Built from GI Lecture 23 (LOs 1–9). Close notes. Fill from memory. Reveal only after a genuine attempt.

LO 1

ON EXAM — parietal cell targets (H+/K+-ATPase, H2R, M3R), H2 blockers vs PPIs (potency/onset), P-CABs, side effects of long-term PPI (hypomagnesemia, B12/Ca2+, C. diff risk)

Parietal cell inputs — what stimulates acid secretion? (3 pathways)

Pathway 1 — _______ cell releases histamine → H2 receptor

ECL (enterochromaffin-like)

Pathway 2 — Parasympathetic (vagus) releases _______ → M3 receptor

Acetylcholine (ACh)

Pathway 3 — _______ cells release gastrin → CCK-B receptor

G cells (antral/duodenal)

Drug classes targeting acid — name mechanism + 1 example

Drug Class	MOA	Example	Speed
Antacids	Neutralize existing acid (raise pH)	CaCO₃, Mg(OH)₂	Fast (immediate)
H2 receptor blockers	Block H2 on parietal cells (reversible)	Famotidine, Cimetidine	1–2 hours
PPIs (proton pump inhibitors)	Irreversibly block H⁺/K⁺-ATPase	Omeprazole, Pantoprazole	Days (reaches full effect)
P-CABs	Competitive (reversible) H⁺/K⁺-ATPase block	Vonoprazan, Tegoprazan	Hours

H2 blockers vs PPIs — key differences

H2 blocker: reversible or irreversible block?

Reversible

PPI: reversible or irreversible block?

Irreversible (covalent binding)

Which is more potent (reduces acid more)?

PPI (blocks final common pathway)

Which has faster onset?

H2 blocker (reversible = faster; PPI takes days)

Name 2 H2 blockers

Famotidine, Cimetidine, Ranitidine

Name 3 PPIs

Omeprazole, Pantoprazole, Lansoprazole

PPI side effects — chronic use complications (fill 4)

Electrolyte — causes seizures/arrhythmias if low

Magnesium (hypomagnesemia)

Vitamin deficiency — intrinsic factor needed for absorption

Vitamin B12 (cobalamin)

Mineral deficiency — reduced absorption in alkaline stomach

Calcium (or phosphate)

What does PPI-induced achlorhydria increase risk of?

C. difficile infection (loss of gastric acid barrier)

LO 2

ON EXAM — quadruple vs triple therapy regimens, which antibiotics, bismuth role, why combination (resistance + PPI dual role), eradication testing (test timing + method)

H. pylori basics — survival + pathogenesis

What enzyme does H. pylori produce to survive gastric acid?

Urease

This enzyme converts urea into _______ and _______, the second of which buffers local acid

NH₃ (ammonia) and CO₂ (carbon dioxide); NH₃ buffers

Untreated H. pylori → chronic gastritis + risk of what 2 serious sequelae?

MALT lymphoma, Gastric adenocarcinoma

H. pylori diagnosis — methods

Test	Mechanism / What It Detects	Invasive?
Urea breath test	Patient ingests ¹³C-urea; H. pylori urease breaks it down → ¹³CO₂ in breath detected	No (non-invasive)
Stool antigen	Detects H. pylori antigens in feces	No (non-invasive)
CLO test (biopsy)	Endoscopic biopsy + urease substrate → color change if H. pylori	Yes (endoscopy required)
Serology (IgG)	Detects anti-H. pylori IgG antibodies	No (blood test)

Quadruple therapy regimen — name all 4 drugs + duration

MNEMONIC ALERT: Quadruple = 2 ABX + PPI + Bismuth. This is the current standard.

Component	Drug Name(s)	Duration
Antibiotic #1	Metronidazole (Flagyl)	7–14 days
Antibiotic #2	Tetracycline	7–14 days
Acid suppression	PPI (any — omeprazole, pantoprazole, lansoprazole)	7–14 days ABX, then continued until ulcer heals
Antimicrobial coating	Bismuth subsalicylate (Pepto-Bismol)	7–14 days ABX, then continued for gastric healing

Why PPI is essential in the regimen (2 reasons)

Reason 1 — treatment goal (healing)

Reduces gastric acid to allow ulcer healing

Reason 2 — antibiotic efficacy (pH-dependent)

Raises gastric pH so antibiotics are more effective (many ABX fail in acid)

Post-treatment monitoring — eradication testing

Test for eradication how many weeks after completing antibiotics?

