Module 8 Pharmacotherapy for Gastrointestinal Disorders

Geriatric Pharmacy Review

Module 8: Pharmacotherapy for Gastrointes;nal Disorders

Copyright 2011 American Society of Consultant Pharmacists

Accreditation Information

ASCP is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

This home study web activity has been assigned 3 credit hours.

ACPE UPN: 0203-0000-10-092-H01-P

Release Date: 5/19/2010

Expiration Date: 6/15/2013

To receive continuing education credit for this course, participants must complete an on-line evaluation form and pass the on-line assessment with a score of 70% or better. If you do not receive a minimum score of 70% or better on the assessment, you are permitted 4 retakes. After passing the assessment, you can print and track your continuing education statements of credit online.

Geriatric Pharmacy Review courses have not yet been approved for Florida consultant pharmacy continuing education.


Content Experts

Current Content Experts:

David P. Elliot, PharmD Department of Clinical Pharmacy West Virginia University

Jennifer L. Hardesty, PharmD, FASCP Clinical Assistant Professor University of Maryland School of Pharmacy

Legacy Content Experts:

Angela C. Cafiero, PharmD, CGP Assistant Professor of Clinical Pharmacy University of the Sciences in Philadelphia Philadelphia College of Pharmacy

William R. Garnett, PharmD Professor of Pharmacy and Pharmaceutics Virginia Commonwealth University Medical College of Virginia


Content Expert Disclosures

David Elliot, PharmD, has no relevant financial relationships to disclose.

Jennifer L. Hardesty PharmD, FASCP has no relevant financial relationships to disclose.

Angela C. Cafiero, PharmD, CGP has no relevant financial relationships to disclose.

William R. Garnett PharmD , discloses the following relationships: Speakers Bureau: Meridian, Shire, Elan and Wyeth Grants: Glaxo-Smith Kline, Ortho McNeil, Meridian, Shire, Elan


Aging and Gastrointestinal Function

Learning Objectives

By the end of this Review Concept you should be able to:

Identify major changes in the gastrointestinal tract due to aging.

List common gastrointestinal complaints of the elderly.

List major concerns of the pharmacist regarding the treatment of gastrointestinal problems in the elderly.

Describe diagnostic methods used to identify and characterize gastrointestinal disorders.

List the major gastrointestinal disorders requiring pharmacological intervention.

Review other problems that can contribute to gastrointestinal disorders.

Outline quality of life issues and the impact of treatment on the elderly patients life.


Age-Related Changes in Gastrointestinal Functioning

Chewing, tasting, and salivary functions decline

Swallowing is less efficient Dental carries and tooth loss impair chewing

Esophageal motility and musculature decrease Delay in gastric emptying

Gastric mucosal cytoprotective prostaglandins decrease Gastrin production increases, acid production decreases, gastric pH increases Small intestines may show impaired absorption of vitamin D, calcium, iron, electrolytes, and water, but increased absorption of vitamins A and K

Colon has less mucosa and musculature and an increase in collagen in the colon wall, reduction in gastric blood flow Anorectal area shows nerve and muscle loss, resulting in decreased perception of anorectal distention

Phase I metabolism decrease (oxidation, reduction, hydrolysis) Phase II metabolism remains the same Bile ducts enlarge, bile synthesis decreases

Gallstone formation increases Pancreas shows enlarged ducts, atrophy of acini glands

Liver decreases in size, blood flow perfusion, and general protein synthesis Increased incidence of diverticulosis due to decreased tensile strength of smooth muscle in colon wall.


Age-Related Changes in Gastrointestinal Functioning

The function of the gastrointestinal system is well preserved during the aging process; however, subtle changes occur that can affect the elder. The clinical significance of these age-related changes range from a minor effect to no effect on normal physiological processes. Mastication may be affected by dental decay and tooth loss, which can result in a decrease in nutritional intake. Chewing, tasting, and salivary functions tend to decline, and swallowing is less efficient.

A decrease in neuromuscular function could affect esophageal motility which could increase development of gastroesophageal reflux. The decrease of gastric prostaglandins results in an increased susceptibility to Helicobacter pylori infections. Gastric acid decreases, thus resulting in a decreased absorption of certain vitamins and minerals such as folic acid and vitamin B-12. The small intestine may show impaired absorption of vitamin D, calcium, iron, electrolytes, and water but greater absorption of vitamins such as A and K.

The colon has less mucosa and musculature and an increase in collagen in the colon wall, which decreases the strength of the colon. This age-related change results in slower transport and increased risk of diverticulitis, colon polyps and constipation. Fecal incontinence can develop from the changes in nerve and muscle loss of the anorectal area. As the liver decreases in size, metabolic functioning decreases. This especially affects medications that undergo phase I metabolism. Bile ducts and the ducts of the pancreas become enlarged, thus increasing the risk of blockage.


Management of GI Problems in the Elderly

Common Patient Complaints:

Heartburn or reflux Constipation Diarrhea Xerostomia Abdominal pain or discomfort Nausea and vomiting

Major Pharmacist Concerns:

Delays in diagnosis due to patient self-treatment Prompt identification of life-threatening disorders Treatment of underlying disease and

symptom management Prevention of drug-induced disorders Monitoring of liver function

Age-related gastrointestinal changes can impact the elders dietary intake and hydration status. In changing their dietary intake and hydration status, elders become more prone to development of constipation, diarrhea, heartburn or gastroesophageal reflux disease, xerostomia, abdominal pain and dyspepsia.

Along with the increased risk of age-related xerostomia, any medication that has the potential to cause xerostomia drastically increases this risk. Proper evaluation of medications will assist in minimizing the risk of xerostomia. Xerostomia also increases the risk of dental caries, due to the lack of saliva and use of hard candy to stimulate saliva. Diarrhea and constipation are among the most common complaints of older adults. Elders seek over the counter self-remedies for theses complaints and are often poorly monitored until the symptoms become difficult to manage.

Once the most life-threatening disorders have been ruled out, proper medications can control many symptoms and help to prevent relapses. For the pharmacist of geriatric patients, major areas of concern include prevention of drug-induced disorders, evaluation of the effectiveness of pharmacological therapy without adverse effects and monitoring liver function to insure maximum drug efficacy.


Diagnostic Testing and Monitoring of Gastrointestinal Disorders

Blood Screening Tests:

CBC with differential Liver function tests (LFTs) such as alkaline

phosphatase and transaminases (e.g., ALT, AST) Serum chemistry panel especially creatinine (Scr),

Blood Urea Nitrogen (BUN), and albumin Viral hepatitis tests Bilirubin levels Protein fractionation Carcinoembryonic antigen (CEA) level

Other Diagnostic Techniques:

Fecal occult and gastric fluid assessment X-rays and contrast media Ultrasound and CT scans Endoscopy techniques H. pylori antibody test Gallstone analysis and enzymatic studies

Early detection and treatment of gastrointestinal disorders is of primary concern in order to avoid invasive and debilitating solutions. Screening and monitoring of gastrointestinal function can range from simple blood tests to complete endoscopic workups. A complete blood count with differential can assist in detection of a gastrointestinal infection. Routine measures of the patients hydration status are evaluated through serum creatinine and blood urea nitrogen. Serum albumin levels are necessary to assess nutritional status.

Without major complaints, the first indication of ulcers, blockages, anemia and cancer may come from a complete blood count. Fecal occult blood test or tests on other body fluids are used to detect the presence of blood. Techniques such as x-rays and contrast media may be used to pinpoint the location of ulcers and other defects. Endoscopy techniques such as the colonoscopy or flexible sigmoidoscopy provide direct evidence of ulcers, blockages and tumors. More specialized tests such as gallstone analysis and H. pylori antibody test may further help in prevention and treatment of gallstones and ulcers.

Enzymatic studies can detect pancreatitis and liver dysfunction. Carcinoembryonic antigen levels can be used for cancer detection. The use of these various tests or techniques can assist in diagnosis of gastrointestinal problems.


Major Gastrointestinal Disorders in the Elderly

Dental caries and periodontal disease Xerostomia Oral Candida Oropharyngeal dysphagia Peptic ulcer disease (PUD), including

gastric and duodenal ulcers Gastroesophageal reflux disease (GERD) Constipation Diarrhea Atrophic gastritis Hemorrhoids Fecal incontinence Inflammatory bowel disease (IBD) Irritable bowel syndrome (IBS) Diverticulosis Bowel obstructions Hepatic disease, including cirrhosis Gall bladder disease Pancreatic disease Obesity and nutritional problems Cancer of the gastrointestinal tract

Aging is associated with an increased prevalence of several gastrointestinal disorders. Each of the major gastrointestinal disorders seen in the elderly can be very debilitating if not properly treated. Prompt and accurate identification of these disorders is important.

Complete medical histories, including self-dosing of over-the counter medications and herbal products, are imperative to review before a treatment plan is devised. Pharmacotherapy must be tailored to the individual needs of each patient and monitored for effectiveness and adverse effects. Treatment of gastrointestinal disorders can vary, depending upon the setting the elder resides in or the cause of the GI disorder.

