3c wednesday polypharmacy wallace

8/13/2019 3C Wednesday Polypharmacy Wallace

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Polypharmacy & Pitfalls inPrescribing for your Older Adults

Internal MedicineJuly 18, 2012

Jeff Wallace, MD, MPHProfessor of Medicine, Division of GeriatricsUniversity of Colorado School of Medicine

Polypharmacy & Pitfalls: Talk Objectives

Describe relevant pharmacokinetic &pharmacodynamic s that occur w/aging

Identify medications that frequently causeproblems in the elderly

Learn and apply approaches to reducepolypharmacy in older adults

Pharmacodynamics

Response that occurs when a druginteracts at its receptor

Pharmacodynamic Changes with Aging

Increased response Opiates Warfarin


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Pharmacodynamic Changes with Aging

Increased response Opiates Warfarin

Decreased response Beta-agonists

Pharmacokinetics

Drug concentration at the site of action

Pharmacokinetics

Drug concentration at the site of action

4 Determinants: Absorption Distribution Metabolism Elimination

Pharmacokinetic Changes with Aging

Absorption gastric pH gastric emptying splanchnic blood flow intestinal motility

Minimal clinical importance


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Pharmacokinetic Changes with Aging Elimination

renal mass, renal blood flow glomerular filtration rate (10 cc/decade)

Most clinically important concentration of drugs dependent on renal

clearance Serum creatinine alone does not provide

adequate information to guide dosing Use Cockcroft-Gault (CG) to estimate GFR in

older adults

CG vs MDRD ( Modification of Diet in Renal Dz)Verhave et al Lamb et al

Mean age (yrs) 71 80

Mean measuredGFR(ml/min/1.73m 2)

79.4 53.3

Subjectcharacteristics

Healthy no DM,CAD, CHF, CRI

Comorbidities andCRI

CG Underestimated GFR Underestimated GFR

MDRD Underestimated GFR Overestimated GFR

Talk Objectives




Hx : 83 yo F with DM (A1C 7.2% on glipizide) &HTN (well controlled w/HCTZ) presents withdysuria & frequency. Low grade fever, nochills, no n/v. NKDA.

Exam : T 100 0F BP 136/78 HR 88 Wt 55kg

Mild low abdominal discomfort to palpation, (-)CVAT, o/w unremarkable

Labs : U/A 10-30 WBC, nitrate (+), electrolytes nl,Bun/Cr 24/1.3

Prescribing in the Elderly: Drugs to avoid?


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Drug Prescribing in the Elderly

Which of the following is the least appropriatechoice for empiric tx of her UTI?

A. Cephalexin

B. Nitrofurantoin

C. TMP/SMX

D. Levafloxacin

The Beers List of PotentiallyInappropriate rx es in older adults First generation antihistamines (eg, diphenhydramine)GI antispasmodics (eg, hyoscyamine)Muscle relaxantsBenzodiazepinesNonbenzodiapine sleepers: avoid use > 90 daysTertiary TCAs (eg, amitriptyline, doxepin > 6mg)Chronic use non-COX selective NSAIDS (unless otherrxs not effective & pt can take gastroprotection rx)

Digoxin > 0.125mg

Central alpha agonists (eg, clonidine)J Am Geriatr Soc 2012:60:616-31

Three Meds I hate to see in older ptsMuscle relaxants

Sedating, anticholinergic, falls/fx , ?able efficacy

Iron more than once daily (or w/PPIs) Marginal gain BID/TID iron, adverse GI effects H+ absorption

Megestrol acetate (Megace) minimal effect on wt, takes months, thrombotic

events, possibly death

Beers Criteria for Potentially Inappropriate Medication Use inOlder Adults. J Am Geriatr Soc 2012:60:616-31

One of the first duties of the physician isto educate the masses not to take medicine - Sir William Osler


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When to Just Say No

NSAIDS - other than short-term use PPIs avoid chronic use Benzodiazepines Sedating antihistamines 1st generation tricyclics Iron > 325mg/d Muscle relaxants

A Case of Syncope A 79 yo M w/HTN, dementia, stage IV CKD,

restless legs & OA presents to ED s/p witnessedsyncopal event while seated shortly after eatingdinner. He denies CP or SOB.

