Geriatric Pharmacology-When More is Not Better

Nathan R. Harmon, DO,CMD,CAQ- Geriatrics, Hospice and

Palliative Medicine

Disclosures

• No Financial Disclosures

Goals• Review elements unique to Geriatric Pharmacology• Define Polypharmacy• Discuss medications potentially to avoid

– Beers List – STOPP and START

• Discuss a methodology in approaching medication use in Geriatrics

• Review a case related to geriatric pharmacology

Factors Influencing Drug Effects in the Elderly

• Multiple Co-existing illnesses, medications may worsen other conditions– CHF (diuretics) CKD AKI

• Increased sensitivity to dosing/adverse effects• Pharmacologic changes with aging

Pharmacokinetics

• What the Body does to the drug• Absorption • Distribution• Metabolism• Excretion

Body Composition Changes with Aging

Age Group Body Wt (kg) Body Fat (kg) Muscle Mass (kg)

20-29 80 15 24

30-49 81 19 20

60-69 79 23 17

70-79 80 25 13

Volume of Distribution (Vd)• We lose muscle (water) as we age

– Water soluble medications (digoxin) are not stored, but enter bloodstream quicker

– Reach steady state faster; higher serum concentration for a given dose

• We gain adipose as we age– Lipid soluble medications (diazepam) are stored, less than

expected initial serum concentration, but leach out over greater time

• Protein (albumin) bound medications (phenytoin) higher serum concentration with malnourishment

Vd of Diazepam

Age

Volume of Distribution

Hepatic Metabolism

• Phase I – oxidative (cytochrome P450 family)– Declines with aging

• Medications take longer to be metabolized• More susceptible to multiple medications

competing for metabolism

Renal Function

• Due to decreased muscle mass, Cr alone is not a good predictor of renal function

• MDRD not validated in patients > 70• Renal dosing of medications should be done

using Cockroft-Gault

Half Life

• t ½ ~ Vd / Clearance• Aging

– Increased Vd (for lipophilic medications)– Decreased Clearance – Longer half-life

Pharmacodynamics

• What the Drug does to the body• In general, more sensitive to effects of

medications– Lower than normal doses may be therapeutic

The “Physics” of Geriatric Pharmacotherapy

• Therapeutic Inertia – drugs continued in the absence of clear benefit– “De-prescribing”

• Therapeutic Momentum – drugs added for questionable indications– Insomnia

• The Prescribing Cascade – Drugs added to treat side effects from other drugs

Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st Annual Review of Geriatric Medicine, 2015.

Prescribing Cascade

Metoclopramide (Reglan)

Extrapyramidal Effects

Levodopa treatment

Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st Annual Review of Geriatric Medicine, 2015.

Prescribing Cascade

Nifedipine for HTN

Increased Edema, Impaired bladder emptying, Constipation

Over active Bladder

Antimuscarinic Added

Laxative Added Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st Annual Review of Geriatric Medicine, 2015.

Prescribing Cascades

• NSAIDs HTN Anti-hypertensives• Thiazides Gout Gout therapy• Glucocorticoids Hypoglycemics • Cholinesterase inhibitors Anticholinergics

for urinary incontinence

I think you may be challenged by polypharmacy.

Polypharmacy Defined• Use of ‘multiple’ drugs• More than 5 (9) medications

– >50% Medicare beneficiaries have 3 or more chronic medical conditions

– 36-37% Community dwelling elders on 5 or more medications– 50% vitamin and/or dietary supplement– 40% NH patients on 9 or more medications

• Use of more drugs than are Medically Necessary– Not indicated, not effective, or therapeutic duplication– Used to treat complication of another drug of marginal benefit

• “Extreme polypharmacy” (20 or more)

Expert Opin Drug Saf. 2014 (Jan);13(1). (NIH Public Access)

Polypharmacy -- How did we get here?

• Great and important changes in medicine.– New tools which are quite powerful

• Cancer medications• Beta blockers and ace inhibitors• Control of metabolic disorders

– Lipids– Diabetes– osteoporosis

– Attempts to standardize our care• Guidelines

• Aging population– Multiple chronic illnesses– Living longer

• Increased specialization– Multiple prescribers.

Consequences of Polypharmacy

Consequences of Polypharmacy

•Observational Studies suggest it is a bad thing

•Associated with multiple co-morbidities and frailty

– Meds are of value– There is some under-prescribing– We do not have a robust science

“BAD” Drugs

• Beers List• STOPP/START Criteria

Beers Criteria: History and Utilization Original 1991 – Nursing home pts

PIMs – Potentially Inappropriate Medications QA/QI

Updates1997 All elderly; adopted by CMS in 1999 for nursing

home regulation2003 Era of generalization to Med D2012 Further adoption into quality measures2015 Updated recommendations with drugs to avoid

d/t renal function, and select drug-drug interactions

Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE

Quality High Evidence

• Consistent results from well-designed, well-conducted studies that directly assess effects on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent observational studies with no significant methodological flaws showing large effects)

Moderate Evidence • Sufficient to determine effects on health outcomes, but the number, quality, size, or

consistency of included studies, generalizability , indirect nature of the evidence on health outcomes

