Treatment Considerations in Relation to Concurrent Pharmacology

Treatment Considerations in Relation to Concurrent Pharmacology Paul J. Christo, MD, MBA

Disclosure Consultant/Independent Contractor: Ameritox, Actavis, Chattem, Inc., Quadrant HealthCom Inc., Perrigo Company Grant/Research Support: Medtronic

Learning Objectives  Describe physiological changes related to older adulthood  Recognize the pharmacodynamic/pharmacokinetic changes that occur in older adults  Review the key recommendations for medical management from the American Geriatrics Society  Describe interventional procedures that may be useful for controlling pain in older adults

Physiological Changes & Aging Disease can present earlier due to impaired physiological reserve Adverse effects can occur with medications and specific doses of medications that are unlikely to be toxic in younger people

Resnick and Marcantonio 1997; Lancet 350: 1157

Physiological Changes & Aging (cont’d)  Overview of Changes – Cardiac output decreases – Blood pressure increases – Arteriosclerosis develops – Impaired gas exchange – Creatinine clearance decreases – Altered gastrointestinal motility – Blood glucose elevation – Decline in bone mass

Boss GR and Seegmiller JE Age-Related Physiological Changes and Their Clinical Significance. West J Med 1981;136: 434-440.

Physiological Changes & Aging (cont’d)  Overview of changes – Atrophy of epidermis – Atrophy of muscle cells – Degenerative joint changes – Decrease in hepatic metabolism and renal clearance – Decrease in protein binding  Aging affects pharmacodynamics and pharmacokinetics of pain medications Boss GR and Seegmiller JE Age-Related Physiological Changes and Their Clinical Significance. West J Med 1981;136: 434-440.

Fine PG. Pharmacological Management of Persistent Pain in Older Patients. Clin J Pain. 2004;20 (4): 220-226

Hepatic Function  Liver decreases in weight by as much as 20% after age 50  Liver function tests show little or no change, however  Decrease in liver blood flow  Large number of drugs metabolize more slowly, perhaps due to alterations in smooth endoplasmic reticulum

Boss GR and Seegmiller JE Age-Related Physiological Changes and Their Clinical Significance.

West J Med 1981;136: 434-440.

Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient.

Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Renal Function  Decrease in kidney volume and weight – by age 90, renal size 70% of size at 30 y/o

 Reduction in glomeruli causes decrease in creatinine clearance – serum creatinine changes little due to age-related decrease in muscle mass (decreased creatinine production)

 Decrease in GFR, renal blood flow Boss GR and Seegmiller JE Age-Related Physiological Changes and Their Clinical Significance.

West J Med 1981;136: 434-440.

Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient.

Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Renal Function Small rise in BUN Drugs principally cleared by glomerular filtration will have prolonged half life (gabapentin) –requires renal dosing based on CrCl

Boss GR and Seegmiller JE Age-Related Physiological Changes and Their Clinical Significance.

West J Med 1981;136: 434-440.

Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient.

Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Pharmacokinetic Considerations  Older adults typically display pharmacokinetic changes that cause more significant and prolonged plasma drug concentrations –this may result in greater toxicity and unfavorable drug interactions  Less total body water and more body fat = accumulation of lipophilic agents (fentanyl, lidocaine), and decreased accumulation of hydrophilic drugs (morphine) Monti D, Kunkel E. Practical Geriatrics: Management of Chronic Pain Among Elderly Patients; Psychiatric Services 49 (12): 1537-1539, December 1998 Strassels SA, McNicol E. Suleman R. Pharmacotherapy of pain in older adults.

