Caveats for Treating Chronic Pain in Older Adults - PowerPoint Presentation

Slide1

Caveats for Treating Chronic Pain in Older Adults

Cynthia Feucht,

PharmD

, BCPS, CGP

October 21, 2016Slide2

ObjectivesDescribe physiological and pharmacokinetic changes in the elderly that impact the use of

opioids.

Discuss alternative (non-controlled) options for treating chronic pain in

older adults.

Describe polypharmacy and its potential consequences in older adults.Slide3

Change is Inevitable…Slide4

Physiological Changes

Aging is a more important predictor of PK/PD changes compared to age

itself!

Physiologic changes can influence

PK/PD

PK (ADME) are more measurable

Increases the risk of adverse effects

Constipation, confusion, falls

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock

G,

Brundage

D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al.,

eds. Pharmacotherapy Self-Assessment Program, 5

th

ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126.Slide5

Trivia QuestionApproximate loss of organ function per year after the age of 30 is:

0.9%

3%

5%

7.5%Slide6

Absorption

Atrophy of gastric cells

Increase in gastric pH

Decrease in gastric acid secretion

Delayed gastric emptying

May alter rate (but note extent) of EC or SR product absorption

May increase contact time for drugs

http://

hubpages.com/education/Absorption-of-drugs-how-drugs-are-absorbed-in-the-body-ePharmacology

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock

G,

Brundage

D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al.,

eds. Pharmacotherapy Self-Assessment Program, 5

th

ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126.Slide7

Distribution

Increase in body fat

Lipid soluble drugs:



Vd

Increased concentration and half-life for lipid soluble drugs

Effect: delayed drug elimination

Examples

:

Benzodiazepines, tricyclic antidepressants

http://

www.fat2fitradio.com/wp-content/uploads/2008/04/elderly.jpgSlide8

Distribution

Decrease

in total body water

Water soluble drugs: 

Vd

↑

drug plasma concentrations & diffusion to receptor sites

Example:

morphine, digoxin

http://

www.alistwellnesscenter.com/images/proportionofwater.gif

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock

G,

Brundage

D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al.,

eds. Pharmacotherapy Self-Assessment Program, 5

th

ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126.Slide9

Metabolism

Liver mass reduction of ~

25-35%

Similar reduction in hepatic blood

flow

Can lead to

↓

drug metabolism &

↑

drug effect

High hepatic extraction ratio agents

May 

bioavailability due to altered first pass

metabolism

Examples

: morphine,

amitriptyline, hydromorphone

http://

hepatitiscnewdrugresearch.com/liver-disease-in-elderly-patients.html

Sera L, et al.

Clin

Geriatr

Med 2012;28:273-286.

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock

G,

Brundage

D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al.,

eds. Pharmacotherapy Self-Assessment Program, 5

th

ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126.Slide10

Metabolism

Phase I reactions (oxidation)

In vitro tests demonstrate inter-patient variability

No clear association for age-related decline

Impact of lifestyle factors

Alcohol intake

Tobacco abuse

Caffeine intake

Impact of disease-related dysfunction

http://

medicineworld.org/images/blogs/old-man-smoking-432510.jpg

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock

G,

Brundage

D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al

.,

eds. Pharmacotherapy Self-Assessment Program, 5

th ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126.Slide11

Excretion

Progressive

age-related

decline

~1% decline/

yr

after the age 50

Scr

poor marker of kidney functionMuscle mass

loss,

↓ tubular function

Assess function using

CrCl

/

eGFR

Can lead to

↓

drug clearance

↑ risk for side effects

http://

www.kidneyfoundationofcentralpa.org/images/kidney.gif

Elliot D. Pharmacokinetics and pharmacodynamics in the elderly. In:

Schumock G, Brundage D,

Dunsworth

T, Fagan S, Kelly H,

Rathbun

R, et al.,

eds. Pharmacotherapy Self-Assessment Program, 5

th

ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115-126

.

