Gastrointestinal agents

Acid-Related Disorders (GERD, PUD, Dyspepsia)

Core Classes and Examples

• Proton pump inhibitors (PPIs): omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (AcipHex), dexlansoprazole (Dexilant)

• H₂-receptor antagonists (H2RAs): famotidine (Pepcid)

• Potassium-competitive acid blocker (P-CAB): vonoprazan (Voquezna)

• Antacids: calcium carbonate (Tums), magnesium/aluminum hydroxide (Maalox, Mylanta)

• Mucosal protectants: sucralfate (Carafate), bismuth subsalicylate (Pepto-Bismol), misoprostol (Cytotec)

Key Points

• PPIs: irreversible H⁺/K⁺-ATPase inhibition; best for mucosal healing and moderate–severe GERD/PUD

• H2RAs: competitive H₂ blockade; useful in mild disease and nocturnal acid breakthrough

• P-CAB: rapid, potent acid suppression; active regardless of meal timing

• Antacids: fast symptom relief; short duration; separate from other meds

• Mucosal protectants: add-on for ulcer protection or functional dyspepsia

Comparison — Acid Suppressants

Attribute	PPIs	H2RAs	P-CAB (vonoprazan)
Onset	Hours to days	Within hours	Rapid (hours)
Potency	High	Moderate	Very high
Dosing	Once daily; can do BID	Once or twice daily	Once daily
Meal timing	30–60 min before meal	Not meal-dependent	Not meal-dependent
Best use	Healing/maintenance	Mild GERD, nocturnal symptoms	Refractory GERD, H. pylori regimens
Cautions	Long-term risks: B12, Mg, fractures, infections	Tolerance with continuous use	Drug interactions subset; new class availability varies

H. pylori Eradication (adult, treatment-naïve, susceptibility unknown)

• Optimized bismuth quadruple (14 days): PPI BID + bismuth + tetracycline + metronidazole

• Alternative: vonoprazan-based dual or triple regimens where available

• Confirmation of cure: urea breath test or fecal antigen ≥4 weeks after therapy and ≥2 weeks off PPIs

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Antiemetics and Nausea/Vomiting (including CINV)

Classes and Examples

• 5-HT₃ antagonists: ondansetron (Zofran), granisetron (Sustol), palonosetron (Aloxi)

• NK1 antagonists: aprepitant/fosaprepitant (Emend), netupitant/palonosetron (Akynzeo), rolapitant (Varubi)

• D₂ antagonists: metoclopramide (Reglan), prochlorperazine, droperidol

• Antihistamine/anticholinergics: meclizine, dimenhydrinate, promethazine, scopolamine

• Corticosteroid adjunct: dexamethasone

• Others: olanzapine (highly emetogenic chemo), ginger as adjunct

CINV Backbone

• Highly emetogenic chemo: NK1 + 5-HT₃ + dexamethasone ± olanzapine

• Moderately emetogenic: 5-HT₃ + dexamethasone ± NK1 depending on regimen

Comparison — Core Antiemetic Classes

Class	Best For	Strengths	Key Adverse Effects
5-HT₃ antagonists	Acute CINV, PONV	Well tolerated, effective	Headache, constipation, QT prolongation (dose/form dependent)
NK1 antagonists	Delayed CINV	Synergy with 5-HT₃ + Dex	CYP interactions (aprepitant/rolapitant)
D₂ antagonists	Breakthrough N/V, migraine	Versatile, low cost	EPS, sedation, QT (droperidol)
Antihist/anticholinergics	Motion sickness, vestibular	Useful prophylaxis	Sedation, anticholinergic burden
Dexamethasone	Acute/delayed CINV adjunct	Potentiates regimens	Hyperglycemia, insomnia

Prokinetics and Motility Agents

Agents and Uses

• Metoclopramide: gastroparesis, refractory GERD adjunct; limit to ≤12 weeks

• Domperidone: gastroparesis (regional access); fewer CNS effects

• Erythromycin: motilin agonist; short-course bridge in severe gastroparesis (tachyphylaxis)

• Prucalopride: selective 5-HT4; chronic idiopathic constipation (CIC)

• Tegaserod: 5-HT4 partial; IBS-C (restricted criteria)

• Neostigmine: acute colonic pseudo-obstruction (monitored IV)