Clin Geriatr Med 2008;24 (2): 275-298, vi-vii

Pharmacokinetic Considerations (cont’d) Decline in serum proteins (albumin) increases bioavailability of highly protein bound drugs (NSAIDS, carbamazepine)

Pharmacokinetic Considerations (cont’d)  Altered GI absorption – slower transit time can prolong onset of oral drugs and increase duration of action – opioid-induced immobility may be more severe – may be more susceptible to NSAID-induced adverse effects

 Transdermal absorption – typically unaffected with aging AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 Abrams, Bernard M.; Kriak, John; Pain Report #12 Optimizing Chronic Pain Management in Elderly Persons: Integrating Pharmacokinetics & Pharmacodynamics; 2010; accessed at www.pain.com Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Pharmacokinetic Considerations (cont’d) Distribution –decreased muscle mass •IM route can cause higher-than-expected drug levels

–decreased albumin •increased blood levels for highly plasma protein bound drugs (NSAIDs) AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 Abrams, Bernard M.; Kriak, John; Pain Report #12 Optimizing Chronic Pain Management in Elderly Persons: Integrating Pharmacokinetics & Pharmacodynamics; 2010; accessed at www.pain.com

Pharmacokinetic Considerations (cont’d)  Distribution – Increased fat mass • May increase volume of distribution of fat soluble drugs (fentanyl)

– Decreased total body water • May decrease distribution of water soluble drugs causing increased blood levels (morphine)

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 Abrams, Bernard M.; Kriak, John; Pain Report #12 Optimizing Chronic Pain Management in Elderly Persons: Integrating Pharmacokinetics & Pharmacodynamics; 2010; accessed at www.pain.com

Pharmacokinetic Considerations(cont’d)  Renal elimination – GFR decreases with increasing age, causing reduced drug and metabolite excretion • Decreased excretion can induce increased incidence of adverse effects (meperidine)

 Hepatic metabolism – Overall decrease in cytochrome drug metabolism system with age AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 Abrams, Bernard M.; Kriak, John; Pain Report #12 Optimizing Chronic Pain Management in Elderly Persons: Integrating Pharmacokinetics & Pharmacodynamics; 2010; accessed at www.pain.com

Pharmacokinetic Considerations (cont’d)  Hepatic metabolism – Phase I metabolism (oxidation, hydrolysis, reduction) may decrease – Phase II metabolism (acetylation, glucuronidation, sulfation) less affected – First pass metabolism (effect) decreased, causing higher drug bioavailability

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 Abrams, Bernard M.; Kriak, John; Pain Report #12 Optimizing Chronic Pain Management in Elderly Persons: Integrating Pharmacokinetics & Pharmacodynamics; 2010; accessed www.pain.com Hanlon JT, Backonja M, Weiner D, et al. Evolving Pharmacological Management of Persistent Pain in Older Persons. Pain Medicine 2009: 10 (6)959-961

Pharmacodynamic Considerations (cont’d)  Effects of analgesic can differ substantially from younger people –leads to unpredictable effects –opioids have increased analgesic sensitivity possibly due to a decline in mu receptor density  Differences in nociceptive pathways and pharmacology of drugs may alter expected responses to analgesics

Strassels SA, McNicol E. Suleman R. Pharmacotherapy of pain in older adults. Clin Geriatr Med 2008;24 (2): 275-298, vi-vii McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643

Pharmacodynamic Considerations (cont’d)  Older patients may require lower doses of opioids, experience a more rapid response to them, & develop tolerance more slowly  Heterogeneity in older adults makes optimal dosing and adverse effects difficult to predict  Key: “start low and go slow” – use longer dosing intervals, esp. with known hepatic or renal disease  Concurrent therapy may be effective (two drugs at low doses minimizes side effects of one drug) McCleane G. Pharmacological pain management in the elderly patient; Clinical Interventions in Aging 2007:2(4) 637–643 AGS Panel on Chronic Pain in Older Persons. The Management of Chronic Pain in Older Persons; JAGS 46(5):635-651, 1998

Biopsychosocial, Complementary, and Alternative Approaches  Shown to reduce pain alone  Benefit usually enhanced with medications  Physical therapy – therapeutic exercise & aquatic therapy better than superficial heat, TENS, acupuncture

 Cognitive behavioral therapy (CBT) – evidence for benefit with CBT, relaxation, biofeedback, coping skills training

 TENS-low freq electrical current to skin via electrodes – some evidence of effectiveness in OA and neuropathic pain

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009.

