JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D IV Year PHARMACOTHERAPEUTICS - III Previous Question Paper (January/February - 2021 - R08)

Peptic ulcer disease results from an imbalance between aggressive factors (gastric acid, pepsin, bile salts) and mucosal defensive factors (mucus, bicarbonate, prostaglandins, mucosal blood flow). The primary mechanisms include:

1. Helicobacter pylori infection: H. pylori colonizes the gastric mucosa, producing urease which neutralizes local acid and releases cytotoxins (CagA, VacA). This triggers an inflammatory response, increasing gastrin release and decreasing somatostatin, leading to hyperchlorhydria and mucosal damage.
2. NSAID-induced injury: NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) enzymes, which are essential for the synthesis of cytoprotective prostaglandins. Reduced prostaglandin levels impair mucus and bicarbonate secretion and decrease mucosal blood flow, making the epithelium susceptible to acid-pepsin injury.
3. Hypersecretion of acid: Conditions like Zollinger-Ellison syndrome involve excessive gastrin production, overwhelming the protective capacity of the duodenum.
4. Impaired mucosal defense: Factors such as smoking, alcohol, and stress can further compromise the integrity of the gastric lining, facilitating ulceration.

Hepatitis is characterized by inflammation of the liver, primarily driven by viral infection, toxins, or autoimmune processes. The pathophysiology involves:

1. Viral Entry and Replication: Hepatotropic viruses (e.g., Hepatitis A, B, C) enter hepatocytes via specific receptors. Viral replication triggers the host immune response.
2. Immune-Mediated Damage: The primary cause of liver injury is not the virus itself, but the host's cytotoxic T-cell response. CD8+ T-lymphocytes recognize viral antigens on the surface of infected hepatocytes and induce apoptosis or necrosis.
3. Inflammatory Cascade: Kupffer cells (resident macrophages) are activated, releasing pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6). This recruits additional inflammatory cells, leading to portal inflammation and hepatocellular damage.
4. Cholestasis and Fibrosis: Ongoing inflammation leads to bile duct injury (cholestasis) and the activation of hepatic stellate cells. These cells transform into myofibroblasts, depositing excessive collagen in the extracellular matrix, which can progress to fibrosis and cirrhosis if the insult is chronic.