Comparison — Prokinetics

Agent	Primary Mechanism	Key Indication	Typical Adult Dose	Major Caution
Metoclopramide	D₂ antagonism, 5-HT4 agonism	Gastroparesis	10 mg before meals/HS	Tardive dyskinesia risk
Domperidone	Peripheral D₂ antagonism	Gastroparesis	10 mg TID	QT prolongation, CYP3A4 interactions
Erythromycin	Motilin receptor agonist	Short-term prokinetic	125–250 mg TID	Tachyphylaxis, QT/drug interactions
Prucalopride	5-HT4 agonist	CIC	2 mg daily (1 mg severe renal)	Headache/diarrhea
Tegaserod	5-HT4 partial agonist	IBS-C (women <65)	6 mg BID	CV risk history
Neostigmine	AChE inhibitor	ACPO	2 mg IV over 3–5 min	Bradycardia, bronchospasm

Constipation Pharmacotherapy (CIC) and IBS-C

Options

• Osmotics: polyethylene glycol (PEG), lactulose, magnesium oxide

• Stimulants: senna, bisacodyl, sodium picosulfate

• Secretagogues: linaclotide (Linzess/Constella), plecanatide (Trulance/Constella), lubiprostone (Amitiza)

• Prokinetic: prucalopride

Comparison — Constipation Agents

Class	Mechanism	Onset	When to Use	Key Adverse Effects
Osmotics	Osmotic water retention	1–3 days (PEG), hours (Mg)	First-line OTC	Bloating; Mg accumulation in CKD
Stimulants	Enteric nerve stimulation	6–12 h	Rescue/adjunct	Cramping
Secretagogues	GC-C agonism or ClC-2 activation	1–2 days	After OTC failure	Diarrhea, nausea (lubiprostone)
5-HT4 agonist	Prokinetic colonic transit	1–2 days	After OTC/secretagogue	Headache, diarrhea

Diarrhea and IBS-D

Agents

• Antimotility: loperamide; diphenoxylate/atropine

• Antibacterial for IBS-D: rifaximin (Xifaxan)

• Mixed opioid: eluxadoline (Viberzi; avoid without gallbladder)

• Bile acid binders: cholestyramine, colesevelam for bile acid diarrhea

• Adjuncts: bismuth subsalicylate; low-dose TCAs for pain modulation

Comparison — IBS-D Options

Option	Best Use	Benefits	Key Cautions
Loperamide	Urgency/loose stool control	Rapid, OTC	Avoid overuse; no global IBS benefit
Rifaximin	Global IBS-D symptoms	2-week course; repeatable	Cost; minimal systemic effects
Eluxadoline	Refractory IBS-D	Improves stool/urgency	Pancreatitis risk, contraindicated without gallbladder
Bile acid binders	Confirmed/likely BAD	Effective in BAD	Bloating, drug binding, titration needed
Low-dose TCA	Pain-predominant	Global relief	Anticholinergic effects

Inflammatory Bowel Disease (Ulcerative Colitis, Crohn’s)

Drug Classes and Examples

• 5-ASA: mesalamine (Pentasa, Asacol HD, Lialda), sulfasalazine

• Corticosteroids: budesonide (MMX, EC), prednisone/methylprednisolone

• Thiopurines: azathioprine, 6-mercaptopurine

• Methotrexate: CD maintenance (parenteral preferred)

• Anti-TNF: infliximab, adalimumab, golimumab (UC), certolizumab (CD)

• Anti-integrin: vedolizumab

• Anti-IL-12/23: ustekinumab

• Anti-IL-23: risankizumab (CD)

• JAK inhibitors: tofacitinib (UC), upadacitinib (UC/CD)

• S1P modulator: ozanimod (UC)

Comparison — IBD Advanced Therapies

Class	Agents	Indications	Route/Frequency	Onset	Key Safety Notes
Anti-TNF	Infliximab, adalimumab, golimumab, certolizumab	UC/CD (agent-specific)	IV or SC; q2–8 weeks	Weeks	Infection/TB reactivation; immunogenicity
Anti-integrin	Vedolizumab	UC/CD	IV then q8w; SC option in some regions	Weeks	Gut-selective; favorable systemic safety
Anti-IL-12/23	Ustekinumab	UC/CD	IV load → SC q8–12w	Weeks	Infection risk; monitor
Anti-IL-23	Risankizumab	CD	IV load → SC q8w	Weeks	Similar to ustekinumab class safety
JAK inhibitors	Tofacitinib, upadacitinib	UC (both), CD (upadacitinib)	Oral daily	Days–weeks	Zoster, VTE, lipid ↑, lab monitoring
S1P modulator	Ozanimod	UC	Oral daily	Weeks	Bradycardia initiation, LFTs, ophthalmic exam