Scudds RJ, Scudds RA. Physical therapy approaches to the management of pain in older adults. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:223-237 Waters S, Woodward JT, Keefe F. Cognitive behavioral therapy for pain in older adults. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press, 2005: 239-261 Keefe FJ, Caldwell DS, Williams DA, et al. Pain coping skills training in the management of OA knee pain I: a comparative study. Behav Ther 1990;21:49-62 Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Typical Analgesics for Older Adults Nonsteroidal Anti-inflammatory Drugs (NSAIDs) –acetaminophen: •first line therapy for mild/moderate pain •maintain dose <4 g/24 hours from all sources •reduce dose up to 75% in hepatic insufficiency or alcohol abuse •effective for OA & low back pain AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

NSAIDs  Over 20% of persons >age 65 take prescription NSAIDs; many more take non-prescription NSAIDs. Thus, older persons with the highest risk for cardiovascular (CV) disease are also the largest segment of the population regularly taking NSAIDs – More effective for short-term relief (6 weeks) of OA pain and low back pain than acetaminophen

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Friedewald VE, Bennett JS, Christo PJ, et al. American Journal of Cardiology Editor’s Consensus: Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk . AJC 2010 ;106:873-884.

NSAIDs (cont’d) Older adults at risk if have low creatinine clearance, gastropathy, cardiovascular disease, intravascular depletion (CHF) Increased GI toxicity with age, but probably dose and duration dependent  Aspirin with chronic NSAID use increases risk of GI bleeding AGS Panel on Pharmacological Management of persistent Pain in Older Persons.

Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

NSAIDs (cont’d)  COX-2 inhibitors offer better, but incomplete GI protection  Traditional NSAIDs and COX-2 inhibitors can interfere with antihypertensive therapy (thiazide & loop diuretics), sodium and water retention, and aggravate CHF  COX-2 inhibitors & traditional NSAIDs increase CV risk, particularly cardiac events  Some NSAIDs can interfere with cardioprotective effects of aspirin Friedewald VE, Bennett JS, Christo PJ, et al. American Journal of Cardiology Editor’s Consensus: Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk . AJC 2010 ;106:873-884.

NSAIDs (cont’d)  Black Box Warning re: increased risk of CV thrombotic events, myocardial infarction, stroke  AGS Panel Recommendation: consider rarely and with caution in selected patients  If use, avoid naproxen, oxaprozin, piroxicam, indomethacin, ketorolac (short-term ok) – risk outweighs benefits Friedewald VE, Bennett JS, Christo PJ, et al. American Journal of Cardiology Editor’s Consensus: Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk . AJC 2010 ;106:873-884.

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

NSAIDs in Older Adults  General considerations for pain (65 years & above): –healthy: naproxen/ibuprofen (2-4 weeks) with proton pump inhibitor (PPI) for gastroprotection.

–with H/O peptic ulcer dz: celecoxib –with HTN: either naproxen (+PPI) or celecoxib –with stable CAD: naproxen + PPI –PPI use with COX-2 if prior history of GI bleed or on long term ASA White WB. Cardiovascular Effects of the Cyclooxygenase Inhibitors. Hypertension 2007;49:408-418 Laine L, White WB, Rostom A, et al. Cox-2 Selective Inhibitors in the Treatment of Osteoarthritis. Semin Arthritis Rheum. 2008 Dec;38(3):165-87

NSAIDs  NSAID plus chronic low dose aspirin (ASA) –take ASA first, then NSAID + PPI at least 2 hours later –timing of ASA not relevant if using COX-2 –ibuprofen (> 600 mg tid), interferes with plt inhibitory effects of ASA and not recommended if ASA used for secondary prevention of cardiovascular disease –intermittent ibuprofen use unlikely to inhibit anti-platelet effects of ASA, but has not been studied FDA. Accessed 6/2010 at http://fda.gov/cder/drug/infopage/ibuprofen/science_paper.htm Friedewald VE, Bennett JS, Christo PJ, et al. American Journal of Cardiology Editor’s Consensus: Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk . AJC 2010 ;106:873-884.