For example if a medication has induced constipation, treating the cause of the constipation by changing the medication to another effective medication would be preferred over treating the adverse effect. Increasing fluid and fiber intake is preferable to routine use of laxatives.


Problems that Can Contribute to Gastrointestinal Disorders

Medications

Co-morbid disease states: Stroke Neurological disorders Psychiatric disorders Diabetes mellitus

Malnourishment

Dehydration

Environment, lifestyle exposures

Low-fiber diet

Evidence is controversial as to the extent and clinical significance of the age-related changes in GI function. Changes in GI function could be due to an increase in the prevalence of certain diseases or medications that affect the GI tract. Some examples of diseases that affect the GI tract are: stroke, Parkinsons disease, depression, dementia, and diabetes mellitus. Some examples of medications that can affect gastrointestinal motility are: antidepressants, antihistamines, antipsychotics, opioid analgesics, calcium channel blockers and antispasmodics. Lifestyle exposures to alcohol or tobacco can impact gastrointestinal function. Clinically significant abnormalities in GI function should be fully evaluated for other causes and not solely attributed to aging.


Quality of Life Issues for the Elderly

Dietary restrictions may be difficult GI discomfort and pain can dominate daily life Bowel habits and symptoms may prevent social interactions Fear of life-threatening diseases can cause elderly to try hiding symptoms and plan life around the malady Weight lose and frailty

Quality of life becomes an issue when the elderly attempt to live with symptoms of gastrointestinal problems and ignore progressive signs of disease. Although dietary restrictions are a source of irritation for the elderly, maintaining control over digestive functions assumes much more importance. For many geriatric patients, medications can determine the extent of control and quality of their daily lives. For the geriatric pharmacist, careful consultation and monitoring can help achieve those goals. Major gastrointestinal disorders and their pharmacotherapy will be presented in the remainder of this module.


Resources

For additional information, see:

Baime MJ, et.al.(1994). Aging of the Gastrointestinal System.In:Hazzard WR, Bierman EL, Blass JP, Ettinger WH, & Halter JB.(Eds.).Geriatric Medicine and Gerontology, 3rd ed.New York:McGraw-Hill:665-681.

Beers MH & Berkow R.(2000).The Merck Manual of Geriatrics. 3rd edition. Section 13, Gastrointestinal Disorders. Whitehouse Station, NJ:Merck Research Laboratories: 1000-1154.

Blechman MB & Gelb AM.(1999).Aging and gastrointestinal physiology.In:Borum ML (ed.).Clinics in Geriatric Medicine.Philadelphia:W.B. Saunders:429-438.

Crotty B & Smallwood RA.Upper gastrointestinal tract.Med J Austral.1995;162(2):95-97.

Duthie B. (1998). Practice of Geriatrics, 3rd ed. Chapter 46:Gastrointestinal disorders. W.B . Saunders Company.

Geokas MC, et.al.The aging gastrointestinal tract, liver, and pancreas.Clin Geriatr Med.1985;1:177.

Greenwald, D.A. (2004) Aging, the Gastrointestinal Tract, and Risk of Acid-Related Disease. Am J Med 117(5A): 8s-13s.

Goldschmeidt M, et.al.Effect of age on gastric acid secretion and serum gastrin concentrations in healthy men and women.Gastroenterology.1991;101:977.

Hall KE, et al.(1999).Age-associated changes in gastrointestinal function.In:Hazzard WR, Blass JP, Ettinger WH, Halter JB, & Ouslander JG.(Eds).Principles of Geriatric Medicine and Gerontology, 4th ed.New York:McGraw-Hill: 835-842.


Resources

Martinez J.P. & Mattu A.M. (2006) Abdominal Pain in the Elderly. Emerg Med Clin N Am. 24:371-388.

McFadden DW & Zinner MJ.Gastroduodenal disease in the elderly patient.Surg Clin North Am.1994;74(1):113-126.

OMahony D, et al.Aging and intestinal motility:A review of factors that affect intestinal motility in the aged.Drugs & Aging.2002;19(7):515-527.

Online Resources:

http://digestive.niddk.nih.gov/ddiseases/a-z.asp

Lexi-Comp Online Drug Information Database

Merck Manual of Geriatrics Online


Peptic Ulcer Disease

Learning Objectives:


Define the major features of peptic ulcer disease (PUD).

Describe the pathogenesis of PUD.List common causes and risk factors for PUD.

Identify important signs and symptoms of PUD.

Describe tests and procedures used to diagnose PUD and select appropriate treatment.

Determine the significance of relevant test results leading to a correct diagnosis.

Outline general principles for the pharmacotherapy of PUD.

Compare and contrast the primary medications used for treatment of PUD in terms of effect, dosing, duration of treatment and adverse reactions.

Describe alternative treatments for PUD and their implications for the elderly.


Introduction to Peptic Ulcer Disease (PUD)

Definition: Erosion in the lining of the stomach or duodenum resulting in ulceration and organ damage

Epidemiology:

Affects up to 10% of the general population 500,000 new cases per year 4 million experience recurrence each year Incidence increases with age Elderly experience increased complications and mortality, with 50% of patients >70 years experiencing complications. Mortality rates are 15% for elderly > 65 years compared with 2% for younger patients


Introduction to Peptic Ulcer Disease (PUD)

Peptic ulcer disease in the elderly primarily refers to gastric and duodenal ulcers that develop in the mucosal lining. Approximately half a million new cases of peptic ulcer disease are diagnosed in the United States each year, many of which occur in individuals over the age of sixty. The elderly are especially susceptible to the complications of peptic ulcer disease and have a much higher risk of mortality than younger adults.


Pathogenesis of Peptic Ulcer Disease

Gastric and duodenal ulcers are defects in the lining of the stomach or duodenum that form when gastric acid overwhelms the normal protective mechanisms of the GI tract. Harmful conditions such as a highly acidic environment or mucosal irritation from bacteria or medications can trigger a cascade of inflammation, cytokine release, and subsequent mucosal injury and ulceration:

Mucosal irritation

Imbalance between hydrochloric acid, pepsin secretions, and the natural defenses of the mucosal lining

Pepsin is activated by the acidic conditions and proceeds to enzymatically digest the mucosal, muscular, and vascular layers

Natural defenses of mucosal lining are further compromised via:

Decreased mucous to lubricate and prevent acid penetration Decreased bicarbonate secretion to neutralize acid, reduce pepsin Decreased healing and cell replacement Decreased blood flow Decreased levels of prostaglandin E2, which enhances all of the above defenses

Ulcer formation


Pathogenesis of Peptic Ulcer Disease

PUD-associated complications occur in about 50% of patients >70 years, and include:

Bleeding elderly patients with ulcers have more frequent and more severe bleeding than younger patients. Perforation ulcer crater burrows through the gastric or intestinal wall; occurs more frequently with duodenal ulcers Gastric outlet obstruction- can result from acute inflammation and edema near the gastroduodenal junction Penetration- less common form of perforation that burrows into an adjacent organ (i.e. pancreas, liver or colon)

The gastric and duodenal ulcers characteristic of peptic ulcer disease or P-U-D result from mucosal irritation and consequent imbalances between hydrochloric acid , pepsin secretions and the natural defenses of the mucosal lining. Pepsin is activated by the acidic conditions and proceeds to enzymatically digest the mucosal, muscular and vascular layers. Mucous, bicarbonate, and prostaglandin production is compromised, allowing for mucosal injury by the caustic acids and enzymes. After an ulcer crater is formed, PUD can progress to complications such as bleeding, obstruction and perforation.


Etiology of Peptic Ulcer Disease

It is estimated that over 90% of duodenal ulcers, and from 70% to 75% of gastric ulcers, are caused by H. pylori. Most of the ulcers not caused by H. pylori are believed to result from irritations and ulcerations from medications such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). . Helicobacter pylori Bacterial Infection: H. pylori is spread through human saliva and feces, and via food and water sources.

May create an ulcer in the mucosal layer by using its toxins, enzymes and inflammatory cytokines to cause injury in the GI mucosa. May increase the release of gastrin which in turn increases acid production, leading to mucosal damage. May impair endogenous protective mechanisms.

NSAIDs: The increasing and widespread use of aspirin for cardiovascular purposes and prescribed or OTC NSAIDs for pain places users at a substantially increased risk for PUD.

NSAIDs:, Act directly on the mucosa, inhibiting prostaglandin E2. This results in:

decreased protective mucous production decreased bicarbonate secretion decreased mucosal blood flow and platelet aggregation, which can interfere with healing processes.

Increase leukotriene release, which adds to mucosal damage Newer COX-2 selective inhibitors do not inhibit prostaglandin E2 in the GI tract to the extent of traditional NSAIDs, and theoretically have a decreased chance of causing ulcers.


Etiology of Peptic Ulcer Disease

Other Potential Causes:

Corticosteroid use Corrosive medications: potassium chloride, bisphosphonates Abnormal motility in the stomach and duodenum leading to more mucosal damage Hypersecretion of acid within affected areas (rare)

In the past, controlling peptic ulcers was based primarily on controlling the amount of stomach acid and the intake of irritating foods. It now appears that many of these ulcers are caused by a bacterium, Helicobacter pylori, which responds to treatment with antibiotics and acid suppression.

