Heartburn & Dyspepsia Treatment Guide PDF

HEARTBURN & DYSPEPSIA Chapter 13 Kelly Orr, PharmD Clinical Professor Heartburn & Dyspepsia ◦ Overall prevalence in US of heartburn is 42% over a 1 year period in healthy, predominantly white population ◦ Weekly symptoms reported in 20% of respondents ◦ Women slightly more than men,...

HEARTBURN & DYSPEPSIA Chapter 13 Kelly Orr, PharmD Clinical Professor Heartburn & Dyspepsia ◦ Overall prevalence in US of heartburn is 42% over a 1 year period in healthy, predominantly white population ◦ Weekly symptoms reported in 20% of respondents ◦ Women slightly more than men, overall incidence increasing in the Western world ◦ Annual cost in US $18.1 billion with direct and indirect costs ◦ Prescription medications large expense (54%) Symptoms ◦ “Heartburn” most common symptom ◦ Burning sensation in stomach, lower chest ◦ May radiate to neck or occasionally back ◦ Also describes as indigestion, acid regurgitation, sour stomach or bitter belching ◦ Dyspepsia is “bad digestion” ◦ Symptoms originating from gastroduodenal region ◦ Includes post-prandial fullness, early satiation, epigastric pain, and epigastric burning ◦ Less specific: bloating, nausea, vomiting, and belching Definitions ◦ GERD = gastroesophageal reflux disorder ◦ Symptoms, esophageal damage, or both resulting from abnormal reflux of gastric contents ◦ Some can also have NERD (nonerosive GERD) ◦ Frequent heartburn ◦ Occurs 2 or more days per week ◦ Persistent heartburn ◦ 3 or more months, typical GERD symptom Contributing Factors (Table 13-1) Type Example Dietary Alcohol, caffeinated or carbonated beverages, chocolate, citrus fruit/juice, fatty foods, garlic, onions, spearmint, peppermint, salt/salt substitutes, spicy foods, tomatoes/tomato juice Lifestyle Exercise, emotions, obesity, smoking, stress, supine body position, tight- fitting clothing Medications µAdrenergic antagonists, anticholingeric agents, aspirin/NSAIDs, barbituates, benzodiazepines, b2-Agonists, Bisphosphonates, CCBs, chemotherapy, clindamycin, dopamine, estrogen, iron, narcotic analgesics, nitrates, potassium, progesterone, prostaglandins, quinidine, TCAs, tetracycline, theophylline, zidovudine Diseases Motility disorders (ie: gastroparesis), PUD, scleroderma, Zollinger-Ellison syndrome, insulin resistance, Sjogren syndrome Others Genetics, pregnancy Treatment Goals ◦ Provide complete relief of symptoms ◦ Reduce recurrence of symptoms ◦ Prevent and manage unwanted effects of medications Treatment Approaches ◦ Review Figure 13-2 ◦ Episodic heartburn ◦ Mild, infrequent ◦ Moderate, infrequent ◦ Frequent heartburn ≥ 2 days per week Exclusions for Self Treatment ◦ Frequent heartburn > 3 months ◦ Heartburn while taking recommended doses of H2RAs or PPI ◦ Heartburn that continues after 2 weeks of treatment with nonprescription H2RAs or PPI ◦ Heartburn that continues while taking prescription H2RAs or PPI ◦ Nocturnal heartburn ◦ Severe symptoms ◦ Difficulty or pain swallowing solid foods * ◦ Chronic hoarseness, wheezing, coughing, or choking Exclusions for Self-Treatment ◦ Note or complain of GI bleeding (melena, hematemesis) * ◦ Unexplained weight loss * ◦ Continuous nausea, vomiting, or diarrhea * ◦ Chest pain accompanied by sweating, pain radiating to shoulder, arm, neck, or jaw, and shortness of breath * ◦ Pregnancy/Nursing mothers ◦ Children ◦ < 2 years old for antacids ◦ < 12 years old for H2RAs ◦ < 18 years for omeprazole ◦ Adults > 45 years with