NSAIDs (cont’d)     

Consider topical NSAIDs and non-acetylated salicylates as alternatives Better safety margin than usual options Topical diclofenac 1% gel; indicated for OA of UE or LE joints Diclofenac topical solution 1.5% indicated for knee OA (40 gtt QID) Diclofenac patch 1.3%; indicated for minor strains, sprains, contusions;1 patch bid

Amar PJ, Schiff ER. Acetaminophen safety and hepatotoxicity-where do we go from here? Expert Opin Drug Saf 2007;6(4):341-355 Coyle N. Pharmacologic management of adult cancer pain. Oncology (Williston park) 2007;21 (suppl 2 Nurse Ed):10-22; discussion 26 AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

NSAIDs: Non-Acetylated Salicylate Choline magnesium trisalicylate –minimal GI toxicity –no effect on platelets –pill or liquid form available

Coyle N. Pharmacologic management of adult cancer pain. Oncology (Williston park) 2007;21 (suppl 2 Nurse Ed):10-22; discussion 26

Opioids ď&#x201A;§ Controlled trials show efficacy in chronic musculoskeletal & low back pain, diabetic peripheral neuropathy, & postherpetic neuralgia (PHN) ď&#x201A;§ Long-term effectiveness for persistent non-cancer pain lacking for all age groups

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

Opioids  Cochrane review: patients continuing long-term opioid therapy derive clinically significant pain relief, and serious adverse events such as addiction are rare  Initiate a “trial,” establish goals, assess risk of abuse using a screening tool, use agreement, & incorporate urine drug monitoring  Older age significantly associated with lower risk of opioid misuse & abuse  Safety of opioids for non-malignant pain (observational study) – associations with increased cardiovascular risk with codeine and propoxyphene; decreased fracture risk with tramadol; increased all cause mortality with codeine and oxycodone  Beware of increased fracture risk in older adults with RA, OA assoc. with short acting opioids versus long acting opioids, esp during first 2 wks of treatment Miller M, Sturmer T, Azrael D, et al. Opioid Analgesics and the Risk of Fractures in Older Adults with Arthritis. JAGS 59:430-438, 2011 Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM. Long-term opioid management for chronic noncancer pain. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD006605. DOI: 10.1002/14651858.CD006605.pub2.

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Solomon DH, Rassen JA, Glynn RJ, Garneau K, Levin R, Lee J, Schneeweiss S. The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults; Arch Intern Med 2010, vol 170 (22): 1979-1986

Opioids AGS Panel Recommendation: consider opioid therapy for patients with moderate to severe pain, or diminished quality of life, or functional impairment Avoid: pentazocine, propoxyphene (withdrawn 2010 from US market), meperidine (Beers criteria of drugs to avoid)

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Hanlon JT, Backonja M, Weiner D, et al. Evolving Pharmacological Management of Persistent Pain in Older Persons. Pain Medicine 2009: 10 (6)959-961

Opioids  No older adult pharmacokinetic studies: nabumetone, hydrocodone, oxymorphone, methadone  Methadone: can be valuable despite complex pharmacokinetics; clinical experience imp.  Buprenorphine: pharmacokinetics & respiratory depression ceiling effect = good choice for older adults (Doses: 5,10, 20 μg/hr every 7 days)

Likar R, Vadlau EM, Breschan C, et al. Comparable analgesic efficacy of transdermal buprenorphine in patients over and under 65 year of age. Clin J Pain 2008;24(6):536-543 Hanlon JT, Backonja M, Weiner D, et al. Evolving Pharmacological Management of Persistent Pain in Older Persons. Pain Medicine 2009: 10 (6)959-961

Opioids (cont’d)  Consider: oxycodone, morphine, hydromorphone, transdermal fentanyl, tapentadol  Tramadol: over age 75, half-life slightly longer and clearance reduced – immediate release: increase dosing interval to 8 to 12 hours – extended release: reduce dose by third to half

