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78 Cards in this Set
- Front
- Back
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GERD Epidemiology
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10-20% prevalence in Western Countries
Affects all age groups > 61 million people have GERD symptoms at least once monthly Patients often first seen in pharmacies |
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Definitions: Dyspepsia
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“Chronic or recurrent pain or discomfort centered in the upper abdomen.”
“Discomfort is defined as a subjective negative feeling that is non-painful, and can incorporate a variety of symptoms including early satiety or upper abdominal fullness” American Gastroenterology Association “The term dyspepsia here will be restricted to mean chronic or recurrent pain or discomfort centered in the upper abdomen (i.e., the epigastria) ..”reflux symptoms alone and acute abdominal conditions will not be included.” Chronic and pain and discomfort are the distinguishing features from GERD |
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definition of GERD
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Gastroesophageal Reflux Disease (GERD)
“a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications.” |
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What's “NERD” or “ENRD”?
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non- errosive reflex disease
endoscopy negative refelx disease |
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2 types of GERD
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esophageal syndromes
extra-esophageal syndrome |
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GERD is a condiditon which developes when the refelx of stomach contents causes ___________ symptoms and or ____________
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troublesome
complications |
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2 groups of esophageal syndrome and the symptoms associated with them
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symptomatic syndromes:
* typical refelx * Reflex chest pain syndrom (mimics a MI, therefore most common type of GERD seen in a hosptial) Syndrome with esophageal injury: * refelx esophagitis * reflex strincture * Barrett's esophagus * Adenocarcinoma |
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2 groups of extra-esophageal syndrome and the symptoms associated with them
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established association:
* reflex cough * reflex laryngitis * reflex asthma * reflex dental errosions Proposed association: * sinusitis * pulmonary fibrosis * pharyngitis * recurrent otitis media |
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Heartburn defintion
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acid and gastric contents reflex from the stomach into the esophagus and cause burning and pain
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what does it mean when a person has "troublesome" GERD
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their GERD interfers with their quality of life and they are seeking help because of it
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grading the severity of GERD
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< or equal to 2 times/week = intermittent--> mild
> 2 times/week moderate--> severe if the patient has complications associated with the GERD they have severe GERD |
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GERD Pathophysiology
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it is caused by multiple facotrs it is not totally related to to acid production
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Drug-Induced GERD that effect the LES tone and pressure
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Alpha adrenergic antagonists
Benzodiazepines Nitrates Calcium channel blockers Barbiturates Anticholinergics Dopamine Theophylline |
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Drug-Induced GERD direct irritants
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Aspirin
NSAIDs Bisphosphonates Iron Potassium |
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drug induced GERD delayed gastric emptying
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Anticholinergics
Estrogen/progesterone Opiates TCAs |
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Typical Features/Symptoms of GERD
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Heartburn
Regurgitation Belching Acid taste Hypersalivation (not common) Often after a meal Often relieved with change in position (distinguishes from an ulcer) |
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Atypical Features/Symptoms of GERD
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Often leads to extensive investigation of non-GI causes of symptoms
Chronic cough Laryngitis/hoarseness Asthma-like symptoms Recurrent sore throat Otitis media Sinusitis Dental enamel loss Non-cardiac chest pain recurrent ear otitis media (especially in children) |
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ALARM Features/Symptoms of GERD
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Dysphagia = difficulty swallowing
Odynophagia = pain with swallowing Bleeding Unintentional weight loss Choking Anemia +/- chest pain REFER PATIENT TO PCP |
