Gastrointestinal & Adjacent Agents – Comprehensive Study Notes

Antacids & Acid-Reducing Agents

• Magnesium-based antacids
– Prototype: milk of magnesia, Maalox formulations
– Adverse: osmotic pull of Mg²⁺ → loose stools/diarrhea
– Most pts never take enough to reach constipation/diarrhea; if they do, refer → GI work-up.

• Calcium-based antacids (e.g., Tums)
– Provide extra elemental Ca²⁺ (bonus for osteopenic pts).
– Frequently recommended as OTC first-line for heartburn.

• H₂-receptor blocker – Famotidine
– MOA: blocks H_2 histamine receptors on parietal cells → ↓ cAMP → ↓ HCl secretion.
– Same clinical endpoint as PPIs (↓ acid) but via different pathway; useful for GERD or mild PUD.

• Sucralfate
– Sucrose–aluminum salt; forms viscous protective coat over ulcer crater → barrier vs. acid/pepsin.
– Dosing obstacle: q6h (≈4×/day) on empty stomach & just before meals → poor adherence compared to once-daily omeprazole.

• Misoprostol
– Synthetic PGE_1 analog → ↑ mucus & bicarbonate, ↓ acid; GI cytoprotection.
– Key contraindication: pregnancy (uterotonic → miscarriage); require neg. test + contraception.

• Clinical pearl: Persistent OTC antacid use → evaluate for GERD/PUD; consider H. pylori testing. Triple therapy after positive test eradicates bug → ulcer heals.

Laxatives (Constipation)

• Lactulose (osmotic)
– Non-absorbable disaccharide; colonic bacteria → lactic/acetic form acids → osmotic water draw.
– Counseling: maintain hydration; sugar molecule raises BG → watch Type 1 diabetics (may need insulin titration).

• Psyllium (bulk-forming)
– Hydrophilic fiber → swells → ↑ stool mass → stretch receptors → peristalsis.
– Require adequate fluid to avoid impaction/hemorrhoids.

• Senna (stimulant)
– Anthraquinone glycosides directly stimulate enteric nerves → contractions → cramping.
– Essential in opioid-induced constipation (OIC) d/t “lazy gut.”
– Best practice mantra: “mush then push” → combine with stool softener docusate for comfort.

Antidiarrheals & IBD adjuncts

• Sulfasalazine
– 5-ASA linked to sulfapyridine; for Crohn’s/Ulcerative colitis.
– Risks: sulfa allergy, photosensitivity, immunosuppression → infection, Stevens-Johnson syndrome.

• Diphenoxylate + Atropine
– Opioid receptor agonist (diphenoxylate) slows motility; atropine anticholinergic adds constipating effect & abuse deterrent.
– Uses: acute diarrhea, ↓ ileostomy output.
– Abuse potential in eating-disorder pts (appetite suppression).

• Probiotics
– Restore “good bugs.” Must specify live cultures.
– Rotate brands/strains for chronic ABX users to avoid mono-dominance.

Antiemetics – Chemotherapy-Induced N/V (CINV)

CINV regimens tailor drugs to emetogenic score & chemo cycle day (Day 0 = infusion).

• 5-HT₃ antagonist – Ondansetron (Zofran)
– ER favorite for any N/V type.
– Adverse: QT prolongation → monitor/high-risk pts (female, hypovolemia, other QT drugs).

• NK-1 antagonist – Aprepitant
– Blocks substance P at NK_1 receptors; adjuvant to 5-HT₃ blocker & steroid.

• Corticosteroid – Dexamethasone
– Synergistic antiemetic; part of many CINV protocols.

• Cannabinoid – Dronabinol
– Oral Δ^9-THC; activates CB₁ receptors → ↓ N/V + ↑ appetite (counter cachexia).

• Benzodiazepine – Lorazepam
– Key for anticipatory N/V (conditioned response before infusion).

Regimen example: highly emetogenic chemo may use \text{Day 0: ondansetron + dexamethasone + aprepitant}; lorazepam pre-infusion; dronabinol PRN appetite.

Motion Sickness / Vertigo Adjuncts

• Scopolamine
– Anticholinergic patch behind ear; prevents vestibular nausea, seasickness.

• Dimenhydrinate
– Antihistamine; OTC motion-sickness tabs; major effect = sedation (“sleep through trip”).

• Metoclopramide
– Dopamine (D₂) antagonist; promotility + CNS antiemetic; can aid vertigo-related dizziness.
– Black box: tardive dyskinesia w/ chronic use; contraindicated in Parkinson’s.
– TV class-action ads reflect litigation history.

Pancreatic Enzyme Replacement

• Pancrelipase
– Mixture of lipase, amylase, protease from porcine pancreas; CF malabsorption.
– Contra: pork allergy, strict vegetarian/vegan, certain religious dietary rules.
– No FDA-approved plant alternative; OTC plant enzymes unproven.

Pharmacologic Weight Management

• Orlistat
– GI lipase inhibitor → ↓ fat absorption → steatorrhea/oily urgency diarrhea unless fat-free diet.
– May ↓ absorption of fat-soluble vitamins A,D,E,K → supplement.
– Historical fiasco: “Olestra/Olean” fat-free chips → population-wide oily diarrhea.

• Phentermine
– Sympathomimetic; ↑ norepi release; appetite suppression & ↑ basal metabolic rate.
– Risks: tachycardia, HTN, insomnia; contra in hyperthyroidism & cardiac disease.
– Approved only short-term (≤3 mo); rebound weight gain common.

• GLP-1 analogs for obesity (e.g., Wegovy, Mounjaro)
– Not tested, but noteworthy: higher doses than T2DM use; induce mixed fat + muscle loss → unknown long-term skeletal & metabolic effects; ongoing research.