Proton pump inhibitors

Medications that profoundly reduce gastric acid secretion by irreversibly inhibiting the H⁺/K⁺-ATPase proton pump in parietal cells (final step of acid production).

• Revolutionized treatment of acid-peptic diseases—healing ulcers and controlling GERD without surgery. PPIs are among the most widely prescribed drugs (omeprazole ranks in the top 10 in the US). Widespread use means their indications, side effects, and key interactions (e.g., with clopidogrel) are high-yield knowledge often tested on boards.

• Patients with chronic GERD (frequent heartburn, regurgitation) often require daily PPI therapy for symptom control and to heal esophagitis.
• Peptic ulcer disease (gastric or duodenal ulcers) is typically managed with PPIs to promote ulcer healing. PPIs are also a key part of H. pylori eradication regimens (e.g., omeprazole + two antibiotics).
• High-risk patients (e.g., long-term NSAID users, older patients with ulcer history) are put on PPIs as ulcer prophylaxis to prevent GI bleeding. Critical care protocols often include PPIs to prevent stress ulcers in ICU patients.
• Zollinger-Ellison syndrome (gastrinoma causing extreme acid overproduction) presents with refractory ulcers; PPIs in high doses are required to control acid hypersecretion and relieve ulcer symptoms.

1. Always confirm the need for long-term PPI: use the lowest effective dose for the shortest necessary duration, and periodically reassess if the PPI can be tapered or discontinued (to avoid unnecessary risk).
2. Advise patients to take PPIs 30–60 minutes before meals (usually before breakfast) for optimal effect. If symptoms persist, ensure compliance and timing; consider twice-daily dosing (morning and pre-dinner) for refractory cases.
3. In ulcer patients, test for H. pylori and treat with appropriate antibiotics plus PPI (rather than using a PPI alone) to address the root cause. For NSAID-associated ulcers, discontinue the NSAID if possible and use PPI for prophylaxis or healing.
4. If alarm features (e.g., dysphagia, bleeding, weight loss) or refractory symptoms are present despite PPI therapy, perform endoscopy to rule out malignancy or other causes.
5. For patients on clopidogrel who need acid suppression, avoid omeprazole/esomeprazole (which inhibit CYP2C19 and reduce clopidogrel activation). Use an alternative PPI (e.g., pantoprazole) if required.

1. GERD/esophagitis: PPI once daily (usually morning) for ~8 weeks; continue maintenance if needed for chronic symptoms. Milder cases can use H₂ blockers or antacids as needed; severe/refractory cases may need BID PPI or further evaluation.
2. H. pylori ulcer: use triple therapy – a PPI (e.g., omeprazole) plus two antibiotics (e.g., clarithromycin + amoxicillin) for 14 days, which achieves ulcer healing by eradicating H. pylori.
3. Ulcer bleeding: initiate high-dose IV PPI (e.g., pantoprazole infusion) after endoscopic treatment of a bleeding ulcer, then continue an oral PPI to promote healing. In Zollinger-Ellison (gastrinoma), use very high-dose PPIs to control acid hypersecretion (often long-term) while addressing the tumor.

• All PPIs have the -prazole suffix (omeprazole, pantoprazole, etc.), making them easy to spot. (By contrast, H₂ blockers end in -tidine – take H₂ blockers before you dine.)
• PPI can remind you: Permanent Pump Inhibitor – they irreversibly shut down the proton pump until new pumps are made.
• Take PPIs before meals (think PPI = Pre-Prandial Intake) to ensure the drug is active when proton pumps are stimulated by food.

• Severe hypomagnesemia (e.g., seizures, arrhythmias) in a patient on long-term PPI – this rare but serious complication won't correct with supplementation until the PPI is stopped.
• Unexplained C. difficile colitis or recurrent pneumonia – chronic PPI use increases infection risk by reducing gastric acidity; consider discontinuation if possible.
• Osteoporosis or frequent fractures in an older patient on PPIs – long-term use is linked to decreased calcium absorption and bone density (advise bone health measures and use the lowest effective dose).
• Acid rebound on withdrawal – stopping a PPI abruptly after long-term use can cause rebound hyperacidity with worsened symptoms; taper gradually if discontinuing.

1. Frequent or severe reflux symptoms (≥2×/week or erosive esophagitis) → start daily PPI trial.
2. If symptoms resolve on PPI → continue for recommended course (e.g., 8 weeks); if they recur after stopping, resume maintenance PPI. If inadequate relief on once-daily dosing → optimize timing and increase to BID as needed.
3. If alarm signs (dysphagia, GI bleeding, weight loss) or no improvement on PPI → perform endoscopy to investigate causes (ulcer, Barrett's, malignancy, etc.).
4. Documented peptic ulcer → test for H. pylori. If positive, treat with PPI-based antibiotic regimen; if negative or ulcer from NSAIDs, use PPI and eliminate risk factors (stop NSAIDs, etc.).
5. Patients requiring long-term NSAIDs or antiplatelets and at high GI risk → add PPI prophylaxis. Reassess PPI need periodically; attempt to taper/stop in low-risk patients to avoid unnecessary long-term therapy.

• Middle-aged adult with chronic GERD and Barrett esophagus whose heartburn is well controlled with a daily "-prazole" medication → expect a question on PPIs (mechanism: irreversible H⁺/K⁺-ATPase inhibition).
• Elderly patient on long-term PPIs develops recurrent C. difficile diarrhea or a hip fracture → highlights an association between prolonged PPI use and infections or decreased bone density/mineral absorption.
• Patient with a coronary stent on clopidogrel and also taking omeprazole who experiences stent thrombosis → points to the PPI interfering with clopidogrel activation (via CYP2C19 inhibition).