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Complications of GERD
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Erosive esophagitis (10-25%)
Grades A-D or 0-5 (least to worst) (can cause upper GI bleed) Stricture: caused by errosive esophagitis it is a blockade in the lower pait of the esophagus Barrett’s Esophagus (6-10%) OR = 3 for GERD 1-5 years OR = 6.4 for GERD > 10 years (pre-cancerous state) Adenocarcinoma (uncommon) - a result of Barrett's esophagus Reductions in quality of life |
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Diagnosis of GERD
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Symptom Based (#1 way to diagnois)
* burning symptoms and acid taste Endoscopy Age > 55 years ( after 55 the risk of cancer greatly increases) Suspected complications Suspected extra-esophageal syndrome |
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Diagnosis: Manometry
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Tests for alterations in esophageal motility or LES pressure
Used prior to pH testing Lack of response to PPIs |
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Ambulatory pH testing
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% time pH > 4 over 24 hour period
GERD with continued symptoms Lack of response or failure of drug therapy |
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Non-pharmacologic Management: dietary
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↓ LES tone: alcohol, caffeine, chocolate, garlic, onions, peppermint, spearmint
Irritants: spicy foods, tomato juice, coffee Avoid high fat meals Smaller, more frequent meals Avoid eating within 3 hours of bedtime |
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what is the main point of non-pharm recommendations
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be patient specific
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lifestyle modifications for GERD
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Reduce/stop nicotine
Avoid tight fitting clothing Weight loss (only for those that are overweight or obese) Elevate head of bed 6 inches |
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expected improvement of GERD from non-pharm
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10-20% maximum decrease in symptoms
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treatment guidelines for GERD
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Empiric therapy OK in patients with typical symptoms consistent with uncomplicated GERD
OTC Acid suppressants and antacids are options for patient directed therapy Acid suppression is mainstay of therapy Especially for severe GERD and esophagitis PPIs are best for symptomatic or erosive disease Surgery is an option if fail PPI therapy or have complications |
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Acid suppression is mainstay of therapy
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Especially for severe GERD and esophagitis
PPIs are best for symptomatic or erosive disease |
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Picking a Drug for GERD
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Frequency/Severity of Symptoms
Effectiveness Onset of action and/or duration of effect Formulation Adverse effects or drug interactions Cost |
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step up strategy for GERD
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start with a low dose antacid and then can increase the dose
if the patient continues to have symptoms change to an H2 if the patient still continues to have sympotoms change to a PPI for moderate to severe GERD this apporach will take longer to relieve the symptoms |
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step down strategy for GERD
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start with the PPI then H2 then antacid
once a patient starts a PPI it is hard to get them off this approach does better control the sympotms but it can be more expensive |
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treatment strategies for GERD
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Frequency of Use
*Continuous (QD) *On-Demand (PRN or when have symptoms) Breakthrough: taking continuously but still having symptoms so need something extra OTC vs. Rx: patient directed is an ok place to start |
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Drug options for GERD
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Antacids
Antirefluxants: Alginic Acid Histamine 2 Receptor Antagonists (H2RAs) Proton Pump Inhibitors (PPIs) Promotility Agents: Metoclopramide |
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Antacids
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Calcium, aluminum, and magnesium-based products
Available OTC in a wide variety of formulations (capsules, tablets, chewable tablets, suspensions) acid neutralizers |
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role of antacids in GERD
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On demand symptom relief
1st line for symptoms < 2 times/week Breakthrough on PPIs or H2RAs work the fastest so good for eposodic heartburn |
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antacids are picked for GERD by....
