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ANTIEMETIC DRUGS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

Vomiting Centre (medulla)

StomachSmall intestine

Higher cortical centres

Chemoreceptor Trigger Zone

(area prostrema, 4th ventricle)

Memory, fear, anticipationSensory input (pain, smell, sight)

SurgerySurgery

Labyrinths

Anaesthetics

Vomiting Reflex

Neuronal pathways

Factors which can cause nausea & vomiting

Chemotherapy

Chemotherapy

Radiotherapy

Opioids

Sites of action of drugs

5HT3

antagonists

Sphincter modulators

Histamine antagonistsMuscarinic antagonists

Gastroprokinetic agents

BenzodiazepinesHistamine antagonistsMuscarinic antagonistsDopamine antagonists

Cannabinoids

Receptors –in Neuro transmision of vomiting

Area Type of receptors Stimulus

Chemoreceptor trigger zone (CTZ)

a) Dopamine D2b) 5HT3c) Opioidd) H1 anti

1) Cancer chemotherapy2) Opioids3) Morning sickness

Vestibular nuclei a) Muscarinicb) Histamine H1

1) Motion sickness

Pharynx and GIT a) 5HT3 1) Cancer chemotherapy2) Radio therapy3) Gastroenteritis

Cerebral cortex 1) Smell2) Sight3) Thought4) Anticipatory emesis

Antiemetics

1. Anti-dopaminergic agents a) Phenothiazines: Prochlorperazine, Promethazine b) Butyrophenones : Droperidol2. Anti- 5 HT3 antagonists: Ondansetron,Granisetron3. Anticholinergics: Atropine, hyoscine , Glycopyrrolate4. Anti-histamines: Cyclizine, diphenhydramine,

Cinnarizine5. Glucocorticoids: Dexamethazone6. Cannabinoids: Dronabinol, Nabilone 7. Miscellaneous: Diphenidol, Droperidol,

Trimethobenzamide

Prokinetic agents

Substituted benzamides : Metoclopramide

Benzimidazole Derivative: DomperidoneAnti -5HT4 agonists: cisapride, mosopride,

zacopride, renzapride, prucaloprideMacrolides: motilin agonists: Erythromycin,

Azithromycin, ClarithromycinCCK1 antagonist: loxiglumide

Phenothizines

Phenothiazines are primarily antipsychotic

Mechanism of the antiemetic action: inhibition of central dopamine, muscarinic and H1 histamine receptors receptors

Use: Chemotherapy-induced vomiting Radiotherapy-induced vomiting postoperative nausea and vomiting

Butyrophenones- droperidol are primarily antipsychotic agents Mechanism of the antiemetic action: inhibition

of central dopamine receptors Use: Chemotherapy-induced vomiting Radiotherapy-induced vomiting postoperative nausea and vomiting Adverse effects: droperidol may prolong the

QT inter, therefore, it should not be used in patients with QT prolongation (should only be used in patients who have not responded adequately to alternative agents).

Serotonin 5 HT3 Antagonist-Potent antiemetics

1. Ondansetron, Granisetron, Dolasetron, Palonosetron

2. Mechanism of action: Peripheral 5-HT3 receptor blockade on intestinal vagal afferents.

Central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone

High first pass metabolism Excreted by liver & kidney

Indiacations

1) Chemotherapy induced nausea and vomiting

2) Post radiation nausea & vomiting

3) Vomiting of pregnancy

4) Postoperative vomiting

Adverse drug reactions Headache and dizziness Constipation or diarrhoea

Corticosteroids

Dexamethazone Corticosteroids have antiemetic properties Mechanism of action: possibly by suppressing

peritumoral inflammation and prostaglandin production.

Use: to enhance efficacy of 5HT3 receptor antagonists in the treatment of chemotherapy-induced vomiting.

H1 receptor antagonists and Anticholinergics

Use: prevention or treatment of motion sickness.Adverse effects: sedation, dizziness,confusion, dry mouth,

cycloplegia, and urinary retention.

.

Diphenhydramine dimenhydrinate

First generation H1 receptor blockers that have anticholinergic and sedating properties

Meclizine First generation H1 receptor blockers that have lesser anticholinergic and sedating properties

Hyoscine Muscarinic receptor blocker

Cannabinoids :Dronabinol, Nabilone

Pharmacokinetics: Readily absorbed after oral administration It undergoes extensive first-pass metabolism with limited systemic bioavailability after single doses. Metabolites are excreted primarily via the biliary-fecal route

Adverse effects: Euphoria or dysphoria, sedation 1. withdrawal syndrome (restless, insomnia and irritability)2. Autonomic effects (sympathetic) in the form of

tachycardia, palpitation, orthostatic hypotension. Use: For the prevention of chemotherapy-induced

nausea and vomiting

Prokinetic agents

Substituted benzamides Metoclopramide

5HT3 and 5HT4 receptor antagonist Mechanism of antiemetic action: Central dopamine-

receptor blockade Prokinetic effects- activation of 5HT4 receptors

Side effects: (mainly extrapyramidal): Restlessness,Dystonias Parkinsonian symptoms Galactorrhoea and gynacomastia

Benzimidazole Derivative Domperidone

Structurally similar to haloperidol MOA similar to metaclopramide Used to prevent emetic side effect of

levodopa or bromocriptine

Emetics

Ipecac is an OTC drug Administration

Take with a glass of water or fluid, not with milk or carbonated beverage

Vomiting occurs in 20 to 30 minutes and if not, repeat dose

Gastric lavage may be needed if vomiting does not occur

Caution: avoid vomiting if substance is caustic or petroleum

Apomorphine is a morphine derive emetic, SQ/IM, Onset 15 min

Anti -5HT4 agonists:

Cisapride, Mosopride, Zacopride, Renzapride, Prucalopride

-no antiemetic effect Promote release of Ach from myentric plexus Cisapride- facilitates gastric motility,

throughout the GIT Hastens gastric emptying, improves LES tone And oesophageal peristalsis.

Anti -5HT4 agonists: adverse reactions

Abdominal cramps, diarrhoea QT prolongation Cytochrome P450 inhibition

Macrolides

Motilin receptors Increase LES tone

CCK1 receptor antagonist Loxiglumide –increase GI motility

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