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide12

Opioids and ADMEAbsorption: usually not affected by aging

Distribution:

Highly lipid soluble: fentanyl & methadone

Hydrophilic:

C

odeine

, hydrocodone, oxycodone, &

tramadol

Morphine & hydromorphone

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed September 19, 2016

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide13

Opioids and ADMETypically exhibit high first pass metabolism:

Morphine, hydromorphone,

oxymorphone

&

tapentadol

May see

↑

drug bioavailability in elderly

Clinically significant active metabolites:

Morphine, codeine, meperidine, tramadol, hydrocodone,

oxymorphone

Avoid in hepatic failure:

codeine, tramadol, meperidine

Preferred (severe): Morphine, fentanyl & methadone

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed September 19, 2016

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide14

Opioids and ADMEPrimary renal excretion:

Morphine, hydromorphone, codeine, fentanyl, tramadol, oxycodone, hydrocodone:

adjust dose in mild to moderate renal failure

Meperidine:

avoid use

Tapentadol

:

avoid with

CrCl

< 30ml/min

Generally safe to use in moderate renal failure:

Hydromorphone, fentanyl

Methadone (moderate to severe)

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed September 19,

2016

Davis M, et al. Drugs Aging 2003;20(1):23-57.

Dean M. J Pain & Symptom Manage 2004;28(5):497-504.Slide15

Opioid CaveatsPoor CYP 2D6 metabolizers:

Affects ~ 5-10% of the

caucasian

population

Also 1-2% of Southeast Asians

Tramadol & codeine

→

lack of efficacy due to reduced conversion to active metabolites

Oxycodone, hydrocodone

→

prolonged effect due to decreased metabolism

https://

memegenerator.net/instance/19879024

Wilkinson G. N

Engl

J Med 2005;352(21):2211-2221.

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide16

Opioid Caveats: MethadoneVariable pharmacokinetics:

Duration of analgesia

↑

with prolonged administration

Half-life range: 8-59

hrs

(avg. 20-35)

Multiple drug interactions

QTc

prolongation & risk for

torsades

:

Risk factors: other

QTc

prolonging meds,

↓

K/Mg, elderly, female, structural heart disease, congenital long QT syndrome

Obtain baseline EKG and risk stratify

Avoid if

QTc

> 500 msec.

http://

www.apsf.org/newsletters/html/2011/spring/01_opioid.htm

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed

September 19, 2016.

Lugo R, et al. J Pain & Palliative Care

Pharmacother

2005;19(4):13-24.

Owens R, et al.

Clin

Infect Dis 2006;43:1603-1611.Slide17

Trivia QuestionWhich of these men has influenced how we treat older adults?

https://images-na.ssl-images-amazon.com/images/I/21AgpWqWMYL._UX250_.

jpg

https://

mibiz.com/media/k2/items/cache/ebe2497a9810ac1c751277b6aacb6b9b_XL.jpg

http://media.mlive.com/kzgazette_impact/photo/8911853-large.jpgSlide18

Criteria Regarding Opioid UseSTART/STOPP Criteria

Avoid high-potency oral or transdermal opioids as 1

st

line therapy in those with mild pain

Use high-potency opioids in mod-severe pain where Tylenol, NSAIDS & low-potency opioids are either inappropriate or ineffective

Beers Criteria

Avoid meperidine: safer alternatives exist

Avoid opioids in those with history of falls/fractures

Avoid total of ≥ 3 CNS-active meds due to risk for falls

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. J Am

Geriatr

Soc

2015.

O’Mahony

D, et al. Age Ageing 2015;44:213-218.

https://ipspotlight.files.wordpress.com/2014/11/17187698_s.jpgSlide19

Guiding PrinciplesEstablish mutually acceptable comfort goals

Use of combined nonpharmacological & pharmacological therapy

Initiate with low dose

Adjust dosing for organ impairment / drug interactions

Reassess frequently / titrate cautiously

Davis M, et al. Drugs Aging 2003;20(1):23-57.

