Management of GERD

Management of GERD:A patient outcome/education-

driven session

Dalia A. Hamdy, BPSc, MSc, PhD, RP(ACP), MRSC

Nahla H. KandilBPSc, MSc, BCPS

GERD (DH/NK-April 2015) 2

Putting issues in perspective: why are we here?


Learning Objectives• Define GERD and recognize its triggers and

pathophysiology• Identify GERD symptoms and red flags• Describe the non pharmacological treatment options for

your patient• Choose the most appropriate therapeutic agent for your

patient• Identify the possible drug-drug interactions• Set the appropriate monitoring plan for your patient


Session outline• GERD pathophysiology, triggers and exacerbating

factors• GERD goals of therapy• GERD symptoms and red flags• GERD non pharmacological treatment• GERD therapy algorithms and drug interactions


References1. Thomson P., Pham Q.D. Patient Self-Care. 2nd Edition. Canadian Pharmacists

Association; 2010. Chapter

2. Shaffer E.A. Therapeutic Choices. 6th Edition. Canadian Pharmacists Association; 2011. Chapter 60

3. Kinnear M. Clinical Pharmacy and Therapeutics, 5th Edition. Elservier; 2012. Chapter 12.

4. Kaiser T.E. Gastrointestinal disorders. ACCP Updates in Therapeutics; 2014.

5. rxPassport. Antacids, H2RA or PPI? Am I Choosing the Best Option for my Patient? Heartburn series; 2015

http://www.rxbriefcase.com/passportdefault.aspx




GERD: pathopysiology• Gastroesophageal Reflux Disease

“Refers to troublesome symptoms (heart burn & regurgitation) and/or complications that result from an excessive reflux of stomach contents into esophagus”

Therapeutic Choices 2011NERD

non erosive

reflux disease


GERD: pathophysiology , triggers ad Exacerbating factors1.Physiologic: -Transient relaxation of the lower esophageal sphincter (LES),

-hypotensive LES -anatomic disruption of the junction; often caused by hiatal hernia

2. Drugs inducing LES relaxation : anticholinergics, aminophyllines, β-adrenergic agonists, benzodiazepines, and nitroglycerines, B-blockers, -blockers, calcium channel blockers, narcotics, nicotine, theophylline.

3. Life style: obesity, smoking, diet (fatty food, chocolate, coffee, alcohol, carbonated drinks)4. Pregnancy5. Stress and anxiety6. Age >65 years


GERD: goals of therapy• Relief symptoms & improve quality of life

• Promote healing of esophagitis

• Prevent complications

• Prevent recurrences


GERD: Visit your patient• Mrs Hoda, a 75-year-old woman, showed up in your pharmacy. She is

suffering from heart burn and acidic taste. Two days ago, she had a coffee ground color vomit. Her past medical history included osteoarthritis, gout, hypertension, and resting tremor secondary to anxiety. She had no known drug allergies and was taking the following prescription drugs: Propranolol 40 mg tid prn

Indometacin 25 mg tidDiclofenac 50 mg qdAllopurinol 100 mg qdRamipril 10 mg qdSimvastatin 40 mg qn


GERD: Questions for your patient

Rxpassport, Heartburn series, 2015


GERD: Red Flags!Alarming symptoms

Description

Chest pain Resembling cardiac pain

Chocking Sensation of acid refluxing into the windpipe causing shortness of breath, coughing or hoarsness

Dysphagia Difficulty swallowing

GIT bleeding Vomiting blood or having tarry or black bowl movement

odynophagia Pain upon swallowingUnintentional weight loss (>3kg in past 6 months)

Anemia

Persistent vomiting

Severe abdominal pain

Refer to a

Doctor!

Therapeutic Choices . 2011Patient Self-Care, 2010


GERD: non-pharmacological treatmentLife style modification:Avoid foods that ppts eventsAvoid lying down right after mealsObtain ideal body weightReduce alcohol intake!Reduce caffeine intake (2-3 cups/day)Smaller more frequent meals


GERD: non-pharmacological treatmentII. Patient recommendations

Reassure patient about the benign nature of diseaseStress reductionAvoid exercising or bending on full stomachAvoid exacerbating foodsAvoid lying down after mealsAvoid tight fitting cloths around the waistRaise head of bed around 10 cmLimit nicotine consumptionObtain ideal body weight


GERD: revisit your patientPatient information:Question is:Guidelines and references states…………….Patient recommendation is………………..Monitoring plan is……………………

