Gastroenterology Pharmacology: Comprehensive Drug Guide

Proton Pump Inhibitors (PPIs)

Primary Uses

PPIs are the most effective antisecretory agents for treating GERD, erosive esophagitis, and peptic ulcer disease, demonstrating superior efficacy compared to H2-receptor antagonists. 1

GERD and Erosive Esophagitis: PPIs are first-line therapy for healing esophagitis and achieving symptomatic relief 1
Peptic Ulcer Disease: Used for treatment and prevention, particularly in high-risk patients 1
H. pylori Eradication: Component of triple or quadruple therapy regimens 1
NSAID-Associated Ulcer Prevention: Essential gastroprotection in at-risk populations 1

Dosing Recommendations

Standard dosing: Once-daily administration (e.g., omeprazole 20mg, pantoprazole 40mg) is appropriate for most indications 2
Twice-daily dosing: Reserved only for patients with documented failure of once-daily therapy, severe erosive esophagitis, or complicated GERD 1, 2
Hepatic impairment: Reduce omeprazole to 10mg once daily in patients with any degree of hepatic dysfunction (Child-Pugh Class A, B, or C) 3

Safety Profile and Patient Selection

High-Risk Patients Requiring Indefinite PPI Therapy:

History of upper GI bleeding on anticoagulants or antiplatelets 2
Age ≥65 years taking NSAIDs plus aspirin 1, 2
Concurrent use of anticoagulants (warfarin, DOACs) with NSAIDs 2
Combination of aspirin plus steroids or warfarin 1, 4
Previous complicated GI events on any antithrombotic therapy 1

Moderate-Risk Patients (PPI Appropriate):

Age ≥65 years on aspirin alone 1
Any age with previous uncomplicated GI event on aspirin 1
Steroid therapy with additional risk factors (age ≥65, previous GI events, concurrent NSAIDs/aspirin/anticoagulants) 4
H. pylori infection with NSAID use 1

Low-Risk Patients (PPI Generally Not Needed):

Age <65 years, no aspirin, no previous GI events, NSAID alone 1

Side Effects and Monitoring

Common adverse effects: Generally well-tolerated; headache and gastrointestinal symptoms most frequent 3
Long-term risks: Increased risk of C. difficile infection, community-acquired pneumonia, bone fractures, chronic kidney disease 2, 5
Pediatric considerations: Respiratory system adverse reactions and accidental injuries reported more frequently in children ages 2-16 years 3
Pregnancy: Limited data suggest omeprazole may be present in breast milk; developmental benefits of breastfeeding should be weighed against maternal need 3
Geriatric patients: Bioavailability increased and elimination decreased, but no dosage adjustment needed except in hepatic impairment 3

Critical Contraindications and Cautions

Absolute contraindications for NSAIDs (making PPI monotherapy insufficient):

Active peptic ulcer disease 1
Chronic kidney disease 1
Heart failure 1

Relative contraindications requiring enhanced gastroprotection:

Hypertension, H. pylori infection, history of peptic ulcer disease, concomitant corticosteroids or SSRIs 1

Common Pitfalls to Avoid

Do not use double-dose PPIs routinely: Associated with higher complication rates including pneumonia, hip fracture, and C. difficile infection without proven additional benefit 4
Do not substitute H2-receptor antagonists in high-risk patients: PPIs are superior for preventing upper GI bleeding in patients on antithrombotic therapy 2
Do not discontinue PPIs in high-risk patients: Those with prior GI bleeding on anticoagulants should never be considered for de-prescribing 2
Do not exceed maximum acetaminophen doses: When using fixed-dose opioid combinations, total daily acetaminophen must not exceed 4g including "hidden sources" 1
Document ongoing indications clearly: All patients on PPIs require regular review with specific documentation of continued need 2

NSAIDs and COX-2 Selective Inhibitors

Appropriate Use Algorithm

For patients <65 years, no previous GI event, not on aspirin:

NSAID alone is appropriate 1

For patients with previous GI event:

Not on aspirin: COX-2 inhibitor OR NSAID + PPI 1
On aspirin: NSAID + PPI OR COX-2 inhibitor + PPI 1

For patients on aspirin (no previous GI event):

COX-2 inhibitor OR NSAID + PPI 1

For patients ≥65 years:

Risk increases 2-3 fold; requires gastroprotection with PPI if using NSAIDs 1

Absolute Contraindications

Current active peptic ulcer disease 1
Chronic kidney disease 1
Heart failure 1

Relative Contraindications

Hypertension, H. pylori infection, history of peptic ulcer disease, concomitant corticosteroids or SSRIs 1

Safety Monitoring

All patients on NSAIDs or COX-2 inhibitors require routine assessment for:

