Lecture 6 OTC GERD/Heartburn Meghji

GASTROESOPHAGEAL REFLUX DISEASE:

• “A condition that develops when the reflux

of stomach contents causes troublesome

symptoms and/or complications”

(Montreal Classification)

• Most common symptoms for mild GERD:

o Heartburn (burning sensation along

esophagus)

o Regurgitation (acid/bile that rises to

the back of the throat)

• Features:

o May wax and wane

o Worse when lying down, bending

over, or after a meal

CAUSE IS MULTIFACTORIAL:

• Relaxation/decreased integrity of the

lower esophageal sphincter

• Increased lower abdominal pressure

• Delayed gastric emptying

• Impaired esophageal clearance/peristalsis

• Excessive acid production

• Hiatal hernia

• Bile reflux

GERD RISK FACTORS/TRIGGERS:

• Being overweight/obese

• Diet

o Fatty foods/spicy foods

o Chocolate*

o Coffee *

o Alcohol *

o Carbonated drinks

o Citrus fruits or juices

o Garlic or onions

o Mint (peppermint, spearmint)

o Tomatoes

• Pregnancy

• Stress and anxiety

• Age ( > 65)

• Smoking *

• Hiatus hernia

* = weak associations

MEDICATIONS THAT LOWER ESOPHAGEAL

PRESSURE can induce or worsen GERD:

• Alpha-adrenergic antagonists

• Anticholinergics

• Beta-agonists

• Benzodiazepines (diazepam)

• CCBs (nifedipine, felodipine, amlodipine)

• Nicotine

• Nitrates

• Opioids

• Progesterone

• Theophylline

DRUG INDUCED DYSPEPSIA/ESOPHAGITIS:

• Acarbose

• Amiodarone

• Antibiotics o Erythromycin o Tetracyclines

• Bisphosphonates

• Potassium chloride

• Clindamycin

• Digitalis

• Ethanol

• Iron

• NSAIDs

• Quinidine

ALARM SYMPTOMS & WHEN TO REFER:

• Chest pain: radiating pain to shoulders, neck, arm, SOB, sweating

• Vomiting: continuous/recurrent

• GI blood loss: hematemesis, melena

• Dysphagia (difficulty swallowing), especially solids

• Odynophagia (severe pain on swallowing)

• Unexplained weight loss > 5%

• Unexplained cough, wheezing, choking, hoarseness

• Age > 50 years old with new symptoms

• Severe symptoms (frequency, rating)

• Nocturnal symptoms

• Failure of 2 week H2RA/PPI therapy

WHY CHECK FOR ALARM SX?

Symptoms could be due or lead to:

• Cardiac disease

• PUD

• Malignancy

• Functional dyspepsia

• Biliary disease

• Other

GOALS OF THERAPY:

• Treat symptoms

(reduce/eliminate)

• Reduce or prevent recurrence

• Prevent structural damage and

thus complications (e.g. ulcers)

• Prevent ADRs of meds

NON-PHARMACOLOGICAL TX:

• Avoid foods/beverages that worsen or trigger symptoms

• Eat small meals and chew food well

• Avoid exercise after meals

• Don’t lie down for 2-3 hours after eating

• Avoid tight clothing

• Encourage smoking cessation

• Elevate head of bed frame (i.e. not extra pillows) about 10 cm

• Achieve ideal body weight

► Individualize non-pharmacological therapy to triggers

► Evidence = inconclusive

ANTACIDS: sodium bicarbonate and salts of aluminium, calcium and magnesium

• MOA: neutralizes gastric acid

• Potency: aluminum (least) < magnesium hydroxide < sodium bicarbonate < calcium carbonate (most potent)

• Used in combination with each other (lots of products); dosing varies with products

Advantages Disadvantages

• Immediate relief of symptoms (faster than H2Ras/PPIs) o Liquids work faster than tablets

• Cheap, unscheduled

• Frequent dosing required o Short duration of action (0.5 – 1 hr,

prolonged by food up to 3 hours)

• Many drug interactions

• Check sodium content

INTERACTIONS:

• May adsorb or chelate with other drugs

( tetracyclines, fluoroquinolones, iron)

o Separate by at least 2 hours

• Increases gastric pH changing

absorption (ketoconazole, iron)

• Premature breakdown of EC meds

Ca carbonate Magnesium Aluminum Sodium bicarbonate

Place in therapy

• Most common agent used

• Preferred in compromised renal function

• Magnesium/aluminum combos used to offset constipation/diarrhea

o Diarrhea dominates

• Generally avoided

• Not first line

Caution/CIs • Hypercalcemia (total Ca intake)