4 weeks

Which test to use (2 acceptable methods)

Urea breath test OR stool antigen

Why NOT use serology (IgG) for follow-up?

IgG stays positive after eradication (does not clear quickly)

LO 3

ON EXAM — antacid choice (Mg/Ca/Al side effects), stepwise GERD treatment (lifestyle → antacid → H2 → PPI), LES physiology, PPIs > H2 for erosive disease

Individual antacids — GI side effects mnemonic

Antacid	Side Effect(s)	Mnemonic / Tip
Magnesium hydroxide	Diarrhea (osmotic)	Mg = Must Go (diarrhea)
Aluminum hydroxide	Constipation; phosphate depletion	Al = All Locked Up (constipation)
Calcium carbonate	Gas, bloating, constipation	Tums; fast-acting but can cause gas
Sodium bicarbonate	CO₂ gas, bloating, belching	Creates CO₂ bubble in stomach
Mg + Al 50/50 combo	Balanced (effects cancel out)	Maalox, Mylanta; ideal combination

GERD stepwise treatment algorithm

Step-wise GERD therapy: empiric treatment first, escalate if inadequate response or if erosive disease confirmed.

Step 1 (initial) — non-pharmacologic

Lifestyle: weight loss, raise head of bed, avoid triggers (spicy, fatty, alcohol, NSAIDs)

Step 2 (mild symptoms) — which drug class?

Antacids or H2 blocker PRN (e.g., famotidine)

Step 3 (moderate or persistent) — which drug class?

PPI once daily (e.g., omeprazole) — more potent than H2 blockers

Step 4 (erosive disease confirmed) — which drug preferred?

PPI (most potent; better at healing erosions than H2 blockers)

LES and acid reflux mechanics

What is the LES and what keeps it normally closed?

Lower esophageal sphincter; maintained by resting tone from VIP/NO inhibitory neurons (between contractions)

What hormones/drugs RELAX the LES (promote reflux)?

Nitrates, CCK, caffeine, alcohol, anticholinergics, chocolate; smoking

What is the pathophysiology of Barrett's esophagus?

Chronic acid reflux → squamous epithelium → metaplasia to columnar (intestinal-type) epithelium → increased adenocarcinoma risk

LO 5 · LO 6

ON EXAM — 5-HT3 antagonists (chemo nausea), 5-HT4 agonists (prokinetics), muscarinic antagonists (motion sickness), metoclopramide (TARDIVE DYSKINESIA risk, D2 block), chemotherapy-induced nausea mechanism

Vomiting reflex anatomy — CTZ and NTS

CTZ = chemoreceptor trigger zone; where is it located?

Postrema (area postrema), base of 4th ventricle

Is CTZ inside or outside the blood-brain barrier?

OUTSIDE (chemosensitive to blood/CSF toxins)

NTS = nucleus tractus solitarius; what does it do?

Receives vagal afferents from GI; integrates signals to dorsal motor nucleus (vomiting center)

Name 3 inputs to the vomiting center that can trigger nausea

(1) CTZ chemoreceptors, (2) GI mechanoreceptors (via vagus), (3) Vestibular system

Antiemetic drugs — class, MOA, clinical use

Drug / Class	MOA	Best For / Indication
Ondansetron (Zofran)	5-HT3 antagonist on vagal afferents	Chemo-induced nausea & vomiting, post-op N/V
Granisetron	5-HT3 antagonist (same as ondansetron)	Chemo-induced nausea & vomiting, post-op N/V
Metoclopramide (Reglan)	D2 dopamine antagonist at CTZ; weak 5-HT4 agonist	Gastroparesis, post-op N/V, migraine-N/V (short-term only)
Prochlorperazine (Compazine)	D2 dopamine antagonist at CTZ	General nausea/vomiting, post-op, migraine
Scopolamine	M1 muscarinic antagonist (blocks ACh on vestibular nuclei)	Motion sickness, vestibular vertigo
Diphenhydramine (Benadryl)	H1 antihistamine + anticholinergic (M1 block)	Motion sickness, vestibular nausea

5-HT3 antagonists vs 5-HT4 agonists — comparison

5-HT3 antagonist examples (2)

Ondansetron (Zofran), Granisetron

5-HT3 use — what type of nausea?