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Medical history
*kidney stones--> no ca *renal disease--> no al mg * constipation--> no ca and al Organ function Potential drug interactions: chelation Preference for formulation Effects are short lived |
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alginic acid for GERD
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Considered an antirefluxant
Gaviscon® Forms a barrier or “raft” on the top of gastric contents Tablets need to be chewed in order to release the alginic acid (will foam in mouth) Don’t suck on or dissolve in water Take after meal Products also include aluminum, magnesium, or calcium Role is same as antacids affects last 30 min to 1 hr |
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H2RAs for GERD
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Reversibly inhibit histamine-2 receptors on the parietal cell
Onset within 30 minutes (may be sooner with antacid included) Duration of action is longer than antacids |
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Role of H2RAs for GERD
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Intermittent-moderate GERD symptoms
On-demand or continuous therapy Breakthrough on PPIs |
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H2RAs are picked base on
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Tolerability
Potential drug interactions (pH or CYP450) Preference for formulation |
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what cpy enzyme does cimetidine go through
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3A4
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what is the dose of H2RAs for the best results
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BID
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do H2RAs require renal adjustment
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yes
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do H2RA's develop tachyphylaxis over time
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they sure do, because it is reversible inhibtion and there is an up regulation of the H2 receptors therefore the dose has to be increased
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PPIs role for GERD
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1st line for symptomatic GERD or esophagitis
May be used for any severity Continuous therapy better than “on-demand” Reflux Chest Pain Syndrome they do work for on demand but they take longer to reduce the symptoms and the max effects take 1-4 days |
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PPIS and GERD
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Irreversibly inhibit the final step in gastric acid secretion
Greater degree of acid suppression achieved Longer duration of action than H2RAs |
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dexlansoprazole (kapidex) differences from lansoprazole
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it is a dual delayed release (DDR)
therefore it has prolonged action so QD dosing |
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compounded PPIS
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Simplified Omeprazole Suspension (SOS)
Simplified Lansoprazole Suspension (SLS) |
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alternative administrations of PPIS
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Intravenous
Open capsules, but do not chew because it compormises the entric coating Nasogastric tubes |
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what is the effect of gastric acid on PPIs
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it destroys the PPI
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PPI dosing
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Once daily dosing appropriate initially for most patients
Twice daily dosing Severe GERD Erosive disease Reflux chest pain syndrome Extraesophageal GERD syndrome |
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duration of treatment of GERD and erosive disease with PPIs
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GERD: reassess initially within a 2 weeks (if symptoms continue--> PCP
Erosive disease: continuous for 4-8 weeks Many patients remain on therapy indefinitely |
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PPI effectiveness
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Considered most effective for GERD and Erosive Disease
Cost and third party payers may dictate ability to use certain agents and duration of therapy Tachyphylaxis should not develop Nocturnal acid breakthrough (NAB) pH < 4 for greater than 1 hour during the night May be up to 50% of patients |
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nocturnal acid breakthrough may be an indication for ______ dosing of PPIs
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BID
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should PPIS be dosed at night to prevent nocturnal breakthrough
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no because they only work on active proton pumps
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management of NAB
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Dose of PPI
Reinforce nonpharmacologic treatments Administer BID (before meals if possible) Not all patients respond Added costs Add another agent? H2 blockers at bedtime |
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PPI adverse effects
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Headache, dizziness, nausea, diarrhea, or constipation.
No significant increases in endocrine neoplasia or symptomatic vitamin B12 deficiency Community acquired pneumonia The adjusted relative risk for pneumonia with PPI use was 1.89 (95% CI 1.36-2.62) Immunocompromised, children, elderly, COPD, asthma are at highest risk well tolerated when a patient has CAP their PPI is not discontinued Clostridium difficile diarrhea Hospitalized patients Receiving antibiotics OR of 2.1 (95% CI, 1.2–3.5) Hip Fracture (JAMA 2006;296:2947-2953). OR 1.44 (95% CI 1.3-1.59) Possibly due to reductions in absorption of calcium in or possibly interference with osteoclast function No support for BMD or Ca+2 supplementation |
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PPI drug interactions
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pH mediated
Ketoconazole, itaconazole HIV medications: atazanavir CYP450 Mediated CYP 2C19 and CYP 3A4 Omeprazole most inhibitory activity Pantoprazole has least 2C19 inhibitory activity Warfarin, phenytoin, diazepam |
