Special Considerations in the Management of Acute and Chronic Pain in the Older Patient

CMSA OKAnnual Conference

Sept. 17, 2013

Mark A. Stratton, Pharm.D., BCPS, CGP, FASHPProfessor of Pharmacy and Langsam Endowed Chair in Geriatric PharmacyDirector, Institute for Geriatric PharmacyCollege of Pharmacy, University of Oklahoma

Disclosures

• I have no financial disclosures to report

Learning Objectives:• At the conclusion of the presentation the attendee will be able to:

• State morbidity and mortality statistics associated with medication related problems in the older patient

• Describe changes that predispose older patients to increased morbidity and mortality from medication therapy

• Understand issues regarding pain assessment in the elderly• Describe principles to guide acute and chronic pain

management in the elderly• List available non-opioid and opioid analgesics appropriate for

the elderly• Understand the risks associated with analgesics for the elderly

and how to avoid those risks.• Appreciate the role of non-analgesic agents and non-

pharmacologic treatments for pain in the elderly• Describe an algorithm for the management of chronic pain.

Did You Know…

• One-third of hospital admissions by patients over 75 are linked to drug related problems (DRPs)

• 51% of all deaths and 39% of hospitalization due to ADRs occur in the elderly

• 50,000-75,000 older people die each year due to a drug related problem…making this the fifth leading cause of death in the geriatric population• Half of these deaths are considered to be preventable

• Estimated cost of inappropriate medications and their consequences in older people approaches $200 billion/year

• Now referred to as “America’s Other Drug Problem”

Contributors to “America’s Other Drug Problem”

• Polypharmacy (Rx and OTC) – Excessive, inappropriate and unnecessary medications

• Decreased physiologic reserve• Pharmacokinetic changes of aging• Pharmacodynamic changes of aging• Effects of co-morbidity on kinetics and dynamics• Consequences of drug-drug interactions• Adherence issues

Pharmacokinetic Changes of Aging• Absorption

• Though numerous structural and physiological age-related changes in the GI tract exist, they are, for the most part, of minimal clinical significance in the absence of gastrointestinal pathology

• Decreased first-pass after oral administration – morphine

• Distribution (volume of distribution)• Body Composition Changes

• Less lean mass, more fat – increased Vd for fentanyl and diazepam• Decreased total body water – decreased Vd for morphine• Protein changes are not a normal part of aging but can be diminished

with many diseases • Metabolism (clearance)

• Liver size, blood flow decline with age altering the metabolism of drugs with high-flow dependent metabolism - morphine.

• Some but not all Phase I metabolic pathways performed by the CYP system (oxidation, reduction, hydrolysis) diminish with age – diazepam

• Phase II (conjugation) metabolic pathways do not appear to diminish with age - lorazepam

Pharmacokinetic Changes of Aging

• Elimination (clearance)• Majority of people over the age of 50 lose 10% of

renal function per decade• Many drugs and those with active metabolites are

dependent upon the kidney for elimination.• Cockroft-Gault equation for estimating CrCl loses its

accuracy with advanced age and/or changing renal function.

• Underestimates true CrCl in older people of normal weight

• Overestimates true CrCl in older people who are under weight

Pharmacodynamic Changes of Aging

• Alterations in receptor affinity and number• Enhanced post-receptor response – increased sensitivity• Central nervous system sensitivity

• Enhanced receptor response• Changes in µ receptors

• increased opioid sensitivity• Reduced CNS dopamine

• increased EPS symptoms• Reduced serotonin receptor function

• enhanced sensitivity to antidepressants• Altered GABA-benzodiazepine receptor function

• increased sensitivity to benzodiazepine, alcohol, barbiturate• Reduced CNS acetylcholine

• enhanced anti-cholinergic side effects

Pharmacodynamic Changes of Aging

• Alterations in Na, K-ATPase and Ca++ channels leads to enhanced toxicity of digoxin and antiarrhythmics

• Changes in homeostatic control mechanisms (baroreceptors) making orthostatic changes in blood pressure more likely from antihypertensive.