Helicobacter pylori bacteria are acid-labile spiral gram negative rods which cause ulceration of the mucosal lining by increasing the release of gastrin and acid production. Nearly all other ulcers are caused by the use of aspirin or other non-steroidal anti-inflammatory drugs. These drugs may act directly on the mucosa inhibiting prostaglandin E2, or they may increase leukotriene release which adds to mucosal damage.

Alternatives such as the COX-2 specific inhibitors, or traditional NSAIDS plus a proton-pump inhibitor confer some protection from NSAID-induced damage.. It is interesting to note that gastric ulcers appear most often with patients over age 50 having group A blood type.


Risk Factors for Peptic Ulcer Disease and Associated Complications

H. pylori infection NSAID use Advanced age Corticosteroid use Warfarin use Cigarette smoking Alcohol Use Chronic diseases such as COPD, cirrhosis,

chronic renal failure, and cystic fibrosis Severe physiologic stress- trauma, burns, surgery Family history

Risk factors for the development of peptic ulcer disease include H. pylori infection, use of certain medications, and alcohol use to name a few. Cigarette smoking is another important risk factor, which reduces prostaglandin E-2 production, inhibits pancreatic bicarbonate production and promotes reflux and gastric emptying.

Genetic predisposition and stress reactions can increase risk as well. Factors Increasing the risk for PUD-related complications include chronic diseases such as COPD, use of anticoagulants and advanced age. Dietary factors such as spices, milk, beer, coffee, tea and sodas may cause dyspepsia but do not, by themselves, increase the risk of peptic ulcer disease.


Signs & Symptoms of Peptic Ulcer Disease

In the elderly, the presentation of PUD is frequently atypical. Classic PUD-associated abdominal pain occurs in only approximately 35% of patients and abdominal pain is absent in 50-60% of NSAID-induced ulcers. Pain may be reported as vaguely located or as simple indigestion.

General: Epigastric pain in clusters that may be characterized as:

vague discomfort abdominal fullness or cramping burning sensation aching or gnawing feeling

Nausea and vomiting Weight loss Fatigue

Gastric Ulcers: Pain occurs 5-15 minutes after eating, and remains until the stomach empties (may be several hours) Pain is generally absent during fasting times. Vomiting blood or coffee ground emesis Abdominal indigestion

Duodenal Ulcers: Pain 1-3 hours after a meal, relieved by simple antacids, milk, or food Pain may awaken patient at night Pain may worsen if no food is eaten Black tarry stools may be present and may be seen with gastric ulcer


Signs & Symptoms of Peptic Ulcer Disease

In many geriatric patients, the signs and symptoms of peptic ulcer disease are not experienced until the stomach or duodenum is actually perforated or gastrointestinal bleeding is evident. Initial symptoms include epigastric pain, nausea and vomiting, weight loss and fatigue. Some elderly may self-medicate with over-the-counter products and simply hide painful symptoms. It is important to note changes in abdominal pain patterns and the ineffectiveness of antacids which signal a more serious condition.

While a detailed history of symptoms may be helpful, more testing is necessary to determine the cause and location of the problem. If a peptic ulcer is suspected, discontinuation of aspirin and other non-steroidal anti-inflammatory agents should be considered until a diagnosis is confirmed.


Diagnostic Testing for PUD

If alarm symptoms such as evidence of GI bleeding, anemia, weight loss, difficulty swallowing, recurrent vomiting newly appear or specific symptoms have been present for a long time, invasive tests are recommended. If no alarm symptoms are present, then non-invasive tests followed by treatment is recommended.

Non-invasive Analysis of stool to detect occult blood CBC, including hemoglobin, hematocrit and other indices to detect anemia Urea breath test for H. pylori (American College of Gastroenterology has identified this test as the noninvasive test of choice for the diagnosis of H. pylori infection) Stool antigen testing for H. pylori Serological blood tests to screen for H. pylori Liver function tests (LFTs), amylase, and lipase to determine differential diagnosis Other tests such as haptoglobin, CEA, amylase and the Schilling test to rule out other disorders

Invasive Direct testing of gastric contents Upper GI series with contrast media to determine type of ulcer Esophagogastroduodenoscopy (EGD) to pinpoint the damaged area and obtain a biopsy for additional testing Endoscopy techniques, including urease test on biopsy tissue, culture and histological studies to confirm H. pylori


Diagnostic Testing for PUD

If the elderly patient presents with alarm symptoms such as evidence of GI bleeding, anemia, weight loss, difficulty swallowing, or has experienced specific symptoms for a long time, invasive tests are recommended. If no alarm symptoms are present, then non-invasive tests followed by treatment is recommended.

Non-invasive testing can help to narrow down the diagnosis and rule out other causes. Other tests such as haptoglobin, CEA, amylase and the Schilling test may help to rule out other disorders with similar symptoms. Serological blood tests can be used to initially screen for Helicobacter pylori infection, however endoscopy is the most definitive test. Invasive testing such as an upper GI series with contrast media will detect type and location of ulcer. . If test results indicate an actively bleeding ulcer, treatment should begin immediately. The site of the ulcer will help determine the most effective treatments and preventative measures for each patient.


Pharmacotherapy for Peptic Ulcer Disease

Patients with suspected or diagnosed PUD should discontinue use of offending substances such NSAIDs, alcohol and tobacco as soon as possible.

Pharmacotherapy for PUD includes using medications that neutralize or inhibit gastric acid secretion, promote healing through simulation of mucosal defense mechanisms, and eradicate H. pylori. First-line therapies for treatment of H.pylori infection are proton-pump inhibitor-based triple therapies, and bismuth-based triple therapies. Monotherapy is not recommended for H. pylori infection due to limited efficacy and potential for antimicrobial resistance. For ulcers not caused by H. pylori, acid suppression or protective therapies are most effective.

Antibiotics (double or triple therapy): Metronidazole Clarithromycin Amoxicillin Erythromycin Tetracycline

Antisecretory Agents: Proton pump inhibitors Histamine2 receptor antagonists

Other Agents: Antacids Misoprostol Bismuth-containing compounds Sucralfate

Examples of Triple- and Quadruple-therapy combinations for H. Pylori:

Clarithromycin 500mg BID + Amoxicillin 1000mg BID + Omeprazole 20mg BID for 10-14 days

Metronidazole 500mg BID + Clarithromycin 500mg BID + Lansoprazole 30mg BID for 14 days

Metronidazole 500mg TID + Bismuth 525mg TID + Tetracycline 500mg QID + Omeprazole 20mg QD for 14 days


Pharmacotherapy for Peptic Ulcer Disease

In recent years, treatment plans for peptic ulcer disease have shifted away from symptom reduction and surgical interventions to the elimination of primary causes and recurrence. When the presence of H. pylori is established, two or three antibiotics combined with an acid suppressing agent for 10-14 days can provide complete healing and prevent recurrence. Reducing the acid environment with acid suppressing agents can help cure the ulcer, mitigate painful symptoms, allow for healing and help to prevent recurrences.


Treatment of PUD with Proton Pump Inhibitors (PPI)

Mechanism of Action: I irreversibly inhibit enzymes in parietal cells necessary for gastric acid secretion

Agents and Dosing Range for PUD:

Omeprazole (Prilosec): 20- 40 mg daily Lansoprazole (Prevacid): 15 -60 mg daily Rabeprazole (Aciphex): 20-40 mg daily Pantoprazole (Protonix): 40mg-80 mg daily Esomeprazole (Nexium): 40mg daily

Duration of Therapy: 4-8 weeks; if part of a double or triple therapy regimen 14 days.

Adverse Drug Reactions: headache, abdominal pain, diarrhea, constipation, flatulence, reduced vitamin B12 absorption, pernicious anemia (with long-term use).

Drug-Drug Interactions:

In general, proton pump inhibitors can reduce the absorption of oral iron, ketoconazole, and itraconazole, and some protease inhibitors.

PPIs can increase serum concentrations of diazepam, amiodarone, phenytoin, warfarin and propranolol, to name a few. Check prescribing information for individual agents for a full review of drug-drug interactions.


Treatment of PUD with Proton Pump Inhibitors (PPI)

Acid reducing agents are an important part of the therapeutic regimen for the elderly patients with peptic ulcer disease. Proton pump inhibitors are often part of such therapies because they irreversibly inhibit enzymes in parietal cells necessary for gastric acid secretion. Agents include omeprazole, esomeprazole, lansoprazole, rabeprazole and pantoprazole.

While expensive, these agents are still cost-effective because they relieve symptoms and heal ulcers more rapidly than either histamine2 receptor antagonists or sucralfate. When used alone, treatment typically lasts four to eight weeks, with increased duration and increased dosage recommended for smokers. Side effects of proton pump inhibitors include headache and irritation of the gastrointestinal tract.

Drug interactions with narrow therapeutic medications like warfarin, phenytoin, and carbamazepine are possible, so these drugs must be monitored closely.