new onset dyspepsia * Denotes ALARM symptoms Non-Pharmacologic Measures ◦ May benefit some individuals but unlikely to completely relieve symptoms in majority of patients ◦ Should be recommended for all patients ◦ Patients should track dietary, lifestyle, medication triggers ◦ Avoid foods that lead to symptoms (keep diary to identify) ◦ Reduce size of meals ◦ Avoid lying down after meals ◦ Eat no later than 3 hours prior to bedtime ◦ Elevate head of bed 6 -8 inches ◦ Blocks under bed or foam wedge pillow ◦ Avoid smoking, alcohol, and caffeine ◦ Weight loss if overweight ◦ If possible, switch medications Antacids ◦ Basic compounds ◦ Acid + Base ® Salt + Water ◦ ­ stomach pH & inhibit pepsinogen ® pepsin (also duodenum) ◦ May also increase LES pressure ◦ Cannot neutralize all stomach acid ◦ pH above 5 blocks pepsinogen conversion ◦ Not effective for healing ◦ Potency ◦ mEq of acid-neutralization capacity (ANC) ◦ Specific dosing per product, not interchangeable ◦ See 13-4 for selected products and dosing ◦ Do not memorize antacid dosing ◦ Onset/Duration ◦ 5 minutes, lasting 20 – 60 minutes (prolonged by food) Indications for Antacids ◦ Treatment of mild, infrequent heartburn, sour stomach, and acid indigestion ◦ Combination products containing acetaminophen or aspirin are indicated for overindulgence in food and drink, and hangover ◦ FDA warning about risk of serious bleeding when using aspirin-containing products ◦ http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsfor HumanMedicalProducts/ucm505190.htm Antacids: Compare and Contrast ◦ Sodium Bicarbonate ◦ Calcium ◦ Aluminum ◦ Magnesium Sodium Bicarbonate ◦ NaHCO3 + HCl ® NaCl + CO2 + H2O ◦ Baking soda, Alka-Seltzer® ◦ Potent and highly soluble ◦ Can be absorbed systemically ◦ Endogenous bicarbonate is “left over” ◦ Amount taken po = amount in blood ◦ Poor renal function = accumulation ◦ Can cause ◦ 1. Alkaloisis when ingested alone ◦ 2. Milk-alkali syndrome when ingested chronically w/ Ca+ Sodium Bicarbonate continued ◦ Adverse events ◦ Belching and flatulence most common (CO2) ◦ Fluid retention, weight gain, edema, CHF, renal failure, and cirrhosis in low-salt diets (Na) ◦ Contraindicated for chronic use due to risks of systemic alkalosis and sodium overload Calcium Carbonate ◦ CaCO2 + 2HCl ® CaCl2 + H2O + CO2 ◦ Tums® products & Mylanta® products ◦ Dissolves more slowly than NaHCO3 ◦ Produces potent & prolonged neutralization ◦ Adverse Events ◦ Belching/flatulence most common, constipation often reported too ◦ Hypercalcemia ◦ Acid Rebound? Calcium Carbonate continued ◦ Hypercalcemia ◦ Up to 2500 mg/day of elemental calcium may be taken safely with normal renal function in ages 19 -50 (2000 mg/day for those 51+) ◦ Those with impaired renal function develop hypercalcemia with high frequent doses ◦ Acid rebound ◦ Sustained hypersecretion of acid ◦ Clinical significance? Aluminum ◦ Al(OH)3 + 3HCl ® AlCl3 + 3H2O ◦ Dissolves slowly ◦ Amphojel®, AlternaGEL®, or Basaljel® ◦ Several salt forms ◦ Hydroxide salt more potent ◦ In comparison to Mg(OH)2, CaCO2, & NaHCO3 has relatively low ANC ◦ Adverse Effects ◦ Constipation ◦ Hypophosphatemia ◦ Aluminum Toxicity Aluminum continued ◦ Constipation ◦ Most frequent side effect ◦ May cause obstruction, hemorrhoids, fissures, or fecal impaction ◦ Dose related, managed w/ stool softeners & combination products ◦ Hypophosphatemia ◦ Phosphate deficiency may occur with frequent and prolonged use of Al(OH)3 ◦ Aluminum Toxicity ◦ May occur with chronic use in renal failure Magnesium ◦ Mg(OH)2 + 2HCl ® MgCl2 + 2H2O ◦ Phillips MOM®, Mag-Ox® ◦ Many salts ◦ Oxide, hydroxide, carbonate, & trisiliciate ◦ ANC: Al(OH)3 < Mg(OH)2 < Na & Ca Bicarb ◦ Adverse Events ◦ Diarrhea = osmotic gradient ◦ Hypermagnesmia Magnesium continued ◦ Hypermagnesia ◦ Rare, significant renal failure ( 4 ◦ Differences in clinical outcomes not established Prevacid 24 HR ◦ OTC lansoprazole ◦ Same formulation as Rx ◦ 15 mg capsule po q am for 14 days ◦ 30 minutes prior to am meal ◦ No clinical advantages over OTC omeprazole Zegerid OTC ◦ Omeprazole 20 mg & sodium bicarbonate 1110 mg ◦ 303 mg sodium – caution in restricted diets ◦ Immediate release formulation ◦ Sodium bicarb increases pH and protects omeprazole degradation in stomach ◦ Rapid absorption from duodenum ◦ Insufficient evidence to claim faster onset ◦ Take in am 1 hour prior to meal Drug Interactions (Table 13 -5) ◦ Drugs requiring low gastric pH: ◦ Ketoconazole, itraconazole, iron salts, calcium carbonate, indinavir, and atazanavir ◦ Avoid concurrent use or monitor therapy ◦ FDA warning of methotrexate toxicity with injectable preparations, use H2RAs instead ◦ May prolong elimination of some drugs metabolized by P-450 2C19 and omeprazole (Prilosec OTC, Nexium 24HR, Zegerid OTC) ◦ Warfarin, theophylline, BZD, phenytoin, tacrolimus ◦ Omeprazole and esomeprazole inhibit metabolism of cilostazol ◦ Lansoprazole may be safer option w/cilostazol PPIs and Clopidogrel ◦ Interaction with with clopidogrel (Plavix) and omeprazole (Prilosec OTC, Nexium 24 HR, Zegerid OTC) ◦ Avoid co-administration ◦ Omeprazole inhibits hepatic CYP2C19 responsible for converting clopidogrel to its active form ◦ Could reduce effectiveness of clopidogrel ◦ Discourage nonprescription use in patients on clopidogrel ◦ ***Don’t stop clopidogrel Adverse Effects ◦ Overall low incidence ◦ Headache, diarrhea, constipation, n/v, stomach pain, cough, cold symptoms, dizziness, rash, or back pain ◦ Chronic acid suppression can impair natural defenses and increase risk of infection ◦ Increased susceptibility for community – acquired pneumonia in first month of therapy, increase risk of traveler’s diarrhea ◦ Increased Clostridium difficile and bacterial gastroenteritis infections, contact PCP if symptoms develop (esp. if on broad spectrum antibiotics) Adverse Effects continued ◦ Unlikely with short-term use, however with prolonged use: ◦ Deficiencies (> 1 year use) ◦ Vitamin B12, hypomagnesia, and malabsorption of iron – not in short-term nonprescription use ◦ Risk of Fracture ◦ FDA warning of possible fracture increase with prolonged use in older patients (> 50 years) ◦ Hip, wrist, and spine ◦ Risk increases at 1 year or longer or at higher doses ◦ Calcium citrate recommended supplementation Bismuth Subsalicylate ◦ Products: Pepto Bismol®, Kao-pectate®, Maalox Total Relief ® ◦ Topical effect on stomach mucosa ◦ Once called an “antacid” but no ANC ◦ Recently added to many reformulated products ◦ Indicated for heartburn, upset stomach, indigestion, nausea, and diarrhea Bismuth Subsalicylate continued ◦ Typical dosage ◦ 262 - 525 mg BSS (2 tablets or 30 mLs) every 30 – 60 minutes as needed up to 4200 mg/day (8 doses) ◦ Adverse effects/drug interactions covered in greater detail under diarrhea section Heartburn Treatment Approach ◦ Figure 13 -2; Review ◦ Mild, episodic heartburn, infrequent ◦ Moderate, episodic heartburn, infrequent ◦ Frequent (≥2 times/week)