Lynsey E. Brandt, MD, PharmD

Christiana Care

Geriatrics Consult Program

April 15, 2016

Geriatrics Consult Program Lynsey Brandt, MD, PharmD

Located at Wilmington Hospital

Gateway Building, 5th floor

Scheduling: 302-320-6475

Falls Polypharmacy Medical Complexity Weight loss/ failure to

thrive Delirium Depression/ Anxiety Insomnia, Urinary

Incontinence, or Fatigue Need for Increased

Social Support Driving Concerns Goals of Care

Learning Objectives

Review risk of adverse drug events in older adults

Summarize pharmacokinetic & pharmacodynamic changes with age

Review drug interactions

Learning Objectives

List classes of medications with increased risk in older adults Beers List

Others

Discuss medication safety at transitions of care

Review the “Prescribing Cascade”

Take-Home Points Older adults are at risk for adverse drug events

Consider risk/ benefit for all medications (i.e. Beers list)

Beware of the prescribing cascade

“Start Low & Go Slow!”

I. Challenges of Prescribing for Older Adults

• Multiple chronic medical problems

• Multiple medications and prescribers

• Different metabolism and responses

• Adherence and cost

• Supplements, herbals, and OTC drugs

Lancet. 1995;346(8966):32–36.

ADR/ADE--defined

Adverse Drug Reaction (ADR)

any undesirable or noxious drug effect at standard drug treatment doses

WHO;1996 Technical Report Series No. 425

Adverse Drug Event (ADE)

ADRs + errors in drug administration

CHAMP. University of Chicago.

Adverse Drug Reactions Older adults 7 times more likely to have unwanted

side effect and 2-3 times more likely to have

ADRs

Multiple meds is the factor most strongly correlated with increased risk of ADRs

Exponential increase in ADRs with addition of more drugs to a regimen (2 drugs-15%, 5 drugs-50-60% )

ADE’s are Preventable

27.6% of adverse events were preventable

58.4% of these were associated with errors in prescribing

Gurwitz et al, JAMA 2003;289:1107-1116

II. Pharmacokinetics in Older Adults

Pharmacokinetics = “what the body does to the drug”

Absorption

Distribution

Metabolism

Excretion

Absorption

Overall absorption is unchanged by aging

Can be altered by drug interactions (i.e. calcium , iron)

Altered absorption of drugs in patients receiving enteral feeds

Distribution Less water

Less muscle

More fat

Lower plasma protein binding with age

Distribution Less water

Lower volume of distribution for water-soluble drugs (i.e. digoxin, lithium)

Less muscle

More fat

Accumulation of fat-soluble drugs, prolonging elimination and effect (i.e. diazepam)

Lower plasma protein binding with age

Increased free fraction of drug (i.e. warfarin)

Metabolism Reduced hepatic mass and blood flow leads to slower

metabolism

Excretion Renal function declines with age

Renal mass declines by 20-25% from age 30 to 80

Glomerular Filtration Rate decreases by 10% per decade of life after age 30

Excretion (cont.) Do not be misled by “normal” serum creatinine.

Adjust dose when creat clearance < 60

Calculate creatinine clearance using the Cockroft-Gault equation:

(140-age in years) x (Ideal body wt) x 0.85 (females)

72 (serum creatinine in mg/ dL)

Drugs with renal elimination (selected examples)

Allopurinol Antibiotics - Aminoglycosides

- Fluoroquinolones - Penicillins - Tetracyclines - Sulfa - Nitrofurantoin!!!

Digoxin

Furosemide Gabapentin H2 antagonists - Cimetidine - Famotidine - Ranitidine

Lithium Metformin

Pharmacodynamics “What the drug does to the body.”

Receptor responses vary with age

Beta adrenergic receptors: decreased sensitivity with age

CNS (increased blood brain barrier permeability, decreased cerebral blood flow)

Blunted baroreceptor reflex

Less predictable & often altered drug response at usual or lower concentrations

Central Nervous System Effects

Increased sensitivity to medications that affect the CNS

Symptoms: delirium, sedation, depression, confusion

Always start at low dose, and titrate slowly.