Treatment of PUD with Histamine2 Receptor Antagonists (H2 RA)

Mechanism of Action: reversibly bind H2 receptors on parietal cells, reducing acid production and partial inhibition of acetylcholine and gastrin-stimulated acid production.

Agents and Initial Dosing for PUD* :

Cimetidine (Tagamet): 800mg-1600mg daily Nizatidine (Axid): 150 -300mg qd Rantidine (Zantac): 300mg QD Famotidine (Pepcid): 20 mg bid or 40 mg qd

(*Note: GERD and PUD prophylactic therapy may have different dosage recommendations; H2 RA doses should be reduced if CrCL


Treatment of PUD with Histamine2 Receptor Antagonists (H2 RA)

Histamine-2 receptor antagonists reversibly bind H2 receptors on parietal cells, reducing acid production and partially inhibiting acetylcholine and gastrin-stimulated acid production. Histamine2 receptor antagonists include cimetidine, nizatidine, ranitidine, and famotidine. Side effects of histamine2 receptor antagonists include drowsiness, headache, and GI irritation. Elderly patients taking cimetidine must be carefully monitored for central nervous system effects and drug-drug interactions. It is also important to note that H2-RA are now available for over-the-counter treatment of meal-induced heartburn, acid indigestion, and sour stomach at lower doses then what are available by prescription.


Treatment of PUD with Antacids

Mechanism of Action:

Antacids form a weak base which reacts with gastric acids to form salts and water As the pH of gastric environment rises above 4, pepsin becomes inactive and gastrin is inhibited Antacids forming aluminum salts enhance mucosal defense mechanisms Effects may last 15-30 minutes, or as long as 1-2 hours with food

Dosing: 100-144 mEq as needed (refer to individual product packaging)

Agents:

Sodium bicarbonate based medications (Alka-Seltzer products,)- Rapid action and relief, but these products may cause electrolyte imbalances, and urinary or systemic alkalosis leading to edema, hypertension and heart failure. Many Alka-Seltzer products also contain aspirin.

Aluminum hydroxide and dihydroxy forms (AlternaGel: ,Maalox, Mylanta) - weaker effects but can inhibit gastric hyperacidity; . Use with caution in patients with CHF, renal failure, edema. Hypophosphatemia and aluminum intoxication may occur with prolonged administration or large doses. Constipation can result from formation of insoluble aluminum chloride. Aluminum antacids can decrease the efficacy of tetracycline and fluroquinolone antibiotics via binding interactions. Also may affect absorption of bisphosphonates, phenytoin, and antifungals.


Treatment of PUD with Antacids

Calcium carbonate (Tums, Titralac, Rolaids,) - a good neutralizer, but may cause constipation and nausea; absorption of calcium chloride may cause hypercalcemia with muscle weakness, kidney stones, gastric acid rebound. May affect absorption of tetracycline, fluroquinolones, digoxin, and levothyroxine.

Many OTC antacid products contain multiple agents: Gaviscon, Rolaids, Di-Gel, Maalox, Mylanta.

Antacids are widely used to relieve the symptoms of peptic ulcer disease and can be effective if properly managed. When ingested, antacids form a weak base which reacts with gastric acids to form salts and water. Effects may last fifteen to thirty minutes, or up to one to two hours when taken with food. Unfortunately, antacids differ in their neutralizing capacity, how quickly and how long they are effective, adverse reactions, palatability, convenience of use and cost. Some, like Alka Seltzer, may also contain aspirin and other non-steroidal anti-inflammatory drugs that cause further damage to the gastrointestinal tract. Combinations of aluminum hydroxide and magnesium hydroxide antacids may cancel out adverse bowel effects such as diarrhea and constipation, but dosage levels must be monitored to ensure concurrent medications are properly absorbed or excreted. Antacids should only be used as PRN therapy to reduce symptoms.


Treatment of PUD with Misoprostol (Cytotec)

Mechanism of Action: reduces gastric acid production and protects mucosa

Indications: Prevention of NSAID-induced gastric ulcers; misoprostol should not be used as a first-line therapy for gastric or duodenal ulcers.

Dosing:

200 mcg QID or 400 mcg BID with food Doses of 100 mcg QID or 200 mcg BID can be used if higher doses are not tolerated. Combination product with diclofenac sodium (Arthrotec) contains 200mcg of misoprostol per tablet to decrease NSAID-induced ulcers

Adverse Drug Reactions:

Abdominal pain, cramping Headache Uterine contractions Diarrhea (dose dependent)


Treatment of PUD with Misoprostol (Cytotec)

Other medications may be used for the primarily for the prophylaxis of PUD, but may not be appropriate for many elderly patients. Misoprostol is a prostaglandin E1 analog that reduces gastric acid production and protects the mucos, facilitating healing. It is used to prevent aspirin and NSAID-related irritation and ulceration. Misoprostol is contained in a combination product with diclofenac sodium called Arthrotec. The combination product is used in patients who are at risk for ulcers. Arthrotec comes in two strengths, 50mg and 75mg, along with 200mcg of misoprostol in each tablet.


Treatment of PUD with Bismuth-Containing Compounds

Mechanism of Action: suppresses H. pylori and stimulates prostaglandins that protect mucosa

Agents and Dosing:

Bismuth subsalicylate (Pepto Bismol, Kaopectate or combination therapy packs): 524mg BID or 262 mg QID x 4 weeks

Helidac combination pack: bismuth subsalicylate + tetracycline 500 mg QID and metronidazole 500 mg TID


Do not use if patient has a hypersensitivity to salicylates or any component of the formulation; history of severe GI bleeding, coagulopathy , or renal failure.

May potentiate effects of aspirin and warfarin May cause black stools or tongue Note: each 262.4 mg tablet of bismuth subsalicylate contains an equivalent of 130 mg aspirin.


Treatment of PUD with Bismuth-Containing Compounds

Bismuth subsalicylate suppresses H. pylori and stimulates prostaglandins that then protect mucosa. One tablet of bismuth subsalicylate taken four times a day with appropriate antibiotics has been found to be effective in eradicating Helicobacter pylori. Side effects of bismuth-containing products include increased risk for bleeding, headache, black tongue and black stools.


Treatment of PUD with Sucralfate (Carafate)


Combines with proteins to form a viscous paste-like barrier resistant to acid and pepsin Binds bile salts Stimulates prostaglandins

Dosing:

1-2 g QID for ulcer healing, 1 g QID for maintenance. Because of the potential for sucralfate to alter the absorption of some drugs, separate administration (take other

medication 2 hours before sucralfate) should be considered when alterations in bioavailability are believed to be critical

Duration of Treatment: 6-8 weeks; elderly may require up to 12 weeks of therapy.


Constipation Nausea Aluminum toxicity/seizures Use with caution in patients with chronic renal failure who have an impaired excretion of absorbed aluminum.

Drug-drug interactions:

reduces absorption of other drugs by binding them (e.g., phenytoin, digoxin, theophylline, warfarin, and quinolone antibiotics)


Treatment of PUD with Sucralfate (Carafate)

Sucralfate is an aluminum salt of a sulfated disaccharide that combines with proteins to form a viscous barrier resistant to acid and pepsin.

It also binds bile salts and stimulates prostaglandins. Treatment is normally six to eight weeks, but may be up to 12 weeks in an older individual. Sucralfate can cause constipation, and nausea; also, aluminum can accumulate in patients with renal insufficiency, leading to seizures.

Sucralfate may bind to drugs in the GI tract, causing decreased absorption. This is particularly important for patients on narrow therapeutic medications such as phenytoin, digoxin, theophylline, warfarin, and the quinolone antibiotics.

The dose of the interacting drug should be separated from sucralfate by 2 hours. Sucralfate has no effect on H. pylori.


Resources


Andersson,T. (1996). Pharmacokinetics, metabolism and interactions of acid pump inhibitors. focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokin; 31(1): 9-28.

Beers, M.H & Berkow, R. (2000). The Merck Manual of Geriatrics. 3nd edition Section 13, Gastrointestinal Disorders. Whitehouse Station, NJ: Merck Research Laboratories: 1000-1154.

Bianchi Porro, G. & Lazzaroni, M. (1993). Prescribing policy for antiulcer treatment in the elderly. Drugs Aging; 3(4): 308-19.

Bianchi, P.G. & Lazzaroni M.(1993). Prescribing policy for antiulcer treatment in the elderly. Drugs Aging, 3(4):308-19.

Buckley, M. & Martin, P, & (1992). O'Morain, C. Helicobacter pylori infection. implications for ulcer therapy in older patients. Drugs Aging; 5(1): 1-7.

Collins J., Ali-Ibrahim A., & Smoot D.T. (2006)Antibiotic Therapy for Heliobacter pylori. Med Clin N Am 90: 1125-1140.

Crotty, B. & Smallwood, R. A. (1995). Upper gastrointestinal tract . Med J Austral; 162(2): 95-7.

Cryer, B., et.al. (1992). Effect of aging on gastric and duodenal mucosal prostaglandin concentrations in humans. Gastroenterology, 102:1118.