 Codeine: analgesia due to morphine metabolism; doses >65 mg/day lower analgesia & ↑ SE

Davis MP, Glare P: Tramadol. In: Davis M, Glare P, Quigley C, Hardy JR, eds. Opioids in Cancer Pain. New York, NY: Oxford University Press, 2009, pp 104-106 AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Hardy JR, Jackson K. Codeine. In: Davis M, Glare P, Quigley C, Hardy JR, eds. Opioids in Cancer Pain. New York, NY: Oxford University Press, 2009, pp 81-82

Opioid Metabolism  Many opioids react with cytochrome P450 (CYP 450) isoenzymes, primarily CYP 2D6 and CYP 3A4  Tramadol, hydrocodone, and codeine converted to active metabolites by CYP 2D6 – CYP 2D6 inhibitors that decrease opioid effect • fluoxetine, paroxetine, duloxetine, sertraline, and others

 Methadone and fentanyl are converted to inactive metabolites by CYP 3A4 (CYP 2B6 for methadone1) – CYP 3A4 inhibitors that increase opioid effect • several anti-retrovirals, antifungals, antibiotics, diltiazem, verapamil, cimetidine, grapefruit juice, and others Totah RA et al. Anesthesiology. 2008;108(3):363-374.

Daniell HW. J Clin Oncol. 2002;20(9):2409-2410. http://www.fda.gov/cder/drug/drugInteractions.

Davis M, Glare P, Quigley C, Hardy JR, eds. Opioids in Cancer Pain. New York, NY: Oxford University Press,

Opioid Metabolism (cont’d) Morphine, hydromorphone, and oxymorphone are not significantly metabolized by CYP 450 isoenzymes Individualize opioid therapy

Davis M, Glare P, Quigley C, Hardy JR, eds. Opioids in Cancer Pain. New York, NY: Oxford University Press, 2009 Daniell HW. J Clin Oncol. 2002;20(9):2409. http://www.fda.gov/cder/drug/drugInteractions

Adjuvants: Tricyclic Antidepressants, Anticonvulsants, Other Agents Tricyclic antidepressants (TCAs) –effective for PHN and DPN (neuropathic pain) –avoid amitriptyline due to cardiac, anticholinergic, sedative side effects –nortriptyline or desipramine better choices with 75 % ↓ side effect incidence •start at 10 mg orally at night initially AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Lussier D, Portenoy RK. Adjuvant analgesics. In : Doyle D, Hanks G, Cherny NI, et al., eds. Oxford Textbook of Palliative Medicine. 3rd edition. Oxford: Oxford University Press; 2004:349-377

Adjuvants  Serotonin norepinephrine reuptake inhibitors (SNRIs) –duloxetine and venlafaxine better tolerated than TCAs –Midalcipran-indicated for fibromyalgia  Anticonvulsants –first line for neuropathic pain in older adults –lower toxicity & fewer drug-drug interactions ↑ usefulness –gabapentin & pregabalin strongly consider –extended release gabapentin every 24 hours

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Lynch ME, Watson CPN. The Pharmacotherapy of chronic pain: a review. Pain Res Manag 2006;11 (1):11-38.

Adjuvants (contâ&#x20AC;&#x2122;d) ď&#x201A;§ AGS Panel Recommendations (Adjuvants): All patients with neuropathic pain candidates for adjuvants; use approved drugs for fibromyalgia, avoid tertiary TCAs, consider use for other types of refractory pain (back pain, HA, bone pain, TMJ disorder)

AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

Other Drugs: Muscle Relaxants Relieve skeletal muscle pain, but have nonspecific effects unrelated to muscle relaxation True muscle spasm: baclofen or benzodiazepine Avoid: methocarbamol, cyclobenzaprine, carisoprodol, chlorzoxazone, –risks outweigh benefits in older adults –consider: tizanidine 2 mg tid initially AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Hanlon JT, Backonja M, Weiner D, et al. Evolving Pharmacological Management of Persistent Pain in Older Persons. Pain Medicine 2009: 10 (6)959-961

