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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 online 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
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
Learning Objectives
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.
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
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.
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 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.
Copyright 2011 American Society of Consultant Pharmacists
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
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.
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
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.
Copyright 2011 American Society of Consultant Pharmacists
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 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.
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.
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.
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.
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.
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.
Adverse Drug Reactions: Abdominal pain, cramping Headache Uterine contractions Diarrhea (dose dependent)
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
Adverse Drug Reactions: 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.
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.
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
For additional information, see: 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
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.
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.
Copyright 2011 American Society of Consultant Pharmacists
Factors citric juices, tomato-based products, soda, coee 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 an/cholinergic agents, narco/c analgesics, overea/ng supine body posi/on, obesity, /ght-Lng clothing NSAIDs hiatal hernia, reclining aOer ea/ng
Delayed gastric emptying Impaired gastroesophageal pressure gradient Mucosal resistance Anatomical changes
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.
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.
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: proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) to reduce acid secretion; promotility agents to improve acid clearance PPIs or H2 RAs; lifestyle modification to minimize risk factors
Acute Maintenance
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
Copyright 2011 American Society of Consultant Pharmacists
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
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.
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.
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.
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.
GERD Information Center at http://www.gerd.com PharmInfo Nets GERD Information Center at http://pharminfo.com/disease/gerd/gerd_info.html
Learning Objectives
By the end of this Review Concept you should be able to: 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.
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
Copyright 2011 American Society of Consultant Pharmacists
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.
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
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.
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 rupture enemas due to ineffectiveness, risk of
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, hyperosmotic laxative or stimulant Follow-up: Evaluate for impaction and treat.
Harari D, Gurwitz JH, & Minaker KL.Constipation in the elderly. J Am Geriatr Soc.1993;41:1130-1140. Herndon CM, Jackson KC, Hallin PA. Management of opioid-induced gastrointestinal effects in patients receiving pallitive care. Pharmacotherapy 2002;22(2):240-50. Landers KT & Elliott DP.Treatment strategies for the management of constipation in long-term care patients.Consult Pharm.2000;15(7):725-733. Locke GR, Pemberton JH, Phillips SF.AGA technical review of constipation.Gastroenterology.2000;119:1766-1778. Monane M, Avorn, J, Beers MH, & Everitt DE.Anticholinergic drug use and bowel function in nursing home patients.Arch Intern Med.1993;153:633-638. Norton C. Constipation in older patients: effects on quality of life. Br J Nurs 2006;15(4):188-92. Schiller LR.Clinical pharmacology and use of laxatives and lavage solutions.J Clin Gastroenterology.1999;28(1): 11-18.
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Define diarrhea and its impact on the elderly population. List the main signs, symptoms, and complications of diarrhea. State the principal causes of diarrhea. List diagnostic parameters that indicate the presence of diarrhea and its severity. Describe the goals of treatment of diarrhea. Explain the importance of oral rehydration therapy in the treatment of diarrhea. Compare and contrast commercially available solutions and home preparations for oral rehydration therapy. Compare and contrast other pharmacological agents that are commonly used to treat diarrhea, in terms of their effects, dosing requirements, and adverse reactions. Identify preventative measures and lifestyle considerations for the elderly.
Etiology of Diarrhea
Infectious: Bacterial (e.g., Campylobacter, Clostridium, E. coli, Salmonella, Shigella, S.aureus, C.difficile) Viral (e.g., adenovirus, rotavirus, calicivirus, coronavirus, Norwalk virus) Parasitic (e.g., cryptosporidium, Entamoeba histolica, Giardia) Latrogenic: Dietary supplements Tube feeding Antibiotics Certain antacids and acid-suppressing medications Bulk and osmotically active laxatives (e.g., milk of magnesia (MOM), lactulose) Other medications (e.g., digoxin, quinidine, methyldopa) Food intolerance Gastrointestinal: Obstructive lesions Motility disorders with impaction Inflammatory bowel disease (Crohns disease) Malabsorption Mesenteric atherosclerosis and ischemia Portal hypertension
Copyright 2011 American Society of Consultant Pharmacists
Etiology of Diarrhea
Systemic: Diabetes mellitus Thyrotoxicosis Uremia Neoplastic: Obstructive lesions Secretory adenomas Hormone-secreting tumors
Common causes of diarrhea include bacterial, viral and parasitic infections, food poisoning, and digestive disorders. Medications such as antibiotics and magnesium containing antacids can also cause diarrhea. The elderly in nursing homes are especially susceptible to causative agents such as the bacterium Clostridium difficile and various viruses.
