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

The pathophysiology of alcoholic liver disease (ALD) involves a progressive spectrum of injury driven by ethanol metabolism and oxidative stress. Ethanol is primarily metabolized in the liver by alcohol dehydrogenase (ADH) into acetaldehyde, a highly reactive and toxic metabolite that forms protein adducts, damaging hepatocytes and triggering an immune response. Chronic consumption leads to the induction of the cytochrome P450 2E1 (CYP2E1) enzyme, which further increases the production of reactive oxygen species (ROS) and promotes lipid peroxidation.

These processes result in:

1. Steatosis: Ethanol metabolism shifts the redox state (increased NADH/NAD+ ratio), inhibiting fatty acid oxidation and promoting lipogenesis, leading to fat accumulation in hepatocytes.
2. Inflammation: Acetaldehyde and ROS activate Kupffer cells, which release pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8, causing alcoholic hepatitis.
3. Fibrosis: Chronic inflammation activates hepatic stellate cells, which transform into myofibroblasts and increase the production of collagen and extracellular matrix, eventually leading to cirrhosis and irreversible liver damage.

Therapeutic management of peptic ulcer disease (PUD) focuses on eradicating causative factors, reducing gastric acid secretion, and protecting the mucosal lining. The primary goals are to relieve symptoms, promote healing, and prevent complications.

1. Eradication of H. pylori: For H. pylori-positive ulcers, a triple or quadruple therapy regimen is used for 10–14 days. This typically includes a proton pump inhibitor (PPI) plus two antibiotics (e.g., clarithromycin and amoxicillin or metronidazole) and, in quadruple therapy, bismuth subsalicylate.
2. Acid Suppression: PPIs (e.g., omeprazole, pantoprazole) are the gold standard as they provide superior acid inhibition compared to H2-receptor antagonists (e.g., famotidine). They are essential for healing both gastric and duodenal ulcers.
3. Mucosal Protective Agents: Agents like sucralfate form a physical barrier over the ulcer crater, while misoprostol (a prostaglandin E1 analog) is used specifically to prevent NSAID-induced ulcers by replacing depleted prostaglandins.
4. Lifestyle Modifications: Patients are advised to discontinue NSAID use, stop smoking, and limit alcohol consumption, as these factors exacerbate mucosal injury and delay healing.