chapter 13 heartburn and dyspepsia

8/10/2019 Chapter 13 Heartburn and Dyspepsia

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It is important to note that frequent heartburn, which persists for more than 3months , is referred to as gastroesophageal reflux disease (GERD). If a patientpresents with frequent heartburn lasting for at least 3 months, he or she must bereferred to the M.D. GERD is usually not relieved by antacids or any other OTC treatment. A diagnosiscannot be made without an upper GI endoscopy and manometry.

Postprandial heartburn : Heartburn that occurs within 2 hours of eating a large meal orother trigger food

Non-erosive gastroesophageal reflux disease (NERD) : frequent and severe heartburn without esophageal damage

Nocturnal heartburn : Heartburn that disturbs restful sleep. This occurs partly because when a person lies flat, gravity no longer pulls down on the gastric juices, inviting the juice towards the esophagus.

Defining DyspepsiaDyspepsia is a synonym for bad digestion.It is defined as consistent or recurring discomfort in the upper abdomen. It is notrestricted to meal related symptoms. Dyspepsia often is associated with bloating,

belching, early satiety, and nausea.

The causes of dyspepsia are:(1) Structural: Peptic ulcer disease or GERD damaging the lining of the

esophageal wall(2) Functional/ idiopathic for 60% of patients

Contributing factors to heartburn and dyspepsia- Weakened LES tone

o Sphincter is more readily opened- Delayed stomach emptying

o Increases the gastric pressure, opening the LES- Increased acid secretion

o Lowers the pH of the gastric juices, further exacerbates painful symptomsheartburn/ dyspepsia

- Decreased salivation with increased ageo May cause stomach to work harder

Risk FactorsDiet LifestyleChocolatesFatty foods increase abdominal pressureSpicy foods directly irritate the upper GItractSpearmint/ peppermintGarlic/ onions

Alcohol and caffeine lower the LES tone

SmokingStressExerciseLaying down within 3 hours after eatingLarge mealsTight fitting clothesObesity

Drugs (direct irritants) Drugs (lowers LES tone)


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Bisphosphonates AspirinNSAIDsIronPotassium

QuinidineTetracyclineEstrogenMorphineNitrates

- Prostaglandins protect the GI lining. NSAIDs inhibit prostaglandin production.- Bisphosphonates are indicated for osteoporosis therapy.- Iron and calcium interact.

Signs and SymptomsCommon Alarm [immediately refer to MD]Burning sensation behind breast boneIncreased salivationBurping/ belchingRegurgitation without nauseaPain around epigastric area

Dysphagia (difficulty swallowing)GI bleed (evidenced by dark stools)Unexplained weight loss (at least 10% of

body weight)Continuous nausea/ vomiting/ diarrhea

Heartburn ComplicationsIf left untreated, heartburn can lead to a wide variety of other medical problems.

- Esophageal ulcers may led to short term and long term bleeding- Esophageal strictures- Trouble swallowing- Cancer- Barretts esophagus- A decreased quality of life

Heartburn and Pregnancy Heartburn occurs in 45-85% of women in the third trimester. For pregnancy-relatedheartburn, antacids are safe as long as they are taken PRN and high doses are avoided.Sodium bicarbonate containing antacids should be avoided, because the sodium

bicarbonate content can lead to fluid accumulation.

Tagamet (H2RA) has been shown to cross the placenta, but adverse effects to the childhave not been proven. Prilosec (PPI) crosses into breast milk, and its administration tolactating women should only be considered if the benefits outweigh the risk. In general,pregnant and lactating women should only take H2RAs and PPIs after M.D.consultation.

Patients should seek medical attention if:- Heartburn symptoms persist after two weeks of treatment with antacids or

H2RAs.- Symptoms such as difficulty swallowing or persistent abdominal pain

occur.- Chest pain occurs, particularly: tight, viselike pain or discomfort that

radiates the neck, shoulder, or left arm.

TREATMENTTreatment of HeartburnThe purpose of treating heartburn and dyspepsia OTC is to achieve the following goals:


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1. Relieve heartburn or prevent its recurrence2. Relieve stomach pain/ discomfort3. Prevent complications, such as ulcer formations4. Improve the patients quality of life

Role of the PharmacistThe pharmacist is responsible for assessing whether the patient is a candidate for self-treatment, or whether the patient will need to be referred to an MD. The pharmacistshould recommend lifestyle changes that will improve the condition or prevent itsrecurrence.

If appropriate, the pharmacist should recommend OTC medications based on thespecific patient, including: symptom presentation, lifestyle, cost issues, druginteractions, and co-morbidities.

