GI Meds Drugs for Acid-Peptic Disease PDF

GI Medications Drugs Used in Acid-Peptic Diseases Debra Forzese, Pharm. D. Antacids Acid-Peptic Diseases Gastroesophageal reflux Peptic ulcer Stress-related mucosal injury Drug Treatment of Acid-Peptic Disorders qAntacids qH2-Receptor Antagonists qProton Pump Inhibitors Antacids Calcium Carbonate (T...

GI Medications Drugs Used in Acid-Peptic Diseases Debra Forzese, Pharm. D. Antacids Acid-Peptic Diseases Gastroesophageal reflux Peptic ulcer Stress-related mucosal injury Drug Treatment of Acid-Peptic Disorders qAntacids qH2-Receptor Antagonists qProton Pump Inhibitors Antacids Calcium Carbonate (Tums) Magnesium Hydroxide Aluminum Hydroxide (Amphojel) Sodium Bicarbonate (Alka Seltzer) Antacids q Mechanism of Action § Neutralize acid in the stomach and inhibit pepsin, a proteolytic enzyme § Reduce acid reaching duodenum § Different agents neutralize acid differently q Aluminum (constipation) and magnesium (diarrhea) combined Calcium Carbonate Indication qAntacid for various GI symptoms including acid indigestion, GERD qCalcium supplement - osteoporosis Calcium Carbonate Dosing q Use as needed for periodic episodes, 1 or less times per week q If needed for more than 1 time per week or symptoms persist longer than 2 weeks, see provider for alternative treatment q Adult – dosing limits vary, avoid hypercalcemia q Pediatric q Renal impairment – no specific dose recommendations, use caution with CKD q Hepatic impairment – no dose change per manufacturer, not studied Calcium Carbonate Pharmacokinetics/Pharmacodynamic Factors qCarbonate requires acid to be absorbed, food helps absorption qAbsorbed in small intestine qOnly approximately 500 mg should be taken at one time qCalcium absorption occurs in small intestine, dependent on transport mechanism which depends on vitamin D and diffusion qIonized form is the physiologic active form found in the blood Calcium Carbonate Mechanism of Action qDissociates in the stomach into ionized calcium and carbonate ion qCarbonate raises pH in stomach by binding hydrogen ions qIncreased pH in stomach causes inhibition of pepsin, bile acids, toxins from Heliobacter pylori Calcium Carbonate Absorption q Vitamin D will increase absorption of calcium carbonate if administered concurrently, patients should be encouraged to take them together q Avoid coadministration with drugs that can reduce absorption such as H2 receptor blockers, glucocorticoids, thiazide diuretics q Because calcium carbonate increases stomach pH it can decrease absorption of bisphosphonates (Fosamax), proton pump inhibitors (Prilosec), tetracyclines, thyroid hormones, antiarrhythmics such as verapamil Calcium Carbonate Excretion qFeces as unabsorbed calcium carbonate qUrinary excretion depends on GFR, renal tubule reabsorption controlled by parathyroid hormone and vitamin D qLungs as carbon dioxide Calcium Carbonate – Adverse Effects q High calcium levels qLow phosphate levels qGI – nausea, vomiting, constipation, anorexia qIrritability qAcid rebound qXerostomia q Large dose over long term – irregular heart rhythm, kidney stones, muscle twitching, pancreatitis Calcium Carbonate Pregnancy qSafe for use in pregnant patients with GERD, prophylaxis before labor Breastfeeding qSafe for nursing Monitoring – check calcium level if used for deficiency H2 Receptor Antagonists H2 Receptor Antagonist Agents Cimetidine (Tagamet) Famotidine (Pepcid) Nizatidine (Axid) Famotidine Indications q GERD – treatment of GERD and esophagitis due to GERD q Promote healing of gastric and duodenal ulcers q Prevent occurrence of stress ulcers q Heartburn – for OTC product only – relief of heartburn, acid indigestion, sour stomach Famotidine Dosing q Adult – mild intermittent symptoms (less than 2 episodes weekly) without evidence of erosive esophagitis, can be used as needed or added to bedtime proton pump inhibitor dose q Pediatric q Renal impairment – reduce dose or increase dosing interval to 36-48 hours instead of daily q Hepatic impairment – no dose reduction Famotidine Mechanism of Action q Blocks H2 receptors in gastric parietal cells q Suppresses basal and meal stimulated acid secretion – dose dependent manner Famotidine – Pharmacokinetic/Pharmacodynamic Factors q Onset of antisecretory effect – within 60 minutes q Peak effect 1-3 hours (oral) q Excreted in urine q Prolonged