Pharmacogerontology

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Pharmacogerontology

  1. 1. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Clinical Pharmacological Issues in the Elderly Dr.E.Koochaki Assistant professor of Kashan University of Medical sciences Evaluation for Possible Polypharmacy In the study of Lesar et al. (1997),the average of drugs per patient in 85 yr. olds and older; were 5-8 drugs per patient. Association exists between increased number and severity of illnesses and increased number of adverse drug reactions 1
  2. 2. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS In the other study (Risk Factors for Adverse Drug Events in the Older Outpatients,2004) Increased risk was for women and those >80 years and increased risk for anticoagulants, antidepressants, antibiotics, cardiovascular, diuretics, hormones and corticosteroids Factors Related to Adverse Drug Drug Reactions are: Chronicity and Multiplicity of Disease Increased Disease-Drug Interactions Increased Drug-Drug Interactions Lanoxin and Quinidine Theophylline and Erythromycin Visiting Multiple Prescribers Visiting Multiple Pharmacies Ref: Schwartz JB. Clinical Pharmacology. In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 326. 2
  3. 3. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Factors Related to Increased Number of Adverse Drug Reactions, Cont’d Multiple Diseases ASHD CHF COPD Diabetes Mellitus PVD Osteoporosis CRF DJD Chronic liver disease Others Dementia Normal Changes of Aging are: Increased Fat Decreased Bone Decreased Muscle Decreased Water Content Ref: Cefalu CA. Clinical Pharamcology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 90. 3
  4. 4. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS and normal physiological changes of the organ Systems in elderly persons are: Liver: decreased blood flow; Decreased Phase I Metabolism Kidney: decreased creatinine clearance with advanced age CNS:increased risk of confusional states primarily secondary to anti-cholinergic agents Intestinal tract: malabsorption-- not clinically significant in absence of disease Normal Changes of Aging-Hepatic Phase I Metabolism-rate of metabolism slows (oxidation, reduction, hydroxylation) Phase II Metabolism-rate stays the same (conjugation or deactivation process-sulfonuralidation, methylation, acetylation) Examples-benzodiazepines Short acting-Phase II only-appropriate Long acting-Phase I and II-inappropriate, long half-lives Reference: Beers MH. Medication Use in the Elderly. In: Calkins, Ford & Katz, 1992, p. 40. 4
  5. 5. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Pharmaceutical Agents That Require Hepatic Metabolism NSAIDs; Aspirin Ca channel blockers Acetaminophen Alpha blockers Erythromycin Statins Ketoconazole Dilantin Tetracyclines Valproic acid Lidocaine Carbamazepine Metoprolol Tricyclic Antidepres SSRIs Neuroleptics Pharmaceutical Agents That Require Hepatic Metabolism Benzodiazepines Cimetidine Ranitidine Famotidine Terfenadine Proton pump inhibitors Schwartz JB. Clinical Pharmacology. In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 309-319. 5
  6. 6. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS And particular agents of concern in the elderly-highly bound to protein are Phenytoin Carbamazepine Barbiturates Warfarin In the elderly persons malnutrition or hypoproteinemia is associated with increased free fraction of drug and increased toxicity Ref: Physicians Desk Reference, Medical Economics-Thomson Healthcare,55th Edition, 2001, p. 2427. Normal Changes of Aging-Renal Age-related reduction in renal blood flow and creatinine clearance in the face of a normal BUN and serum creatinine: Implications- Adjust dose of renally excreted drugs with age according to the following formula 6
  7. 7. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Creatinine Clearance Calculation (140-age) x weight (kg) ____________________________ Cr Clearance= serum creatinine x 72 (serum cr adjusted to 1, multiplied x .85 for female) Ref: Ref: Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 92. Pharmaceutical Agents Primarily Eliminated In the Kidneys Requiring Dosage Adjustment Penicillins Procainamide Aminoglycosides Atenolol Fluroquinolones Clofibrate Lithium Ace Inhibitors Digoxin Metformin Fluconazole Bisphosphonates Thiazides Nizatidine Ref: Schwartz JB. Clinical Pharmacology. In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 309-319. 7