Diagnostic indicators for diarrhea include orthostatic changes in blood pressure, total plasma protein, and plasma specific gravity. Urine tests such as timed sodium, potassium, and osmolality may also be of value to determine significant volume loss. Utilization of blood tests is necessary to assess for dehydration or anemia. Stool cultures will identify if there is an infectious cause to the diarrhea. Diagnostic testing is often limited and may only indicate that damage has already been done. Initiating treatment early can shorten the course, severity, and recovery time from diarrhea.
Goals of the treatment of diarrhea start with providing symptomatic relief. It is important to identify and control the underlying cause of diarrhea. Maintaining fluid and electrolyte balance is a priority.
Non-Pharmacological Therapy
Avoid dairy products Avoid caffeine containing products Oral rehydration therapy
Further, management of the patients dietary intake should include avoidance of dairy and caffeine containing products. As mentioned on the previous screen, it is imperative to increase fluid and electrolyte intake to restore a normal hydration level and prevent further dehydration and electrolyte loss.
While oral rehydration is the first choice for treating most diarrheas, other medications may be useful in treating specific cases of acute diarrhea. One example is the use of bismuth subsalicylate for relieving travelers diarrhea and other non-specific acute diarrhea. Bismuth subsalicylate combines antimicrobial activity with an antisecretory function. Bismuth subsalicylate is initially dosed at thirty milliliters or 2 tablets every hour for up to eight doses in 24 hours or until diarrhea stops. Adverse reactions in the elderly involve immediate salicylate sensitivity and irritation from longer-term use. Utilize caution when patients are using bismuth subsalicylate with other medications as this agent can bind to some medications and decrease absorption of other medications such as warfarin.
Opioids act by slowing gastrointestinal motility, allowing for greater absorption. They also decrease cramping. Four opioids used in the treatment of diarrhea include: (1) diphenoxylate with atropine; (2) difenoxin, an active metabolite of diphenoxylate, with atropine; (3) loperamide, which is used for chronic diarrhea in certain diseases; and (4) paregoric. If diarrhea is caused by enteric bacteria or toxic medications, use of opioid medications can cause more damage by delaying the elimination of those toxins. Patients purchasing OTC agents should be warned that they should not be used if the diarrhea is from enteric bacteria or toxic drugs..
Polycarbophil, attapulgite and charcoal preparations act as adsorbents of noxious compounds, but because they can interfere with drugs necessary to treat other disorders, they are not widely recommended. Kaopectate formerly contained attapulgite, but recently was reformulated to contain bismuth subsalicylate. Antimotility medications can decrease the duration of diarrhea, but do not affect the amount of fluid loss. The use of antibiotics to treat elderly patients with diarrhea remains controversial. Even when there is clear evidence of invasive processes and specific organisms, the benefits of antibiotics must be weighed against their side effects. Adverse reactions to antibiotic use include frequent reinfection, the so-called antibiotic diarrhea, and destruction of normal protective gut flora. It is this kind of disruption of the normal gut flora that can lead to the overgrowth of Clostridium difficile and more serious conditions such as pseudomembranous enterocolitis.
Treatment of chronic diarrhea is dependent upon controlling the underlying cause. As with acute diarrhea, use of oral hydration therapy is important to keep the patient hydrated. In patients with pseudomembranous colitis or bile acidinduced diarrhea, use of bile acid sequestrants such as cholestyramine, can assist in controlling the diarrhea. Monitor other medications used with bile acid sequestrants as there is the possibility of drug-drug binding thus decreasing absorption. Opioids are the most effective, nonspecific agents. Octreotide should be reserved as a second line agent or in patients with intestinal peptide secreting tumors. Parenteral nutrition is reserved for patients who can not maintain adequate nutritional status with the diarrhea.
Seeking a referral for medical care is dependent upon the elders nutritional and hydration status and other co-morbid conditions. General guidelines include unexplained diarrhea lasting for over 2 weeks, the presence of blood in the stool, high unresolved fever, and increased weight loss. Further medical work-up is necessary in these individuals in order to identify the underlying cause of the diarrhea.