Gastrointestinal toxicity 1
Renal toxicity 1
Hypertension 1
Heart failure 1
Drug-drug and drug-disease interactions 1

Critical Drug Interactions

Do not combine ibuprofen with aspirin for cardioprophylaxis: Ibuprofen interferes with aspirin's antiplatelet effect 1
Never use more than one NSAID or COX-2 inhibitor simultaneously 1

Gastroprotection Requirements

Nonselective NSAIDs: Use PPI or misoprostol for GI protection 1
COX-2 inhibitors with aspirin: Use PPI or misoprostol for GI protection 1
High-risk scenarios: Consider COX-2 inhibitor + PPI for patients with previous GI bleeding on aspirin or combination antithrombotic therapy 1

Special Populations

Older persons (use rarely and with extreme caution):

Only after safer therapies have failed 1
Requires evidence of continuing unmet therapeutic goals 1
Demands ongoing assessment of risks and complications 1

Anticoagulants and Gastroprotection

Risk Stratification for PPI Therapy with Anticoagulants

Definite indications for PPI (continue indefinitely):

History of upper GI bleeding on any anticoagulant 2
Age >60 years with additional risk factors 2
Concurrent antiplatelet therapy (aspirin or P2Y12 inhibitors) 2
Multiple antithrombotic agents 2
Concurrent NSAID or steroid use 2

Risk factors warranting PPI consideration:

Prior GI bleeding history (strongest predictor of recurrence) 2
Advanced age (≥75 years increases bleeding risk) 2
Concurrent use of anticoagulants, steroids, or NSAIDs 2
H. pylori infection 2
Impaired renal function (increases anticoagulant exposure and bleeding risk) 2

Specific Anticoagulant Scenarios

DOACs (Direct Oral Anticoagulants):

PPI recommended for entire duration when combined with antiplatelet agents due to high bleeding risk 2
Standard once-daily PPI dosing appropriate (e.g., omeprazole 20mg, pantoprazole 40mg) 2
No clinically significant drug-drug interactions between PPIs and apixaban (unlike clopidogrel) 2

Warfarin:

PPI co-therapy rated as "appropriate" for patients on warfarin with additional risk factors 1
Combination of warfarin + aspirin + age/previous GI event requires PPI 1

Special Considerations for Renal Impairment

Renal impairment independently increases bleeding risk, especially with dabigatran and rivaroxaban 2
Monitor renal function periodically as both anticoagulants and PPIs may affect kidney function 2
Dose-adjust anticoagulants appropriately for renal function 2

Critical Management Points

Screen for H. pylori: Eradication recommended as additional protective measure in patients with any history of peptic ulcer disease 2
Consider NSAID alternatives: NSAIDs combined with anticoagulants carry substantial bleeding risk even with PPI therapy 2
Ensure adherence: Poor PPI adherence increases risk of NSAID-induced upper GI adverse events 4-6 fold 2
Duration of therapy: PPI indication persists as long as patient remains on anticoagulant 2

Medications for Chronic Idiopathic Constipation (CIC)

First-Line Agents

Fiber Supplements:

Psyllium, bran, methylcellulose, inulin 1
Minimum treatment duration: 4 weeks 1

Osmotic Laxatives:

Polyethylene glycol (PEG): Preferred osmotic agent 1
Magnesium oxide (MgO): Alternative option 1
Lactulose: Less preferred due to gas and bloating 1

Stimulant Laxatives:

Bisacodyl, senna, sodium picosulfate 1
Appropriate for patients requiring more aggressive therapy 1

Second-Line Agents (Prescription)

Secretagogues:

Lubiprostone: Chloride channel activator 1
Linaclotide: Guanylate cyclase-C agonist 1
Plecanatide: Guanylate cyclase-C agonist 1
Minimum treatment duration: 4 weeks for clinical trials 1

5-HT4 Agonist:

Prucalopride: Serotonin type 4 receptor agonist 1
Prokinetic mechanism of action 1

Outcome Measures

Critical outcomes for treatment success:

Complete spontaneous bowel movements (CSBMs) per week 1
Spontaneous bowel movements (SBMs) per week 1
Responder rate: CSBM ≥3 per week AND increase of ≥1 from baseline 1

Secondary outcomes:

Adverse events (particularly diarrhea) leading to discontinuation 1
Serious adverse events 1
Global relief 1
Quality of life scores (PAC-QOL) 1
Stool form 1

Excluded Populations

Opioid-induced constipation (requires different management) 1
Constipation due to hypothyroidism or celiac disease 1
Irritable bowel syndrome with constipation (IBS-C) - covered by separate guidelines 1

