Lecture 6 OTC GERD/Heartburn Meghji

GASTROESOPHAGEAL REFLUX DISEASE: ALARM SYMPTOMS & WHEN TO REFER: • “A condition that develops when the reflux • Chest pain: radiating pain to shoulders, neck, arm, SOB, sweating of stomach contents causes troublesome • Vomiting: continuous/recurrent symptoms and/or complications” • GI blood loss: hematemesis, melena WHY CHECK FOR ALARM SX? (Montreal Classification) • Dysphagia (difficulty swallowing), especially solids Symptoms could be due or lead to: • Most common symptoms for mild GERD: • Odynophagia (severe pain on swallowing) • Cardiac disease o Heartburn (burning sensation along • Unexplained weight loss > 5% • PUD esophagus) • Unexplained cough, wheezing, choking, hoarseness • Malignancy o Regurgitation (acid/bile that rises to • Age > 50 years old with new symptoms • Functional dyspepsia the back of the throat) • Severe symptoms (frequency, rating) • Biliary disease • Features: • Nocturnal symptoms • Other o May wax and wane • Failure of 2 week H2RA/PPI therapy o Worse when lying down, bending over, or after a meal NON-PHARMACOLOGICAL TX: GOALS OF THERAPY: • Avoid foods/beverages that worsen or trigger symptoms • Treat symptoms CAUSE IS MULTIFACTORIAL: • Eat small meals and chew food well (reduce/eliminate) • Relaxation/decreased integrity of the • Avoid exercise after meals • Reduce or prevent recurrence lower esophageal sphincter • Don’t lie down for 2-3 hours after eating • Prevent structural damage and • Increased lower abdominal pressure • Avoid tight clothing thus complications (e.g. ulcers) • Delayed gastric emptying • Encourage smoking cessation • Prevent ADRs of meds • Impaired esophageal clearance/peristalsis • Elevate head of bed frame (i.e. not extra pillows) about 10 cm • Excessive acid production • Achieve ideal body weight • Hiatal hernia • Bile reflux ► Individualize non-pharmacological therapy to triggers ► Evidence = inconclusive GERD RISK FACTORS/TRIGGERS: • Being overweight/obese ANTACIDS: sodium bicarbonate and salts of aluminium, calcium and magnesium • Diet • MOA: neutralizes gastric acid o Fatty foods/spicy foods • Potency: aluminum (least) < magnesium hydroxide < sodium bicarbonate < calcium carbonate (most potent) o Chocolate* • Used in combination with each other (lots of products); dosing varies with products o Coffee * Advantages Disadvantages o Alcohol * • Immediate relief of symptoms (faster than • Frequent dosing required o Carbonated drinks H2Ras/PPIs) o Short duration of action (0.5 – 1 hr, o Citrus fruits or juices o Liquids work faster than tablets prolonged by food up to 3 hours) o Garlic or onions • Cheap, unscheduled • Many drug interactions o Mint (peppermint, spearmint) • Check sodium content o Tomatoes • Pregnancy Ca carbonate Magnesium Aluminum Sodium bicarbonate • Stress and anxiety Place in • Most common • Magnesium/aluminum combos • Generally avoided • Age ( > 65) therapy agent used used to offset • Not first line • constipation/diarrhea • Smoking * Preferred in compromised renal o Diarrhea dominates • Hiatus hernia function

Caution/CIs • Hypercalcemia • Avoid in • Avoid in • High Na content = * = weak associations (total Ca intake) renal renal avoid in high BP, HF, • Can lead to milk- dysfunction dysfunction renal dysfunction, MEDICATIONS THAT LOWER ESOPHAGEAL alkali syndrome & and elderly • Can lead to edema, cirrhosis, PRESSURE can induce or worsen GERD: hypophosphatemia (risk of hypo-PO4 pregnancy, etc • Alpha-adrenergic antagonists (prolonged/use hyperMg) (prolonged • Can cause metabolic • Anticholinergics high doses) use/high alkalosis (prolonged • Beta-agonists doses) use/high doses) • Benzodiazepines (diazepam) Notable SEs • Belching • Diarrhea • Constipating • Flatulence • CCBs (nifedipine, felodipine, amlodipine) • Flatulence • Belching • Nicotine • Progesterone • Constipating • Abdominal distension • Nitrates • Theophylline Examples • Tums • Milk of • Alugel, • Alka-Seltzer (+ASA), • Opioids • Maalox Magnesia amphogel ENO (sodium citrate) • Diovol • Gaviscon • Gaviscon RS ES, max DRUG INDUCED DYSPEPSIA/ESOPHAGITIS: strength • Acarbose • Clindamycin • Amiodarone • Digitalis INTERACTIONS: ALGINATE + ANTACID: alginic acid/sodium alginate • Antibiotics • Ethanol • May adsorb or chelate with other drugs • MOA: alginate forms a viscous layer on top of gastric o Erythromycin • Iron ( tetracyclines, fluoroquinolones, iron) contents = protective barrier o Tetracyclines • NSAIDs o Separate by at least 2 hours • Advantages: immediate relief of symptoms • Bisphosphonates • Quinidine • Increases gastric pH changing o Formulated with antacids • Potassium chloride absorption (ketoconazole, iron) • Disadvantages:

• Premature breakdown of EC meds o Insufficient evidence as monotherapy o Unproven if combo with antacid is better o May contain high sodium content

Lecture 6 OTC GERD/Heartburn Meghji HISTAMINE-2 RECEPTORS: Ranitidine (Zantac), famotidine (Pepcid), cimetidine and nizatidine (Rx) • MOA: decreases gastric acid secretion • Equi-efficacy: minor differences in potency, onset, duration, side effects, interactions, etc • Dose: famotidine 10-20 mg BID PRN, ranitidine 75-150 mg BID PRN Advantages Disadvantages • Longer duration of action than antacids, quicker onset than a PPI • Not as rapid onset as an antacid • Can be used with a prn antacid • Tachyphylaxis (use PRN?) o Famotidine: available in combination with an antacid (Pepcid complete) • Reduce dose in renal impairment • Used for prevention (30 min-1 hr before aggravating food or trigger) • Usually well tolerated (diarrhea, headache, dizziness, rash & tiredness)

Schedule 1 Ranitidine and its salts (except when sold in concentrations of 150 mg or less per oral dosage unit and indicated for treatment of heartburn) 3 Ranitidine and its salts (when sold in concentrations of 150 mg or less per oral dosage unit and indicated for the treatment of heartburn, in package size containing more than 4500 mg of ranitidine) 1 Famotidine and its salts (except when sold in concentrations of 20 mg or less per oral dosage unit and indicated for the treatment of heartburn) 3 Famotidine and its salts (when sold in concentrations of 20 mg or less per oral dosage unit and indicated for the treatment of heartburn, in package size containing more than 600 mg of ranitidine) 1 Cimetidine and its salts (except when sold in concentrations of 100 mg or less per unit dose) 3 Cimetidine and its salts when sold in concentrations of 100 mg or less per unit dose (NO PRODUCTS CURRENTLY AVAILABLE) 1 Nizatidine (Rx only)

INTERACTIONS: • Cimetidine inhibits 3A4, 2D6, 1A2, 2C9 and 2C19 = stay away as possible • CYP450 interactions uncommon with non-prescription doses for ranitidine and famotidine • Increases gastric pH changing absorption (ex// ketoconazole, iron, etc)

PPIS: omeprazole and esomeprazole (OTC) • MOA: decrease stomach acid production by blocking proton pump inhibitor (more potent) • Similar effectiveness and safety profiles within class when given at eqipotent doses • Dose: 20 mg once daily, best taken 30 minutes – 1 hour before meals Advantages Disadvantages

• Prolonged duration of action and better symptomatic relief compared to H2Ras • Onset: 3 hours (not for immediate relief) • Once daily dosing • Increased infections (CAP, C. diff), fracture risk?, B12 deficiency, • Induces remission more frequently than H2Ras hypomagnesia, iron malabsorption (not an OTC use concern) • Usually mild SEs (constipation, diarrhea, headache)

Schedule 1 Esomeprazole and its salts except when sold for the 14-day treatment for frequent heartburn, at a daily dose of 20 mg and in package sizes of no more than 280 mg of esomeprazole 2 Esomeprazole and its salts when sold for the 14-day treatment for frequent heartburn, at a daily dose of 20 mg and in package sizes of no more than 280 mg of esomeprazole 1 Omeprazole or its salts except when sold for the 14-day treatment for frequent heartburn at a daily dose of 20 mg in package sizes of no more than 280 mg of omeprazole 2 Omeprazole or its salts when sold for the 14-day treatment for frequent heartburn at a daily dose of 20 mg in package sizes of no more than 280 mg of omeprazole

