πŸ’Š Lecture 23 β€” GI Pharmacology
Acid Suppression Β· H. pylori Β· GERD Β· Cytoprotection Β· Antiemetics Β· Antidiarrheals Β· Laxatives Β· IBD Biologics
βœ… View Answer Key
GI Pharmacology β€” Active Recall Drill Close notes. Fill from memory. Check against the answer key (opens in new window). High-yield focus: parietal cell targets, PPI vs P-CAB, H. pylori quadruple therapy, vomiting reflex receptors, antiemetic class selection, laxative onset/class, IBD biologic targets.
Parietal Cell Targets
3 Stimulatory Inputs to Parietal Cell (NT β†’ Receptor β†’ Cell of Origin)
1.
2.
3.
Final Common Pump Blocked by PPIs/P-CABs
Why Anticholinergics Are Rarely Used for Acid Suppression
Which Target Has the Most Potent Acid Suppression?
Hβ‚‚ Receptor Antagonists ("-tidines")
DrugUnique FeatureKey ADR / Concern
Cimetidine
Think: CYP450 inhibitor + anti-androgen effects.
Ranitidine
Think: withdrawn from market β€” contamination issue.
Famotidine
Think: most potent Hβ‚‚ blocker, minimal CYP interactions.
MOA of Hβ‚‚ Blockers (Mechanism Class, Reversibility)
1.
↓
2.
↓
3.
Key Limitation of Long-Term Hβ‚‚ Blocker Use
🚩 TRAP β€” CIMETIDINE DRUG INTERACTIONS
Proton Pump Inhibitors ("-prazoles")
MOA (Complete Chain β€” Prodrug β†’ Activation β†’ Binding Type)
1.
↓
2.
↓
3.
↓
4.
When Must PPIs Be Taken (Meal Timing)? Why?
Why No Tolerance Develops (vs Hβ‚‚ Blockers)
PPI with LEAST CYP450 Interactions
PPICYP Effects / Notes
Omeprazole / Esomeprazole
Pantoprazole
Lansoprazole
5 Long-Term PPI Adverse Effects
1.
2.
3.
4.
5.
Mechanism β€” Why PPIs Cause B12 Deficiency
1.
↓
2.
↓
3.
🚩 TRAP β€” PPI + CLOPIDOGREL
P-CABs (Potassium-Competitive Acid Blockers)
FeaturePPIsP-CABs (e.g., Vonoprazan)
Binding
Requires Acid Activation?
Onset
Meal-Timing Required?
Antacids
AntacidKey Side EffectUnique Fact
Aluminum Hydroxide
Think: binds phosphate in gut β€” used in CKD hyperphosphatemia.
Magnesium Hydroxide
Think: "Milk of Magnesia" β€” also used as an osmotic laxative.
Calcium Carbonate
Think: rebound acid + a named syndrome from chronic excess use.
Sodium Bicarbonate
Think: fastest onset + risk of systemic alkalosis and Na⁺ load.
Mnemonic: Mg vs Al GI Effect
M
G
A
L
Milk-Alkali Syndrome β€” Triad + Causative Antacid
🚩 TRAP β€” ANTACID DRUG INTERACTIONS
H. pylori β€” Virulence & Diagnosis
Key Virulence Enzyme + Mechanism of Acid Survival
Long-Term Complications of Untreated H. pylori (2)
1.
2.
Gold-Standard Non-Invasive Dx Test + How It Works
Why Serology (IgG) Is NOT Used to Confirm Eradication
Treatment Regimens
RegimenDrugs (all 4 / all 3)Duration / When Used
Quadruple Therapy (preferred, 1st-line)
Triple Therapy (older, falling out of favor)
Why Is Triple Therapy Falling Out of Favor?
PPI's Dual Role in H. pylori Therapy
1.
2.
Post-Treatment Retesting: When? Which Test(s)?
Bismuth in Quadruple Therapy β€” Why Added? (2 roles)
1.
2.
Cytoprotective Agents
DrugMOAKey Use / Unique FactContraindication / ADR
Sucralfate
Think: requires acidic pH β€” don't co-administer with PPI/Hβ‚‚ blocker.
Misoprostol
Think: PGE₁ analog β€” prevents NSAID ulcers, used in OB for labor induction.
Bismuth subsalicylate
Think: black stools + black tongue; part of quadruple H. pylori therapy.
πŸ›‘ HARD TRAP β€” MISOPROSTOL IN PREGNANCY
GERD Pathophysiology
Primary Mechanical Defect in GERD
Normal LES Resting Pressure (mmHg)
3 Normal Esophageal Defense Mechanisms
1.
2.
3.
Progression: Chronic GERD β†’ ??? β†’ ??? (name both)
1.
2.