Meds: amlodipine 5mg, hctz 25mg, donepezil 10mg,sinemet 25/100 qhs, tylenol & tramadol prn.

VS are 134/76, HR 52 supine, 128/72 & 54 standing.Exam is o/w unremarkable. EKG - sinusbradycardia, HR often in 40s on ED monitor.

Medication Issues

Assuming his syncope is med related, themost likely medication implicated is :

A. Donepezil

B. Amlodipine

C. Sinemet

D. Tramadol

E. HCTZ

Cholinesterase inhibitors and bradycardia ChE-I RR bradycardia 1.4 (95% CI, 1.1 1.6) Dose effect: donepezil > 10mg 2.1 risk

Clinical significance: ChE-I use associated with Syncope: HR 1.76 (95% CI, 1.57-1.98)

ED visits for bradycardia: HR 1.69 Pacemaker placement: HR 1.49 Hip Fx: HR 1.18 (95% CI, 1.03-1.34)

Was it in your bradycardia differential diagnosis?

Its the Drugs!: Include in every Diff Dx

J Am Geriatr Soc 2009;57:1997

Arch Intern Med 2009;169:867


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Elderly Bear Burden of Injuries from Rxs

American Geriatrics Society GRS6 Teaching Slides

ADEs are responsible for 5% - 28% of acutegeriatric hospital admissions

Can we identify common offending meds?

Emergency Hospitalizations for AdverseDrug Events (ADEs) in Older Americans

National electronic ADE surveillance 2007-09

Hospitalization rates after ED visits for ADEs

Pts age 65+ had 100,000 admits/yr

Four meds/classes causes 2/3 of the mayhem Warfarin 33% - oral antiplatelet drugs 13% insulins 14% - oral hypoglycemics 11%

high risk meds implicated in only 1% of admits

NEJM 2011;365:2002-12

Polypharmacy and the Elderly12% of the population aged 65+

30% of all prescription druguse among those aged 65+

50% of all OTC druguse is among pts 65+

Adverse Drug Reactions

106,000 deaths in 1994 (5 th leading cause death)

$177 billion in 2000

For every $1 spent on drugs, $1 spent on ADRs

7-fold increased risk in the elderly Changes in pharmacodynamics/kinetics Drug-disease and drug-drug interactions Related to Polypharmacy


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Exponential Relation BetweenPolypharmacy and ADRs

L Nolan, JAGS, 1988; 36: 142-9.

# of Drugs Taken

P e r c e n t o f

P a t

i e n t s

w i t h a n

A D R

Talk Objectives




Plus prescribing tips in the elderly

Reducing PolypharmacyAs long -term management of multiplecomorbid chronic diseases among anincreasingly older population becomes theface of modern medicine, disentanglingadverse drug events will become moreblurred by the growing epidemic ofpolypharmacy. This remains a challenge tobe appropriately addressed.

Editorial re: Dabigatran and bleeding concerns in elderlyArch Intern Med 2012;172:403

Optimizing Therapies and Care Plans

Recognize opportunities to stop meds

Review existing meds before starting new rx

Annual/semiannual medication review

Care transitions are key opportunities

Is pt managing current care plan

Is complexity impacting adherence & safety

Have pt preferences changed?


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Apply clinical practice guidelines with caution

Almost all existing guidelines have single dz focus

Application of CPGs to hypothetical 79yo ptw/COPD, DM, HTN, OP, OA

12 medications, complicated regimen $406 monthly cost

Studies rarely include frail elderly, mult comorbid dz

Risks (drug-drug, drug-dz interactions) likely are

Do CPGs address short & long term goals?