Chemotherapy-induced nausea & vomiting, post-operative N/V

5-HT4 agonist examples (2)

Cisapride, Prucalopride

5-HT4 use — what GI problem does it treat?

Gastroparesis (↑ACh release → ↑motility/peristalsis)

Metoclopramide — MOA + major side effect concern

Metoclopramide blocks which dopamine receptor?

D2 dopamine receptor (at CTZ and in GI)

What is the serious long-term neurological side effect?

Tardive dyskinesia (involuntary orofacial/limb movements) — BLACK BOX WARNING

Risk is highest if used > _______ months at high dose

3 months

LO 7 · LO 8

ON EXAM — laxative onset categories (bulk/osmotic/stimulant timing), diphenoxylate vs loperamide, when to AVOID antidiarrheals (toxin-mediated/invasive), ORS rationale (glucose-sodium coupling)

Laxative classification by onset — name drugs in each category

Laxative Type	Onset	MOA	Example Drug(s)
Bulk	12–24 hours	Absorbs water → ↑stool bulk → triggers peristalsis	Psyllium husk (Metamucil), methylcellulose
Osmotic	2–3 hours	Draws water into lumen via osmotic gradient	MgCl₂, Lactulose, PEG (MiraLAX)
Stimulant	6–12 hours	Directly stimulates smooth muscle + ↑secretion	Bisacodyl (Dulcolax), Senna, Castor oil
Stool softener	Days (slow)	Reduces surface tension → water penetrates stool	Docusate (Colace), Mineral oil

Antidiarrheals — drugs + mechanism

Diphenoxylate (Lomotil) — MOA + concern

μ-opioid agonist in GI → ↓motility; + atropine (abuse deterrent); opioid abuse potential

Loperamide (Imodium) — MOA + difference from diphenoxylate

μ-opioid agonist (peripheral only, poor BBB penetration); NO abuse potential; safer

Bismuth subsalicylate (Pepto-Bismol) — MOA

Antimicrobial, anti-inflammatory, forms protective mucosal coating

When to AVOID antidiarrheals — contraindications

CRITICAL: Never give antidiarrheals in inflammatory diarrhea (toxin-mediated or invasive). They worsen outcomes by trapping toxins/bacteria.

Condition: C. difficile toxin-mediated diarrhea → why avoid diphenoxylate/loperamide?

Antidiarrheals trap toxins in colon → prolonged exposure → worse outcomes, megacolon risk

Condition: Shigella or EAEC invasive diarrhea → why avoid?

Slows gut motility → organisms trapped in lumen longer → worse systemic invasion, complications

General rule: avoid antidiarrheals if _______ and _______ are present

Fever AND bloody diarrhea (signs of invasion/inflammation)

Diarrhea management — ORS and fluid/electrolyte rationale

ORS contains what 2 key components that work synergistically?

Glucose and Sodium

Mechanism: how does this combo reduce stool losses?

Glucose-sodium co-transporter (SGLT1) drives Na+ and water absorption even during diarrhea

Why is ORS preferred over plain water?

Plain water may worsen osmotic diarrhea; ORS replaces electrolytes + restores sodium gradient

LO 9

ON EXAM — 5-ASA location (colon-targeted for UC), anti-TNF biologics (infliximab/adalimumab both GI+systemic), anti-IL-23 (risankizumab), Crohn's vs UC drug choice, steroid role (acute flare only)

IBD classification — Crohn's vs UC key differences

Feature	Crohn's Disease	Ulcerative Colitis
Location(s)	Mouth to anus (segmental, skip lesions); usually terminal ileum	Colon and rectum only (continuous)
Depth of inflammation	Transmural (all layers through muscularis)	Mucosa + submucosa only (superficial)
Complications (fistula/stricture?)	YES — fistulas, strictures, abscesses	NO — toxic megacolon, perforation (fulminant colitis)

5-ASA compounds — drugs + mechanism

What does 5-ASA stand for?

5-Aminosalicylic acid

Mesalamine (Asacol) — how is it formulated for colon delivery?

pH-dependent coating (dissolves at pH >6 in terminal ileum/colon)

Sulfasalazine — what is it + why useful?