Factors That Reduce LES Pressure (Drug/Food)
CategoryExamples to List
Dietary (β‰₯4)
Drugs (β‰₯5 classes)
Systemic disease
Physiologic
Stepwise Treatment
Step 1 (Lifestyle)
Step 2 (On-Demand Drug Class)
Step 3 (Mild/Intermittent Symptoms)
Step 4 (Frequent/Severe or Erosive)
Step 5 (Refractory / Failed BID PPI)
Surgical Option for Refractory GERD
🚩 TRAP β€” DRUG-INDUCED GERD
Vomiting Reflex β€” 4 Centers & Receptor Profiles
CenterLocation / FeatureKey ReceptorsStimulus
Emetic Center
CTZ (Area Postrema)
NTS (Nucleus Tractus Solitarius)
Vestibular System
Why Is the CTZ Uniquely Accessible to Blood-Borne Toxins?
Which 2 Receptors Dominate Motion Sickness (Vestibular)?
1.
2.
Antiemetic Classes
ClassPrototype Drug(s)Best UseKey ADR
5-HT₃ Antagonists
NK₁ Antagonists
Dβ‚‚ Antagonists
H₁ Antagonists
M₁ Antagonists
Cannabinoids
Corticosteroids
Best Regimen for Chemo-Induced N/V (Acute, Triple Therapy β€” 3 drug classes)
1.
2.
3.
Ondansetron Key ADR to Monitor on ECG
Prokinetics
DrugMOA (Dual)Clinical UseKey ADR / Black Box
Metoclopramide
Erythromycin
πŸ›‘ HARD TRAP β€” METOCLOPRAMIDE IN PARKINSON'S
Antidiarrheal Agents
DrugMOAKey Use / Unique Fact
Loperamide
Think: OTC; P-glycoprotein keeps it out of CNS at therapeutic doses.
Diphenoxylate/Atropine
Think: why is atropine added? (Schedule V controlled drug.)
Bismuth subsalicylate
Think: traveler's diarrhea + avoid in children (Reye syndrome β€” salicylate).
Octreotide
Think: somatostatin analog β€” VIPoma, carcinoid, variceal bleeding.
Rifaximin
Think: non-absorbable β€” hepatic encephalopathy (↓ NH₃-producing flora).
πŸ›‘ HARD TRAP β€” LOPERAMIDE IN C. DIFFICILE / EHEC
Laxatives by Class
ClassPrototype Drug(s)OnsetMOA / Unique Fact
Bulk-Forming
Think: absorb water β†’ ↑ stool bulk; safest for chronic use.
Osmotic
Think: lactulose also traps NH₃ in gut (hepatic encephalopathy).
Stimulant
Think: long-term use β†’ melanosis coli (benign pigmentation).
Stool Softener
Think: surfactant β€” limited efficacy; prophylactic use.
Cl⁻ Channel Activator
Think: ClC-2 channel activator β€” used in IBS-C / opioid-induced constipation.
Guanylate Cyclase-C Agonist
Think: ↑ cGMP β†’ ↑ Cl⁻/HCO₃⁻ secretion; for IBS-C.
PAMORA (peripheral ΞΌ-opioid antag.)
Think: excluded from CNS β†’ doesn't reverse central analgesia.
Lactulose Dual Use β€” Laxative AND ???
Why Do PAMORAs NOT Reverse Central Analgesia?
IBD Treatment Pyramid (Bottom = Mild β†’ Top = Severe)
Step 1 (Mildest)
Step 2 (Induction only β€” NOT maintenance; why?)
Step 3 (Immunomodulators β€” name 2)
1.
2.
Step 4 (Biologics β€” 3 target categories)
1.
2.
3.
Step 5 (Last-Line)
5-ASAs (Mesalamine & Related)
MOA (Local Anti-Inflammatory)
1.
↓
2.
↓
3.
More Effective in UC or CD? Why?
Sulfasalazine β€” What Is the 2nd Component? ADR It Causes?
Key Renal ADR of Mesalamine
Biologics
Class / DrugTargetBlack Box / Key Concern
Anti-TNF-Ξ± (infliximab, adalimumab)
Ustekinumab
Risankizumab
Vedolizumab
Natalizumab
πŸ›‘ HARD TRAP β€” NATALIZUMAB & PML
Immunomodulators
Azathioprine / 6-MP β€” What Enzymes to Check Before Starting? Why?
Azathioprine / 6-MP Key ADRs (3)
1.
2.
3.
Methotrexate β€” Preferred in UC or CD?
MTX Pre-Screening Before Starting for IBD (Tests)
Anti-TNF Pre-Screening & ADRs
Mandatory Infectious Pre-Screens Before Anti-TNF (2)
1.
2.
Malignancy Risk Increased with Anti-TNF + Thiopurine Combo
FMT (Fecal Microbiota Transplant)
Gold-Standard Indication for FMT
Emerging (Non-Standard) Indication

Drill complete. When you've attempted every field, open the answer key and self-grade. Circle anything you missed and review the relevant lecture section.