Preventive measures can be taken to avoid outbreaks and recurrence of diarrhea for the elderly living in the community and in the nursing home environment. Proper hand washing techniques, proper food and water preparation, and a healthy diet can help prevent diarrheal infections. The consulting pharmacist can facilitate this process by monitoring for medications that have been implicated in causing diarrhea in the elderly. This includes monitoring the use of laxatives and other medications that can cause diarrhea and current antibiotic therapy.
Resources
For additional information, see: American Gastroenterological Association Medical Position Statement:Guidelines for the evaluation and management of chronic diarrhea.Gastroenterology.1999;116:1461-1463. Aranda-Michel J, Giannella RA.Acute diarrhea: a practice review.Am J Med.1999;106(6):670-676. Beers MH & Berkow R.(2000).The Merck Manual of Geriatrics. 3nd edition. Section 13, Gastrointestinal Disorders. Whitehouse Station, NJ:Merck Research Laboratories:1000-1154. Bennett RG & Greenough WB.(1994).Diarrhea. In:Hazzard WR, Bierman EL, Blass JP, Ettinger WH, & Halter JB. (Eds.).Geriatric Medicine and Gerontology, 3rd ed.New York:McGraw-Hill:1275-1284. Duthie EA.(Ed).(1998).Modells drugs in current use and new drugs, 44th ed.New York:McGraw-Hill. Greenough WB, et al.Causes of diarrhea in the elderly:Impact on intestinal function and treatment by oral rehydration therapy.Clin Res.1992;40:438. Holt PR.Gastrointestinal diseases in the elderly. Curr Opin Clin Nutr Metab Care.2003;6:41-48. Lewis JH.(1994).A pharmacologic approach to gastrointestinal disorders.Baltimore:Williams & Wilkins. Lichtblau L.(1998).Drugs affecting the gastrointestinal tract, lecture from ISAP.
Resources
Margolis S.(Ed.).(1993).The Johns Hopkins handbook of drugs for the 100 major medical disorders of people over the Age of 50. New York:McGraw-Hill. Pizarro D, Posada G, Sandi L, & Moran JR.Rice-based oral electrolyte solutions for the management of infantile diarrhea.NEJM.1991;374(8):517-521. Spruill WJ and Wade WE.Diarrhea, constipation, and irritable bowel syndrome. In:Pharmacotherapy: a pathophysiologic approach, 5th ed.Dipiro JT, Talbert RL, Yee GC, et al., eds.New York:McGraw-Hill.2002:655-669. Online resources: Diarrhea information at: http://www.acg.gi.org/ Lexicomp Online, Lexi-Comp, Inc (2006) http://www.crlonline.com/crlonline Merck Manual of Geriatrics (2006) http://www.merck.com/mrkshared/mmg/home.jsp
By the end of this Review Concept you should be able to: Define the major disorders of the colon seen in the elderly and their impact on geriatric health. Describe the incidence, common signs and symptoms and causes of diverticular disease. List the types of colitis commonly found in the elderly. Describe the incidence, common signs and symptoms, and causes of irritable bowel syndrome and inflammatory bowel disease. Identify relevant diagnostic tools for identifying colonic disorders seen in the elderly. Outline treatment priorities and protocols for elderly patients with diverticular disease and colitis. Compare and contrast pharmacological agents used in the treatment of irritable bowel syndrome and inflammatory bowel disease in terms of effectiveness, administration and adverse reactions.