  8. 8. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Renal function is often overlooked when prescribing renally excreted drugs to older long-term care residents and emphasizes the need for consideration of creatinine clearance when prescribing such drugs in this population. Ref: Papaioannou A et al. Assessment of Adherence to renal dosing guidelines in long-term care facilities. J Am Ger Soc. 48(11), Nov. 2000, p. 1470-3. Aminoglycoside Dosing in the Elderly With Impaired Renal Function Once daily dosing of aminoglycosides associated with reduced risk of morbidity (ototoxicity and renal failure) in patients with reduced creatinine clearance (usually below 50 ml/minute). Also alleviates the need for expensive peak and trough testing. Ref: Cefalu CA & Agcaoli D. Preventing antibiotic misuse in older patients. Hospital Medicine, December 1998, p. 39-43. 8
  9. 9. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS “conclusion: We must be cautious in prescribing drugs in the elderly persons. For example we must Reduce by half the dose of the particular renally excreted agent with a creatinine clearance of 50 ml/minute or less. Physiological changes of the GI Tract Stomach- little change in gastric acidity with aging. In presence of dsyphagia and H2 blocker therapy, may increase risk of morbidity and mortality from pneumonia (bacteria more viable after aspiration due to reduced acidity) Decreased GI motility and blood flow-- increased frequency of constipation Ref: In: Hall KE, Wiley JW. Age-Associated Change in Gastrointestinal Function. In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 835-842. 9
  10. 10. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS CNS Changes with Aging Reduced numbers of receptors Subtle structural and physiological changes consistent with Alzheimer's and Vascular Dementia Increased susceptibility to drugs with anti-cholinergic properties resulting in: urinary retention; constipation; dry mouth; blurred vision; sedation; cognitive dysfunction Ref: Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 90. Anticholinergic Agents Phenothiazine major tranquilizers (promethazine, chlorpromazine, haloperidol) Tricyclic anti-depressants (imipramine, amitriptyline, nortriptyline, desipramine) Narcotics-demerol, codeine, morphine Anti-spasmotics-oxybutynin, diclomine, tolterodine, probanthine, atropine, hyoscyamine, probanthine, belladonna alkaloids 10
  11. 11. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Anti-cholinergic Agents-continued Anti-histamines Diphenhydramine Cyproheptadine OTC cold medications OTC sleep agents Trihexyphenidyl Benztropine Common Clinical Conditions Necessitate Adjustment of Dosage in the Elderly: Liver: cirrhosis, malnutrition, malignancy, hepatitis with resultant decreased albumin and total protein levels (ex: sodium warfarin and phenytoin Kidney: chronic renal insufficiency, renal failure Brain: dementia, delirium Intestinal tract: malabsorption syndrome Stomach: gastritis, malignancy 11
  12. 12. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Anorexia and Aging Reduced thirst and appetite with normal aging Reduced thirst and appetite is associated with depression and/or dementia Ref: Singh MAF & Rosenberg IH. Nutrition and Aging. IN: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 88. Anorexia-Drug Induced: Theophylline Macrodantin Pronestyl Digoxin Thyroxin SSRIs Ref: Thompson MP, Morris LK. Unexplained Weight Loss In the Ambulatory Elderly. J Am Geriatr Soc. 39, 1001, p. 497-500. 12
  13. 13. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Screening for potential toxicity of prescription drugs-H2 Blockers: Confusion at high doses- Creatinine clearance below 50/ml/min.= reduce dose, except famotidine (below 20 ml/min) Nonspecific use associated with inadequate healing of gastric and duodenal ulcerations and greater chance of recurrence Nonspecific use for prophylaxis when used with NSAIDs Only two specific indications for prophylaxis to prevent gastrointestinal bleeding in the ICU setting: respiratory failure or coagulopathy H2 Blockers-continued Very common to use these agents in nursing home without specific indications Ref: Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 93. 13