Assessment


GERD: therapeutic algorithmsThe choice of agent should be based on:• Severity of GERD symptoms• Impact of symptoms on the patient’s daily life• Previous experience with GERD pharmacotherapy• Current medications, adverse effects and potential drug

interactions• Cost


GERD: therapeutic algorithmsA 43-year-old man with type 2 diabetes mellitus and hypertension presents with a 6-week history of intermittent regurgitation occurring about every other day and an acidic taste in his mouth. He takes metoprolol 100 mg once daily and states that his diabetes is controlled by diet. He avoids chocolate and spicy foods, sleeps with his head elevated on a wedge pillow, and uses OTC famotidine 10 mg when symptoms intensify and when he remembers. He admits that he rarely takes it before eating; instead, he usually takes it only once the symptoms are present and do not dissipate. The symptoms have been so significant that he has not slept and has missed 2 days of work recently. Which is the best course of action to address his symptoms?

A. Administer metoclopramide 10 mg four times daily.B. Administer esomeprazole 20 mg/day.C. Continue famotidine 10 mg, but take on a scheduled frequency of three or four times daily.D. Continue famotidine, but increase dose to 20 mg, scheduled three or four times daily.


GERD: therapeutic algorithms

Pharmacological Group Choice

Rxpassport, Heartburn series, 2015






GERD: therapeutic algorithmsA 43-year-old man with type 2 diabetes mellitus and hypertension presents with a 6-week history of intermittent regurgitation occurring about every other day and an acidic taste in his mouth. He takes metoprolol 100 mg once daily and states that his diabetes is controlled by diet. He avoids chocolate and spicy foods, sleeps with his head elevated on a wedge pillow, and uses OTC famotidine 10 mg when symptoms intensify and when he remembers. He admits that he rarely takes it before eating; instead, he usually takes it only once the symptoms are present and do not dissipate. The symptoms have been so significant that he has not slept and has missed 2 days of work recently. Which is the best course of action to address his symptoms?

A. Administer metoclopramide 10 mg four times daily.B. Administer esomeprazole 20 mg/day.C. Continue famotidine 10 mg, but take on a scheduled frequency of three or four times daily.D. Continue famotidine, but increase dose to 20 mg, scheduled three or four times daily.


GERD: therapeutic algorithmsProkinetics

• Prokinetics are not widely used to treat GERD because they are not as effective as other treatments and are associated with numerous side effects (sedation, anxiety, extrapyramidal symptoms, etc.).

• Prokinetics are reserved for patients who are refractory to other available treatment options or who have delayed gastric emptying


Which of the following is inappropriate monotherapy for mild, intermittent GERD?

1. Omeprazole2. Metoclopramide3. Famotidine4. Calcium carbonate





• L.F. is a 48-year-old woman who presents to her primary-care provider complaining of recurrent heartburn occurring daily for the past 6 weeks. She states that the heartburn occurs frequently after meals and often wakens her at night. Lately, she has been experiencing difficulty swallowing solid foods. L.F. currently smokes two packs of cigarettes per day and likes to have two glasses of wine each night with her dinner. She states that she occasionally uses OTC ranitidine 150 mg orally up to twice daily, which temporarily relieves her symptoms. Which medication do you suggest?




a) It should be taken 30 minutes prior to a mealb) It takes 1-3 days for a clinical responsec) It is associated with a therapeutic effect that last for more than the 14 days of treatmentd) All of the above

Which of the following statements should be used when counselling a patient taking non-prescription PPI therapy?


Maintenance Therapy

L.F.’s symptoms resolved in about 2 weeks after starting PPI therapy, and she remained asymptomatic after 8 weeks. She then underwent endoscopy, which revealed that the esophagus had healed completely.Her primary-care physician then stopped the PPI.• Now, 2 weeks later, she is experiencing mild heartburn. Is

L.F. a candidate for long-term maintenance therapy?



Stepping down treatment if patient responds adequately

It includes:1- Discontinuing PPI Therapy 2- Switching To Symptom-driven Therapy3- Reducing dose of daily PPI





GERD: therapeutic algorithmsKey Points on Non-Prescription PPI

• Most patients will respond to PPI therapy within 1-3 days of treatment. Maximum acid suppression with PPIs is seen after 3-5 days of treatment.

• Patients should be instructed to take their full course of therapy and to not discontinue it when the symptoms start to improve.

• This medication is NOT recommended for PRN use like antacids or H2-receptor antagonists.

• It should not be taken more frequently than every 4 months

Bottom Line: A 14-day course of non-prescription omeprazole is the first-line treatment of choice for patients with heartburn symptoms occurring on 2 or more days per week. This course will most often resolve the condition.


