Geriatric Pharmacotherapy SHC Lecture

Geriatric Pharmacotherapy: 

Geriatric Pharmacotherapy Staff Health Lecture By Mansoor Khan, BS,MS, BCOP Clinical Pharmacist, NGHA, Jeddah

Objectives: 

Objectives Understand key issues in geriatric pharmacotherapy Understand the effect of age on Pharmacokinetics & Pharmacodynamics Discuss risk factors for adverse drug events and ways to mitigate them Understand the principles of drug prescribing for older patients (START-STOPP Criteria)

The Aging Imperative: 

The Aging Imperative Persons aged 65y and older constitute 14% of the population and purchase 33% of all prescription medications By 2040, 25% of the population will purchase 50% of all prescription drugs 25% ER visits due to ADEs in elderly 50% of hospitalization due to ADEs are in the elderly

Challenges of Geriatric Pharmacotherapy: 

Challenges of Geriatric Pharmacotherapy Effects of aging physiology on drug therapy Multiple co-morbid states Polypharmacy Advanced understanding of drug-drug interactions Medication compliance New drugs available each year FDA approved and off-label indications are expanding Medication cost

Pharmacokinetics: ADME: 

Pharmacokinetics: ADME A bsorption D istribution M etabolism E xcretion

Aging Effects on Absorption: 

Aging Effects on Absorption Rate of absorption may be delayed Lower peak concentration Delayed time to peak concentration Overall amount absorbed (bioavailability) is unchanged For drugs with extensive first-pass metabolism, bioavailability may increase because less drug is extracted by the liver

Aging Effects on Distribution: Vd: 

Aging Effects on Distribution: Vd Aging Effect Vd Effect Examples  Body water  Vd for hydrophilic drugs Ethanol, lithium  Lean body mass  Vd for for drugs that bind to muscle Digoxin  Fat stores  Vd for lipophilic drugs Diazepam, trazodone  Plasma protein (albumin)  % of unbound or free drug (active) Diazepam, valproic acid, phenytoin, warfarin  Plasma protein ( 1 -acid glycoprotein)  % of unbound or free drug (active) Quinidine , propranolol , erythromycin, amitriptyline

Aging Effects on Hepatic Metabolism: 

Aging Effects on Hepatic Metabolism Metabolic clearance of drugs by the liver may be reduced due to: Decreased hepatic blood flow Decreased liver size and mass Examples : morphine, meperidine, metoprolol, propranolol, verapamil, amitryptyline, nortriptyline

Aging Effects on Excretion Estimating GFR in the Elderly: 

Aging Effects on Excretion Estimating GFR in the Elderly Creatinine clearance (CrCl) is used to estimate glomerular rate Serum creatinine alone not accurate in the elderly  lean body mass  lower creatinine production  glomerular filtration rate Serum creatinine stays in normal range, masking change in creatinine clearance

Example: Creatinine Clearance vs. Age in a 5’5”, 55 kg Woman: 

Example: Creatinine Clearance vs. Age in a 5’5”, 55 kg Woman 30 1.1 90 41 1.1 70 53 1.1 50 65 1.1 30 CrCl Scr Age

Estimation of Creatinine Clearance: 

Estimation of Creatinine Clearance Estimate Cockroft Gault equation (140-Age) x (IBW in kg) ------------------------------ x (0.85 for females) 72 x (Scr in mg/dL)

Measurement of creatinine clearance: 

Measurement of creatinine clearance Time consuming Requires 24 hr urine collection U Creat (mg/dL) x 24 h Urine Vol (ml) --------------------------------------------- S Creat (mg/dL) X 1440

Pharmacodynamics (PD): 

Pharmacodynamics (PD) Elderly have altered drug response or “Sensitivity” due to changes in receptor number or receptor affinity Examples of Age-related changes:  sensitivity to sedation and psychomotor impairment with benzodiazepines  level and duration of pain relief with narcotic agents  drowsiness and lateral sway with alcohol  sensitivity to anti-cholinergic agents  cardiac sensitivity to digoxin  HR response to beta-blockers

PK and PD Summary: 

PK and PD Summary PK and PD changes generally result in decreased clearance and increased sensitivity to medications in older adults Use of lower doses, longer intervals, slower titration are helpful in decreasing the risk of drug intolerance and toxicity Careful monitoring is necessary to ensure successful outcomes

Polypharmacy: 

Polypharmacy Either the concomitant use of multiple drugs or administration of more drugs than are indicated” How many prescription medications are too many? >4 or >6. Many elderly people receive 12 medications per day Can increase the risk of geriatric syndrome (falls, cognitive impairment etc)

“Hit list” of the medications to be avoided in the elderly?: 

“Hit list” of the medications to be avoided in the elderly? 1. Beers Criteria 2. Canadian Criteria 3. START-STOPP Criteria Opioid analgesics NSAIDs Anticholinergics Benzodiazepines Also : CVS, CNS, musculoskeletal agents

Example of Beers Criteria: 

Example of Beers Criteria Drug Concern Severity GIT Antispasmodics Highly anticholinergic and uncertain efficacy & should be avoided for long-term use High Anticholinergic & Antihistamine (Phenergan, Avil Benedril, hydroxyzine) All non-prescription and many prescription antihistamines have potent anticholinergic effects, sedative effetcs , cognitive impairment non- anticholinergic antihistamines are preferred High Barbiturates Highly addictive and more side effects than sedative and hypnotics High

START-STOPP Criteria: 

START-STOPP Criteria START = Screening Tool to Alert doctors to Right Treatment STOPP = Screening Tool of Older Person’s potentially inappropriate Prescriptions More comprehensive and gives therapeutic alternatives May work better than Beers to identify meds that result in negative outcome but there is no evidence that it reduces morbidity, mortality or cost.

Take Home Message: 

Take Home Message Age alters PK and PD Follow START-STOPP Criteria Start with a low dose and titrate slowly Consider risk vs. benefit Avoid prescribing to treat side effect of another drug Consider drug-drug and drug-disease interactions Use simplest regimen possible avoiding Polypharmacy Adjust doses for renal and hepatic impairment ADEs are common & preventable among the elderly

References: 

References Pharmacist’s Letter/ Prescriber’s Letter September 2011. STARTing and STOPPing medications in elderly. PL Detail-Document # 270906. September 2011. Hutchison & Sleeper. Fundamentals of Geriatric Pharmacotherapy an evidenced-based approach 2010; American Society of Health System Pharmacists. Pharmacotherapy 6 th Edition, A pathophysiologic approach. Copyright 2005, 2002 by The McGraw-Hill Companies, Inc. All rights reserved. A chapter on Geriatrics; 103-113. www.pharmaotherapyonline.com Donna M. Fick, PhD, RN; James W. Cooper, PhD, RPh; William E. Wade, PharmD, FASHP, FCCP; Jennifer L. Waller, PhD; J. Ross Maclean, MD; Mark H. Beers, MD. Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Results of a US Consensus Panel of Experts. Arch Intern Med. 2003;163:2716-2724 Spinewine A, Schmader KE, Barber N, Hughes C, Lapane K, Swine C, Hanlon JT. Appropriate prescribing in elderly people: How can it be measured and optimized? Lancet 2007;370:173-184. Essentials of Clinical Geriatrics, 4 th Edition. Kane, Ouslander, Abrass, Eds. McGraw-Hill.

Questions: 

Questions