Primary Treatment OptionsOnce it has been assessed that the patient is experiencing simple heartburn and doesnot need to be referred to a physician, there are three main drug classes which mayhelp treat the patient:

AntacidsHistamine-2 Receptor Antagonists (H2RAs)Proton Pump Inhibitors (PPIs)

Remember, the pharmacist must always recommend lifestyle modifications .

Lifestyle Modifications- Elevate the head of bed at least 6 inches before sleeping- Eat no later than 3 hours before going to bed to allow adequate time for gastric

emptying- Avoid foods that trigger heartburn- Avoid lying down after meals- Limit alcohol intake- Smoking cessation- Weight loss, if obese

Antacids Antacids are used for temporary relief of mild and infrequent heartburn and dyspepsia.It is not used for prevention.

Common antacid- containing products include Mylanta, Maalox, Milk of Magnesia,Tums, Rolaids, Pepto Bismol, and Simethicone

Mechanism of action of antacids(1) Increases LES tone to restore normal LES activity(2) Neutralize stomach acid by acting as a pH buffer

All antacids contain at least one salt, which acts as a base, therebyneutralizing gastric juices: sodium bicarbonate, calcium carbonate,aluminum salts, and magnesium salts

Pharmacokinetics of antacids Antacids begin working in less than 5 minutes.


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On an empty stomach, they will work for 20- 40 minutes. When taken within one hourof eating a meal, they will work for 2-3 hours.Up to 10% of calcium will be systemically absorbed.

About 15-30% of magnesium and aluminum may be absorbed and renally excreted.

Potency of antacidsSodium bicarbonate and magnesium salts dissolve more quickly in the stomach, buthave short durations of action.

Calcium and aluminum salts dissolve more slowly in the stomach, but have longerdurations of action.

Common side effects of antacidsMagnesium : Diarrhea without abdominal cramping

Aluminum : Constipation and hemorrhoidsCalcium carbonate : acid rebound and formation of kidney stonesSodium bicarbonate : water retention

Antacids: Drug interactions- Drugs, such as certain antibiotics, may chelate to the multivalent cations in the - -

antacids.- Because antacids increase the pH of the gastric juices, drugs that require a lowintagastric pH for disintegration, ionization, or activation, may be affected- Drugs with enteric coating may not uncoat due to the increased pH.- Drugs that are affected by urine alkalinization.

Simethicone is an agent found in some antacids or by itself (Gas-X).

It is an anti-gas agent, which decreases bloating, abdominal pain, and discomfort.It alters the surface tension of intestinal gas bubbles. Patients may experiencemild diarrhea and nausea while taking simethicone.

Tums is calcium carbonate.

Tums = 500 mg (200 mg calcium)Tums EX = 750 mg (300 mg calcium)Tums ultra = 1000 mg (400 mg calcium)

Patient education:(1) Chew 1-2 tablets thoroughly up to every 2 hours(2) Take with a full glass of water(3) Take at least 1-2 hours before taking iron supplements(4) Avoid alcohol, other antacids, caffeine, or other calcium supplements(5) The maximum daily intake is 7000 mg of calcium.

Alka-Seltzer contains aspirin, sodium bicarbonate, and citric acid.

Sodium triggers the retention of water in the body, leading to potential fluidoverload. It may also lead to systemic alkalosis.

Patient education:


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(1) Dissolve completely in water and wait until bubbles subside beforedrinking

Bismuth subsalicylate is the active ingredient (525 mg/ 30ml) in Maalox Total Reliefand Pepto-Bismol.

Avoid in:(1) Children below 16 years old, as they may be at risk for Reyes syndrome(2) Pregnant or nursing mothers(3) Patients with allergies to aspirin (acetylsalicylic acid) or salicylates

Patient Education(1) Shake well(2) Take 2 tablespoons every hour as needed with a full glass of water.

Maximum is 16 tablespoons.

Side EffectsCan cause temporary darkening of stool and tongue.

Patient Counseling Points of Antacids- Take at onset of symptoms

o Taking it one hour after a meal will greatly increase the duration of action- Consult label for ingredients, dosing- See physician if symptoms persist for more than 2 weeks- Inform them of the potential side effects- Separate by 2 hours from interacting drugs- Refrigerate liquids to improve taste

Histamine-2 Receptor AntagonistsH2RAs treat mild to moderate infrequent heartburn.Like antacids, H2RA OTC therapy should not be used for longer than 2 weeks withoutM.D. consultation.

OTC doses of H2RAs are lower than prescription doses.

A combined product (Pepcid Complete) contains both H2RAs and an antacid. It is usedfor postprandial heartburn with patients who have not premedicated with an H2RA.

Mechanism of action of H2RAsHistamine blockers work to prevent stomach release by inhibiting the proton pump.However, it does not help to reduce the frequency of heartburn events.