• Impaired glucose counter-regulation predisposes elders to hypoglycemia from antidiabetic agents

Pain Assessment and Aging

• 25 to 50% of community dwelling elders and up to 80% of nursing home patients have complaints of chronic pain

• Diseases of abnormal aging which are accompanied by pain• Degenerative bone, joint and spine disease• Neuropathic pain from DM, PHN, CVA or amputation• Cancer

• 22% of older people have cancer and up to 80% of these patients experience pain.

• Degree of pain control which can be achieved will play a significant role in QOL

• Elderly patients probably have higher pain thresholds than younger people

Pain Assessment and Aging (cont.)

• Elderly patients tend not to report pain• Elderly patients tend to have multiple

problems such that pain is low on the priority list

• Elderly patients tend to believe that one must bear pain as a part of life

• Elderly patients tend to fear expressing the complaint of pain because of past taboos

Pain Assessment and Aging (cont.)

• Older patients with complaints of chronic pain of vague etiology should be evaluated for depression

• Useful assessment tools for cognitively intact older patients are a pain diary and a numerical rating scale• Measure degree of relief and duration of relief

• Cognitive impairment may prevent the interpretation of pain and its response to therapy

• For patients with cognitive impairment observations by caregivers is vital• Writhing, grimacing, withdrawal on touch, agitation,

anxiety, moaning, elevations in blood pressure or pulse

Acute Pain Management Guidelines for the Elderly

• Post-operative or post-trauma • Opioids remain the gold standard for the treatment

of acute pain• Increased risk of post-operative delirium and

cognitive decline• Be aware of all other centrally acting medications• Be aware of renal function• PCA useful for cognitively intact elder

• Morphine – predictable, easy to titrate, inexpensive, easily reversible

• If renal function is diminished then use fentanyl (carefully, especially in the opioid naïve patient!)

• Start low, go slow

Acute Pain Management Guidelines for the Elderly

• Controlled release oxycodone also poses a valuable alternative with stable plasma levels and improved pain control

• Adequate treatment with opioids for postsurgical pain actually speeds recovery and discharge but may lead to tolerance

• Consider the use of non-opioids - scheduled• Acetaminophen• NSAIDs – carefully!• Gabapentin, pregabalin – perioperatively

• Avoid promethazine for post-operative nausea – anticholinergic effects

• Consider spinal anesthesia• Consider post-op nerve block

Chronic Pain Management Guidelines for the Elderly

• Break the pain cycle• Monitor for effectiveness of analgesic regimen

• Measure degree of pain relief using a visual analog scale and measure duration of relief

• Monitor for toxicity of analgesic regimen• Educate patient about realistic expectations

from analgesics

Chronic Pain Management Guidelines for the Elderly

• WHO analgesic ladder• Non-pharmacologic therapies (PT/OT, appliances,

devices, heat, hydrotherapy)• Non-analgesic therapy (antidepressants,

neuroleptics, anxiolytics)• Tolerance to opioids – down regulation of µ receptor• Opioid-induced hyperalgesia

• 30-40% of patients who chronically consume opioids• generalized and increasing pain sensitivity (body hurts “

all over”).

Chronic Pain Management Guidelines for the Elderly

• 2009 AGS Persistent Pain Guidelines for the Older Person• Acetaminophen as initial and ongoing for treatment

of persistent pain.• NSAIDs may be considered rarely. Use with PPIs to

minimize risk of GI bleed. Frequently evaluate renal function and effects on patient with HTN or CHF

• Earlier consideration of opioids in persistent pain (?)