Drug facts and comparisons. (1998). Facts and Comparisons, 1998 ed., St. Louis.


Resources

Garnett, W. R. (1992). Patient-outcome management of gastric acid-related disorders. Consult Pharm; 7(Suppl B): 15-26.

Gonzalez, E. R., et al. (1994). National antiulcer therapy surveillance study in long-term care facilities. Consult Pharm; 9(10): 1131-1140.

Graham, D. Y. (1996). Nonsteroidal anti-inflammatory drugs, Helicobacter pylori, and ulcers: where we stand. Am J Gastroenterol; 91(10): 2080-6.

Greenwald, D.A. (2004) Aging, the Gastrointestinal Tract, and Risk of Acid-Related Disease. Am J Med 117(5A): 8s-13s.

Lewis, J. H.(1994). A pharmacologic approach to gastrointestinal disorders. Baltimore:Williams & Wilkins.

McFadden, D. W. & Zinner, M. J. (1994). Gastroduodenal disease in the elderly patient. Surg Clin North Am; 74(1): 113-26.

Pitner, J. K., et al. (1994). Prevention of NSAID-induced gastropathy in the elderly. Consult Pharm; 9(5): 568-579.

Roth, S. H. (1995). From peptic ulcer disease to NSAID gastropathy. an evolving nosology. Drugs Aging; 6(5): 358-67.

Sand R.J. & Scheiman J.M. (2004) Diagnosis and Management of Peptic Ulcer Disease. Clin Fam Prac; 6(3): 569-587.

Sipponen, P. (1995).Helicobacter pylori: a cohort phenomenon. Amer J Surg Pathol; 19(Suppl 1): S30-6.


Resources

Smith, J.D. and Nguyen, B.N. (1997) Peptic ulcer disease and gastroesophageal reflux disease. Preparatory Program for the Certifciation Exam in Geriatric Pharmacy, Alexandria, VA: American Society of Consultant Pharmacists

Stucki, G., Johannesson, M., & Liang, M. H. (1996). Use of misoprostol in the elderly: is the expense justified. Drugs Aging; 8(2): 84-8.

Web Sites:

Drug Information Resources: A Guide for Pharmacists

Lexi-Comp Online Drug Information Database

Merck Manual of Geriatrics Online

Thomson Micromedex

NCG Helicobacter pylori in peptic ulcer disease

PharmInfo Nets Gastrolinks Peptic Ulcer Disease


Gastroesophageal Reflux Disease

Learning Objectives:


Define gastroesophageal reflux disease (GERD) and its prevalence among the elderly.

Describe the pathogenesis of GERD.List factors that contribute to the development of GERD.

List the major signs and symptoms of GERD.Identify important tools used to diagnose GERD.

Outline therapeutic goals and suggested treatment regimens for GERD.

Compare and contrast medications commonly used to treat GERD in terms of effectiveness, dosing, and adverse side effects.

Describe non-pharmacological options for the treatment of GERD.


An Overview of Gastroesophageal Reflux Disease (GERD) in the Elderly

Definition: the abnormal and repetitive regurgitation of gastric contents

Epidemiology:

Affects at least 30% of elderly Prevalence increases with age Accounts for much of the $2 billion expenditure for antacids, proton pump inhibitors, and other medications

Long-term Consequences of GERD:

Heartburn Esophagitis Esophageal stricture Barretts esophagus Carcinoma Decreased quality of life Extra esophageal symptoms

cough wheezing horseness sore throat dysphagia


An Overview of Gastroesophageal Reflux Disease (GERD) in the Elderly

Gastroesophageal reflux disease is a condition characterized by the abnormal and repetitive regurgitation of gastric contents causing inflammation. The condition affects as much as thirty percent of the elderly population. Milder cases present as occasional heartburn which may be managed by avoiding certain foods and environmental factors. As the lower esophageal sphincter loses its tone, recurrent reflux leads to a shortened esophagus and permanent reflux. Damage to the esophageal lining can be quite severe and lead to major bleeding, stricture, or even cancer in the esophagus. Treatment plans for the elderly rely primarily on pharmacotherapy designed to decrease acid production.


Spectrum of GERD

There is no data that GERD is progressive. The current view is that mild esophagitis tends to remain mild on follow-up, and the progression of GERD to erosive esophagitis to Barrett's esophagus occurs in a small proportion of patients.

The development of gastroesophageal reflux disease can be traced to frequent relaxation of the lower esophageal sphincter allowing gastric contents to inflame the area thus impairing sphincter function and esophageal motility. As gastric reflux volume increases, esophagitis may shorten the esophagus leading to a permanent malfunction of the gastroesophageal junction and greater inflammation or ulcers. If left untreated, columnar epithelium may develop to resist acids in the esophagus which in turn may develop into adenocarcinoma. However, this occurs in a minority of patients.


Factors that Affect the Development of GERD

Mechanism Factors

Direct esophageal irrita/on citric juices, tomato-based products, soda, coee

Reduced Lower Esophageal Sphincter (LES) tone

faAy foods, alcohol, chocolate, caeine, nico/ne, alpha-adrenergic blockers, an/cholinergic agents, benzodiazepines, beta-2 agonists, progesterone, calcium channel blockers, dopamine, nitrates, prostaglandins, theophylline, TCAs

Delayed gastric emptying an/cholinergic agents, narco/c analgesics, overea/ng

Impaired gastroesophageal pressure gradient supine body posi/on, obesity, /ght-Lng clothing

Mucosal resistance NSAIDs

Anatomical changes hiatal hernia, reclining aOer ea/ng

Several factors can affect the development of gastroesophageal reflux disease, including foods, eating habits, and various medications. These factors are shown on your screen, along with the mechanisms through which they exacerbate the disorder.


Signs & Symptoms of GERD

Typical:

Substernal burning or heartburn after eating certain foods Heartburn when reclining or bending at the waist Belching Regurgitation Nausea Vomiting/bitter or sour taste in mouth

Atypical:

Hoarseness of voice Wheezing Sore throat Cough

Alarm:

Swallowing difficulties Unintentional weight loss Blood in vomit or stool Inability to eat solid food

Classical symptoms of gastroesophageal reflux disease include heartburn after eating certain foods or events, and heartburn when either lying down or bending at the waist after large meals.

Other symptoms include belching, regurgitation, and nausea. More atypical symptoms of GERD include hoarseness, sore throat, and cough.

The frequency and severity of heartburn symptoms do not correlate with the severity of erosive disease. Symptoms such as swallowing difficulties, bleeding and unintentional weight loss are cause for alarm and immediate evaluation.

Some patients- the elderly in particular- may be asymptomatic before a bleed, and have no warning signs.


Methods Used to Diagnose GERD

GERD may mimic angina, asthma, COPD and throat infections. Medical history and symptom analysis are important to diagnosis 24-hour ambulatory esophageal monitoring is definitive, especially for patients with atypical symptoms:

A drop in intra-esophageal pH to less than 4 for more than 7 % of the 24 hours or A drop of 1 pH unit or more from a reliable baseline pH

Factors such as a hiatal hernia, delayed gastric emptying, and a non-functional pyloric sphincter should be considered in the prognosis If patient is unresponsive to drug therapy or has additional complications, assess esophageal damage with endoscopy Testing vomit and stool for blood Esophageal manometry can detect abnormal lower esophageal sphincter pressure

Although gastroesophageal reflux disease may initially mimic other disorders, a good medical history or esophageal pH monitoring is helpful in diagnosing the disease. Careful analysis of symptoms is also important. If further evidence is needed or if treatment is ineffective, endoscopy can determine the current condition of the first esophageal lining. When determining the status and progression of the disease, the clinician should consider the contribution of other pathological factors such as hiatal hernia, delayed gastric emptying, and a non-functional pyloric sphincter. If the patient does not respond to drug therapy or additional complications are suspected, endoscopy with biopsy can determine esophageal damage. Other tests check for blood in vomit or stool, and for abnormal pressure in the lower esophageal sphincter. Endoscopy would be done before pH monitoring; patients who do not respond to PPIs are not likely to have GERD and need endoscopy.


Diagnostic Classification of GERD

Differential Diagnoses:

Reflux without esophagitis Reflux with esophagitis Reflux with severe esophagitis

Evaluation of Esophageal Lining:

Grade 0 - normal Grade I - single or isolated erosive lesions Grade II - multiple lesions Grade III - circumferential lesions Grade IV - columnar epithelium (Barretts), ulcers or strictures

For the purposes of selecting treatment, GERD is typically classified as reflux without esophagitis, reflux with esophagitis and reflux with severe or erosive esophagitis. Diagnostic test results may also provide data for grading the extent of damage to the esophageal lining. This grading scheme is shown on your screen.


Treatment of GERD

Therapeutic Goals:

Alleviate symptoms Heal any ulcers Avoid adverse reactions to medications Prevent additional complications Prevent recurrence

Step-Down Approach:

Treatment for gastroesophageal reflux disease relies on pharmacotherapy for symptomatic relief and long-term management. Other therapeutic goals include healing any ulcers, avoiding adverse reactions to medications, and preventing additional complications in the esophagus. For elderly patients, the step-down approach is favored because it can improve quality of life almost immediately.

