34.1 Digestive Pharmacology: Portal Hypertension and Variceal Bleeding, Acid-Peptic Disease, H. pylori and GERD, Antiemetics, Laxatives and Antidiarrheals, Biliary and Pancreatic Disease, GI Infections and Parasites, Viral Hepatitis, C. difficile, Candidiasis and GI Cancer Chemotherapy

Why this area matters

The TOS digestive area asks for drug treatment of:

• GI bleeding and portal hypertension;
• acid-peptic disease and GERD;
• motility and bowel disorders;
• biliary and pancreatic disease;
• GI infections and parasites;
• hepatitis;
• GI cancer.

Upper GI bleeding, gastroenteritis, typhoid, helminths, hepatitis B and liver cancer are common in the Philippines.

Portal hypertension and GI bleeding

• Acute variceal bleeding:
  • resuscitation with restrictive transfusion (hemoglobin target about 7 to 8 g/dL);
  • a vasoactive drug at once: octreotide (a somatostatin analog) or terlipressin (a vasopressin analog that causes ischemia and hyponatremia);
  • prophylactic antibiotics (ceftriaxone) to reduce infection and death;
  • endoscopic band ligation within 12 hours;
  • lactulose to prevent encephalopathy.
• Secondary prevention: non-selective beta-blockers (propranolol, nadolol, carvedilol), which reduce portal pressure, plus band ligation.
• Ascites: spironolactone with furosemide (in a 100:40 ratio), salt restriction and albumin with large-volume paracentesis.
• Peptic ulcer bleeding: IV PPI (bolus then infusion or intermittent high doses) after endoscopic therapy. Stop NSAIDs. Restart aspirin early for secondary prevention when hemostasis is secure.

Acid-peptic disease, H. pylori and GERD

• H. pylori eradication:
  • triple therapy: PPI, amoxicillin and clarithromycin for 14 days, where clarithromycin resistance is low;
  • or bismuth quadruple therapy: PPI, bismuth, metronidazole and tetracycline;
  • confirm eradication with a urea breath test or stool antigen at least 4 weeks after antibiotics and 2 weeks off PPIs.
• GERD:
  • lifestyle measures: weight loss, head-of-bed elevation, avoiding late meals;
  • a PPI for 8 weeks, then step down to the lowest effective dose;
  • alarm features (dysphagia, bleeding, weight loss, anemia) need endoscopy.

Antiemetics, laxatives and antidiarrheals

• Antiemetics:

• Constipation:
  • bulk-forming laxatives (psyllium; take with water);
  • osmotic laxatives (polyethylene glycol, lactulose, magnesium salts, avoided in renal failure);
  • stimulant laxatives (senna, bisacodyl);
  • stool softeners;
  • for opioid-induced constipation, always give a laxative with the opioid (methylnaltrexone if refractory).
• Diarrhea:
  • ORS and zinc for acute diarrhea in children;
  • loperamide (a peripheral opioid agonist) for non-inflammatory diarrhea in adults; avoid it in dysentery, C. difficile and young children;
  • racecadotril (an enkephalinase inhibitor) is an option.

Biliary, pancreatic and GI infections

• Cholelithiasis:
  • ursodeoxycholic acid dissolves small cholesterol stones in selected patients, but cholecystectomy is definitive;
  • biliary colic is treated with NSAIDs.
• Acute cholangitis: IV antibiotics covering Gram-negatives and anaerobes (piperacillin-tazobactam, ceftriaxone plus metronidazole, or a carbapenem when severe) plus biliary drainage (ERCP).
• Acute pancreatitis:
  • early IV fluids (Ringer's lactate), analgesia (opioids are acceptable) and early oral or enteral feeding;
  • no prophylactic antibiotics; give antibiotics only for infected necrosis or cholangitis.
• GI infections:
  • typhoid: azithromycin, ceftriaxone (or a fluoroquinolone where susceptible);
  • shigellosis: azithromycin, ciprofloxacin or ceftriaxone;
  • cholera: single-dose doxycycline (azithromycin in children and pregnancy) with rehydration;
  • non-typhoidal Salmonella gastroenteritis: usually no antibiotics.
• Clostridioides difficile:
  • oral vancomycin or fidaxomicin (metronidazole only if these are unavailable);
  • stop the offending antibiotic;
  • for fulminant disease: high-dose oral or rectal vancomycin plus IV metronidazole;
  • for recurrent disease: fidaxomicin, bezlotoxumab or fecal microbiota transplantation.
• Candidiasis:
  • oral thrush: nystatin or clotrimazole;
  • esophageal candidiasis: oral fluconazole.
• Antiparasitic drugs:
  • albendazole and mebendazole inhibit worm tubulin and are used for ascariasis, hookworm, trichuriasis (3 days), enterobiasis (repeat in 2 weeks), capillariasis (prolonged) and neurocysticercosis (with steroids). Albendazole is avoided in the first trimester;
  • praziquantel increases calcium permeability in the worm and treats schistosomiasis, other flukes and tapeworms;
  • metronidazole or tinidazole treats amebiasis and giardiasis, followed by diloxanide or paromomycin as a luminal agent for amebiasis;
  • ivermectin treats strongyloidiasis;
  • pyrantel treats ascariasis and pinworm.

Viral hepatitis and GI cancer

• Hepatitis B:
  • tenofovir (TDF or TAF) or entecavir, nucleos(t)ide analogs with a high barrier to resistance, given long-term when HBV DNA and ALT are high or there is fibrosis or cirrhosis;
  • TDF has renal and bone toxicity, which TAF reduces;
  • stopping therapy can cause hepatitis flares;
  • tenofovir is used in pregnancy to prevent transmission.
• Hepatitis C:
  • pangenotypic direct-acting antivirals (sofosbuvir-velpatasvir for 12 weeks, glecaprevir-pibrentasvir for 8 weeks) cure over 95%;
  • screen for hepatitis B first, because reactivation can occur;
  • amiodarone with sofosbuvir can cause severe bradycardia.
• Hepatitis A and E: supportive care.
• GI cancer chemotherapy:
  • 5-fluorouracil or oral capecitabine (thymidylate synthase inhibition, enhanced by leucovorin) is the backbone for colorectal and gastric cancer, with oxaliplatin (FOLFOX: cold-induced neuropathy) or irinotecan (FOLFIRI: diarrhea, neutropenia);
  • DPD deficiency causes severe fluoropyrimidine toxicity;
  • capecitabine causes hand-foot syndrome;
  • targeted drugs include anti-EGFR antibodies for RAS wild-type colorectal cancer, anti-VEGF bevacizumab (hypertension, bleeding, perforation) and sorafenib or atezolizumab-bevacizumab for hepatocellular carcinoma.