1. Pharmacology – II PHL-322 Chapter : 05 ANTI-EMETICS AND ANTI-TUSSIVES
By Majid Ahmad Ganaie M. Pharm., Ph.D. Assistant Professor Department of Pharmacology E mail:

2. Antiemetics
Vomiting :The act of vomiting and the sensation of nausea that accompanies it are protective reflexes that serve to rid the stomach and intestine of toxic substances and prevent their further ingestion

3. Pathophysiology of Emesis
Cerebral cortex
Cancer chemotherapy
Opioids
Smell
Sight
Thought
Anticipatory emesis
Chemoreceptor Trigger Zone (CTZ)
Vestibular nuclei
Vomiting Centre (medulla)
Motion sickness
Muscarinic Histaminic H1
Muscarinic, 5 HT3 & Histaminic H1
(Outside BBB)
Dopamine D2
5 HT3,,Opioid Receptors
Chemo & radio therapy Gastroenteritis
(vagus)
Pharynx & GIT
5 HT3 receptors

4. Area
Type of receptors
Stimulus
Chemoreceptor trigger zone (CTZ)
Dopamine D2
5HT3
Opioid
Cancer chemotherapy
Opioids
Vestibular nuclei
Mscarinic
Histamine H1
Motion sickness
Pharynx and GIT
Radio therapy
Gastroenteritis
Cerebral cortex
Smell
Sight
Thought
Anticipatory emesis
Serotonin 5HT3 receptor antagonists
5HT3 receptor
Phenothiazines
Dopamine D2 receptors
Antihistaminic
Anticholinergic
Substituted benzamides
Anticholinergic drugs
Muscarinic receptors
Antihistaminic drugs
Histamine H1 receptors

5. Indications of antiemetics
1- Chemotherapy-induced vomiting 2- Post irradiation vomiting 3- Postoperative vomiting 4- Vomiting of pregnancy 5- Motion sickness
Group of drugs used as antiemetics
Serotonin 5 HT3 Antagonists:
Dopamine D2 Antagonist:
Anticholinergics:
H1 Antihistaminics

6. Serotonin 5 HT3 Antagonist
Potent antiemetics
Mechanism of action:
1- Peripheral 5-HT3 receptor blockade on intestinal vagal afferents.
2- Central 5-HT3 receptor blockade in the vomiting center and chemoreceptor trigger zone
Antiemetic action is mainly against:
Emesis mediated by vagal stimulation (e.g. postoperative and chemotherapy)
High first pass metabolism
Excreted by liver & kidney
No dose reduction in renal insufficiency but needed in hepatic insufficiency

7. Drugs Available
Ondansetron
Granisetron
Dolasetron
Palonosteron
Adverse Effects
The most common adverse effects are:
1- Headache and dizziness
2- Constipation or diarrhoea
Indications
Chemotherapy induced nausea and vomiting
postradiation nausea & vomiting
Vomiting of pregnancy
Postoperative vomiting

8. Corticosteroids
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.

9. Phenothiazines Phenothiazines as promethazine are antipsychotic agents
Use:
Chemotherapy-induced vomiting
Radiotherapy-induced vomiting
postoperative nausea and vomiting
Mechanism of the antiemetic action: inhibition of central dopamine, muscarinic and H1 histamine receptors receptors

10. Butyrophenones Butyrophenones as Droperidol are 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).

11. Substituted Benzamides
1- Metoclopramide
2- Trimethobenzamide
Mechanism of antiemetic action: Central dopamine-receptor blockade
Side effects: (mainly extrapyramidal):
Restlessness
Dystonias
Parkinsonian symptoms

12. 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

13. Benzodiazepines Uses:
Benzodiazepines such as diazepam are used prior to the initiation of chemotherapy to reduce anticipatory vomiting or vomiting caused by anxiety

14. Cannabinoids (Dronabinol)
The mechanisms for the antiemetic effects is not known.
Pharmacokinetics.
readily absorbed after oral administration
It undergoes extensive first-pass metabolism with limited systemic bioavailability after single doses Mmetabolites are excreted primarily via the biliary-fecal route
Adverse effects include:
Euphoria or dysphoria, sedation and hallucinations
Abrupt withdrawal leads o withdrawal syndrome (restless, insomnia and irritability)
Autonomic effects (sympathetic) in the form of tachycardia, palpitation, conjunctival injection, and orthostatic hypotension.
Use:
For the prevention of chemotherapy-induced nausea and vomiting

15. ANTI-TUSSIVES
Cough is a protective reflex, which serves the purpose of expelling sputum and other irritant materials from the respiratory airway.
Anti-tussives are drugs used to suppress the intensity and frequency of coughing.

16. Two Types of Anti-tussives:
1. Central anti- tussives - Suppress the medullay cough center and may be divided into two groups:
Opoid antitussive e.g. Codeine, Hydrocodeine
Non opoid antitussives e.g. Dextromethorphan
2. Peripheral antitussives - Decrease the input of stimuli from the cough receptor in the respiratory passage:
Demulcents e.g. liquorices lozenges, honey
Local anesthetics e.g. lidocaine aerosol

17. Opioid Antitussives
Suppress the cough reflex by direct action on the cough center in the medulla
Example:
codeine + guiafenesin = Robitussin AC

18. Non-narcotic Antitussives
Dextromethorphan
Suppresses the cough reflex by direct action on the cough center in the medulla; a chemical derivative of the opiate narcotics
Result: diminished cough
Produces no respiratory depression, analgesia, or dependence
Example: Robitussin-DM

19. Antitussive Agents: Side Effects
Dextromethorphan
Dizziness, drowsiness, nausea
Opioids
Sedation, nausea, vomiting, lightheadedness, constipation

20. THANK YOU