• JAGS 57:1331-1346, 2009

Non-opioid analgesics

• Acetaminophen• Analgesic with some anti-inflammatory effect• Dose – Up to 3 grams per day• Toxicity

• Hepatoxicity• Dose and duration related• Pre-existing liver disease and/or concomitant chronic

alcohol use increases risk

Nonsteroidal anti-inflammatory agents (NSAIDs)

• Aspirin and Non-acetylated salicylates (Salsalate, Diflunisal, Choline salicylate)

• Antipyretics, analgesic, anti-inflammatory• Kinetic considerations: First order to zero order• Toxicity – GI

• At least 20 additional NSAIDs on the market• None are more effective than aspirin• Side-effect profile, kinetics and cost

determine preference of one agent over another

NSAIDClasses

Celecoxib

Ketorolac

MeclofenamateMefenamic acid

Nambumetone

Etodolac

FenoprofenFlurbiprofen

IbuprofenKetoprofenNaproxenOxaprozin

PiroxicamMeloxicam

DiclofenacIndomethacin

SulindacTolmetin

oxicams

naphthylalkones

fenamates

cox-2 inhibitors

acetic acids

pyrrolizinecarboxylic acid

pyranocarboxylicacid

propionic acids

NSAIDClasses

Trade Names

CelebrexToradol

Ponstel

Relafen

Lodine

NalfonAnsaidMotrinOrudis

NaprosynDaypro

FeldeneMobic

VoltarenIndocinClinoril

Kinetics of NSAIDs

• Poor correlation between serum levels and analgesic effects

• Piroxicam (Feldene*), - daily dosing• Naproxen (Naprosyn*), sulindac (Clinoril*),

celecoxib (Celebrex*), - bid dosing• Ketoprofen (Orudis*) and naproxen (Naprosyn*)

are highly protein bound - risk of drug interactions

Recommendations for NSAID Monitoring

• Baseline• CBC and differential, platelet count, creatinine,

LFTs• Systematic review

• Dark/black stool, dyspepsia, N/V, abdominal pain, edema, shortness of breath

• CBC, LFTs, creatinine

Toxicities of NSAIDs

• Dyspepsia • 25 to 28 % with COX-2 Inhibitor• 31% with Non-specific NSAIDS

• Gastric or duodenal ulceration: 1 - 10%• Ulceration, bleeding, perforation

• Celecoxib (Celebrex*) vs. Other NSAIDs• 12 month: 0.4% vs. 1.27%

• Renal toxicity: 5%• Sodium and water retention• Analgesic nephropathy• Interstitial nephritis

• CNS < 1%• Aseptic Meningitis

NSAID Toxicities of Importance in the Elderly

• Risk of serious gastrointestinal toxicity is 2.5 to 5.5 times greater in the elderly

• Complications of salt and water retention can worsen hypertension and CHF

Risk Factors for Serious Upper GI Complications Associated with NSAIDs

• Older age• Hx of PUD, upper GI bleeding• Arthritis related disability• High-dose NSAID or multiple NSAIDs• Concurrent steroid use• Prior GI side effects

Recommendations for Decreasing Risk of NSAID Toxicity

• Gastrointestinal• Dyspepsia

• Take dose with at least 8 ounces of water• Take with food or antacids

• Prevention of ulceration and bleeding• In patients with history of PUD or GI bleeding or

complications from NSAID• Co-administration with a PPI• Selective cyclo-oxygenase 2 inhibitors (COX-2) –

celecoxib (Celebrex*)• Use minimally effective doses, monitor duration

of use

Recommendations for Decreasing Risk of NSAID Toxicity (cont.)

• Cardiovacular effects (HTN, CHF) from renal effects• Salt and water retention• All NSAIDs may have a slight CV risk. Risk may be

greater in in patient with existent CV disease, HTN or hyperlipidemia (ie. most older people)

• Monitor use, avoid prolonged use (no greater than 10 days).