  14. 14. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS High Risk Drugs-Beta Blockers B-Blockers (propranolol)-side effects of: Precipitation of or exacerbation of CHF Masking of hypoglycemia Development of hypotension Masking of symptoms of endocrine disease (hypothyroidism) . Reduction in exercise capacity Exacerbation of chronic lung disease or bronchospasm Depression Memory loss Production of arthropathy Ref: Cahill et al: Beta-adrenergic activation and memory for emotional events, Nature, 371, P. 702-704. Newbern et al. Cautionary Tales on Using Beta Blockers. Geriatric Nursing. 12(3); 1991, p. 119-122. Beta Blockers-continued use selective ones: atenolol and metoprolol Less side-effect profile Better compliance-once or twice daily Use associated with reduced cardiovascular morbidity and mortality in high risk patients Ref: Mangano DT et al. Effect of atenolol on mortality and cardiovascular morbidity after non-cardiac surgery. N Engl J Med, 335, 1996, p. 1713-20. Australia/New Zealand Heart Failure Research Collaborative Group, 1997 14
  15. 15. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Antihypertensives that cause Postural Hypotension or Sedation: Alpha-methyl-dopa Clonidine Alpha-blocking agents: useful for combined hypertension and prostatic hyperplasia Reserpine Ismelin- same as reserpine Physicians Desk Reference, 2003 Diuretics Once daily dosing increases compliance Inexpensive First line agents effective in reducing risk of stroke and CV disease Doses above 50 mg ineffective in achieving blood pressure control Thiazides generally not effective in the presence of renal insufficiency May cause hypercalcemia Contribute to or cause incontinence Use not associated with adverse effects on lipids 15
  16. 16. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Diuretics-continued Use in older caucasian women associated with reduced risk of hip fracture Adverse reactions Dehydration; postural hypotension; K loss (especially during the summer and sweating) Consider discontinuing in elderly when possible, especially advanced, demented, or depressed elderly (reduced thirst and appetite drive) Diuretics-References Ref: SHEP (Systolic Hypertension in the Elderly) Cooperative Research Group, 1991 Heidrich et al. Diuretic drug use and the risk of hip fracture Ann Intern Med., 115, 1991, p. 1-6. Physicians Desk Reference, 2003 Gurwitz MM et al. The impact of thiazide diuretics on the initiation of lipid-reducing agents in older people: a population-based analysis. J Am Geriatr Soc., 45(1), Jan. 1997, p. 71-5. 16
  17. 17. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Major and Minor Tranquilizers* and Hypnotics: Worsen dementia and delirium Cause hip fractures and falls Cause postural hypotension Risk of tardive dyskinesia with phenothiazines *Especially long acting minor and sedating, highly anti- cholinergic major ones Ref: Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 100-101. Oral Hypoglycemics: Cause Hypoglycemia-- chlorpropamide glibenclamid 17
  18. 18. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS NSAIDs*: Can Worsen HBP- removal of NSAID can affect mean blood pressure control Fluid retention Worsen CHF Cause confusion GI bleeding Newer Cox-2 agents, gastric sparring Less risk of Alzheimer's and cognitive decline *In big doses or used chronically Ref: Carson JL & Strom BL. Use of Nonsteroidal Anti-Inflammatory Drugs. In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 1113-1119; Stewart WF et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology, 48, 1997, p. 626-632. “Tips” for Safe Traditional NSAID Use Substitute acetaminophen when possible around the clock instead of NSAID Use PRN when possible Use lowest dose possible Use for acute flare for 7-10 days then d/c When necessary for chronic use, insist on routine q 3 month BUN and CBC 18
  19. 19. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Narcotics: May cause cognitive dysfunction Have anti-cholinergic side effects urinary retention constipation dry mouth sedation Theophylline Adverse Reactions: Anorexia Nausea Arrhythmias Hypotension Drug-drug interactions:erythromycin, cimetidine, diazepam, phenytoin Useful for acute wheezing or asthma, not for COPD Ref: Physicians Desk Reference, 2003; Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA. Primary Care of the Older Adult. 2000, p. 112. 19
