Prescribing and Pharmacokinetic Considerations in the Elderly

Size: px

Start display at page:

Download "Prescribing and Pharmacokinetic Considerations in the Elderly"

Loraine Morris
5 years ago
Views:

1 Prescribing and Pharmacokinetic Considerations in the Elderly Melanie A. Dodd, Pharm.D., Ph.C., BCPS Associate Professor of Pharmacy in Geriatrics College of Pharmacy The University of New Mexico

2 OBJECTIVES At the conclusion of the lecture the student shall be able to: Describe the effects of aging on pharmacokinetic parameters (absorption, distribution, metabolism, and elimination) Describe the effects of aging on pharmacodynamic parameters Discuss basic principles of prescribing for older patients to avoid adverse drug effects Identify potentially inappropriate medications in a given elderly patient based on the Beers criteria Slide 2

3 Why are geriatric pharmacokinetics important? Persons aged 65 and older are prescribed the highest proportion of medications in relation to their percentage of the U.S. population Now, 13% of total population buy 33% of all prescription drugs By 2040, 25% of total population will buy 50% of all prescription drugs Slide 3

4 Why are geriatric pharmacokinetics important? Increased risk of adverse drug reactions Multiple medications >20% of elderly use 5 or more medications Increased frequency of drug-drug interactions Decreased medication adherence Multiple comorbidities Age-related changes in drug pharmacokinetics Age-related changes in drug pharmacodynamics Slide 4

5 The Burden of Injuries from Medications ADEs are responsible for 5% to 28% of acute geriatric hospital admissions ADEs occur in 35% of community-dwelling elderly persons ADEs incidence: 26/1000 hospital beds In nursing homes, $1.33 spent on ADEs for every $1.00 spent on medications Slide 5

6 RISK FACTORS FOR ADEs 6 or more concurrent chronic conditions 12 or more doses of drugs / day 9 or more medications Prior adverse drug reaction Low body weight or body mass index Age 85 or older Estimated CrCl < 50 ml / min Slide 6

7 ADE PRESCRIBING CASCADE DRUG 1 Adverse drug effectmisinterpreted as a new medical condition - DRUG 2 Adverse drug effectmisinterpreted as a new medical condition Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315(7115):1097. Slide 7

8 Principles of prescribing for older patients: The Basics Start with a low dose Titrate upward slowly, as tolerated by the patient Avoid starting 2 drugs at the same time Slide 8

9 Before Starting a New Medication, Ask: Is this medication necessary? What are the therapeutic end points? Do the benefits outweigh the risks? Is it used to treat effects of another drug? Could 1 drug be used to treat 2 conditions? Could it interact with diseases, other drugs? Does patient know what it s for, how to take it, and what ADEs to look for? Slide 9

10 PHARMACOKINETICS Absorption Distribution Metabolism Elimination Slide 10

11 Aging and Absorption Clinical significance is not well characterized Most drugs absorbed through passive diffusion in the proximal small bowel Exception: levodopa Threefold increase in bioavailability due to reduced activity dopa-decarboxylase in the stomach wall Slide 11

12 Absorption Alterations in GI function Decreased gastric parietal cell function Decrease in secretion of hydrochloric acid Increase in gastric ph Ex: tetracycline, Fe, ketoconazole Decreased rate of gastric emptying Ex: anticholinergics, opiates, Fe, anticonvulsants Drug-drug interactions Divalent cations (calcium, magnesium, iron) and fluoroquinolones (e.g., ciprofloxacin) Slide 12

13 Absorption Topical absorption (patches, creams, ointments, etc.) Thinning and reduction of absorptive surface Skin atrophy and decreased fat content» Reduction in vascular network and risk of contact dermatitis Slide 13

14 Effects of aging on volume of distribution (Vd) Depends mostly on physiochemical properties of individual medications t ½ = (0.693 x Vd)/Cl Slide 14

15 Distribution body water (10-15%) lower Vd for hydrophilic drugs Ex: warfarin, digoxin, lithium, cimetidine, APAP, ETOH lean body mass lower Vd for drugs that bind to muscle fat stores higher Vd for lipophilic drugs Ex: diazepam, lidocaine, TCAs, propranolol Slide 15