Diverticular Disease
Definition: Disease associated with sac-like outpouchings of the gastrointestinal tract, which can trap feces and become infected, bleed, or rupture. Incidence: Occurs in approximately 30% of the population >45 years old, and 65% of the population over 85 years of age. Principal Cause: Low intake of dietary fiber leads to formation of abnormal loops and out-pouchings of tissues in the colon; also an inherent weakening of the colonic wall as the GI tract ages. Signs & Symptoms: May be asymptomatic or very painful (only 15-30% of patients experience complications). Painful diverticular disease presents with tender left lower colon and colicky attacks Often associated with constipation or diarrhea, and symptoms increase after eating. Diverticulitis, or infection arising in the diverticula, is mainly found in the sigmoid colon and is indicated by fever, leukocytotsis, and rebound tenderness. Bleeding diverticula occurs primarily in the right colon Diagnosis: CT scans to pinpoint acute diverticular problems Anemia testing to detect large bleeding diverticula Tests for blood in stool Flexible sigmoidoscopy Radiographic barium enema
Copyright 2011 American Society of Consultant Pharmacists
Diverticular Disease
Diverticular disease describes a range of conditions caused by the formation of abnormal loops and pockets of tissues in the colon. In industrialized countries, at least fifty percent of adults over 70 develop diverticula primarily due to a lack of dietary fiber. The disease may be asymptomatic or very painful. Painful diverticular disease is seen with tender left lower colon and colicky attacks. Diverticulitis, the inflammation of diverticula, develops in 15-25% of persons with diverticulosis, and occurs mainly in the sigmoid colon . It is caused by an infection and abscess in the diverticula. Bleeding diverticula occurs in the right colon two-thirds of the time and is caused by thinning of the inflamed diverticular walls. CT scans can pinpoint acute diverticular problems while anemia testing can detect large bleeding diverticula. Other diagnostic tools include flexible sigmoidoscopy and radiographic barium enema.
Diverticular disease is treated conservatively if possible and surgically only as a last resort. Painful diverticular disease without inflammation is mainly treated non-pharmacologically; instituting a high fiber, low irritating diet, and removing drugs with adverse effects can be very effective. Treatment for diverticulitis, when acute, consists of broad spectrum antibiotics such as ampicillin, metronidazole and gentamicin. The patient must be monitored closely for signs of peritonitis and potential need for surgery. Bleeding diverticula should be conservatively treated unless large and rapid blood loss necessitates surgery.
Inflammation of the colon or colitis describes a variety of disorders in the elderly that include irritable bowel syndrome, inflammatory bowel disease, and various other forms of colitis. Colitis may occur at any age and cause a wide range of painful and distressing symptoms. For the elderly, chronic conditions may worsen simply with age or as a result of medications that irritate the colon. Inflammatory bowel disease and irritable bowel syndrome are disorders that must be treated when painful symptoms appear.
Diagnosis: Dependent on symptoms, medical history, and ruling out other problems.
Irritable bowel syndrome, known also as functional colitis or spastic colon, is defined as abnormal increases in spontaneous movement of the large and small intestine. These movements may be caused by colon muscular disturbances, enhanced visceral sensitivity, and factors such as diet, stress, depression, and laxative use. Irritable bowel syndrome is seen more frequently in females, and may begin around the ages of twenty or thirty. Symptoms can be either constipation-predominant, diarrhea- predominant, or alternating diarrhea-constipation. The main symptoms include persistent abdominal discomfort, abnormal stool frequency and consistency, flatulence, bloating, distension, and intermittent pain following meals but relieved by bowel movements. Definitive diagnosis depends on symptoms, medical history, and the exclusion of any other mechanical, inflammatory, or biochemical explanations..
Irritable bowel syndrome is treated by reducing symptoms. Non-pharmacologic treatment includes dietary changes such as increasing fiber, eliminating stimulants like caffeine, and removing irritants such as spices and sweets. Also, stress reduction such as meditation, exercise, or counseling can help reduce triggers such as anxiety and depression which may aggravate symptoms. Pharmacological plans involve monitoring and removal of irritating medications, including those that cause constipation and/or diarrhea. Anticholinergic medications are sometimes effective in reducing smooth muscle contractility or hyperreactivity although these drugs have potentially dangerous side effects.. Alosetron, a selective and potent inhibitor of serotonin 5-H-T-3 receptors is indicated for the use of diarrhea predominant IBS and is only indicated for use in women.. Only physicians entered into an industry sponsored program can prescribe alosetron, and patients must understand and comply with a Patient-Physician agreement .
Adverse Drug Reactions: May cause confusion, drowsiness, dizziness, blurred vision, dry mouth, difficult urination. With larger doses: pupillary dilation , tachycardia sweating.
Therapeutic Goals: Control inflammation Correct nutritional deficiencies Alleviate symptoms Nutritional Interventions: Ensure adequate calories, vitamins, and protein Avoid foods and substances that aggravate diarrhea and other symptoms Avoid blockages by eliminating raw fruits and vegetables and hard to digest foods such as milk products. Pharmacological Interventions: Monitoring and removal of irritating medications Anti-inflammatory agents to control flare-ups Use of antibiotics if abscesses are present Use of other pharmacological options such as immunopsuppressants and monoclonal antibodies . Surgical Interventions: Crohns disease is not cured by surgery, but it may be necessary if the patient is unresponsive to other treatments.