  20. 20. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Oxybutynin Anticholinergic- Sedation Cognitive dysfunction Dry mouth Blurred vision Constipation Urinary retention Ref: IR Katz et al. Identification of medications that cause cognitive impairment in older people: The case of oxybutynin chloride. J AM Geriatr Soc., 46, 1998, p. 8-13. Ophthalmologic Preparations Beta blocker preparations-can achieve significant systemic absorption leading to heart block, CHF, bronchospasm. Physicians Desk Reference, 2003 20
  21. 21. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS List Of Inappropriate Drugs In Elderly- Journal of American Medical Association-July 27, 1994; Archives of Internal Medicine-July 28, 1997 Inappropriate Drugs in Elderly: Diazepam Chlordiazepoxide- long acting Flurazepam- long acting Muscle relaxers- sedation, anticholinergic Vasodilators- ineffective, cause “Steal Syndrome” and postural hypotension Dipyridamole- ineffective Amitriptyline- sedation, anticholinergic Propranolol J of Am Med Assoc, July, 1994, Arch of Int Med, July, 97 21
  22. 22. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Inappropriate Drugs in Elderly-Cont,d Alpha-methyl dopa Depression Hemolytic anemia Drug-induced lupus Inappropriate Drugs in Elderly-Cont,d Reserpine Depression Impotence Sedation Orthostatic hypotension 22
  23. 23. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Inappropriate Drugs in Elderly- Cont,d Short-acting Benzodiazepines in excess of the following doses: Lorazepam- 3mg Oxazepam- 6mg Alprazolam- 2mg Temazepam- 15mg Zolpidem- 5mg Triazolam- .25mg Inappropriate Drugs in Elderly-Cont,d Anticholinergic Diclomine Hyoscyamine Probanthine Belladonna alkaloids 23
  24. 24. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Inappropriate Drugs in Elderly-Cont,d Chlorpropamide Indomethacin (neurotoxic)- confusion, bleeding Propoxyphene- sedation and no more effective than acetaminophen Trimethobenzamide- extra-pyramidal side- effects and least effective anti-emetic Inappropriate Drugs in Elderly-Cont,d Pentazocine- sedation, confusion, and hallucinations Meprobamate- addictive and sedating Lanoxin (if higher than .125mg)- reduced renal clearance with normal aging Disopyramide- negative inotropic effect, may cause CHF 24
  25. 25. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Inappropriate Drugs in Elderly-Cont,d Phenylbutazone- excess bleeding Doxepin- anticholinergic and sedating Ticlopidine- no more effective than aspirin Meperidine- addicting, short-acting associated with breakthrough, sedation, anticholinergic Barbiturates- sedation Inappropriate Drugs in Elderly-Cont,d Iron in doses greater than 325mg iron sulfate- constipation and no greater absorption at higher dose 25
  26. 26. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Screening for Toxicity of OTC Drugs Laxatives- chronic use associated with development of chronic megacolon, terminal reservoir syndrome, subsequent fecal impaction, and cancer Vitamins A, C and E- added toxicity with little added benefit Acetaminophen or aspirin- several different doctors, different brand names Screening for Toxicity-OTC Drugs-Cont. Especially diphenhydramine-containing OTC agents Sleep aides Cold Medications 26
  27. 27. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Rules for Prescribing to the Elderly Start with one-third to one-half the normal starting dose Use one drug to treat two clinical conditions PAT and HBP HBP and angina Rules, cont’d Maximize dose of one agent before adding second agent to treat same clinical condition (HBP) Less confusing for elderly Less expensive Less risk of adverse drug reactions Maximize compliance to no more than once or twice daily 27
  28. 28. Generated by Foxit PDF Creator © Foxit Software Concepts in Geriatric Pharmacology- http://www.foxitsoftware.com For evaluation only. 8/12/99 Charles A. Cefalu MD, MS Rules, cont’d Use cheapest drug possible Review medications patient brings in at each visit Discontinue unnecessary drugs and taper psychotropic drugs when possible Consider drug holidays 28

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