The H-2 receptor typically binds histamine, resulting in a signaling cascade thatactivates the proton pump to deliver protons to the lumen. H2RAs block the H-2receptor, preventing the activation of this signaling cascade.

PharmacokineticsOnset of action: 30- 45 minutesDuration of action: 6-10 hours (cimetidine shortest, famotidine longest)Clearance: Combination of hepatic metabolism and renal elimination.Food does not alter the bioavailability of H2RAs.


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Tolerance develops in persons who take H2RAs long- term daily.

For best results, H2RAs should be taken one hour before symptoms are anticipated.

PotencyThe effects of H2RA usually begin within 1 hour of administration and last for 6-10hours.

There is a modest difference between non-prescription H2RAs, but they can be usedinterchangeably. The exception to this generalization is cimetidine, which has theshortest duration of action.

Only prescription strength H2RAs are proven and indicated for the healing of theesophagus.

PrecautionsCommon Side effectsHeadacheDrowsiness

General GI distress: Constipation, diarrhea, nausea, and abdominal pain

Dose adjustments are required in patients with renal impairment (Creatinine clearanceof less than 50 mL/min)

Drug InteractionsBecause H2RAs increase the pH of the gastric environment, drugs that require a lowintragastric pH for disintegration, dissolution, or ionization (e.g. atazanavir, phenytoin,ketoconazole) will decrease in levels.

Cimetidine inhibits CYP450 isozymes (3A4, 2D6, 1A2, 2C9), resulting in increased

levels of other drugs that are substrates.The most significant drugs to take into consideration are warfarin, phenytoin,and theophylline, as they all have narrow therapeutic windows.Interaction potential of cimetidine and these other drugs are dose-related andpatient-specific.

Proton Pump Inhibitors (PPIs)OTC PPIs are indicated to treat frequent heartburn in adult (over 18) patients withsymptoms 2 or more days per week.If they experience heartburn 2 or more days per week for at least 3 months,immediately refer them for M.D. consultation, because they may have GERD.

Chronic use (more than 2 weeks) is indicated to help heal an ulcer or for patients on acourse of NSAIDs, but only an M.D. may recommend this regimen.

Mechanism of actionPPIs bind irreversibly to the hydrogen- potassium ATPase in gastric parietal cells,

blocking the final step in gastric acid secretion. It is only effective in active pumps.

Pharmacokinetics


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Onset of action: Symptom relief begins in 2-3 hours, but complete relief may take 1-4daysDuration of action: 12-24 hoursPrilosec OTC, Nexium 24 hr, and Prevacid 24 hr contain multiple enteric-coated pelletsfor delayed release.

Zegerid OTC is formulated with sodium bicarbonate for immediate release.

Precautions Common Side EffectsHeadacheMild RashDizzinessCold SymptomsCoughGeneral GI distress: Diarrhea, Nausea, and Vomiting, Stomach pain

Potential Long Term Complications (if taken for longer than 2 weeks)Pneumonia

Chronic atrophic gastritis and gastric cancerB12 malabsorption with chronic use of omeprazoleHip fracture/ calcium malabsorptionIncreased risk of C. diff infection

Acid rebound with chronic use

Drug InteractionsIncreased bleeding with warfarinDrugs that require an acidic environment for absorption (e.g. iron, tetracyclineantibiotics, digoxin)

2009 FDA warning for clopidogrel and omeprazoleClopidogrel is a blood thinner. Proton pump inhibitors, specifically omeprazole, has benshown to inhibit CYP450 2C19, which is necessary for the activation of clopidrogel.

Cost comparisons of PPIsLansoprazole and omeprazole are roughly the same price, while esomeprazole is themost expensive when sold as prescription medication.

SUMMARY OF KEY FACTS


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KEY POINTS OF CLINICAL PRACTICE- Heartburn and dyspepsia are common GI symptoms- When heartburn is the dominant symptom, it is usually associated with GERD- All patients may benefit from lifestyle modifications at any point of diagnosis- Always be cognizant of alarm symptoms and refer patients immediately to an

M.D.- Any patient self- treating longer than 14 days should be referred to an MD.

H2RAsBrand Generic DosingPepcid Famotidine 10-20 mg prn up to 2x/dayZantac Ranitidine 75-150 mg

Axid Nizatidine 75 mg Tagamet Cimetidine 200 mg Pepcid Complete Famotidine + CaCO3 +

MgOH1 tab prn

PPIsBrand Generic DosingPrilosec Omeprazole 20 mg 1x/dayNexium Esomeprazole 20 mg Prevacid Lansoprazole 15 mg Zegerid Omeprazole + NaHCO3 1 cap

chapter 13 heartburn and dyspepsia

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