Opioid Analgesics in Gastroenterology Context

Indications

Patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life should be considered for opioid therapy. 1

Dosing Strategies

Frequent or continuous daily pain: Around-the-clock time-contingent dosing aimed at achieving steady-state opioid therapy 1
Long-acting preparations: Anticipate and treat breakthrough pain using short-acting immediate-release opioid medications 1

Safety Considerations

Fixed-dose combinations: Do not exceed maximal safe doses of acetaminophen (4g/24 hours) or NSAIDs when using combination agents 1
Anticipate adverse effects: Clinicians must proactively assess for and identify potential opioid-associated adverse effects 1

Special Agent: Methadone

Only clinicians well-versed in methadone use and risks should initiate and titrate it cautiously 1

Corticosteroids and Gastroprotection

Indications for Steroid Use in GI Conditions

Pain-associated inflammatory disorders 1
Metastatic bone pain 1
Osteoarthritis is NOT considered an inflammatory disorder and should not be treated with long-term systemic corticosteroids 1

PPI Co-therapy with Steroids

Risk assessment for PPI initiation:

Steroid therapy alone increases GI events approximately 2-fold 4
Age ≥65 years increases risk 2-3.5 fold 4
Previous GI events increase risk 2.5-4 fold 4

PPI regimen recommendations:

Standard once-daily PPI dosing for most patients requiring gastroprotection 4
Continue PPI for duration of steroid treatment 4
Discontinue PPI after steroid completion unless other ongoing indications exist 4

Specific scenarios:

Age ≥65 years with previous complicated GI events AND on steroids: PPI strongly recommended 4
Age <65 years with no previous GI events on steroids alone: PPI still considered appropriate 4
Steroids combined with NSAIDs or aspirin: PPI becomes even more important due to additive risk 4

Monitoring

Regular reassessment of ongoing PPI need 4
Document indication clearly in medical record to facilitate appropriate discontinuation 4
Consider de-prescribing once steroids discontinued if no other definitive indication 4

Topical Agents for Localized Pain

Topical Lidocaine

All patients with localized neuropathic pain are candidates 1
Patients with localized non-neuropathic pain may be candidates (weaker evidence) 1

Topical NSAIDs

All patients with localized non-neuropathic persistent pain may be candidates 1

Emerging and Alternative Agents

Tegaserod (5-HT4 Agonist for IBS-C)

FDA-approved exclusively for women under age 65 years without cardiovascular ischemic events history. 6

Dosing: 6 mg twice daily for 12 weeks 6
Efficacy: FDA responder endpoint 35.1% vs. 23.4% placebo 6
Common adverse effects: Diarrhea (1.6%), headaches (1.0%) leading to discontinuation 6
Contraindications: History of myocardial infarction, stroke, TIA, or angina 6
Cardiovascular safety concerns: Particularly in individuals with pre-existing cardiovascular disease or risk factors 6

Tegoprazan (Potassium-Competitive Acid Blocker)

Should NOT be used as first-line therapy for GERD. 6

Appropriate use: Second-line treatment after documented failure of twice-daily PPI therapy in patients with confirmed acid-related reflux 6
Dosing: 50 mg once daily for erosive esophagitis, treatment duration 4-8 weeks 6
Advantages: Faster onset of action and longer duration of acid suppression compared to traditional PPIs 6
Limitations: Higher costs compared to PPIs; limited long-term safety data 6

Clinical Decision-Making Framework

Empirical Therapy Approach for GERD

For patients <50 years with uncomplicated GERD, empirical therapy with antacids or H2-receptor antagonists is appropriate initial management. 7

Endoscopic evaluation indicated for:

Age ≥50 years 7
Presence of complications 7
Failure to respond to empirical therapy 7
"Alarm" symptoms (weight loss, dysphagia, bleeding) 8

Important Diagnostic Considerations

Poor correlation between reflux symptoms and endoscopic findings: Positive predictive value of heartburn/regurgitation for endoscopy-positive GERD is only 0.37 9
High prevalence of H. pylori populations: Significant proportion of patients with GERD symptoms have concomitant peptic ulcer disease; empirical treatment based on "typical" GERD symptoms alone may be inappropriate 8
Risk factors for peptic ulcer in GERD patients: Male gender (OR 1.8), age >60 years (OR 2.2), H. pylori infection (OR 3.6) 8

Treatment Resistance

GERD is generally more resistant to antisecretory pharmacologic therapy than peptic ulcer disease. 7

Patients failing standard twice-daily H2-receptor antagonist dosing may require high-dose H2-receptor antagonists or omeprazole therapy 7
Twice-daily PPI dosing should be considered for inadequate response to once-daily dosing before declaring treatment failure 1

Help us tailor your experience