Pharmacological Treatment of Crohns Disease with Prednisone, Immunosuppressants and Infliximab (Remicade)
Prednisone: Dosage: 20-30mg BID , tapered down by 5-10 mg/week as symptoms subside. ADRs: Hyperglycemia, skin atrophy, mood swings, insomnia, edema, osteoporosis Azathioprine (Imuran): Dosage (unlabeled use): 50 mg daily; may increase by 25 mg/day every 1-2 weeks as tolerated to target dose of 2-3 mg/kg/day; reduced dose for renal insufficiency. ADRs: blood dyscrasias, liver abnormalities, nausea/vomiting/diarrhea, neurological disturbances, emotional and metabolic disturbances. Black Box Warning: Chronic immunosuppression increases the risk of neoplasia and serious infections. Other agents: cyclosporine (Sandimmune), budesonide (Entocort EC), mercaptopurine(Purinethol)
Infliximab (Remicade): Mechanism of Action: blocks intestinal inflammation by binding to and neutralizing tumor necrosis factor alpha (TNF-alpha) and TNF-alpha-producing cells Dosage: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter. If no response by week 14, consider discontinuing therapy.
Pharmacological Treatment of Crohns Disease with Prednisone, Immunosuppressants and Infliximab (Remicade)
ADRs/ Black Box Warnings: Infections: Serious and potentially fatal infections (including sepsis, pneumonia, and invasive fungal and other opportunist infections) have been reported in patients receiving TNF-blocking agents. T-cell lymphoma has been reported (rarely) in adolescent and young adults with Crohns disease treated with infliximab and azathioprine or 6-mercaptopurine. Reactivation of latent infections have been associated with infliximab therapy. Blood dyscrasias, liver toxicities, anaphylactic reactions
Azathioprine has been found to be beneficial in the treatment of Crohns disease through its steroid sparing and antiinflammatory activity. Other immunosuppressants such as cyclosporine and budenoside may also be considered for treatment of more severe cases of Crohns disease; however, the patient must be carefully monitored for neurological and metabolic side effects. In patients with treatment-resistant disease, a newer drug, infliximab, was shown to relieve symptoms in fifty to eighty-nine percent of patients. Patients showed signs of relapse eight to twelve weeks after a single infusion but responded to additional infusions of the drug. Infliximab is believed to block intestinal inflammation by binding to and neutralizing TNF-alpha on the cell membrane and in serum and by destroying the TNF-alpha-producing cells. Many of these immunomodulating medications can cause blood dyscrasias and hepatotoxiciy,, so appropriate monitoring should be maintained.
Like Crohns disease, treatment for ulcerative colitis depends on the seriousness of the disease. Dietary interventions include the avoidance of irritating foods and medications. Pharmacotherapy typically involves the initial use of aminosalicylates such as sulfasalazine or the newest approved drug, balsalazide . Balsalazide is a non-sulfa prodrug and has been shown to be better tolerated than sulfasalzine for patients with mild to moderate disease.
By the end of this Review Concept you should be able to: Define and list the most common hepatobiliary disorders seen in the elderly. Describe clinical presentation and progression ofliver cirrhosis. Describe diagnostic indicators and treatment options used to diagnose and manage elderly patients with cirrhosis. Describe the clinical presentation and progression of biliary obstructions and gallbladder disease. Describe diagnostic indicators and treatment options used to diagnose and manage elderly patients with biliary obstruction or gallbladder disease. Describe clinical presentation and progression of pancreatitis. Describe diagnostic indicators and treatment options used to diagnose and manage elderly patients with pancreatitis.
In the geriatric population, hepatobiliary disorders are commonplace. For those between the ages of fifty-five and seventy-four, cirrhosis is the fifth leading cause of death in men and the sixth leading cause in women. The most common surgery in the elderly is cholecystectomy, performed at least a half a million times annually in the United States alone. Slow to develop, hepatobiliary disease is often undetected until symptoms begin making their appearance in late adulthood. Because of the built-in redundancy and capacity of the liver, liver function tests often remain normal until a threshold of damage is reached. This damage results in major disorders such as cirrhosis, biliary obstructions and cholecystitis. Medication-induced injury to the liver and other tissues are a major etiological factor in these disorders, as well as bacterial or viral exposure, alcohol abuse and dietary intake.