Pharmacological Management of Persistent Pain in Older Adults. J Am

Geriatr

Soc. 2009;57:1331-1346.

http://images.addictionblog.org/cherrycake/wp-content/uploads/2016/02/Is-methadone-safe-1.pngSlide20

What Do Older Patients Want: Preferred

Lansbury G.

Disabil

Rehab 2000;22(1-2):2-14.

http://

www.epainassist.com/images/Article-Images/home-remedies-arthritis.jpg

http://

mymedsupply.com/wp-content/uploads/2015/03/Hot-and-Cold-Therapy-Shoulder.jpg

http://

salonpas.us/wp-content/uploads/2016/01/FamilyShot-FS-Gel-Spray-GelPatch-NHP-Trans-01262

016a-Small-2.jpg

http://www.dignicareins.com/wp-content/uploads/2013/12/Nursing-Home-Insurance-The-Benefits-of-Socialization-for-the-Elderly.jpgSlide21

What Do Older Patients Want: Least Preferred

Lansbury G.

Disabil

Rehab 2000;22(1-2):2-14.

http://

www.reputehealthcare.com/eldercare.html

http://

www.consumerreports.org/content/dam/cro/news_articles/health/71262728_health_pills.jpg

http://scrubbing.in/encouraging-the-elderly-to-exercise/Slide22

Alternative Approach: NonpharmacologicalSlide23

Pain Management AlternativesOver-the-Counter

Topical counterirritants

Topical lidocaine

Acetaminophen

Oral NSAIDs

Prescription

Topical / oral NSAIDs

Lidocaine patch

Tricyclic antidepressants

Duloxetine

Anticonvulsants

http://www.browardcountypainclinics.com/wp-content/uploads/2012/12/pain-relief21.jpgSlide24

Topical OTCsCounterirritants: induces a less intense pain to counteract a more severe one

Examples: methyl salicylate, camphor,

menthol, capsaicin,

trolamine

salicylate

Up to 3-4 applications per day

Don’t apply heat or wrap bandage tightly

Multiple formulations: cream, ointment, gel, patch

Names don’t change but ingredients often do!

http://

salonpas.us/wp-content/uploads/2012/02/family-of-products-small.jpg

https://audubonparkwellness.brimhallwebsite.com/istore/4233_biofreeze__

pain_cream.html

http://www.icyhot.com/wp-content/uploads/2014/01/pro_img03.jpgSlide25

Newest OTC ingredient: Lidocaine

http://

www.aspercreme.com/img/portfolio/lidocaine-patch-slider-1-sm.jpg

https://www.walgreens.com/images/drug/0163481068706.jpgSlide26

NSAIDS: OTC & Rx

Analgesic, anti-inflammatory &

antipyretic

In a variety of combination products:

Aleve PM (NSAID + antihistamine)

Vimovo

(NSAID + PPI)

Treximet

(NSAID +

triptan

)

Vicoprofen

(NSAID + opioid)

In 2000: 70% over age 65 took NSAIDs at least once weekly

http://neuropathyandhiv.blogspot.com/2016/01/nsaids-like-ibuprofen-and-advil-can-be.html#.V-1IXIWcGEYSlide27

NSAID Mechanism of Action

http://www.voltarengel.com/HCP/images/charts/MOA_chart.jpgSlide28

Herndon C, et al. Pharmacotherapy 2008;26(6):788-805Slide29

NSAID Gastrointestinal Toxicity

Herndon C, et al. Pharmacotherapy. 2008;28(6):788-805.

http://

infohealth.net/wp-content/uploads/2013/04/ulcer-s.jpg

http://www.health.harvard.edu/blog/can-heartburn-medication-cause-cognitive-problems-201603219369Slide30

Additional NSAID Toxicity

Herndon C, et al. Pharmacotherapy 2008;28(6):788-805.Slide31

NSAIDs and Cardiovascular RiskFDA Warning July 2015

Precision Trial

Started 2006, ended 2016

Compared celecoxib to naproxen and ibuprofen

Combined endpoint:

CV death

Nonfatal MI, CVA

Hospitalization for UA, TIA

Revascularization

http://blog.affordablehealthinsurance.org/2015/08/fda-says-that-taking-advil-motrin-and.html#.V-w-3oWcGEY

https://clinicaltrials.gov/ct2/show/NCT00346216Slide32

Scarpignato

C, et al. BMC Medicine 2015;13:1-22.Slide33

Guideline Recommendations…..ACR (2012)

Hand OA: oral and topical NSAIDs including

trolamine

salicylate

Age ≥ 75: topical preferred

Knee & Hip OA: oral NSAIDs and topical NSAIDs (knee)

Age ≥75: topical preferred

Beers (2015)

Avoid NSAIDs (exception: celecoxib) for chronic use unless other alternatives are not effective & patient can take PPI

HF & CKD: avoid NSAIDs and COX-2 inhibitors

Gastric/duodenal ulcers: avoid non-selective NSAIDs

Hochberg M, et al. Arthritis Care and Research. 2012;64(4): 465-474.

American Geriatrics 2015 Beers Criteria Update Expert Panel. J Am

Geriatr

Soc. 2015.Slide34

Topical NSAIDs

Diclofenac gel

Indication: OA

Application 4 times daily

Dose differentiated by lower/upper extremity

Diclofenac solution

Indication: Knee OA

Two strengths / product type

Systemic bioavailability: ~1%

Preferred in elderly!

http://

www.onlinepharmacynz.com/images/products/414-299-Voltaren_Emulgel.jpg

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed September

29, 2016

http://www.pennsaid.com/img/hcp_2.0_img1.pngSlide35

Adjuvant AgentsAntidepressants

S

erotonin-norepinephrine reuptake inhibitors (SNRIs)

Tricyclic antidepressants (TCAs)

Anticonvulsants

Gabapentin,

pregabalin

Origination in treatment of cancer pain

Useful for neuropathic pain

May be used alone or with another agent

Pharmacological management of persistent pain in older persons. J Am

Geriatr

Soc. 2009;57:1331-1346.

http://chronicpainreliefoptions.com/wp-content/uploads/2016/08/np3.jpgSlide36

DuloxetinePros

Useful when concomitant depression/anxiety

Indicated for diabetic neuropathy & chronic musculoskeletal pain

Trial benefits: reduction in pain & improved physical functioning

Cons

Side effects: N/V/D, dizziness, fall risk, hyponatremia

Must taper to avoid withdrawal symptoms

Avoid in mod-severe renal failure

Makris

U, et al. JAMA 2014;312(8):825-836.

Chappell A, et al. Pain 2009;146(3):253-260.

http://pharmamkting.blogspot.com/2008/08/cymalta-buzz-machine-is-at-full.htmlSlide37

Tricyclic AntidepressantsUseful for a variety of indications

Depression

Diabetic neuropathy

Migraine prophylaxis

Chronic pain

Small study in older adults found equal efficacy in diabetic PN when compared to

pregabalin

& duloxetine

http://pharmacologycorner.com/differences-between-tricyclic-antidepressants-and-selective-serotonin-norepinephrine-reuptake-inhibitors-mechanism-of-action

/

Boyle J, et al. Diabetes Care 2012;35(12):2451-2458.Slide38

TCAs: Comparison Profile

Anti-cholinergic

Sedation

OSH

Seizures

Conduction

abnormalities

Amitriptyline*

++++

++++

+++

+++

+++

Doxepin*

+++

++++

++

+++

++

Desipramine

++

++

++

++

++

Nortriptyline

++

++

+

++

++

Teter

CJ,

Kando

JC,

Wells BG. Chapter

51. Major Depressive Disorder. In:

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey

L. eds

.

Pharmacotherapy

: A Pathophysiologic Approach, 9e.

