Pharmacology – II PHL-322 Chapter : 05 ANTI-EMETICS AND ANTI-TUSSIVES

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Presentation transcript:

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: majidsays@gmail.com

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

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

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

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

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

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

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.

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

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).

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

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

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

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

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.

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

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

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

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

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