Copyright 2011 American Society of Consultant Pharmacists
Cirrhosis of the liver is a chronic disease leading to liver tissue damage, reduced function, scarring, and portal hypertension. The disorder is seen frequently in the geriatric population, most often associated with the long-term abuse of alcohol and drugs. However, there are numerous causes for liver cirrhosis; the type of cirrhosis depends on the underlying causes of the liver damage. The most common causes are listed above.
Hepatotoxic Medications
Decreased hepatic volume and decreased blood flow with increased age may predispose the elderly to more frequent drug-related liver problems. Medications may cause damage to the liver in different ways: Damaging the liver cells directly (hepatotoxicity) Causing cholestasis, or impairment /lack of bile flow) Through a combination of both hepatoxicity and cholestasis. Through immume-mediated hypersensitivity. Commonly Used Hepatotoxic Drugs: Acetaminophen ACE inhibitors Allopurinol Amoxicillin and clavulanic acid Amiodarone Anesthetic agents Androgenic steroids Azathioprine Carbamazepine Dantrolene Erythromycin Estrogens and oral contraceptives Isoniazid Ketoconazole Methyldopa Nevirapine Nitrofurantoin NSAIDs Oral hypoglycemic agents Penicillins Phenothiazines Phenytoin Prochlorperazine Propylthiouracil Sulfonamides Tamoxifen Tricyclic antidepressants Valproic Acid
Commonly used medications can potentially have toxic effects on liver function, leading to injury and liver disease. Many of these medications are listed on your screen. Careful dosing and monitoring should be implemented when these drugs are used in the elderly.
Copyright 2011 American Society of Consultant Pharmacists
Typical symptoms of cirrhosis include weight loss, nausea, vomiting, and weakness. Ascites, edema, and abdominal pain are also common. If left untreated, cirrhosis of the liver can lead to vitamin deficiencies, bleeding disorders, encephalopathy, liver failure and death. Prognosis is poor in advanced cirrhosis, with a fifty-percent survival rate after two years. Survival in alcohol related cirrhosis depends on severity of the disease prior to stopping the use of alcohol.
Cirrhotic damage may not be detected until routine tests of liver enzymes show elevated values. Diagnostic examination and X-rays may reveal an enlarged liver, with additional test results showing anemia, abnormal coagulation, low serum albumin, and elevated immunoglobulins. Other blood, urine and body fluid tests can refine the diagnosis and rule out other conditions. After long standing disease the LFTs may be low or normal. This is a bad prognostic sign.
Treatment of cirrhosis is aimed at inhibiting its progress, minimizing damage to liver cells, and reducing complications. For many drug-induced cases, removing the offensive agent will allow for healing and a return of full liver functioning. Treatment plans for chronic cirrhosis focus on the prevention of fluid imbalances, encephalopathy, and coma. They involve vitamin therapy, sodium-restricted-low protein diet and rest. Patients must be watched for spontaneous peritonitis, which can occur with ascites.
Bleeding disorders (e.g., coagulopathy, esophageal varices): Vitamin K supplementation Beta-blocker or isosorbide mononitrate to reduce portal hypertension and risk for esophageal varices Fluid accumulation/Ascites: Diet modifications to improve nutrition Low sodium (<2000mg/day) Low protein (20 to 40 g/day) Fluid restriction Diuretic use (spironolactone 100-300 mg/day in divided doses to reduce ascites without decreasing potassium; hydrochlorothiazide or furosemide may be added) Antibiotic use for prevention or treatment of bacterial peritonitis Encephalopathy: Lactulose 30-45ml PO TID to QID (enough to produce 2 or 3 loose stools per day Neomycin 4-12g PO per day in divided doses
Surgical Interventions: Liver resection Transjugular intrahepatic portalsystemic shunt (TIPS) to relieve esophageal varices due to portal hypertension
Patients with acute disease and serious complications require pharmacotherapy, surgery and/or blood transfusions. For example, oral neomycin is often given in divided doses to reduce bacterial toxins, while thirty to forty-five grams of lactulose helps reduce serum ammonia buildup.Beta blockers may be prescribed to reduce portal hypertension and the risk of varices. Potassium-sparing diuretics such as spironolactone can be used to reduce ascites and edema without decreasing potassium. For viral cases, interferon therapy can be used to prevent further disease progression. Although sometimes used to treat acute alcohol-induced liver damage, corticosteroids such as prednisone and methylprednisolone are generally avoided in the elderly due to their side effects.