New York, NY: McGraw-Hill; 2014.

http

://accesspharmacy.mhmedical.com.ezproxy.ferris.edu/content.aspx?bookid=689&Sectionid=45310502. Accessed September 30, 2016Slide39

TCAs and Beers CriteriaAvoid: highly anticholinergic, sedation and cause

orthostasis

Avoid if history of:

Syncope, delirium, dementia, cognitive impairment, falls/fractures, & BPH

Often related to anticholinergic properties

American Geriatrics 2015 Beers Criteria Update Expert Panel. J Am

Geriatr

Soc. 2015.Slide40

Caveats for TCA UseUse secondary amines:

Less anticholinergic effects, fewer associated falls, less confusion &

↓

risk for OSH

Use low dose at bedtime (sedation)

Caution use in:

BPH, urinary retention, constipation, CV disease, 2

nd

/3

rd

degree heart block, prolonged

QTc

interval, severe liver disease, seizure disorder & closed angle glaucoma

http://

lionsheartcounseling.com/wp-content/uploads/2015/08/small-pills1.jpg

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide41

Pregabalin & Gabapentin

Lexi-Comp, Inc. (Lexi-Drugs

®

). Lexi-Comp. Accessed September 29,

2016

Davis M, et al. Drugs Aging 2003;20(1):23-57.Slide42

Cross sectional survey of 3005 elderly (57-85 yrs)At least 5 Rx medicines: 29%Concurrent OTC use: 46%

Concurrent dietary suppl.: 52%

At least 5 dietary supplements: nearly 1 in 8

Medication Use in the Elderly

Qato

D, et al. JAMA 2008;300(24):2867-2878)Slide43

Conditions

Medications

Medications

Chronic

pruritis

Restoril

15mg

qhs

Hydroxyzine

25mg bid

Chronic cough

Lamictal

100mg

qhs

Ativan

0.5mg

tid

prn

Diabetes mellitus type 2

Effexor

XR 150mg

qd

Tussionex 5ml bid prnHypertensionDetrol LA 4mg dailyVicodin

5/500mg bid

prn

Urinary incontinence

Cymbalta

20mg daily

Motrin 800mg

tid

prn

Insomnia

Catapres

0.3mg

qhs

Depression / anxiety

Diovan

40mg daily

Osteoarthritis

Activella

1/0.5mg daily

Sleep apnea

Omeprazole

20mg daily

GERD

Melatonin

5mg

qhs

Personality disorder

What is Polypharmacy?Slide44

PolypharmacyMedication Count

Arbitrarily defined

Often > 5 medicines

Range 2-9

Controversial

May be appropriate if multiple disease states

Unnecessary Use

Not clinically indicated

Lack of indication

Suboptimal

Duplication

More practical approach

Shah B, et al.

Clin

Geriatr

Med 2012;28:173-186

.

http://www.wur.nl/en/project/pandemics.htmSlide45

Consequences

http://

www.slideshare.net/EdricPawChoSing/epidemiology-of-polypharmacy-and-potential-drugdrug-interactions-among-pediatric

-patients-in-

icus

-of-us-

childrens

-hospitals

Shah B, et al.

Clin

Geriatr

Med 2012;28:173-186.Slide46

Designed to optimize medication use in older adultsSix questions:Is the patient undertreated & is additional therapy indicated?Does the patient adhere to current regimen?

Which drug(s) can be withdrawn or is inappropriate?

Which adverse effects are present?

Which clinically relevant interactions could be expected?

Should the dose frequency or drug form be changed?

Prescribing Optimization Method

Drenth

-van

Maanen

A, et al. Drugs Aging 2009;26(8):687-701.

Gokula

M, et al.

Clin

Geriatr

Med 2012;28:323-341.

http://askapharmmedicationreview.com/uploads/3/6/3/2/3632226/2322479.jpg?200Slide47

Customize therapy for each patientMonitor & reassess for efficacy & toxicityMany adverse effects mimic underlying disease

processes

Consider any symptom an ADR until proven otherwise!

Minimize withdrawal effects by tapering dose

Managing

Older Adults

Steinman M, et al. JAMA 2010;304(14):1592-1601.

http

://www.health-heart.org/NoBadCholesterol.jpgSlide48