5-ASA linked to sulfapyridine (prodrug); colonic bacteria cleave bond → releases 5-ASA locally

Role of 5-ASA in Crohn's vs UC: which is better indicated?

Better for UC (colon-targeted); less effective in Crohn's (spread throughout GI)

Biologic agents — anti-TNF and anti-IL-23

Drug	Target / MOA	GI + Systemic Effect?	Crohn's / UC?
Infliximab (Remicade)	Monoclonal antibody against TNF-α	YES (both local + systemic Th1/Th17)	BOTH Crohn's AND UC
Adalimumab (Humira)	Fully human monoclonal antibody against TNF-α	YES (both local + systemic TNF blockade)	BOTH Crohn's AND UC
Risankizumab	Blocks IL-23 (prevents Th17 differentiation)	YES (reduces Th17 both local + systemic)	Crohn's (increasingly used, newer)

Steroids in IBD — role and limitations

When are systemic steroids (prednisone) used in IBD?

Acute flares ONLY (high-dose for 1–2 weeks, then taper)

Why are steroids NOT used for maintenance therapy?

Unacceptable long-term side effects (osteoporosis, immunosuppression, adrenal suppression, etc.)

What is budesonide and when is it used?

Inhaled/topical corticosteroid with high first-pass liver metabolism; used for distal/mild Crohn's (minimizes systemic absorption)

Practice Questions

Q1: Acid suppression mechanism

A 38-year-old man with erosive GERD is started on omeprazole. Which of the following best describes the mechanism of this drug?

A) Reversible blockade of H₂ histamine receptors on parietal cells
B) Irreversible blockade of the H⁺/K⁺-ATPase (proton pump) in parietal cell canaliculus
C) Neutralization of existing gastric acid via alkaline ions
D) Inhibition of gastrin release from G cells
E) Competitive blockade of H⁺/K⁺-ATPase (reversible)

Correct Answer: B

Omeprazole is a proton pump inhibitor (PPI) that irreversibly blockades the H⁺/K⁺-ATPase. This is the final common pathway for acid secretion, making PPIs the most potent acid suppressors. They are activated in the acidic canalicular space and bind irreversibly to the pump. A is H₂ blockers (reversible). C is antacids. D is not a mechanism of any major acid-suppressive drug. E describes P-CABs, which are newer.

Q2: H. pylori eradication regimen

A 45-year-old woman is diagnosed with H. pylori by urea breath test and presents with a peptic ulcer. She is prescribed quadruple therapy. Which of the following is the correct combination?

A) Amoxicillin + Clarithromycin + PPI
B) Metronidazole + Tetracycline + PPI + Bismuth subsalicylate
C) Levofloxacin + Clarithromycin + H₂ blocker
D) Amoxicillin + Doxycycline + PPI + Antacid
E) Triple therapy is sufficient; quadruple is not standard

Correct Answer: B

Quadruple therapy (the current standard per Medical Letter) consists of: Metronidazole + Tetracycline + PPI + Bismuth subsalicylate for 7–14 days. The PPI reduces acid (heals ulcer) AND improves antibiotic efficacy. Bismuth has intrinsic antimicrobial activity. A is older triple therapy (falling out of favor). C uses wrong drugs. D mixes different agents. E is incorrect; quadruple is now preferred due to clarithromycin resistance.

Q3: Antacid side effects

A patient is given aluminum hydroxide for 2 weeks to treat GERD symptoms. Which side effect would you expect?

A) Diarrhea and hypermagnesemia
B) Constipation and phosphate depletion
C) Hypercalcemia and bloating
D) Hypomagnesemia and loose stools
E) Metabolic alkalosis and muscle weakness

Correct Answer: B

Aluminum hydroxide causes CONSTIPATION (not diarrhea) and binds phosphate in the gut, leading to phosphate depletion. Magnesium hydroxide does the opposite (diarrhea). Remember: "Mg = Must Go" (diarrhea), "Al = All Locked Up" (constipation).

Q4: 5-HT3 antagonists and chemotherapy nausea

A 52-year-old woman receiving chemotherapy for breast cancer develops severe nausea. She is prescribed ondansetron IV before her next infusion. What is the mechanism of this drug?