16 Distribution Protein Binding Decreased serum albumin 10 to 20% in hospitalized or poorly nourished pt. Increase in unbound fraction of highly protein bound acidic drugs Monitor drug levels free phenytoin level with low albumin Ex: warfarin, phenytoin, naproxen Increased α-1 acid glycoprotein Decrease in unbound fraction of highly protein bound basic drugs Ex: lidocaine, propranolol, imipramine Slide 16

17 Aging and Metabolism The liver is the most common site of drug metabolism Metabolic clearance of a drug by the liver may be reduced because Decrease in liver blood flow 40 to 45% with aging, related to cardiac function Increase in bioavailability Decreased 1 st pass effect = more parent drug Reduce initial dose, then titrate Decrease in liver size 20 to 50% decrease in absolute weight up to age 80 Reduction of total amount of metabolizing enzymes Leads to decrease in Cl and increase in t ½ Start with lower dosage Caution with toxic metabolites Ex: meperidine and propoxyphene Slide 17

18 Other Factors that Affect Drug Metabolism Gender Hepatic congestion from heart failure Smoking Slide 18

19 Elimination Most drugs exit body via kidney Reduced elimination drug accumulation and toxicity Aging and common geriatric disorders can impair kidney function Slide 19

20 The Effects of Aging on the Kidney kidney size renal blood flow ~1%/year after age 50 number of functioning nephrons renal tubular secretion Result: Lower glomerular filtration rate ~35% in healthy individuals between ages 20 and 90 Accumulation increased risk of toxicity» Ex: lithium, aminoglycosides, captopril, NSAIDs Slide 20

21 Serum Creatinine does NOT reflect Creatinine Clearance lean body mass lower creatinine production and glomerular filtration rate (GFR) Result: In older persons, serum creatinine stays in normal range, masking change in creatinine clearance (CrCl) Slide 21

22 How to Calculate Creatinine Clearance Measure: Time-consuming to be accurate Requires 24-h urine collection 8-h collection may be accurate but not widely accepted Estimate: Cockroft and Gault equation MDRD Slide 22

23 Cockroft and Gault Equation (Ideal weight in kg) (140 - age) x (0.85 if female) (72) (serum creatinine in mg/dl) Slide 23

24 Pharmacodynamics Definition Time course and intensity of pharmacologic effect of a drug Impairment varies considerably from person to person All organ systems are affected Kidneys, liver, GI, CNS, CV, GU Slide 24

25 Altered Pharmacodynamic Mechanisms Change in receptor numbers Change in receptor affinity Postreceptor alterations Age-related impairment of homeostatic mechanisms Slide 25

26 CNS Changes are significant, yet idiosyncratic Decrease in weight and volume of brain Alterations in cognition Increased sensitivity to medications Ex: benzodiazepines, opioids, anticholinergics, NSAIDs Slide 26

27 CNS Cholinergic blockade results in Sedation, confusion, and reduced ability to recall Ex: TCAs, diphenhydramine, antispasmodics, antipsychotics Benzodiazepines can cause severe CNS depression Leads to falls and hip fractures Use caution and small dosages Slide 27

28 Cardiovascular Decreased baroreceptor responsiveness Results in orthostatic hypotension Ex: Antihypertensives use caution and counseling Slide 28

29 GU Urinary incontinence 15 to 30% of community-dwellers 50% of nursing home residents Enlarged prostate, urine retention Ex: anticholinergics Slide 29

30 Inappropriate Medication Use in Older Adults (Beers Criteria update) Fick DM, et al. Arch Intern Med 2003;163: medications or classes to avoid in older adults 20 diseases/conditions and medications to avoid in older adults with these diseases Medications to be used with caution in the elderly: a statewide clinical recommendation on potentially inappropriate medications guideline.php

31 Inappropriate Drug Therapy based on Beers Criteria Authors Setting Prevalence of Inappropriate Prescribing Goulding MR 2004 Zhan et al Simon SR, et al Ambulatory care visits Community dwelling elderly Elderly in managed care Golden et al Nursing homeeligible NM Medicare Advantage plans 2009 New Mexico Medicare patients 7.8% of visits 21.3% of patients 28.8% of patients 39.7% of patients 21.5% of patients Slide 31