This approach emphasizes the initial use of proton pump inhibitors or histamine-2 receptor antagonists to reduce gastric secretion. Promotility agents can be useful in some cases during the healing stage but caution must be taken to avoid adverse reactions and drug-interactions. Proton pump inhibitors are the most effective form of extended therapy for more severe GERD producing eighty to ninety percent remission.

Acute proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) to reduce acid secretion; promotility agents to improve acid clearance

Maintenance PPIs or H2 RAs; lifestyle modification to minimize risk factors


Treatment of GERD with Antacids

Mechanism of Action: Form a weak base which reacts with gastric acids to form salts and water; effects may last as long as 1-2 hours with food.

Dosing: One dose taken 30 minutes after meals and at bedtime x 4-8 weeks. Consult individual prescribing information for exact dosing.

Agents:

Sodium bicarbonate-based medications (e.g. Alka-Seltzer products) - Rapid action and relief, but these products may cause electrolyte imbalances, and urinary or systemic alkalosis leading to edema, hypertension and heart failure. Many Alka-Seltzer products also contain aspirin, which can cause GI irritation and breakdown.

Aluminum hydroxide and dihydroxy forms (AlternaGel, Maalox, Mylanta) - weaker effects but can inhibit gastric hyperacidity; use with caution in patients with CHF, renal failure, edema; hypophosphatemia and aluminum intoxication may occur with prolonged administration or large doses. Constipation can result from formation of insoluble aluminum chloride .Aluminum antacids can decrease the efficacy of tetracycline and fluroquinolone antibiotics via binding interactions; also may affect absorption of bisphosphonates, phenytoin, and antifungals.

Magnesium hydroxide (Phillip's Milk of Magnesia, Di-gel, Maalox, Mylanta, Rolaids) - longer lasting effects due to slower stomach emptying; can cause diarrhea and cramping. Use with caution in patients with severe renal impairment. May decrease absorption of tetracyclines, fluroquinolones, digoxin, or iron salts


Treatment of GERD with Antacids

Calcium carbonate (Tums, Titralac Rolaids) - a good neutralizer, but may cause constipation and nausea; absorption of calcium chloride may cause hypercalcemia with muscle weakness, kidney stones, gastric acid rebound. May affect absorption of tetracycline, fluroquinolones, digoxin, and levothyroxine.

Many OTC antacid products contain multiple agents: Gaviscon, Rolaids, Di-Gel, Maalox, Mylanta.

Patients with mild and infrequent symptoms may begin with lifestyle changes, antacids, or over-the-counter histamine-2 receptor antagonists. Antacids are effective in controlling symptoms in the majority of these patients, however, the neutralizing effects usually last only forty-five minutes to an hour when taken on an empty stomach. Some antacids, like Alka-Seltzer, may also contain aspirin and other non-steroidal anti-inflammatory drugs that cause further damage to the gastrointestinal tract. Alginic acid-antacid combinations (Gaviscon) form a viscous foam which floats on the surface of gastric contents acting as a mechanical barrier. The usual dose is two tablets chewed after meals and at bedtime. Over-the-counter histamine-2 receptor antagonists can be taken prophylactically and provide longer-lasting relief from the symptoms of GERD.


Treatment of GERD with Proton Pump Inhibitors (PPIs)

Mechanism of Action: Irreversibly inhibit enzymes in parietal cells necessary for gastric acid secretion.

Agents and Dosing for GERD:

omeprazole (Prilosec): 20-40 mg daily x 4-8 weeks lansoprazole (Prevacid): 15-30 mg daily x 4-8 weeks rabeprazole (Aciphex): 20 mg daily x 4-8weeks pantoprazole (Protonix): 20-40 mg daily x 4-8 weeks esomeprazole (Nexium): 20-40 mg daily x 4-8 weeks

Adverse Drug Reactions: Headache, abdominal pain, diarrhea, constipation, flatulence, reduced vitamin B12absorption, pernicious anemia (with long-term use).

Drug-Drug Interactions:

In general, proton pump inhibitors can reduce the absorption of oral iron, ketoconazole, and itraconazole, and some protease inhibitors. PPIs can increase serum concentrations of diazepam, amiodarone, phenytoin, warfarin, and propranolol, to name a few. Check prescribing information for individual agents for a full review of drug-drug interactions


Treatment of GERD with Proton Pump Inhibitors (PPIs)

PPIs have the greatest effect on decreasing acid production. These agents allow for more rapid and complete healing. PPIs irreversibly inhibit enzymes in parietal cells necessary for gastric acid secretion. Higher doses of any of these drugs may be needed for more severe cases, including those with erosive esophagitis, or Zollinger-Ellison syndrome. Side effects of these drugs are usually limited to headaches and diarrhea. Although, reduced vitamin B12 absorption may occur with long-term therapy of greater than 3 years as intrinsic factor requires an acidic environment to absorb vitamin B12. Maintenance therapy is based on long-term administration of effective therapeutic dosages.


Treatment of GERD with Histamine-2 Receptor Antagonists (H2 RA)

Mechanism of Action: Rreversibly bind H2 receptors on parietal cells, reducing acid production and partially inhibiting acetylcholine and gastrin-stimulated acid production.


cimetidine (Tagamet): 300-400 mg QID or 800 mg twice daily for 12 weeks nizatidine (Axid): 150 mg BID rantidine (Zantac): 150 mg BID famotidine (Pepcid): 20 mg BID

(Note: GERD and PUD prophylactic therapy may have different dosage recommendations; H2 RA doses should be reduced if CrCL


Treatment of GERD with Histamine-2 Receptor Antagonists (H2 RA)

Although not as effective as proton pump inhibitors, patients who have more severe GERD with esophagitis can be treated with higher doses of histamine-2 receptor antagonists such as cimetidine, famotidine, ranitidine and nizatidine. These agents reversibly bind H2 receptors on parietal cells reducing acid production and partially inhibiting acetylcholine and gastrin-stimulated acid production. In doing so, they not only reduce the need for antacids, but allow healing of esophagitis.

When used to treat gastroesophageal reflux disease, histamine-2 receptor antagonists are administered in divided doses. While doubling the dosage of these agents may be more effective in relieving symptoms and healing esophagitis, the cost may be prohibitive for all but the most severe cases. Because over eighty percent of patients relapse when these agents are discontinued, maintenance therapy may be necessary. Side effects to watch for include drowsiness, headache, and GI irritation. The best use of H2 antagonists is for PRN and prophylaxis of events known to cause reflux. They are not as effective as PPIs and tolerance develops, perhaps through up-regulation of receptors. PPIs are essential for moderate to severe GERD, and for erosive disease. It is also important to note that H-RAs are now available for over-the-counter treatment of meal-induced heartburn, acid indigestion, and sour stomach at lower doses then what are available by prescription.


Treatment of GERD with Promotility Agents

Effects:

Improve gastric emptying Maintain lower esophageal sphincter tone Improve esophageal clearance


Metoclopramide ((Reglan)


Cholinergic activity with dopamine antagonism. Enhances the response to acetylcholine of tissue in upper GI tract, causing enhanced motility and accelerated gastric emptying without stimulating gastric, biliary, or pancreatic secretions; increases lower esophageal sphincter tone

Dosing: 5-10 mg TID-QID, 30 minutes before meals and at bedtime.

Adverse Reactions: Drowisiness, fatigue, dystonic reactions

Drug-Drug Interactions: Anticholinergics may antagonize the mechanism of action; may increase risk of dystonic reactions if given concomitantly with antipsychotics.


Treatment of GERD with Promotility Agents

Bethanechol (Urecholine)

Mechanism of Action: Cholinergic agent with relatively selective muscarinic activity on smooth muscle in GI tract and bladder; results in increased peristalsis, increased GI and pancreatic secretions.

Dosing: (unlabeled use for GERD): 10 mg TID-QID

Adverse Reactions: GI irritation, hypotension, headaches, urinary urgency

Drug-Drug Interactions: Bethanechol and ganglionic blockers may cause a critical fall in blood pressure. Cholinergic drugs or anticholinesterase agents may have additive effects


Treatment of GERD with Sucralfate (Carafate)

Mechanism of Action: Combines with proteins to form a viscous paste-like barrier resistant to acid and pepsin

Dosing: (unlabeled use for GERD) 1 g 30 minutes before meals and bedtime x 4-8 weeks; may be more effective when given as a slurry.

Adverse Drug Reactions: Constipation Nausea Aluminum toxicity/seizures Use with caution in patients with chronic renal failure who have an impaired excretion of absorbed aluminum.

Drug-Drug Interactions: Because of the potential for sucralfate to alter the absorption of some drugs (e.g. phenytoin, digoxin, theophylline, warfarin, and quinolone antibiotics), separate administration (take other medication 2 hours before sucralfate) should be considered when alterations in bioavailability are believed to be critical.