GERD: therapeutic algorithmsRebound Acid Secretion

• Antacids can be prescribed as “rescue” medication for rebound acid secretion

• Medicines that contain both an antacid and an anti-foaming agent are likely to be the most effective treatment for rebound acid secretion.


• Rapidly neutralize esophageal acid within 15-30 minutes and will typically provide modest relief for up to 90 minutes.

• Alginic acid does not neutralize acid but acts as a physical barrier. Currently combined with an antacid, as it offers limited benefit when administered alone.

• Generally well tolerated but can lead to constipation (calcium, aluminum) or diarrhea (magnesium).

• Interact with many medications• Caution in older patients and those with renal disease • Alginic acid contains a large amount of sodium and could be an issue in

patients with congestive heart failure or renal disease

Bottom Line: Inexpensive and rapid relief. The major limitation is the short duration of action. Guidelines

recommend considering it for episodic (≤1 day/week) and/or mild symptoms.

GERD: therapeutic algorithmsKey Points on Antacids


Which of the following disorders is an adverse event associated with aluminum hydroxide?

1.Tinnitus2.Diarrhea3.Constipation 4.Hyperkalemia



Antacid component

Adverse effects Drug interactions

Notes

•Calcium salts•Magnesium salts•Aluminum salts•Magnesium/aluminum antacids•Alginic acid

•Aluminum: Constipation•Accumulation in patients with renal failure•Hypophosphatemia•Calcium: Constipation•Rebound hyperacidity•Magnesium: Diarrhea•Accumulation in patients with renal impairment•Magnesium/aluminum comboMinor changes in bowel habits•Alginic AcidFlatulence, belching

•Allopurinol•Bisphosphonates•Iron salts•Quinolones•Tetracyclines•Digoxin•RosuvastatinTo minimize the interaction with these products patients should separate antacid dosing by 1-2 hours

•Dosing should be taken within 20-60 minutes and/or after a meal at bedtime as needed•Relieves symptoms but unlikely to heal inflamed esophagus•Dosing for magnesium/aluminum antacids is 10-30 mL PC and HS


W.J. is a 39-year-old, 130-kg, 170-cm-tall man who presents with complaints of indigestion. He describes a burning sensation behind his breastbone and some belching that is often associated with an acid taste in the back of his mouth. He indicates that his symptoms began a few months ago, and they only occur a few times a month, especially after eating large or spicy meals. Also, if he eats too close to his bedtime, the burning keeps him up at night. He has used liquid antacids in the past for these symptoms and states they work fairly well, but he has to take frequent doses, as the symptoms return quickly. He does not take any other medications. Which medication do you suggest?



• Mild symptoms and occur infrequently, and no alarm symptoms.

• To specifically “prevent” meal-related symptoms, he should take an H2RA 30 to 60 minutes before eating or drinking.

• If symptoms remain infrequent but are unrelated to meals, the use of an OTC H2RA as needed for symptoms may be required.



a) Famotidine is usually superior to ranitidine at equivalent dosesb) Tachyphylaxis commonly develops with these medicationsc) They provide symptom relief in approximately 50% of patientsd) Most drug interactions with these medications are clinically significant

You start to discuss H2-receptor antagonists with the patient. Which one of the following statements is TRUE?



The H2RA associated with the most significant drug interactions due to inhibition of CYP450 enzymes is

a)ranitidine b) cimetidine c) Nizatidined) famotidin


Drug Metabolism!! Stay Tuned!


• Bind to the H2-receptors on the gastric parietal cells to reduce gastric acid secretion.

• They start to reduce gastric acid within 1 to 2 hours of dosing and the effects last up to 9 hours.

• In equivalent doses, ranitidine and famotidine are equally effective for mild symptoms but are generally not effective for more frequent or severe symptoms.

• Provide complete symptom relief in only 15% of GERD patients. • Tachyphylaxis (decrease in acid-lowering response over time) commonly develops and has

been reported within a few doses with these medications; this can limit their use beyond the on-demand treatment of mild heartburn.

• H2RAs are generally very well tolerated and adverse effects are infrequent.

Bottom Line: Slower onset but longer duration of action compared to antacids. Guidelines recommend their use for mild

and episodic (≤1 episode per week) heartburn or occasional meal-provoked heartburn.

GERD: therapeutic algorithmsKey Points on H2 Receptor Antagonists


BACK TO PPIs!

The pharmacology of proton pump inhibitors



• The gastrointestinal adverse effects of PPIs can be mistaken for symptoms of GORD, sometimes resulting in increased doses of PPI being prescribed.

PPIs Adverse Effects



Which adverse event can occur in a patient receiving chronic PPI therapy?