32 Beers Criteria: Independent of Diagnosis Analgesics Meperidine (long t 1/2 metabolite, CNS) Non-steroidal anti-inflammatory drugs Indomethacin (CNS) Ketorolac-immediate and long-term use (GI bleeds)* Non-COX selective NSAIDs, longer t 1/2 -long-term use (GI bleeds, renal failure)* Propoxyphene Pentazocine (CNS) Slide 32

33 Beers Criteria: Independent of Diagnosis Psychiatric Antidepressants Amitriptyline/doxepin (anticholinergic) Daily fluoxetine (CNS)* Anxiolytics Long-acting benzodiazepines-chlordiazepoxide, flurazepam (sedation/fractures) Doses of short-acting benzodiazepines Meprobamate (addiction/sedation) Antipsychotics Thioridazine (CNS/EPS)* Mesoridazine (CNS/EPS)* Slide 33

34 Beers Criteria: Independent of Diagnosis Cardiovascular Ticlopidine (no better than aspirin) Disopyramide (negative inotrope/anticholinergic) Amiodarone (QT interval/torsades de pointes)* Methyldopa (bradycardia/depression) Clonidine (CNS/orthostatic hypotension)* Doxazosin (hypotension/dry mouth)* Short-acting nifedipine (hypotension/constipation)* Ethacrynic acid (HTN, fluid imbalances)* Slide 34

35 Beers Criteria: Independent of Diagnosis Antihistamines (anticholinergic) Diphenhydramine (confusion/sedation) Chlorpheniramine Promethazine Hydroxyzine Stimulant laxatives, long term use: e.g., bisacodyl (bowel dysfunction) Cimetidine (CNS, confusion)* Chlorpropamide (hypoglycemia/siadh) Slide 35

36 Beers Criteria Considering Diagnosis Heart failure-disopyramide (negative inotropic effect) Gastric or duodenal ulcers-nsaids and aspirin >325 mg (exacerbate existing ulcers or produce new ulcers) Epilepsy-clozapine, chlorpromazine (may lower seizure threshold) Insomnia-decongestants, theophylline, methylphenidate (CNS stimulants) Slide 36

37 Beers Criteria Considering Diagnosis Depression-long-term benzodiazepines (exacerbate depression)* Syncope or falls-tcas and short to intermed acting benzodiazepines (may produce syncope/additional falls)* Chronic constipation-ccbs, anticholinergics, TCAs Slide 37

38 Alternatives to Beers criteria Stefanacci RG, Cavallaro E, Beers MH, Fick DM. Developing explicit positive beers criteria for preferred central nervous system medications in older adults. Consult Pharm Aug;24(8): Slide 38

39 STOPP and START Criteria Screening Tool of Older Persons Prescriptions (STOPP) Screening Tool to Alert doctors to Right Treatment (START) Gallagher P, Ryan C, Byrne S, Kennedy J, O Mahony D. STOPP and START. Consensus validation. Int J Clin Pharmacol Ther 2008;46: Slide 39

40 Conclusions Age alters pharmacokinetics (drug absorption, distribution, metabolism, and elimination) Age alters pharmacodynamics ADEs are common among older patients Successful drug therapy means: Choosing the correct dosage of the correct drug for the condition and individual patient Monitoring the therapy Slide 40

41 References/Additional Reading Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2: Fick DM, et al. Arch Intern Med 2003;163: (Beers criteria) Gallagher P, et al. STOPP and START. Consensus validation. Int J Clin Pharmacol Ther 2008;46: Golden AG, et al. J Am Geriatr Soc 1999;47(8): Goulding MR. Arch Intern Med (3): Levy HB, et al. Ann Pharmacother 2010;44:xxxx. Simon SR, et al. J Am Geriatr Soc 2005;53(2): Stefanacci RG, et al. Consult Pharm. 2009;24(8): Zhan C, et al. JAMA 2001;286(22): Slide 41

America s other drug problem: How to avoid medication-related problems in older adults

America s other drug problem: How to avoid medication-related problems in older adults Melanie A. Dodd, Pharm.D., Ph.C., BCPS Associate Professor of Pharmacy in Geriatrics Vice-Chair, Department of Pharmacy