Low Evidence• Insufficient to assess effects on health outcomes because of limited number or power of

studies, large and unexplained inconsistency between higher-quality studies; important flaws in study design or conduct, gaps in the chain of evidence

• Or lack of information on important health outcomes

Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE

Strength of RecommendationStrongBenefits clearly > risks and burden OR risks and burden clearly >

benefits

WeakBenefits finely balanced with risks and burden

InsufficientInsufficient evidence to determine net benefits or risks

Beers List

• Only 40% of the categories of medications listed have High Quality evidence

• Alternatives to medications are not given• Medications may be appropriate in certain

clinical situations– Digoxin, Spironolactone for CHF

• Does give medications to avoid for certain clinical situations

STOPP/START Criteria • The STOPP (Screening Tool of Older Persons’ potentially

inappropriate Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment)

• STOPP might work better than Beers to identify meds that result in negative outcomes, such as hospital admission.

• But as with Beers criteria, there is no convincing evidence that using the START/STOPP criteria reduces morbidity, mortality, or cost.

• Use these lists to identify red flags that might require intervention, not as the final word on medication appropriateness; look at the total patient picture.

Gallagher P, O’Mahony D. STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers’ criteria. Age Ageing 2008;37:673-9. Barry PJ, Gallagher P, Ryan C, O’Mahony D. START (screening tool to alert doctors to the right treatment)―an evidence-based screening tool to detect prescribing omissions in elderly patients. Age Ageing 2007;36:632-8.

ADE’S-Common Drug Classes

•Cardiovascular drugs•NSAIDs•Hypoglycemics•2nd Gen Antipsychotics•Anticoagulants and Antiplatelet agents•Antihistamines (medications “PM”)•Anticholinergics

Drug Comparison Charts RxFiles 10th Ed., 2014.

ADE’s-Risk Factors

•Age>84•Low BMI•6 or more Chronic Illnesses•CrCl <50 mL/min•9 or more medications•12 or more medication doses/day•Prior ADE

Drug-Drug Interactions

• http://www.uptodate.com • Example of medications – See Case later

De-prescribing

•Stopping Wisely•“…as complicated as starting a new medication”

An Approach• Patient goals• Safety

– Any possible ADE’s– DDI– High risk medications

• Anticholinergics• Efficacy

– Medical goals in relation to time to benefit and prognosis– Evidence base for elderly

• Complexity and cost– Compliance

Case

• 85 y/o WF presents to establish care– Alzheimer’s disease diagnosed two years ago– COPD– CAD (40% RCA in FL after presenting with dyspnea and edema)– HLD– HTN (160/90 on 2 ED visits)– CHF– UI– Depression– DJD– Constipation

Case

• PMH– Ex-smoker

• Lives alone– Housekeeper for heavy cleaning and laundry– Daughter helps with checkbook and shopping

Case

• BP 130/60 sitting 120/55 standing• Height 62 inches• Weight 137 lbs

– BMI 25.1• Mildly antalgic gait and uses cane• Bright alert, slightly vague

A Patient

• FEV1 55% Pred, SpO2 92%• Cr 1.1/K+ 5.0• EF 45%• LDL 85

Brown Bag Meds (21)• Amlodipine 10 mg q AM• Atorvastatin 10 mg q PM• Fluticasone/salmeterol 100/50

bid• Oxybutynin 15 mg q AM• Donepezil 10 mg q AM• Fluoxetine 20 mg qAM + 10

mg (1/2) prn agitation and stress

• Meloxicam 7.5 mg qAM• Ranitidine 150 mg bid• Ibuprofen 200 mg q hrs prn• ASA 81 mg daily

• Proventil HFA prn• Ipratropium/Albuterol neb 2-4

times a day• Multi Vit qAM• Vit C qAM• Miralax 1 tsp/8 oz H2O qAM• Hydrocodone/Acetaminophen

5/325 tid• Lisinopril 40 mg daily• Metoprolol 25 mg bid• Lasix 40 mg daily• KCL 20 meq daily• Tylenol PM qhs

Comments

Brown Bag Meds Re-organizedCategory Category

CV/HTN--Amlodipine--Lisinopril--Metoprolol--Lasix--Atorvastatin--Aspirin

Psychiatric--Fluoxetine--Donepezil

Respiratory--Fluticasone/Salmeterol--Proventil HFA--Ipratroprium/Albuterol

GI--Ranitidine--Miralax

Musculoskeletal--Ibuprofen--Hydrocodone/Acetominophen--Meloxicam--Tylenol PM

Misc--Oxybutynin--MVI--Vit C--KCL

Comments

Safety

•Any possible ADE’s•DDI•High risk medications•Anticholinergics

Patient goals

Drug-Drug Interactions

• http://www.uptodate.com

Summary• Geriatric Pharmacology

– Physiological changes affect distribution, metabolism and clearance

– Consider Polypharmacy• Redundant Medications• Group by system or condition

– Beers list, STOPP/START, Common ADEs/DDIs– Make use of outpatient lists, pharmacy consultation– Deprescribing – Patient preference, Goals of Care, Life

Expectancy, Medication Efficacy, DDI’s, ADE’s

Questions

References

• As cited in presentation