Pt preferences?JAMA 2005;294:716

Use of EBM to Optimize Care of the Elderly EBM to Optimize Care of the Elderly Apply clinical practice guidelines with cautionCHF Guidelines: based on excellent RCT data

Issue: Older Adults w/CHF often w/comorbid dz

Characteristics 2.5 million Medicare BeneficiariesHospitalized for Heart Failure, 2001-2005

mean age 80 years old, nearly 60% women 2/3 of pts w/chronic atherosclerosis 67% HTN 42% COPD 42% diabetes mellitus each of these w/CPGs 30% renal failure 14% dementia

Arch Intern Med 2008;168(22):2481-8

Evidence for the best care of frail older ptsw/multimorbidity is often lacking

" Absence of evidence i s not evidence of absence " --Carl Sagan, Astronomer (and Donald Rumsfeld)

EBM for the Frail Older AdultDoes the Emperor have any clothes? Reducing Polypharmacy

Tools to identify potentially inappropriate meds

Beers Criteria

STOPP/START

Good Palliative- Geriatric Practice Algorithm

J Am Geriatr Soc 2012:60:616-31

Arch Intern Med Oct 2010;170:1648

Int J Clin Pharmacol Ther 2008;46:72


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Reducing Polypharmacy in the Elderly

Polypharmacy & inappropriate meds common

Results in compliance, D.I.s, ADEs

RCTs: Rx reviews by PharmDs 1 rx

Good Palliative -Geriatric Practice algorithm

NH: 3 rx s hosp (30 v 12%), mort (45 v 21%)

Outpt: n 70, x age 83, x 8 meds by 4, 19 mo f/u- 2% failed rx d/c, resumed d/t sxms, no M&M


Good Palliative -Geriatric Practice Algorithm

Prescribing Tips in the Elderly

The Prescribing cascade

Avoiding drug-drug interactions

Be aware of non-adherence

Patient education MD Education: Know what your pt is taking

Avoid the Prescribing Cascade

Drug 1

Adverse effectmisinterpreted as new

medical condition

Drug 2

PA Rochon, BMJ, 1997; 315:1096-9 .


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Avoid the Prescribing Cascade

HCTZ Allopurinol

NSAIDs Antihypertensives

Metoclopramide Carbidopa/Levodopa

Cholinesterase inhibitors Tolterodine

Prudent Prescribing:Beware of Drug-Drug Interactions

100% chance of DDI with 8 drugs

Nearly 50% of community-dwelling geriatricpatients had at least one DDI

DDI can result in ADRs or suboptimal dosing

A key: Avoid Polypharmacy

Relation Between Polypharmacyand Compliance

# of Drugs Prescribed

% C o m p l

i a n c e

Improving Medication Compliance

Why arent pts more compliant? Compliance 50%, dramatically after 6 mo

Number of meds the key factor

Other potential factors lack of information/understanding

side-effects forgetfulness emotional factors costs

NEJM 2005;353:487


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Prudent Prescribing:Improving Medication Compliance

Explain why, what and when of any new rx MDs often fail in this regard

FP and IM docs observed for 243 new rxs never stated name of new med explicit directions, duration 50% of time

Write indication ON RX it will be on bottle! Lisinopril to improve heart function Metoprolol to help prevent heart attack


Methods to Improve Compliance # of drugs, prescribers and pharmacies Once or twice daily dosing Pill boxes, medication reminder charts Pay attention to costs - 13% elderly w/cost

related non-adherence (gen not inform MD) frequency of clinic visits


Do you know whats in yourpatients medicine cabinet? The Knowledge Factor

~20% of drugs found on home inventorywere not revealed by physician interview

Most frequently unreported class of drugs?


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The Knowledge Factor

20% of drugs found on home inventorywere not revealed by physician interview

Most frequently unreported class of drugs?

BENZODIAZEPINES!!!

How can we improve ourknowledge of patient drug use?

Is this medication necessary/non-pharm options?

What are the therapeutic end points?

Do the benefits outweigh the risks?

Is it used to treat effects of another drug?

Could it interact with diseases, other drugs? Consider compliance and cost challenges

Does patient know what its for, how to take it,and what ADEs to look for?

Before Prescribing New Med Consider:

AGS GRS6 Teaching Slides

3c wednesday polypharmacy wallace

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