Obstruction of the ducts leading to and from the gallbladder is usually caused by gallstones. Tumors, cysts, and enlarged nodes in the porta hepatis may also play a role. While these kinds of obstructions can usually be resolved, delays in treatment can lead to complications such as liver disease, cirrhosis and cancer, which are often difficult to treat.
Symptoms of choledocholithiasis include jaundice, dark urine, pale stools, constant itching and upper right quadrant abdominal pain. Test results may show elevated bilirubin fractions, liver enzymes, alkaline phosphatase and isoenzymes, and urine bilirubin. Tests such as endoscopic retrograde cholangiopancreatography, ultrasound, and percutaneous transhepatic cholangiograms can be used to confirm diagnosis.
Treatment of Choledocholithiasis
Endoscopic sphincterotomy Extracorporeal shock wave lithotripsy Direct laser lithotripsy Electrohydraulic lithotripsy
For the elderly with choledocholithiasis or stones in the bile duct, endoscopic sphincterotomy can avoid major surgery and is successful at least seventy-four percent of the time. Although the procedures take some time, older patients can also use extracorporeal shock wave lithotripsy and direct laser or electrohydraulic lithotripsy. Once the obstruction is cleared, underlying causes such as gallbladder disease must be addressed.
Cholelithiasis
Pathogenesis: Gallstones containing cholesterol, calcium, bile salts and protein in varying amounts impair gallbladder function and produce obstructions in ducts. The chance of having gallstones increases with age; 10-15% of men and 25% - 30% of women will eventually develop gallstones. Risk Factors Associated with Formation of Gallstones: Diabetes mellitus Female gender Cystic fibrosis High fat, low fiber diet Obesity Prolonged fasting Total parenteral nutrition Rapid voluntary weight loss Oral contraceptive use Hyperlipidemia
Signs and Symptoms: Severe right upper or upper middle abdominal pain following meals and taking deep breaths Nausea Vomiting Heartburn, chills and shaking
Cholelithiasis
Diagnostic Methods: Ultrasound (effective in 93% of cases) Oral cholecystography (effective in 65% of cases) CT scan showing stones or common bile duct dilatation (present in 75% of patients, but not a definitive diagnosis) Laboratory abnormalities- In patients with simple acute cholelithiasis there may not be marked laboratory abnormalities. However, if an infection ensues (cholangitis), pain, fever, and lab abnormalities will be present in a majority of cases. Other radiographic techniques
Cholelithiasis or the presence of gallstones is the source of most gallbladder disease in the elderly. While many patients are initially asymptomatic, the onset of symptoms can be quite severe, especially after a meal containing fatty foods. These symptoms include nausea, vomiting, heartburn, chills and shaking. Abdominal ultrasound is successful in detecting gallstones ninety-three percent of the time while oral cholecystograms will detect them sixty-five percent of the time.
Treatment of Cholelithiasis
Surgical: Cholecystectomy remains the most consistently effective treatment Pharmacological: Oral bile acid acids may be used to dissolve gallstones but have limited effectiveness; agents include: ursodiol (Actigall): 8-10 mg/kg; headache, dizziness, and constipation possible.
Elderly patients with stones but no symptoms are usually not treated. Non-surgical treatment of symptomatic cholelithiasis includes dissolution with the oral bile acid solutions ursodiol. Unfortunately, this therapy is not typically used since it is time-consuming and successful in only twenty-nine percent of cases after one year. Instead, cholecystectomy remains the medical standard for dealing with the problem.