Treatment of GERD with Sucralfate (Carafate)

While its efficacy has not been proven, sucralfate is sometimes prescribed for treatment of GERD. Sucralfate is an aluminum salt of a sulfated disaccharide that combines with proteins to form a viscous barrier resistant to acid and pepsin.

Taken orally, therapy consists of one gram taken thirty minutes before meals and at bedtime. However, sucralfate is often more effective if given to patients as a slurry. Sucralfate causes constipation, hypophosphatemia, and nausea and reduces absorption of other drugs. Aluminum can also accumulate in elderly with renal problems and ultimately lead to seizures.

Given these side effects, sucralfate cannot compare with the more effective proton pump inhibitors for the treatment of gastroesophageal reflux disease. Because of the potential for sucralfate to alter the absorption of some drugs, separate administration of narrow therapeutic drugs by 2 hours from sucralfate dose.


Non-Pharmacological Treatments for GERD

Lifestyle and Dietary Changes:

Avoid foods and medications known to trigger reflux (fatty or fried foods, alcohol, peppermint, garlic, onion, caffeine, nicotine)

Eat smaller, more frequent meals Stay upright 2-3 hours after eating Elevate head of bed 6 inches for sleeping Stop smoking Lose extra weight Reduce stress Follow maintenance care plan

Support Groups:

Provide strategies for successful self-care Help monitor progress Provide access to specialists, clinical pharmacists and current information

Surgical Interventions:

Surgical reinforcement of the LES area: fundoplication, endoluminal gastroplication Stretta procedure: radiofrequency energy to create scar tissue and tighten LES junction


Non-Pharmacological Treatments for GERD

While medications such as proton pump inhibitors and histamine-2 receptor antagonists are the key to maintenance therapy, lifestyle and dietary changes are often part of long-term treatment of gastroesophageal reflux disease. Common strategies include the avoidance of irritating foods and medications, changes in eating habits, and stress reduction. Geriatric patients tend to have more difficulty making and sustaining these changes. A support group may help the patient maintain a healthy lifestyle and find alternatives to foods and medications that trigger the disease. If conventional pharmacological and non-pharmacological therapies are unsuccessful, surgery is necessary to avoid life-threatening conditions.


Resources and References


Beers, M.H & Berkow, R. (2000). The Merck Manual of Geriatrics. 3rd edition Section 13, Gastrointestinal Disorders. Whitehouse Station, NJ: Merck Research Laboratories: 1000-1154.

Devault, K. R.(1996). Current management of gastroesophageal reflux disease. Gastroenterologist; 4:24-32

Duthie B. (1998). Practice of Geriatrics, 3rd ed. Chapter 46:Gastrointestinal disorders. W.B . Saunders Company.

Elliot, D., Small, S. (1997). Gastroesophageal reflux disease (GERD). Journal of the American Society of Consultant Pharmacists, 13 (Suppl.5)

Fennerty, M. B., et.al. (1996). The diagnosis and treatment of gastroesophageal reflux disease in a managed care environment: suggested disease management guidelines. Arch Intern Med;156:477-84

Fullard M, et al. (2006) Systematic Review: Does Gastro-oesophageal Reflux Disease Progress? Aliment Pharmacol Ther;24 (1):33-45.

Garnett, W. R.(1998). Considerations for long-term use of proton-pump inhibitors. American Journal of Health-system Pharmacy; 55:2268-79.

Lewis, J. H.(1994). A pharmacologic approach to gastrointestinal disorders. Baltimore:Williams & Wilkins.

Nelson, J. B., Castell, D. O.(1988). Esophageal motility disorders. Dis Mon, 34:299

Richter, J. E., et.al.(1998). Helicobacter pylori and gastroesophageal reflux disease: The bug may not be all bad. Am J Gastro; 93:1800-02


Resources and References

GERD Information Center at http://www.gerd.com

PharmInfo Nets GERD Information Center at http://pharminfo.com/disease/gerd/gerd_info.html


Constipation in the Elderly

Learning Objectives


Define constipation, its prevalence and impact on the elderly population.

List the major causes of constipation, including medications.

Identify the signs and symptoms of constipation, and the diagnostic methods used to characterize the disease.

Describe non-drug treatment options for constipation.

Compare and contrast different kinds of laxatives in terms of effectiveness, dosing, and adverse reactions.

Outline general guidelines for treating and maintaining quality of life in elderly adults with chronic constipation.


Introduction to Constipation in the Elderly

Constipation: Less than three bowel movements each week (many definitions exist, however, this one is frequently used).

Types: Slow-transit constipation Rectal-outlet delay

Epidemiology: Affects 20 30% of the elderly population

Impact: If untreated, may lead to complications such as fecal impaction, anal fissures, prolapse or hemorrhoids, megacolon, volvulus, and a tendency to develop colorectal cancer.

Symptoms of constipation are extremely common, with prevalence being reported as high as 30%. Many patients seek medical care for constipation, but fortunately most do not have a life-threatening or disabling disorder, and the primary need is for control of symptoms. The impressive number of people affected and the cost of most diagnostic tests dictate that in the next century we can manage this symptom in a cost-effective manner. Constipation is defined as having less than 3 bowel movements each week and can be sub-categorized as slow-transit constipation or as rectal outlet delay. Most patients have the slow transit form and will experience additional aspects of the problem including straining, hard stools, or incomplete evacuation on more than 1 in 4 occasions. Patients with rectal outlet delay will complain of having a feeling of anal blockage or prolonged defecation for more than 10 minutes. Constipation is a common complaint of the elderly, with nearly one-third of adults over age sixty reporting symptoms and the use of laxatives. The prevalence of constipation is higher in nursing home patients, especially those with impaired mobility, compared to community dwelling patients.


Etiology of Constipation

Dietary and lifestyle changes Functional outlet obstruction due to striated muscle failure Decreased internal and external anal sphincter tone Diseases such as

Colon cancer Stroke Hypothyroidism Neurological disorders Hypercalcemia Scleroderma Hyperparathyroidism Depression Diabetic neuropathy

Dehydration Medications

In the elderly, the decreased gastrointestinal motility can be related to reduced dietary fiber, decreased fluid intake, lack of activity, or common diseases including: colon cancer, stroke, hypothyroidism, diabetes, and Parkinsons disease. Many patients with chronic symptoms have developed a pattern of suppressing the urge to defecate and waiting until a more convenient opportunity to have a bowel movement. Unfortunately, the urge may not return. A common, and, often overlooked, cause of constipation is use of certain medications.


Medications That Are Commonly Associated With Constipation

Analgesics Narcotic analgesics NSAIDs

Anticholinergics Older antihistamines Tricyclic antidepressants Antispasmodics Anticholinergic anti-Parkinsons medications

Diuretics

Metallic cations Aluminum Calcium Iron Barium Bismuth

Calcium channel blockers

Many medications are culprits in causing or contributing to constipation. Sometimes constipation is well recognized and preventive measures are taken to avoid constipation, as with narcotics. However, drug-induced constipation may go unrecognized.


Assessing Constipation

Symptoms:

Hard stool Painful bowel movements Straining during defecation Reduced frequency of bowel movements Bloating Malaise

Diagnosis:

Abdominal exam Rectal exam Occult blood tests Colonoscopy Radiographic studies Sigmoidoscopy

Major symptoms of constipation include hard stool, painful bowel movements, and straining during defecation. Bloating and malaise are also common. Diagnostic testing is sometimes appropriate and may include a rectal exam, occult blood tests, colonoscopy, radiographic studies with a barium enema, and sigmoidoscopy. These tests are done primarily to rule out other disorders. Sometimes a person with impacted stool may actually experience diarrhea as liquid stool passes the impacted stool. A careful abdominal exam is helpful in differentiating impaction from loose stools.


Non-Pharmacologic Treatment of Constipation

Primary Strategies:

Regular exercise as tolerated Development of regular stool schedule Removal of unnecessary constipating medications

Dietary Adjustments:

Increase fiber consumption up to 10+ grams / day Vegetables, fruits, cereals

Increase fluids up to 1500+ mL / day Add prunes or prune juice as a source of fiber and sorbitol Add a bulk forming product as a fiber source

Bulk-Forming Products:

Calcium polycarbophil (Fiberall), FiberCon) Psyllium (Metamucil) Methylcellulose (Citrucel)


Non-Pharmacologic Treatment of Constipation

Non-drug approaches should be first line therapy tried prior to using laxatives and other medications. Regular exercise and scheduled bowel movements may help to establish and maintain regularity. Constipating medications should be substituted with non-constipating ones when possible. Increasing dietary fiber to ten grams or more each day and fluids to fifteen hundred milliliters or more is recommended. Prunes and prune juice are preferred by some patients although there is some debate on their mechanism of action. They are a source of fiber and sorbitol but may have some stimulant effects as well. Bulk-forming products, such as calcium polycarbophil, methylcellulose or psyllium, may be substituted for dietary fiber.