Comparative Cost

• Celebrex 200mg #30 = $142.99• Generic Naproxen 500 gm #60 = $19.99• Generic Ibuprofen 600 mg # 90 = $14.99• OTC ibuprofen 200 mg #500 = $16.99• Acetaminophen 500 mg #100 = $4 to 8

• www.drugstore.com

Narcotic-like agents

• Tramadol (Ultram*)• Possible adjunct, half-life is prolonged in the

elderly• Lowers seizure threshold

Opioid Analgesics

• Elderly patients have prolonged elimination of some narcotics

• Elderly patients have increased pharmacodynamic response to narcotics as manifest by EEG (efficacy and toxicity)

• General recommendation is that elderly patients require about one-half the dose of a narcotic than younger people

• Start-low, go-slow

Opioid Analgesics (cont.)

• Morphine - gold standard• Overcome oral bioavailability problems by

giving more drug orally (3 to 6:1)• Extended release formulations • Predictable, reversible, short duration of

action• Potential for accumulation of active

metabolites with reduced renal function of aging

Opioid Analgesics (cont.)• Other acceptable narcotics

• Codeine - One-tenth as potent as morphine, good oral to parenteral efficacy ratio but poor GI tolerance

• Hydrocodone – Equipotent to oral morphine, only available in combination

• Oxycodone – 30 mg chronic oral morphine = 20 mg chronic oral oxycodone. Good oral to parenteral efficacy ratio

• Hydromorphone – More potent than morphine, poor oral to parenteral efficacy ratio. Overcome oral bioavailability issue by giving more drug orally than parenterally (5:1)

• Oxymorphone – 30 mg oral morphine = 5 mg oral oxymorphone• Methadone - Equipotent to morphine, good oral to parenteral

efficacy ratio, long duration of action, biphasic half –life. Change doses slowly.

• Fentanyl patch - (?) in the elderly

Opioid Analgesics (cont.)

• Unacceptable narcotics• Meperidine - poor bioavailability,

accumulation of normeperidine which produces agitation, tremor, seizures in the elderly

• Pentazocine or butorphanol - delirium, agitation, dysphoria

Toxicity of Opioids• Sedation and confusion

• Tolerance to these effects usually occurs in several days to weeks• If intolerant of these effects: decrease dose, change agent

• Nausea and vomiting• Tolerance may develop• If intolerant to these effects: change agent or decrease dose,

consider anti-nauseant• Anti-nauseants

• metoclopramide or promethazine: elderly however are usually intolerant to these agents due to anticholinergic effects and they may cause EPS

• ondansetron may be a safer alternative to treat nausea• Constipation

• Stool softeners, senna extracts

Other Pharmacologic Alternatives to Pain Management in the Elderly

• Antidepressants - avoid higher doses of tertiary agents (amitriptyline). Lower doses work. Other antidepressants that are considered safer for older people may be more acceptable (SSRIs, duloxetine, etc.)

• Anxiolytics - avoid long acting agents (diazepam)• Gabapentin, pregabalin• Topical analgesic therapies

• OTC• capsaicin cream

• Rx• lidocaine patch• diclofenac 1% gel, patch or solution• compounded prescriptions with NSAIDs

• Alternative therapies for OA• Glucosamine with chondroitin or MSM• Hyaluronic acid injections

Non-Pharmacological Modalities For Chronic Pain from OA

• Weight reduction• Education• Assistive devices/orthotics• Thermal modalities• Hydrotherapy• Magnetic therapy• Muscle strengthening and ROM exercises• Social support

Algorithm for Chronic Pain Management in the Elderly

Acetaminophen or NSAID (PRN)

Acetaminophen or NSAID (Fixed dose)

Add Codeine, or Tramadol (PRN) if tolerated

Add Codeine, or Tramadol (Fixed dose)if tolerated

Change to Hydrocodone, Oxycodone, Oral Morphine or Methadone with Non-narcotic (Fixed dose)

Change to fentanyl patch q 3 days

Change to PCA or Nerve block

(Consider adding non-analgesic agents at any time in algorithm)

(Utilize non-pharmacologic modalities at any time in algorithm)

Algorithm for Chronic Pain Management (cont.)

Questions?