1. Gynecomastia2. Increased infection risk3. Extrapyramidal side effects4. Altered calcium and vitamin D levels



Adverse effects due to chronic use• May 2010 - Decreased calcium absorption, leading to

increased risk of fracture• March 2011- may cause low hypomagnesium if taken

for prolonged periods (in most cases, greater than 1 year).

• Gastric acid suppression with PPIs increases the risk of infection with gastrointestinal (C.difficile) or respiratory pathogens, although the absolute risk to most patients remains low.



GERD: therapeutic algorithmsPPI-Drug interactions

Drug Metabolism

Phase 1: Functionalization reactions (introduction of a functional group)

Phase 2: Conjugative reactions(Conjugation with endogenous compounds)

Drug

AND /OR

PPI-Drug interactionsPhase 1 metabolismBy introducing or unmasking more polar a functional group

more readily eliminated


Chemical reactionsOxidationReductionHydrolysisHydrationIsomerizationDethioacetylation


PPI-Drug interactionsPhase 2 metabolismBy conjugation with an more polar and water soluble endogenous substance

more readily excretable in

urine or bile


Chemical reactionsGlucuronidation/glycosidationSulfationMethylationAcetylationAmino acid conjugationFatty acid conjugation


PPI-Drug interactions

PPI’sOmeprazoleEsomeprazoleLansoprazolePantoprazole (Na or Mg)Rabeprazole



All metabolized by CYP P450, 2C19 and 3APossibility of drug-drug interactions

Pantoprazole lower affinity to CYP P450 enzyme system + mostly sulfation

Rabeprazole metabolized through non enzymatic pathways

Less drug interactions possibilities

Clinical Pharmacy and Therapeutics 2012

PPI-Drug interactions

PPI’sOmeprazoleEsomeprazoleLansoprazolePantoprazole (Na or Mg)Rabeprazole



Inhibition of CYP2C9 and CYP2C19D-D interactions possibility with (Monitoring, sp. With >20 mg/day dose)Phenytoin (2C9) diazepam (2C19)S-Warfarin (2C9) R-Warfarin (2C19)Weak Induction of CYP1A2

D-D interactions possibility with (Monitoring) Theophylline

Clinical Pharmacy and Therapeutics 2012


Interaction with clopidogrel • While there was evidence that PPIs may affect clopidogrel

activity ex vivo, the available evidence suggested that this would not translate to clinically significant adverse outcomes.

• However, if considering prescribing a PPI at the same time as clopidogrel then pantoprazole is the recommended choice. Pantoprazole is known to have less of an inhibitory effect on the CYP2C19 enzyme compared with omeprazole or lansoprazole.



GERD: Visit your patient• Mr. Hassan, a 45-year-old man, showed up in your pharmacy. His past

medical history included hypertension and . One week ago, he suffered from heart burn and acidic taste and was prescribed omeprazole to alleviate this symptom and was asked to decrease smoking and coffee intake. Yesterday he noticed bruising in his leg and arm. He is coming to ask for heamoclare and wondering if there is better suggested brand. He had no known drug allergies and was taking the following prescription drugs:

Omeprazole 40 mg qdIbuprofen 400 mg prn

Warfarin Ramipril 10 mg qd


GERD: revisit your patientPatient information:Question is:Guidelines and references states…………….Patient recommendation is………………..Monitoring plan is……………………

Assessment



PPIs dose adjustment GERD: therapeutic algorithms


Formulations



Calcium carbonate

Aluminium hydroxide

Magnesium hydroxide

Sodium bicarbonate

Which of these antacids is available as a combination product with a proton pump inhibitor (PPI)?



Use a combination or not?



What is the drug of choice for GERD during pregnancy?

• Between 30 – 50% of pregnant women experience symptoms of GORD and this is considered a normal part of pregnancy

• Antacids > ranitidine >PPIs



Gastroprotective Therapy A 67-year-old woman with rheumatoid arthritis is taking naproxen 500 mg by mouth daily, metoprolol 25 mg by mouth twice daily, aspirin 81 mg by mouth once daily, and alendronate 70 mcg by mouth weekly.• Which gastroprotective therapy is best to recommend?

A. Lansoprazole 30 mg daily.B. No gastroprotective therapy necessary.C. Misoprostol 200 mcg twice daily.D. Esomeprazole 40 mg twice daily.



Gastroprotective Therapy



SUMMARY! Monitoring Plans!Your symptoms should not require more than 2 weeks of continuous medication every 6 months

See your doctor if- Red Flags- symptoms persist after treatment- any side effects of the monitored drugs

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Health & Medicine

Management of GERD