A) Dopamine antagonist at the CTZ
B) Blocks 5-HT3 receptors, preventing vagal afferent signaling from GI to vomiting center
C) M1 muscarinic receptor antagonist (motion sickness pathway)
D) Increases gastric motility via 5-HT4 agonism
E) Reduces intracranial pressure in the CTZ

Correct Answer: B

Ondansetron (and other setrons like granisetron) are selective 5-HT3 receptor antagonists. They block 5-HT3 receptors on vagal afferent neurons, preventing the transmission of chemotherapy-induced nausea signals to the vomiting center. A is metoclopramide. C is scopolamine/antihistamines. D is cisapride/prucalopride (prokinetics). E is not a mechanism of any antiemetic.

Q5: Metoclopramide safety concern

A 40-year-old man with gastroparesis is treated with metoclopramide for 18 months at standard doses. He begins to develop involuntary orofacial movements. Which adverse effect is this consistent with?

A) Extrapyramidal side effects (acute dystonia)
B) Neuroleptic malignant syndrome
C) Tardive dyskinesia
D) Parkinsonism (tremor)
E) Akathisia

Correct Answer: C

Tardive dyskinesia (involuntary dyskinetic movements, especially orofacial) is a serious long-term risk of metoclopramide (a D2 blocker), especially with prolonged use (>3 months) at higher doses. This is an FDA black box warning. A/B/D/E are other dopamine antagonist side effects but occur acutely. The 18-month duration and specific presentation point to tardive dyskinesia.

Q6: Laxative onset classification

An elderly patient with constipation needs immediate bowel evacuation for a colonoscopy tomorrow morning. Which laxative has the fastest onset (hours)?

A) Psyllium husk (Metamucil)
B) Magnesium citrate (osmotic)
C) Docusate (stool softener)
D) Bisacodyl (stimulant)
E) Mineral oil

Correct Answer: B

Osmotic laxatives like magnesium citrate work within 2–3 hours by drawing water into the intestinal lumen. This makes them ideal for rapid bowel evacuation (prep). A (bulk) takes 12–24 hours. C (softener) is very slow. D (stimulant) takes 6–12 hours. E (mineral oil) takes 6–8 hours.

Q7: Antidiarrheal contraindication

A 35-year-old man presents with acute bloody diarrhea, fever, and positive stool culture for Shigella. He requests medication to stop the diarrhea. What is the best recommendation?

A) Prescribe loperamide (Imodium) to reduce symptoms
B) Prescribe diphenoxylate with atropine (Lomotil)
C) Avoid antidiarrheals; they worsen invasive bacterial infections by trapping organisms and toxins
D) Give bismuth subsalicylate for symptom relief
E) Both A and B are acceptable first-line treatments

Correct Answer: C

Antidiarrheals (loperamide, diphenoxylate) are CONTRAINDICATED in invasive bacterial diarrhea (Shigella, EAEC, Salmonella, Campylobacter) and toxin-mediated diarrhea (C. difficile, Enterotoxigenic E. coli) because they trap organisms/toxins in the gut, prolonging infection and worsening complications. Supportive care with ORS is preferred. D (bismuth) is less problematic but still used cautiously.

Q8: IBD drug choice — anti-TNF vs anti-IL-23

A 28-year-old woman is diagnosed with moderate Crohn's disease and is started on anti-TNF biologic therapy with infliximab. Which of the following best describes infliximab's role in IBD?

A) It blocks IL-23 signaling, preventing Th17 differentiation
B) It is a monoclonal antibody that binds TNF-α, preventing its interaction with TNFR1 and TNFR2, reducing pro-inflammatory cascade
C) It inhibits 5-HT4 receptors to reduce intestinal motility
D) It replaces missing 5-ASA at mucosal sites
E) It repairs the intestinal barrier by blocking zonula occludens proteins

Correct Answer: B

Infliximab is a chimeric monoclonal antibody against TNF-α. It binds TNF and prevents its interaction with tumor necrosis factor receptors, reducing the pro-inflammatory Th1/Th17 response in both GI and systemic sites. A describes anti-IL-23 agents like risankizumab (newer, also effective). C is antiemetic/prokinetic. D and E are not mechanisms of biologics.

GI Pharmacology — Answer Key