Anticholinergics

Antidepressants

Antihistamines

Analgesics

Benzodiazepines

Neuroleptics

Digoxin

Anticonvulsants

Anticholinergic properties frequently overlooked:

Elavil (amitriptyline) Flexeril (cyclobenzaprine)

Cogentin (benztropine) Atarax/Vistaril(hydroxyzine)

Bentyl (dicyclomine) Welbutrin/Zyban (bupropion)

Ditropan (oxybutynin) Antivert (meclizine)

Detrol (tolterodine) Ipratropium (atrovent)

Benadryl (diphenhydramine) Phenergan (promethazine)

Levsin (hyoscyamine) Atropine

Quinidine

3 factors to consider for ALL prescriptions: Allergies

Renal function

Drug interactions!

Safe-Prescribing Survey

Garbutt JM, et al. Acad Med. 2005 Jun;80(6):594-9.

Drug/ Drug Drug/ Disease Interactions

85 yo woman with history of CHF, admitted for a fall & CHF exacerbation.

PMH: CKD (GFR 40ml/min), Atrial Fibrillation, CHF, Diabetes

Develops right knee pain & swelling on 2nd hospital day

Aspiration of synovial fluid shows uric acid crystals.

Medication list: Lasix 40 mg qd

Coumadin 5 mg qd

Toprol xl 50 qd

Glipizide 5 mg qd

Case (cont.) Which of the following would you give for this patient:

a.) Indomethacin 50 mg TID

b.) Colchicine 0.6 mg BID

c.) Prednisone 60 mg QD

d.) Allopurinol 300 mg QD

e.) None of the above

Drug- disease interactions a.) Indomethacin 50 mg TID (CKD/ CHF)

b.) Colchicine 0.6 mg BID (CKD – renal dosing!)

c.) Prednisone 60 mg QD (DM)

d.) Allopurinol 300 mg QD (CKD- renal dosing!)

e.) None of the above

Drug-Disease Interactions Confusion benzodiazepines or anticholinergics

Bladder outlet obstruction anticholinergics, TCAs, antispasmodics, antihistamines

CKD, CHF, PUD NSAIDS

Constipation anticholinergics, TCAs, calcium channel blockers

Falls TCAs, benzodiazepines, SSRIs, antihypertensives

Fick DM Arch Intern Med 2003;163:2716-2724

Beers MH Arch Intern Med 1997;157:1531-1536

Drug-disease interactions

Key is to be aware of these potential interactions

Select the therapeutic plan with best benefit/ risk ratio.

Case (cont) On hospital day 4, patient develops low-grade temps

and dysuria.

UA shows 5-10 wbc, +leuk esterase, +nitrites

Urine culture with >100,000 E Coli, pan-sensitive

Patient has no known drug allergies

Case 2 (cont). Which antibiotic is the best choice for this patient:

a.) Bactrim DS -1 tab po BID x 3 days

b.) Bactrim DS- 1 tab po BID x 7 days

c.) Cipro 500 mg po BID x 7 days

d.) Amoxicillin 250 TID x 7 days

e.) Macrobid – 1 tab BID x 3 days

Case 2 (cont.) Which antibiotic is the best choice for this patient:

a.) Bactrim DS -1 tab po BID x 3 days

b.) Bactrim DS- 1 tab po BID x 7 days

c.) Cipro 500 mg po BID x 7 days

d.) Amoxicillin 250 TID x 7 days

e.) Macrobid – 1 tab BID x 3 days

Cytochrome P450 Systems

CYP3A Metabolizes >60% of prescribed drugs including:

Calcium channel blockers, certain beta-blockers, most “statins”, warfarin, amiodarone

CYP2D6 Metabolizes:

metoprolol, propranolol, tramadol, codeine,oxycodone,TCAs, SSRIs

Cytochrome P450 Inhibitors

CYP3A Inhibitors

Amiodarone, cimetadine, cyclosporin, erythromycin, itra-/ketoconazole, grapefruit juice

CYP2D6 Inhibitors

Cimetidine, SSRIs, quinidine

Strategies to check for drug interactions

Micromedex

Epocrates

The pharmacist!!