Hepatic and Portal Hypertension

Key Agents

• Hepatic encephalopathy: lactulose, rifaximin

• Variceal bleeding: octreotide (acute), terlipressin (where available), nonselective beta-blockers for prophylaxis (propranolol, nadolol, carvedilol)

• Cholestatic disease: ursodeoxycholic acid; obeticholic acid (selected PBC patients)

Comparison — HE and Variceal Therapy

Indication	First-line	Adjuncts	Notes
Hepatic encephalopathy	Lactulose	Rifaximin for recurrence prevention	Titrate to 2–3 soft stools/day
Acute variceal bleed	Octreotide infusion + endoscopic therapy	Antibiotic prophylaxis	Start vasoactive agent promptly
Primary prophylaxis	Nonselective beta-blocker	Endoscopic ligation if intolerant	Carvedilol potent portal pressure reduction

Pancreatic Disorders

Agents

• Pancreatic enzyme replacement: pancrelipase (Creon, Zenpep, Pancreaze, Pertzye)

• Adjuncts: PPI/H2RA if persistent steatorrhea on adequate enzymes

• Acute pancreatitis: supportive care (fluids, analgesia, nutrition); antibiotics only if infected necrosis suspected/confirmed

Comparison — Pancrelipase Products

Attribute	Key Point
Dosing	By lipase units per meal/snack; titrate to symptoms and stool fat
Administration	With meals/snacks; avoid crushing; consider acid suppression if inadequate response
Safety	Mouth irritation if chewed; hyperuricemia at high doses; rare fibrosing colonopathy at very high doses

Antispasmodics and Functional GI Pain

Agents

• Anticholinergic antispasmodics: dicyclomine, hyoscyamine

• Peppermint oil: enteric-coated formulations for IBS pain/bloating

• Neuromodulators: low-dose tricyclics (amitriptyline, nortriptyline), SNRIs for selected patients

Comparison — IBS Pain Modulators

Option	Use Case	Pros	Cons
Antispasmodics	Meal-related cramping	Rapid relief	Dry mouth, constipation, blurry vision
Peppermint oil	Bloating, crampy pain	Well tolerated	Reflux symptoms in some
Low-dose TCA	Pain-predominant IBS	Global relief including sleep	Anticholinergic effects

Diarrhea, Infectious and Traveler’s

Agents

• Symptomatic: loperamide, bismuth subsalicylate

• Pathogen-directed: azithromycin for severe traveler’s diarrhea/dysentery; rifaximin for noninvasive E. coli; avoid antimotility alone in dysentery/fever

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Bowel Preparation for Colonoscopy

Options

• Polyethylene glycol-electrolyte solutions: GoLYTELY, MoviPrep, PEG 3350 + sports drink split dosing

• Sodium picosulfate/magnesium citrate: Prepopik (regional)

• Sodium phosphate: effective but higher renal/electrolyte risk; use selectively

Comparison — Bowel Prep

Regimen	Volume	Tolerability	Key Cautions
Split-dose PEG	2–4 L total	Good with split dosing	Hyponatremia if overhydration with water alone
Low-volume PEG + adjuncts	1–2 L	Better taste	Follow exact instructions
Na picosulfate/mag citrate	Low	Palatable	Electrolyte shifts; renal caution
Na phosphate	Very low	Palatable	Nephropathy risk; avoid in CKD, HF, elderly

Upper and Lower GI Bleeding Supportive Pharmacotherapy

Agents

• Proton pump inhibitor: high-dose IV for nonvariceal UGIB

• Octreotide: suspected variceal bleeding until endoscopic confirmation

• Antifibrinolytic: tranexamic acid not routinely recommended; selective use per local protocol

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Antidiarrheals and Adsorbents

Agents

• Loperamide, bismuth subsalicylate, kaolin-pectin (legacy)

• Racecadotril (regional): enkephalinase inhibitor for secretory diarrhea

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Special Populations and Safety Pearls

• Elderly: minimize anticholinergic load; favor gut-selective agents (vedolizumab) in IBD; adjust renal-cleared drugs

• Pregnancy: prefer nonpharmacologic first; use PPIs/H2RAs with established safety; avoid misoprostol and many IBD small molecules unless specialist-directed

• CKD: avoid magnesium osmotics and sodium phosphate; dose-adjust H2RAs, prucalopride

• QT risk: macrolides, domperidone, ondansetron high doses, droperidol, cisapride (restricted)

• Polypharmacy: check interactions with PPIs (clopidogrel for some agents), NK1 antagonists (CYP), bile acid binders (drug binding)