Cholecystitis
Definition: An infection of the gallbladder initiated by an obstruction of the cystic duct Primary Cause: Calculi in the cystic duct Signs and Symptoms: Abdominal tenderness and pressure Disorientation Toxic appearance Low-grade temperature Leukocytosis Complications: Empyema, perforation, gangrene (40%) Subphrenic, subhepatic or liver abscesses (15%)
Cholecystitis develops after calculi or inflammation blocks the cystic duct, resulting in infection. The cause of the blockage is usually calculi in the cystic duct itself, producing a lack of drainage and resulting pressure. The presentation of cholecystitis may be subtle in elderly patients; abdominal tenderness and pressure present in only half of the patients. Disorientation and a toxic appearance may be accompanied by a low-grade fever despite acute underlying infection. About forty percent of acute cases show empyema, perforation or evidence of gangrene, and fifteen percent have subphrenic, subhepatic or liver abscesses.
Pancreatitis
Definition: An infection, inflammation or irritation of the pancreas Incidence: More common in elderly men Causes: Gallstones Alcohol abuse Viral infections Surgery or trauma ( i.e. steering wheel injury) Medications Acetaminophen Azathioprine Corticosteroids Didanosine Estrogens Furosemide Metronidazole Pentamidine Salicylates Sulfonamides Tamoxifen Tetracycline Thiazide diuretics Valproic acid
Copyright 2011 American Society of Consultant Pharmacists
Pancreatitis is an infection, inflammation or irritation of the pancreas which presents as either a chronic or acute disease, or as a pancreatic abscess. The disease is commonly seen in the elderly, especially elderly men. The most common causes of pancreatitis in the elderly are gallstones, alcohol abuse, , surgery and medications. Several medications implicated in the acute pancreatitis can be found above.
Chronic Pancreatitis: Pancrelipase (pancreatin, pancrelipase): doses are individualized, but typically given before each meal/snack. H2 receptor antagonists (e.g., cimetidine, famotidine): to increase gastric pH and improve absorption of pancreatic enzymes Vitamin supplements: to correct for vitamin malabsorption secondary to pancreatic insufficiency
Although no specific pharmacological agents have been shown to affect the course of severe pancreatitis, some agents may provide supportive therapy. The use of antibiotics such as imipenem, for example, may be helpful in reducing the pancreatic sepsis that often results from necrotizing pancreatitis and pancreatic abscesses. Patients with chronic pancreatitis who do not respond to low fat diets may be given oral pancreatic enzyme supplements at mealtime to correct for malabsorption. PPIs, which increase gastric pH and improve the absorption of pancreatic enzymes, may be used with these patients to improve absorption of fat nutrients. Vitamin B-12 supplementation and fat soluble vitamins may be needed to correct for malabsorption due to pancreatic insufficiency.
Resources
For additional information, see: 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. Drug Information for the Health Care Professional. (1992). USP DI, 12th ed., Rockville, MD: The US Pharmacopeial Convention 1992. Duthie B. (1998). Practice of Geriatrics, 3rd ed. Chapter 46:Gastrointestinal disorders. W.B . Saunders Company. Gilliam, J. .H. (1994). Hepatobiliary disorders In Hazzard, W. R., Bierman, E.L., Blass, J. P., Ettinger, W. H. & Halter, J. B. (Eds.). Geriatric Medicine and Gerontology, 3rd ed.New York:McGraw-Hill: 707-15. Heidelbauch J.J. & Sherbondy MA. (2006) Cirrhosis and Chronic Liver Failure: Part II. Complications and Treatment. Am Fam Phys.75(5): 767-776.
Kaplan, A., et.al. (1995). The Liver and Tests of Hepatic Function.In Harris, J. M., et.al. (Eds). Clinical Chemistry Interpretation and Techniques, 4th ed:31 3-45. Lewis, J. H.(1994). A pharmacologic approach to gastrointestinal disorders. Baltimore:Williams & Wilkins. Lichtblau, L.(1998). Factors that modify drug effects and drug interactions, lecture from ISAP, online, http:// www.university.com/ISAP, update 9/11/98. Nathwanti, RA (2006). Drug Hepatotoxicity. Clin Liver Dis 10:207-217.
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Resources
Rybacki, J. J., Long J. W. (1997). Guidelines for the use of drugs by the elderly. In The Essential Guide to Prescription Drugs, 1997 ed. 16-18. Sherman S. & Lehman G. Opioids and the sphincter of Oddi.(1994) Gastrointest Endosc 40:1056. Warren, K. W. et. al.(1987). Diseases of the gallbladder and bile ducts, in Schiff, L., Schiff, E. R. (Eds.). Diseases of the Liver, 6th ed. Philadelphia: Lippincott, p.1289.
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