JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B. Pharmacy III PHARMACOLOGY-III Previous Question Paper (July - 2021 - R17)

Anti-asthmatic agents are classified based on their pharmacological action and clinical utility as follows:

1. Bronchodilators: These include Beta-2 sympathomimetics (Salbutamol, Salmeterol), Methylxanthines (Theophylline), and Anticholinergics (Ipratropium bromide, Tiotropium).
2. Leukotriene Antagonists: Montelukast, Zafirlukast.
3. Mast Cell Stabilizers: Sodium cromoglycate, Nedocromil sodium.
4. Corticosteroids: Inhaled (Beclomethasone, Fluticasone) and Systemic (Prednisolone).
5. Anti-IgE Monoclonal Antibodies: Omalizumab.

Mechanisms of Action:

• Beta-2 agonists: Stimulate beta-2 receptors, activating adenyl cyclase to increase intracellular cAMP, leading to bronchial smooth muscle relaxation.
• Methylxanthines: Inhibit phosphodiesterase (PDE) enzymes, increasing cAMP levels and antagonizing adenosine receptors.
• Anticholinergics: Block M3 muscarinic receptors in the airways, preventing acetylcholine-induced bronchoconstriction.
• Leukotriene antagonists: Selectively block CysLT1 receptors, preventing the inflammatory effects of leukotrienes.
• Corticosteroids: Inhibit phospholipase A2, reducing the synthesis of inflammatory mediators like prostaglandins and leukotrienes, and decrease airway hyper-responsiveness.
• Mast cell stabilizers: Prevent the degranulation of mast cells, inhibiting the release of histamine and other mediators.

Adverse Effects:

• Beta-2 agonists: Muscle tremors, tachycardia, and palpitations.
• Methylxanthines: Gastric irritation, nausea, vomiting, and cardiac arrhythmias at high doses.
• Anticholinergics: Dry mouth, urinary retention, and blurred vision.
• Corticosteroids: Oropharyngeal candidiasis, dysphonia, and systemic effects like adrenal suppression with long-term use.
• Leukotriene antagonists: Headache, abdominal pain, and rarely Churg-Strauss syndrome.

Anti-emetics are agents used to prevent or treat nausea and vomiting. They are classified based on their primary site of action and receptor antagonism:

1. 5-HT3 Receptor Antagonists: Ondansetron, Granisetron, Palonosetron.
2. D2 Receptor Antagonists: Metoclopramide, Domperidone, Prochlorperazine.
3. H1 Receptor Antagonists: Promethazine, Dimenhydrinate, Meclizine.
4. Muscarinic Receptor Antagonists: Hyoscine (Scopolamine).
5. NK1 Receptor Antagonists: Aprepitant, Fosaprepitant.
6. Cannabinoids: Dronabinol, Nabilone.
7. Corticosteroids: Dexamethasone, Methylprednisolone.

Mechanisms of Action:

• 5-HT3 Antagonists: Block serotonin receptors in the chemoreceptor trigger zone (CTZ) and on vagal afferents in the GI tract.
• D2 Antagonists: Block dopamine D2 receptors in the CTZ. Metoclopramide also increases lower esophageal sphincter tone and promotes gastric motility.
• H1 and Muscarinic Antagonists: Block receptors in the vestibular apparatus and the vomiting center to reduce motion-induced nausea.
• NK1 Antagonists: Block substance P receptors in the brainstem, preventing the emetic signal.
• Corticosteroids: Mechanism is not fully understood but likely involves inhibition of prostaglandin synthesis and modulation of inflammatory pathways.

Adverse Effects:

• 5-HT3 Antagonists: Headache, constipation, and transient elevation of liver enzymes.
• D2 Antagonists: Extrapyramidal symptoms (dystonia, parkinsonism), sedation, and hyperprolactinemia.
• H1/Muscarinic Antagonists: Dry mouth, blurred vision, urinary retention, and significant drowsiness.
• NK1 Antagonists: Fatigue, dizziness, and diarrhea.

Therapeutic Uses:

• 5-HT3 Antagonists: First-line for chemotherapy-induced nausea and vomiting (CINV) and post-operative nausea.
• D2 Antagonists: Used for drug-induced emesis, gastroparesis, and migraine-associated nausea.
• H1/Muscarinic Antagonists: Primarily used for motion sickness and vertigo.
• NK1 Antagonists: Used in combination with 5-HT3 antagonists for highly emetogenic chemotherapy.
• Corticosteroids: Adjunct therapy for CINV and nausea associated with radiotherapy.