., Veterinary Pathologist,

Research Fellow, NRCE, India

DEFINITION

Antiemetics control vomiting by either a

central action or a local protectant effect.

Centrally acting antiemetics may either

block dopaminergic receptor in the CTZ or

depress the emetic centre in the medulla.

Locally acting antiemetics protects the GI

epithelium from further irritation.

Antiemetic therapy should only be

considered as symptomatic therapy

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Clinical applications

Antiemetics are indicated to:

● Control vomiting, when profuse and protracted vomiting may lead to fluid, electrolyte or acid–base disturbances or is causing distress to the patient

● Prevent vomiting predicted to occur with use of emetic drugs, e.g. cisplatin, amphotericin.

Use of antiemetics is not necessary if vomiting is intermittent, the patient is not distressed.

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CLASSES OF ANTIEMETICS

1. Phenothiazines


Phenothiazines are broad-spectrum antiemetics that have efficacy against vomiting initiated by central and peripheral stimuli.

Mechanism of action

Phenothiazines antagonize α1- and α2-adrenergic receptors, D2-dopaminergic receptors, H1- and H2-histaminergic receptors and muscarinic cholinergic receptors (weakly).

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Dosage DOGS AND CATS

Prochlorperazine

• 0.1–0.5 mg/kg IV, IM, SC q.6-8 h

• 0.5–1.0 mg/kg PO q.8-12 h

NB: Intramuscular injection may be painful

Chlorpromazine

• 0.1–0.5 mg/kg IM, SC q.8 h

Promethazine

Large animals – 1.5-2mg/kg IM

Dog - 1.5-2mg/kg, IM, IV, oral

Triflupromazine

Dog – 2-4mg/kg IM, 1-2mg/kg IV

Cat 2.2-4.4mg/kg IM

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Preparations

Prochlorperazine Emidoxyn - 5mg tablet

Stemetil -5mg tablet

-12.5mg/ml injection

Chlorpromazine Megatil – 25mg tablet

-25mg/ml injection

Chlorpromazine -10mg tablet

Promethazine Avomine -25mg tablet

Phenergan -10mg tablet

-5mg/ml syrup

-25mg/ml injection

Triflupromazine Neocalm – 5mg tablet

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Adverse effects

● Phenothiazines may cause hypotension, arteriolar

vasodilation.

● Sedation, rigidity, tremors, weakness and

restlessness may occur at high dose.

Prochlorperazine may lower the seizure

threshold.

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Known drug interactions

● Phenothiazines should not be given within 1

month of worming with an organophosphate

agent as the effect of either drug may be

potentiated.

● Other CNS-active drugs such as barbiturates,

narcotics and anesthetic agents may cause

additive CNS depression.

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2. Antimuscarinic

i. Metoclopramide Clinical applications Metoclopramide is indicated for control of vomiting

associated with:

● Various emesis-inducing disorders involving

stimulation of the CTZ

depressed gastrointestinal motility

● Cancer chemotherapy

● Gastroesophageal reflux

● Decreased gastric emptying associated with:

– inflammatory gastrointestinal disorders

– gastric ulcers

– gastric neoplasia

– autonomic neuropathy (diabetes mellitus)

– postoperative gastric dilation and volvulus

surgery/intervention

– abnormal gastric motility.

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Mechanism of action

Centrally, metoclopramide antagonizes D2-

dopaminergic receptors and 5-HT3

serotonergic receptors and peripherally

cholinergic effect.

The antiemetic properties of

metoclopramide related to 5-HT3receptor

antagonism

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Dosage

DOGS AND CATS

• 0.2–0.5 mg/kg PO q.6–8 h

0.01- 0.2mg/kg SC,IM,IV

Preparations Emenil – 10mg tablet

- 5mg/ml injection

Perinorm – 10mg tablet

- 5mg/ml injection

Reglan – 10mg tablet

- 5mg/ml injection

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Adverse effects

Side effects more often in cats than in dogs.

Metoclopramide should not be used when

gastrointestinal hemorrhage, obstruction or

perforation is suspected.

Contraindicated in patients with seizure

Use with caution renal insufficiency because it

reduces renal blood flow

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● Excellent synergy with metoclopramide and

phenothiazines

● Anticholinergic drugs (e.g. atropine) affects metoclopramide on gastrointestinal tract motility.

● The gastrointestinal stimulatory effects of metoclopramide may affect absorption of many drugs.

● Metoclopramide may enhance the absorption of cimetidine, aspirin, tetracyclines, diazepam.

● Metoclopramide antagonizes the antiprolactinemic effects of cabergoline.

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ii. Domperidone


Domperidone is a dopamine antagonist at D2-

receptors which has similar actions to

metoclopramide.

Mechanism of action

Domperidone is a dopamine antagonist in

the CTZ and GI tract. It also is an α2- and

β2-adrenergic antagonist in the stomach.

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Dosage

DOGS AND CATS

• 5-10 mg per animal q.8 h

Preparations

Domel-MT - 10mg tablet

Domstal – 10mg tablet

-1mg/ml susp

Tridom - 5mg tablet

-1mg/ml susp

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Adverse effects

It may cause gastroparesis.

The drug is teratogenic at high doses in mice, rats and rabbits.

Domperidone may increase prolactin levels resulting in galactorrhea or gynecomastia.

There may be an impact on fertility


Domperidone should not be used with dopaminergic

drugs such as dopamine or dobutamine.

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3. 5-HT3 antagonists

Ondansetron


Extremely potent antiemetics

Clinical efficacy is better than metoclopramide

Used in cases when ‘first-line’ antiemetics (e.g.metoclopramide or chlorpromazine) are ineffective.

Control vomiting in puppies with parvoviral gastroenteritis.

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Mechanism of action

5-HT3 receptors are located in the CTZ and,

peripherally, on vagal nerve terminals and

on enteric neurones in the gastrointestinal

tract.

5-HT3 antagonists have a central action on

the CTZ and peripheral 5-HT3 receptors in

the gut.

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Dosage

DOGS

• 0.5 mg/kg IV as a loading dose and then 0.5

mg/kg/h as an infusion for 6 h

0.5-1 mg/kg oral

Contraindicated in cats

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Preparations

Emeset - 4mg tablet

-2m/5 ml syrup

-2mg/ml injection

Vomiz- 4mg tablet

-2mg/ml syrup

Zondan – 4mg tablet

-2mg/ml syrup

Vomidon - 2mg/ml injection

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Adverse effects

Showing minimal toxicity at doses up to 30 times greater.

Should be used with caution in cases where gastrointestinal obstruction cannot be excluded.

Some time produce constipation, headaches, alterations in liver enzymes and rarely hypersensitivity reactions .

Should be used with caution in pregnant animals.

Ondansetron is a potential substrate of P-glycoprotein. Some rough collies have a mutation causing a nonfunctional protein, these dogs and associated breeds may be more sensitive to the effects of 5-HT3 antagonists.

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Inappropriate use of

antiemetics

Use of antiemetics in the following situations is

inappropriate:

● Gastrointestinal obstruction – antiemetics may delay

diagnosis

● Gastrointestinal toxicity – antiemetics may prevent

the patient from eliminating the toxin

● Systemic hypotension – the phenothiazines and

α2-adrenergic antagonists, when used in high doses, can intensify hypotension.

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Antiemetics by dr. pavulraj.s angels presentation

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