III. Potentially inappropriate meds

Sensitivity to CNS -active agents

Sedative- hypnotic meds associated with increased risk of:

Falls

Hip fractures

Delirium

Beers list

The Beers List List of drugs which are potentially inappropriate in the

elderly

Developed by consensus panel of geriatricians in 1991

Used by regulators to evaluate nursing home medication lists

The Beers List (selected examples)

Drug Reason Alternative

Antihistamines- 1st

generation

(diphenhydramine)

Anticholinergic

effects

Nonsedating

antihistamines

(loratadine)

Long-acting

benzodiazepines

(diazepam)

Sedation Short-acting

benzodiazepines

(lorazepam)

Narcotics (meperidine) Active metabolite Morphine

Hypoglycemic agents

(chlorpropamide)

Long half-life,

renally excreted,

risk of

hypoglycemia

Shorter-acting

agents (glipizide)

Other high-risk medications Study of 177.504 ER visits for adverse drug events

33% of the visits were due to:

Digoxin

Warfarin

Insulin

(“DWI”)

Drugs on the Beers list accounted for only 3.6% of visits

Budnitz et al. Annals of Internal Medicine. December 4, 2007 vol. 147

no. 11 755-765

IV. Medication Safety/ Transitions of Care

Home

ER

MICU

General Medical Ward

Rehab

Home!

“Too Many Cooks….”

Transitions of Care

Patients are vulnerable to experience medication problems at each “handoff”

Active vs. Passive role of patient

Problems with transitions: What the literature shows 20% incidence of adverse drug events (hospital to

home)

Patients’ limited recall of discharge instructions

Problems with adherence

Frequency of errors of discharge medication lists

Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.

Posthospital Medication Discrepancies

Looked at discrepancy between pre-hospital med lists, post-hospital med lists, and what the patients actually were taking.

Pts admitted with 1 of 9 selected conditions

Home visit 24 to 72 hours post-discharge

Prevalence & type of med discrepancies categorized

Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.

Posthospital Medication Discrepancies

14.1% of pts had at least 1 med discrepancy

51% patient-associated; 49% system-associated

5 med classes accounted for half of all discrepancies

Med discrepancies associated with total # of meds & presence of CHF

Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.

Posthospital Medication Discrepancies

Risk of Rehospitalization within 30 days!!! 14.3% of those with med discrepancies

rehospitalized

vs.

6.1% of those without a discrepancy (p=.04)

Coleman et al. Posthospital Medication Discrepancies. Arch Internal Medicine 2005.

Strategies for improving medication safety at transitions What strategies do you utilize??

Recommendations

Obtain & review med bottles from home

Separate those that no longer using.

Compare pre-hospitalization meds with current list

Contact PCP and/or pharmacy

Verbally reconcile meds with pt/ caregiver (USE “TEACH BACK TECHNIQUE”)

Kackman, et al. Medication Reconciliation for Older Adults Transitioning from Long-Term Care to Home. Annals of Long-Term Care. August 2011.

Part V. Case example 85 yo man referred to PM&R for evaluation and

management of lumbar stenosis.

Exam: significant spasm of paraspinal muscles & EMG suggestive of radiculopathy.

He was prescribed gabapentin and diazepam.

Case example (cont) Two weeks later, the patient was seen by his Primary

MD because of visual hallucinations. Laboratory evaluation & head CT were unremarkable. Risperidone was prescribed.

While out of town one month later, patient developed tremors and a shuffling gait, and was taken to an urgent-care center. He was diagnosed with Parkinson’s and sinemet therapy was initiated….

Prescribing Cascade

Geriatrics Review Syllabus

Take-Home Points Older adults are at risk for adverse drug events

Consider risk/ benefit for all medications (i.e. Beers list)

Medication-related problems at transitions of care are associated with increased rate of readmissions

Beware of the prescribing cascade

“Start Low & Go Slow!

Geriatrics Consult Program Lynsey Brandt, MD, PharmD

Located at Wilmington Hospital

Gateway Building, 5th floor

Scheduling: 302-320-6475

Falls Polypharmacy Medical Complexity Weight loss/ failure to

thrive Delirium Depression/ Anxiety Insomnia, Urinary

Incontinence, or Fatigue Need for Increased

Social Support Driving Concerns Goals of Care