T1/2 with renal impairment q Available in oral and parenteral preparations q Suppresses basal and nocturnal acid secretion by about 70% Famotidine Adverse Effects q Diarrhea q Headache q Drowsiness q Muscular pain q Constipation q Elevated liver enzymes q Vitamin B12 deficiency (reduced absorption) q Thrombocytopenia (rare) q Less common – can cause confusion in elderly Famotidine Cautions q Use with caution with kidney impairment, increased risk of QT prolongation, need to adjust dose Drug interactions q Cefpodoxime, Cefuroxime – decreased absorption by famotidine q Itraconazole, ketoconazole – decreased absorption by famotidine Famotidine Pregnancy q Other agents may be preferred for initial therapy (antacids first) Breastfeeding qConsidered safe qAccording to manufacturer, decision to breastfeed during therapy should consider the risk of infant exposure, benefits of breastfeeding to infant, benefits of treatment to mother qFamotidine has lower concentration in breastmilk than other H2 antagonists Famotidine Monitoring q CBC q Gastric pH q Occult blood in patient with GI bleeding Proton Pump Inhibitors (PPI) Proton Pump Inhibitors – Agents Omeprazole (Prilosec) Esomeprazole (Nexium) Lansoprazole (Prevacid) Rabeprazole (Aciphex) Pantoprazole (Protonix) Proton Pump Inhibitors – Indications q Peptic ulcer disease – first line q GERD – treatment of erosive esophagitis and as maintenance with Barrett’s esophagus and severe erosive esophagitis q Zollinger-Ellison syndrome – high doses often needed to control gastric acid hypersecretion q NSAID associated ulcers – prevention of gastric ulcers associated with NSAID use q Eradication of Helicobacter pylori – part of multidrug regimen Omeprazole Dosing q Adult - do not administer concomitantly with other antisecretory meds such as H2 receptor blockers, if needed space doses q Lowest dose possible for shortest duration q Administer dose 30-60 minutes before breakfast for maximum therapeutic activity q Pediatric q Renal impairment – no dose adjustment q Hepatic impairment – dose adjustment for maintenance treatment of erosive esophagitis only Omeprazole Mechanism of action qReduces gastric basal and stimulated acid secretion by inhibiting H+/K+/ATP pump Omeprazole Pharmacokinetic/Pharmacodynamic Factors qTakes 3-4 days of treatment to achieve maximal acid inhibition potential qAcid inhibition lasts up to 24 hours (irreversible effects on proton pump) qOnset of action 1 hour qPeak effect 2 hours qHalf life 30 – 60 minutes qHepatic metabolism qEliminated mainly in urine, small amount in feces Omeprazole Adverse effects q Headache q Abdominal pain q Diarrhea q Nausea/vomiting Omeprazole – Warnings/Cautions qCutaneous lupus erythematosus (widespread skin rash, lesions) q Enteric infections including C difficile associated diarrhea q Increased risk of bone fractures – FDA mandated safety information about possible increased risk of fractures of hip, wrist, spine q Gastric polyps q Hypersensitivity reactions including anaphylaxis Omeprazole – Warnings/Cautions q Hypomagnesemia – 3months – 1 year of therapy q Vitamin B12 deficiency – interferes with absorption q Dementia – inconclusive q Pneumonia – inconclusive q Mortality - inconclusive q Specific FDA approved patient medication guide must be dispensed with omeprazole (serious potential adverse effects, how to take med, who should not take omeprazole) Omeprazole Drug Interactions – many significant drug interactions q Amphetamine – omeprazole increases absorption of amphetamine q Citalopram – omeprazole increases citalopram level – limit citalopram dose to 20 mg daily q Clopidogrel – omeprazole reduces antiplatelet effect of clopidogrel by decreasing active metabolite q Use caution when administered with CYP2C19 substrates (phenytoin, diazepam, digoxin) Omeprazole Pregnancy – may be used if clinically indicated Breastfeeding – according to manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother Omeprazole Monitoring q Magnesium level prior to therapy and then periodically q B12 levels periodically q Bone loss, fracture q Signs/symptoms of cutaneous or systemic lupus erythematosus Omeprazole Rebound Acid Hypersecretion after discontinuing a PPI q The increase in gastric acid secretion to above pre-treatment or baseline levels after withdrawal from PPIs has been well documented in several studies