Adequate fluid intake is required while using these products to prevent GI obstruction or impaction. Bulk forming laxatives are primary used for chronic constipation as these agents assist in maintaining regular bowel movements and will not help to relieve acute symptoms. For the ambulatory and alert elder, these non-pharmacological treatments may be sufficient to control and prevent constipation. Non-pharmacological therapies should continue even if other interventions are necessary.


Treatment of Constipation with Emollients and Lubricants

Mineral Oil or Liquid Petroleum:

Role in Therapy Use should be discouraged Other therapies are as effective and are safer

Comments Penetrates and softens stool May impair absorption of fat-soluble vitamins Contraindicated in patients who are bedridden or have dysphagia or GERD Potential exists for aspiration Typical dose:15 45 mL

Docusate:

Role in Therapy Prevent constipation Ineffective for acute or chronic management of constipation

Comments Products: docusate sodium (Colace), docusate calcium (Surfak) Promotes mixing of fatty and aqueous substances, leading to evacuation by mucosal irritation Also promotes net intestinal secretion of water PRN use not appropriate due to onset of action Typical dose:50 360 mg QD


Treatment of Constipation with Emollients and Lubricants

Most laxatives are available as over-the-counter medications, allowing anyone to self-medicate. Mineral oil is often used but its potential adverse effects outweigh its potential advantages, particularly for chronic use. Mineral oil can be aspirated and a small amount absorbed systemically resulting in acute adverse effects such as lipoid pneumonia and inflammation of intestinal mucosa, liver, and spleen. Systemic absorption may be increased when used with docusate. Long-term use may place patients at risk of fat soluble vitamin deficiency.

Docusate is a stool-softener and is usually used as either the sodium salt (e.g. Colace) or the calcium salt (e.g. Surfak) however, products containing the potassium salt are also available. The three salts are considered to be clinically equivalent. Products containing docusate are the most commonly prescribed laxative to the elderly, especially nursing home elderly. While they improve the miscibility of fatty substances and water, allowing for better mixing and eventual evacuation of the stool, they have also been show to promote the net intestinal secretion of water.

Stool softeners have slow onset of action of 1 to 3 days and thus are not beneficial for acute constipation. Controlled trials have not proven that docusate is effective in treating chronic constipation in elderly patients. Docusate is often used in combination with a stimulant laxative, however, controlled studies are not available that demonstrate that the combination is more effective than the stimulant alone.

Docusate is perhaps best reserved for prevention of constipation in patients who may be at increased risk for a limited period of time (e.g. period of bed rest due to an acute illness).


Treatment of Constipation with Saline Laxatives

Mechanism of Action: Increase intra-luminal water content and net secretion of fluid into colon

Role in Therapy: Typically used for patients with acute constipation Can be used for chronic constipation in low doses

Contraindications: Patients with renal failure

Adverse Reactions: Depends on extent of renal impairment and amount of stool loss. Low doses can be used to manage chronic constipation. Excessive dosing will produce diarrhea and dehydration. Specific electrolyte disturbances depend on salt.

Agents and Dosing:

Magnesium Salts Products Magnesium hydroxide (Milk of Magnesia):2.4 4.8 oz Magnesium sulfate:10 30 g Magnesium citrate (Citro-Mag):18 g or 12 oz Possible Electrolyte Disturbance Hypermagnesemia


Treatment of Constipation with Saline Laxatives

Sodium Phosphate Salts Products

Sodium phosphate and sodium biphosphate (Fleet enema, Fleet phospo soda) Possible Electrolyte Disturbances Hypocalcemia, hypernatremia, hyperphosphatemia, hypocalcemia, hypokalemia

Saline laxatives produce soft stools through their osmotic effects. The increased retention of fluid in the small intestine results promotes the release of cholecystekinin and an increase in peristalsis. The most commonly used saline laxatives contain magnesium salts such as magnesium hydroxide or magnesium citrate. Phosphate is the poorly absorbed anion in products containing sodium phosphate.

Saline laxative are often used to manage acute constipation, however, lower doses administered on a regular schedule can be used to manage chronic symptoms. However, electrolyte absorption becomes more of a concern when used chronically, particularly in patients with renal impairment. Magnesium can accumulate in patients with severe renal function. Sodium phosphate products should also be avoided in patients with renal impairment.

This belongs with osmotic agents (sorbitol, lactulose)


Treatment of Constipation with Hyperosmolar Laxatives

Role in Therapy: Chronic constipation: low doses Bowel evacuation: high doses of polyethylene glycol (PEG) 3350 with electrolytes (e.g. Colyte, GoLYTELY)

Mechanism of Action: Poorly absorbed agents that retain water in the gut lumen

Agents and Dosing for Chronic Constipation: Lactulose: 20 40 g daily in divided doses Sorbitol 70%: 20 40 g daily in divided doses Glycerin suppositories: 3 g rectally Polyethylene glycol 3350: 17 g in 8 oz of fluid (e.g. Miralax)

Adverse Reactions: Bloating, flatulence, cramps High doses: diarrhea with electrolyte disturbances


Treatment of Constipation with Hyperosmolar Laxatives

Hyperosmolar laxatives are non-absorbable sugars that draw water into the lumen. They may also lower the pH of the colon and produce peristalsis. In low doses, they can be used in place of a bulk laxative to treat chronically constipated patients. Large doses of PEG 3350 are administered in electrolyte solutions (e.g. Colyte, GoLYTELY) as part of bowel preparation protocols.

Lactulose is a semisynthetic disaccharide that is metabolized into hydrogen and organic acids. These acids increase the osmolarity of the colon, altering electrolyte transport and colonic motility. Lactulose is usually well-tolerated but may cause bloating. Sorbitol has been shown to be as effective as lactulose, with a similar side effect profile; however, sorbitol has historically been less expensive than lactulose. Due to their sweet taste, some elderly patients prefer these agents. PEG 3350 is available in powder form for administration with fluid and can be used instead of either lactulose or sorbitol solutions.


Treatment of Constipation with Stimulant Laxatives

Role in Therapy

Acute constipation Used on a PRN basis

Chronic constipation After trial or consideration of other agents Used on a regular schedule (e.g. 3-5 days per week)


Directly stimulating the myenteric plexuses of the colon, increasing motility Impair active transport mechanisms resulting in retention of water and electrolytes in gastrointestinal contents Produces a soft stool making combination with a stool softener unnecessary

Agents and Dosing:

Senna (e.g. Senokot, Ex-Lax): Senna concentrate 374 748 mg Sennosides 8.6-17.2 mg

Bisacodyl (e.g. Dulcolax):10 30 mg) Castor Oil: 15- 60 mL


Treatment of Constipation with Stimulant Laxatives

Adverse Reactions:

Flatulence, cramps Diarrhea and electrolyte disturbances in higher doses Chronic use

Possible dependence (controversial) Colon pigmentation (unknown significance)

Stimulant laxatives are used when constipating medications must be continued, or acute constipation is non-responsive to other drugs. Their shorter onset of action of 6 to 12 hours allows for their use in acute constipation. These agents exert their effects by directly stimulating the myenteric plexuses of the colon, thus increasing motility. The stimulant laxatives that remain on the US market contain senna or bisacodyl.

Castor oil may have multiple mechanisms of action. It may act as a surfactant, but it also is thought to induce significant water and electrolyte secretion. There is some concern that castor oil could cause destruction of intestinal epithelium. Castor oil has a quick rapid of action and is often reserved for bowel preparation before diagnostic or surgical procedures.


Other Agents Used to Treat Chronic Constipation

Role in Therapy Constipation refractory to other agents.

Examples Lubiprostone (Amitiza): a prostaglandin E1 derivative

NOTE: Tegaserod (Zelnorm): a selective serotonin partial agonist was approved for use in women with constipation associated with irritable bowel syndrome. However, it was withdrawn from the market in March, 2007 due to an increased risk of serious cardiovascular adverse events, including myocardial infarction, unstable angina and stroke-associated with the use of the medication.

Many other agents can be used in an attempt to normalize bowel function in patients with chronic constipation. Lubiprostone has received FDA indication for chronic constipation in selected patients. This and other less commonly used agents are most often reserved for patients who have not responded to more conventional therapy.


Guidelines for the Treatment of Constipation

Acute Constipation: Initial: Tap water enemas, glycerin suppositories, milk of magnesia (MOM), or low dose stimulant laxatives Follow-up: Implement preventative measures to obtain > 3 stools per week

Impaction: Initial: Tap water enemas daily until empty with concomitant manual disimpaction

Sodium phosphate, biphosphate enema, polyethylene glycol may be used cautiously MOM may be used if necessary

Follow-up: Enemas for 5-6 weeks after clear, until sensation returns Contraindicated: Irritants such as magnesium agents, soap water enemas due to ineffectiveness, risk of rupture

Chronic constipation: Initial: Bulk-forming laxative, hyperosmotic laxative, low dose magnesium hydroxide, or stimulant Follow-up: Continue therapy, increase dose, or add another initial agent

Opioid-induced: Initial: Bulk-forming laxative, hyp

Module 8 Pharmacotherapy for Gastrointestinal Disorders

Documents

Transcript of Module 8 Pharmacotherapy for Gastrointestinal Disorders