• Can lead to milk-alkali syndrome & hypophosphatemia (prolonged/use high doses)

• Avoid in renal dysfunction and elderly (risk of hyperMg)

• Avoid in renal dysfunction

• Can lead to hypo-PO4 (prolonged use/high doses)

• High Na content = avoid in high BP, HF, renal dysfunction, edema, cirrhosis, pregnancy, etc

• Can cause metabolic alkalosis (prolonged use/high doses)

Notable SEs • Belching

• Flatulence

• Constipating

• Diarrhea • Constipating • Flatulence

• Belching

• Abdominal distension

Examples • Tums

• Maalox

• Diovol

• Milk of Magnesia

• Gaviscon ES, max strength

• Alugel, amphogel

• Gaviscon RS

• Alka-Seltzer (+ASA), ENO (sodium citrate)

ALGINATE + ANTACID: alginic acid/sodium alginate

• MOA: alginate forms a viscous layer on top of gastric

contents = protective barrier

• Advantages: immediate relief of symptoms

o Formulated with antacids

• Disadvantages:

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

• Can be used with a prn antacid o Famotidine: available in combination with an antacid (Pepcid complete)

• Used for prevention (30 min-1 hr before aggravating food or trigger)

• Usually well tolerated (diarrhea, headache, dizziness, rash & tiredness)

• Not as rapid onset as an antacid

• Tachyphylaxis (use PRN?)

• Reduce dose in renal impairment

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

• Once daily dosing

• Induces remission more frequently than H2Ras

• Usually mild SEs (constipation, diarrhea, headache)

• Onset: 3 hours (not for immediate relief)

• Increased infections (CAP, C. diff), fracture risk?, B12 deficiency, hypomagnesia, iron malabsorption (not an OTC use concern)

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

• May be effective for abdominal gas

• S/E: black stool (might be mistaken for GI bleed), black tongue, diarrhea, nausea, vomiting

• Contains salicylate (caution allergy, GI bleeding/ulcers, children, renal failure, pregnancy, etc)

PREGNANCY:

• Heartburn common during pregnancy (30-80%)

• Relief if no improvement after 7 days

Yes No

• Ca antacids (space from iron)

• Magnesium (avoid trisilicate)

• Alginic acid

• Ranitidine, famotidine

• PPI (if other therapies fail) o Omeprazole

• ASA (Alka-Seltzer)

• Sodium bicarbonate

• Magnesium trisilicate

LACTATION:

Yes Insufficient info

• Al, Ca, Mg antacids

• Famotidine (preferred to ranitidine)

• Omeprazole

• Esomeprazole

MONITORING OF THERAPY:

• REFER: no resolution within 1-2 weeks of therapy, new alarm sx, worsening sx

• RECURRENCE: if at least 3 months after last episode, consider new discrete episode

and treat with therapy that was previously effective

Lecture 6 OTC Dyspepsia, Abdominal Gas, Lactose Tolerance Meghji

DYSPEPSIA:

SYMPTOMS: “upset stomach” or “indigestion”

• Rome IV criteria (1 or more of the following sx):

o Postprandial fullness

o Early satiation (can’t finish a normal sized meal)

o Epigastric pain or burning

CAUSES:

• Specific causes or structural abnormalities (25%)

o PUD, GERD, cancer, infections, other diseases

o Food intolerances (lactose deficiency)

o Medications (NSAIDs), NHPS (garlic, feverfew, etc)

• No specific cause or structural abnormality (75%)

o Functional/idiopathic dyspepsia (full criteria for 3 m at least 3 days/wk) TREATMENT:

• Only treat dyspepsia if you are able to identify a (self-

treatable) cause without alarm symptoms

ABDOMINAL GAS:

SYMPTOMS:

• A normal bodily process

• On average, gas expulsion = 500-700 mL/day

• Can sometimes lead to bothersome sx:

o Increased belching/burping (eructation)

o Bloating

o Increased farting (flatulence)

o Cramping/pain/discomfort

• Need to differentiate people with transient symptoms

from those who could be experiencing another GI

condition (IBS, celiac, etc)

TRIGGERS:

Med • Fibre

• Drugs that affect flora (lactulose, antibiotics), alpha-glucosidase inhibitors (acarbose, biguanides), orlistat, narcotics, anticholinergics, CCB, cholestyramine, effervescent solutions

Diet • Large meals, eating too quickly

• Dietary sugars (lactose, fructose, sucrose, glucose)

• Fatty foods

• Complex carbs (wheat germ, brown rice, bran and corn)

• Indigestible oligosaccharides (asparagus, brocooli, Brussel sprouts, cabbage, soy beans, etc)