DRUG INTERACTIONS: • Omeprazole and esomeprazole inhibit CYP2C19 • Increases gastric pH changing absorption (ex// ketoconazole, iron, etc)

BISMUTH SUBSALICYLATE: Pepto-Bismol; marketed for heartburn, upset stomach, nausea, indigestion, diarrhea, intestinal gas • MOA: bismuth (antimicrobial), salicylate (antisecretory and anti-inflammatory) • Dose: 262-524 mg every 30 minutes to 1 hour prn (8 tabs/24 hours) Advantages Disadvantages • None for OTC heartburn • S/E: black stool (might be mistaken for GI bleed), black tongue, diarrhea, nausea, vomiting • May be effective for abdominal gas • Contains salicylate (caution allergy, GI bleeding/ulcers, children, renal failure, pregnancy, etc)

PREGNANCY: LACTATION: • Heartburn common during pregnancy (30-80%) Yes Insufficient info • Relief if no improvement after 7 days • Al, Ca, Mg antacids • Omeprazole Yes No • Famotidine (preferred to ranitidine) • Esomeprazole • Ca antacids (space from iron) • ASA (Alka-Seltzer) • Magnesium (avoid trisilicate) • Sodium bicarbonate MONITORING OF THERAPY: • Alginic acid • Magnesium trisilicate • Ranitidine, famotidine • REFER: no resolution within 1-2 weeks of therapy, new alarm sx, worsening sx • PPI (if other therapies fail) • RECURRENCE: if at least 3 months after last episode, consider new discrete episode o Omeprazole and treat with therapy that was previously effective

Lecture 6 OTC Dyspepsia, Abdominal Gas, Lactose Tolerance Meghji

DYSPEPSIA:

SYMPTOMS: “upset stomach” or “indigestion” CAUSES: • Rome IV criteria (1 or more of the following sx): • Specific causes or structural abnormalities (25%) o Postprandial fullness o PUD, GERD, cancer, infections, other diseases o Early satiation (can’t finish a normal sized meal) o Food intolerances (lactose deficiency) o Epigastric pain or burning o Medications (NSAIDs), NHPS (garlic, feverfew, etc) • No specific cause or structural abnormality (75%) TREATMENT: o Functional/idiopathic dyspepsia (full criteria for 3 m at least 3 days/wk) • Only treat dyspepsia if you are able to identify a (self- treatable) cause without alarm symptoms

ABDOMINAL GAS:

SYMPTOMS: TRIGGERS: • A normal bodily process Med • Fibre • On average, gas expulsion = 500-700 mL/day • Drugs that affect flora (lactulose, antibiotics), alpha-glucosidase • Can sometimes lead to bothersome sx: inhibitors (acarbose, biguanides), orlistat, narcotics, o Increased belching/burping (eructation) anticholinergics, CCB, cholestyramine, effervescent solutions o Bloating Diet • Large meals, eating too quickly o Increased farting (flatulence) • Dietary sugars (lactose, fructose, sucrose, glucose) o Cramping/pain/discomfort • Fatty foods • • Need to differentiate people with transient symptoms Complex carbs (wheat germ, brown rice, bran and corn) • Indigestible oligosaccharides (asparagus, brocooli, Brussel sprouts, from those who could be experiencing another GI cabbage, soy beans, etc) condition (IBS, celiac, etc) • Sorbitol and mannitol • Carbonated beverages ALARM SYMPTOMS: new onset, persistent, frequent, severe Conditions • IBS, celiac, diabetes • Sx for more than several months or occur more often than Other • Smoking, chewing gum, sucking hard candies, poor fitting dentures occasionally (ex// several times a month)

