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

The pathophysiology of gastroesophageal reflux disease (GERD) is primarily driven by the failure of antireflux barriers, allowing gastric contents to enter the esophagus. Key mechanisms include:

1. Transient Lower Esophageal Sphincter Relaxations (TLESRs): This is the most common cause, where the lower esophageal sphincter (LES) relaxes independently of swallowing, often triggered by gastric distension.
2. Hypotensive LES: A chronically weak or low-pressure LES fails to maintain a sufficient barrier against gastric pressure.
3. Anatomic factors: The presence of a hiatal hernia disrupts the crural diaphragm, which acts as an external sphincter, further compromising the antireflux barrier.
4. Impaired Esophageal Clearance: Reduced peristaltic amplitude or frequency prevents the effective clearing of refluxed acid, prolonging contact time with the esophageal mucosa.
5. Delayed Gastric Emptying: Increased gastric volume and pressure promote reflux episodes.

Once the barrier is breached, the acidic gastric contents, bile salts, and pepsin cause chemical injury to the esophageal squamous epithelium, leading to inflammation, erosions, and potential complications like Barrett's esophagus.

The therapeutic management of ulcerative colitis (UC) aims to induce and maintain remission while minimizing toxicity. Treatment is stratified based on disease severity and extent:

1. Aminosalicylates (5-ASAs): Sulfasalazine, mesalamine, and balsalazide are first-line agents for inducing and maintaining remission in mild-to-moderate UC. They act topically on the colonic mucosa.
2. Corticosteroids: Oral (prednisone) or intravenous (hydrocortisone) steroids are used for short-term induction of remission in moderate-to-severe disease. They are not effective for maintenance.
3. Immunomodulators: Thiopurines (azathioprine, 6-mercaptopurine) are used for steroid-sparing maintenance therapy in patients who are steroid-dependent or refractory to 5-ASAs.
4. Biologic Agents: Anti-TNF agents (infliximab, adalimumab, golimumab), integrin receptor antagonists (vedolizumab), and IL-12/23 inhibitors (ustekinumab) are indicated for moderate-to-severe UC unresponsive to conventional therapy.
5. JAK Inhibitors: Tofacitinib and upadacitinib are oral small-molecule options for moderate-to-severe disease.
6. Surgical Intervention: Colectomy is curative for patients with refractory disease, severe hemorrhage, toxic megacolon, or high-grade dysplasia/carcinoma.