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PPI/clopidogrel drug interaction
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omeprazole inhibits the conversion of clopidogrel to the active metabolite and therefore the patient is at higher risk to have a recurrent event
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what are the considerations for the PPI/clopidogrel
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omeprazole and clopidogrel should be avoided when the patient is taking clopidogrel
may not get the full protective anti-clotting effect if they also take prescription omeprazole or the OTC form (Prilosec OTC). Separating the dose of clopidogrel and omeprazole in time will not reduce this drug interaction. Other drugs that should be avoided in combination with clopidogrel because they may have a similar interaction include: esomeprazole (Nexium), cimetidine (which is available by prescription Tagamet and OTC as Tagamet HB), |
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PPI/Clopidogrel Drug Interaction and possible alternatives
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PPIs reduce platelet effects of clopidogrel
Conflicting evidence on outcomes Effects may also be due to CYP 2C19 polymorphisms May considers using prasugrel Alternate PPI? Some institutions are using H2RAs |
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Metoclopramide and GERD
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Dopamine 2 receptor antagonist
Efficacy similar to H2RAs Role Possibly as adjunctive therapy, but limited by the SE Adverse effects Dizziness, fatigue, somnolence, drowsiness, hyperprolactinemia FDA Warning: Tardive dyskinesia (neurological deficit that is irreversible) Requires dose adjustment for renal disease |
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what does metoclopramide promote
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increased motility--> promotes esophageal CL
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B12 in regards to PPIs
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B12 requires an acidic enviroment to be absorbed ans as age increases there is a decrease in the acidicy of the stomach therefore it is common to see a deficiency in the elderly
However, when a patient is on a PPI it is not recommended to supplement B12 because the patient will not usulaly develop a deficiency most B12 is orally ingested |
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Ranitidine (Zantac) class, OTC and prescription oral formulations
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H2RA
OTC; 75-mg tablet 150-mg tablet (+/-mint) RX: 150-mg tablets/EFFERdose tablets/granules 300-mg tablet 15 mg/mL syrup |
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Cimetidine (Tagamet) class, OTC and prescription oral formulations
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H2RA
OTC: 200-mg tablet RX: 300-, 400-, 800-mg tablets 300 mg/5 mL solution |
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Nizatidine (Axid) class, OTC and prescription oral formulations
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H2RA
OTC: 75-mg tablet RX: 150-mg/300-mg capsules 15 mg/mL solution |
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Famotidine (Pepcid) class, OTC and prescription oral formulations
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H2RA
OTC: Pepcid AC 10mg tablets, gel caps, chewable tablets 20-mg tablets and chewable tablets (maximum strength) RX: 20-mg/40-mg tablets 20-mg/40-mg rapidly disintegrating tablet 40 mg/5 mL suspension |
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Pepcid Complete OTC formulation
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H2RA
OTC only 10 mg + 800 mg of calcium carbonate + 165 mg of magnesium hydroxide chewable tablets |
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Esomeprazole (Nexium): class, oral OTC formulation, and RX doasage forms
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PPI
no OTC products RX: Delayed-release capsule (20 mg/40 mg) IV solution (20- and 40-mg vials) Delayed-release oral suspension (10mg, 20mg, 40mg packets) |
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Omeprazole (Prilosec): class, oral OTC formulation, and RX doasage forms
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PPI
OTC: Prilosec OTC delayed-release 20-mg tablet (magnesium salt) RX: Delayed-release capsule (10 mg/20 mg/40 mg) Generic available |
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Zegerid: class, oral OTC formulation, and RX doasage forms
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PPI
OTC: Zegerid OTC 20 mg immediate release capsules with sodium bicarbonate (1100 mg/capsule RX: Immediate-release powder for oral suspension (20- and 40-mg packets); sodium bicarbonate buffer = 460 mg of Na+/dose -two 20mg packets are not equivalent o one 40 mg packet 20mg and 40 mg capsules (1100 sodium bicarb per capsule) |
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Lansoprazole (Prevacid): class, oral OTC formulation, and RX doasage forms
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PPI
PTC: Prevacid 24HR 15 mg delayed release capsule RX: Delayed-release capsule (15 mg/30 mg) Generic available Delayed-release oral suspension (15 mg/30 mg) Delayed-release orally disintegrating tablet (15 mg/30 mg) IV solution (30 mg/vial) |
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Rabeprazole (AcipHex): class, oral OTC formulations, RX dosage forms
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PPI
No OTC formulations RX: Delayed-release enteric-coated tablet (20 mg/40 mg) |
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Pantoprazole (Protonix): class, oral OTC formulations, RX dosage forms
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PPI
No OTC formulations RX: Delayed-release tablet (20 mg/40 mg) Generic available IV solution (40 mg/vial) |
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Dexlansoprazole (Kapidex): class, oral OTC formulations, RX dosage forms
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PPI
NO OTC formulations RX: Delayed-release capsule (30 mg/60 mg) |
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what PPIs come in an IV formulation
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Esomeprazole
Lansoprazole Pantoprazole |
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what H2RAs come in an IV formulation
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Ranitidine
Famotidine Cimetidine |