• Severe debilitating symptoms NON-PHARMACOLOGICAL RECOMMENDATIONS: provide both general info and help • Significant abdominal discomfort, or sudden change in patients identify triggers location of abdominal pain • Avoid washing food down with a beverage • Eat and drink slowly • Significant increase in frequency or severity of sx • Avoid gulping or sipping liquid • Quit/reduce smoking • Onset of sx in >40 yrs old • Don’t try and induce belching • Avoid chewing gums/ • Sudden change in bowel function (diarrhea/constipation) • Do not lie down after eating for 2-3 hours hard candies • Severe/persistent diarrhea or constipation, GI bleeding, • Avoid gas producing foods/ foods with • Eat smaller meals fatigue, unintentional weight loss, frequent nocturnal sx added air or that release air • Chew food thoroughly • Presence of long-standing diabetes, celiac disease or other o Food diary • Avoid tight-fitting clothing GI conditions o Diet low in FODMAPS

THERAPY: limited evidence, correct underlying causes; OTC = antiflatulent (simethacione), adsorbent (bismuth), digestive enzymes, probiotics

ANTIFLATULENT: FIRST OPTION - Ovol, Gas-X, Phazyme DIGESTIVE ENZYMES: • MOA: inert silicon polymers, coalesces gas bubbles • Lactase enzyme (Lactaid, Lacteeze): when sx are linked to lactose (reduces surface tension) • Alpha-galactosidase (Beano): when sx linked to nonabsorbable carbs • Dose: 80-160 mg QID • Caution in diabetics – can absorb more carbs per gram

ALPHA-GALACTOSIDASE (BEANO): Advantages Disadvantages • MOA: enzyme (hydrolyzes oligosaccharides) • Not absorbed • No proven efficacy on • Very well tolerated decreasing sx of • Dose: 150-450 GaIU with first bite of food (300-1200 GaIU/day) • May be useful in diarrhea abdominal gas o Don’t use enzyme on hot food with loperamide • No proven efficacy in • Caution/CI: rare allergic reactions (rash, itching) GERD over antacid alone • Indicated: when abdominal gas associated with high fibre foods (contain high amounts of oligosacch), foods high in oligosaccharides ADSORBENT : SECOND OPTION – Bismuth subsalicylate o Vegetables: parsley, onions, lettuce, leeks, cucumbers, corn, cauliflower, cabbage, brussel sprouts, broccoli, beets • Can bind sulfide gas o Beans: black-eyed, broad, chickpeas, bag beans, lima beans, mung beans, peanuts • Only use short-term to avoid toxicity & peanut butter, punto, red kidney, seed flour (sesame, sunflower), soy products) o Grains: bagels, barley, breakfast cereal, granola, pasta, rice, bran, rye, sorghum grain, wheat bran, whole wheat flour, whole-grain breads Lecture 6 OTC Dyspepsia, Abdominal Gas, Lactose Tolerance Meghji LACTOSE INTOLERANCE:

BASICS: 3 CLASSIFICATIONS OF LACTASE DEFICIENCY: • Lactase = enzyme that digests lactose (disaccharide sugar) into glucose Primary • Most prevalent & galactose • Occurs with increasing age • Deficiency of natural lactase enzyme causes bloating, flatulence, • Variable tolerance to lactose cramping and diarrhea Secondary • Short-lived (transient) o During interview: do sx correlate to consumption of lactose? • Secondary to an illness or disease (due to mucosal inury-gastroenteritis) Congenital • Rare VARIABLE TOLERANCE TO LACTOSE: individuals who identify as lactose (galactosemia) • Requires lactose-free or very-low lactose diet deficient/intolerant

1. Have different natural levels of lactase enzyme in the body 2. At baseline, can tolerate/digest different levels of lactose (w/o txt) TREATMENT OPTIONS: 3. Amount of lactose consumed + relative lack of enzyme = extent of sx • Lactose avoidance or restricted diet • Lactase-treated food products (milk, cheese, yogurt) or substitutes DAIRY PRODUCTS: (fortified soy milk, almond milk, rice milk products) • Processed foods • Lactase supplementation • Drugs (capsules, tablets, DPIs?) and other pharmaceutical products may o Large amounts of lactose will still be incompletely broken down = also contain lactose (ex// as a filler) consume in moderation o Not usually a concern but check ingredients if severe intolerance o Negligible adverse effects, no drug interactions o Dose: 9000 FCC lactase units to start (max 18000 FCC units at MONITORING OF THERAPY: one time), adjust based on foods consumed ▪ • Alarm symptoms Taken ideally just before or with lactose (first bite/drink) ▪ Liquid = to be added to milk 24 h before consumption • Symptoms persist for > 1-2 weeks despite OTC treatment • Ensure patients have enough calcium/vitamin D in their diet