• Sorbitol and mannitol

• Carbonated beverages

Conditions • IBS, celiac, diabetes

Other • Smoking, chewing gum, sucking hard candies, poor fitting dentures

ALARM SYMPTOMS: new onset, persistent, frequent, severe

• Sx for more than several months or occur more often than

occasionally (ex// several times a month)

• Severe debilitating symptoms

• Significant abdominal discomfort, or sudden change in

location of abdominal pain

• Significant increase in frequency or severity of sx

• Onset of sx in >40 yrs old

• Sudden change in bowel function (diarrhea/constipation)

• Severe/persistent diarrhea or constipation, GI bleeding,

fatigue, unintentional weight loss, frequent nocturnal sx

• Presence of long-standing diabetes, celiac disease or other

GI conditions

NON-PHARMACOLOGICAL RECOMMENDATIONS: provide both general info and help

patients identify triggers

• Avoid washing food down with a beverage

• Avoid gulping or sipping liquid

• Don’t try and induce belching

• Do not lie down after eating for 2-3 hours

• Avoid gas producing foods/ foods with added air or that release air

o Food diary o Diet low in FODMAPS

• Eat and drink slowly

• Quit/reduce smoking

• Avoid chewing gums/ hard candies

• Eat smaller meals

• Chew food thoroughly

• Avoid tight-fitting clothing

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

ANTIFLATULENT: FIRST OPTION - Ovol, Gas-X, Phazyme

• MOA: inert silicon polymers, coalesces gas bubbles

(reduces surface tension)

• Dose: 80-160 mg QID

Advantages Disadvantages

• Not absorbed

• Very well tolerated

• May be useful in diarrhea with loperamide

• No proven efficacy on decreasing sx of abdominal gas

• No proven efficacy in GERD over antacid alone

ADSORBENT: SECOND OPTION – Bismuth subsalicylate

• Can bind sulfide gas

• Only use short-term to avoid toxicity

DIGESTIVE ENZYMES:

• Lactase enzyme (Lactaid, Lacteeze): when sx are linked to lactose

• Alpha-galactosidase (Beano): when sx linked to nonabsorbable carbs

• Caution in diabetics – can absorb more carbs per gram

ALPHA-GALACTOSIDASE (BEANO):

• MOA: enzyme (hydrolyzes oligosaccharides)

• Dose: 150-450 GaIU with first bite of food (300-1200 GaIU/day)

o Don’t use enzyme on hot food

• Caution/CI: rare allergic reactions (rash, itching)

• Indicated: when abdominal gas associated with high fibre foods

(contain high amounts of oligosacch), foods high in oligosaccharides o Vegetables: parsley, onions, lettuce, leeks, cucumbers, corn, cauliflower, cabbage,

brussel sprouts, broccoli, beets

o Beans: black-eyed, broad, chickpeas, bag beans, lima beans, mung beans, peanuts

& 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:

• Lactase = enzyme that digests lactose (disaccharide sugar) into glucose

& galactose

• Deficiency of natural lactase enzyme causes bloating, flatulence,

cramping and diarrhea

o During interview: do sx correlate to consumption of lactose?

DAIRY PRODUCTS:

• Processed foods

• Drugs (capsules, tablets, DPIs?) and other pharmaceutical products may

also contain lactose (ex// as a filler)

o Not usually a concern but check ingredients if severe intolerance

VARIABLE TOLERANCE TO LACTOSE: individuals who identify as lactose

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)

3. Amount of lactose consumed + relative lack of enzyme = extent of sx

3 CLASSIFICATIONS OF LACTASE DEFICIENCY:

Primary • Most prevalent

• Occurs with increasing age

• Variable tolerance to lactose

Secondary • Short-lived (transient)

• Secondary to an illness or disease (due to mucosal inury-gastroenteritis)

Congenital (galactosemia)

• Rare

• Requires lactose-free or very-low lactose diet

TREATMENT OPTIONS:

• Lactose avoidance or restricted diet

• Lactase-treated food products (milk, cheese, yogurt) or substitutes

(fortified soy milk, almond milk, rice milk products)

• Lactase supplementation

o Large amounts of lactose will still be incompletely broken down =

consume in moderation

o Negligible adverse effects, no drug interactions

o Dose: 9000 FCC lactase units to start (max 18000 FCC units at

one time), adjust based on foods consumed

▪ Taken ideally just before or with lactose (first bite/drink)

▪ Liquid = to be added to milk 24 h before consumption

• Ensure patients have enough calcium/vitamin D in their diet

MONITORING OF THERAPY:

• Alarm symptoms

• Symptoms persist for > 1-2 weeks despite OTC treatment