Other Drugs  Benzodiazepines – no direct analgesic effect – high risk profile, but may be needed for anxiety, muscle spasm, end of life – consider: clonazepam

 Topical analgesics – lidocaine 5% patch indicated for PHN – used off label for DPN, LBP, OA, bone mets – contraindicated in liver failure due to ↓ lidocaine clearance AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

Other Drugs  Topical analgesics – 2.5% lidocaine/2.5% prilocaine • cutaneous anesthesia for needle puncture or incision – Capsaicin cream • benefit in neuropathic pain (PHN) and non-neuropathic pain (OA) • burning sensation can limit use – 8% capsaicin patch • pain reduction up to 12 weeks after treatment AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Backonja M, Wallace MS, Blonsky ER, et al: NGX-4010, a high concentration patch for the treatment of postherpetic neuralgia: a randomized double blind study. Lancet Neurol 2008;7:1106-12

Other Drugs Topical analgesics –aspirin, indomethacin, piroxicam, ketoprofen mixed results in neuropathic and non-neuropathic pain

Cannabinoids –antinociceptive effects in animal and human controlled trials –therapeutic window narrow due to dysphoric response in older adults AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009

Other Drugs  Corticosteroids –analgesic effects for rheumatic, autoimmune conditions (RA, polymyalgia rheumatica, giant cell arteritis) •neuropathic pain (RSD), cancer pain (bone, infiltration, nerve compression, ↑ ICP) –LBP with sciatica: generally ineffective –side effects limit use to low dose & short term or at end of life AGS Panel on Pharmacological Management of persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons; JAGS 57:1331-1346, 2009 Chou R, Huffman LH: Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med 2007;147:505

Other Drugs AGS Panel Recommendations (Other Drugs): patients with localized neuropathic or non-neuropathic pain are candidates for topical lidocaine, localized nonneuropathic pain for topical NSAIDS, & regional pain syndromes for capsaicin

Interventional Therapies  Important option for older adults  May reduce need for oral analgesics (polypharmacy) – lower dose or eliminate a medication

 Serve diagnostic and therapeutic functions  Outpatient setting – monitoring equipment – resuscitation supplies

Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283

Interventional Therapies (cont’d)  Epidural steroid injections – Radiculopathy – can improve mobility, reduce pain, reduce fall risk, enhance quality of life  Sacroiliac joint injections (15-20% of axial pain 2° SI joint) – LBP/Buttock pain with joint dysfunction – trauma, OA, ligamentous strain – consider joint denervation for extended relief Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283 Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Interventional Therapies(cont’d)  Trigger point injections – myofascial pain – controlled studies show significant relief

 Facet joint injections/denervation – LBP – inflammatory arthritis, microtrauma, OA – local anesthetic as diagnostic, then denervation

Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283

Interventional Therapies (cont’d)  Vertebral Augmentation Techniques: Vertebroplasty (Vplasty)/Kyphoplasty – treats osteoporotic vertebral compression fractures causing back pain – also treats painful vertebrae from metastatic disease, multiple myeloma, angiomas – incidence of fractures: 26% in women over 50 yrs & 40% ≥ 80 yrs • associated with pain in up to 84% of cases – inject polymethylmethacrylate (PMMA) into vertebral body – kyphoplasty inserts balloon first, then PMMA – studies show good short-term relief; long-term success varies (2-5 years); both procedures show similar outcomes; not reduce risk of future osteoporotic fractures Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283 Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Li, X, Yang H, Tang T, et al: Comparison of kyphoplasty and vertebroplasty for treatment of painful osteoporotic vertebral compression fractures. J Spinal Disord Tech; 25 (3) 2012.

Boonen S, Wahl DA, Nauroy ML, et al: Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures. Osteoporosis Int (2011) 22:2915-2934

Interventional Therapies (cont’d)  Percutaneous disc decompression –treats contained, herniated discs causing lower extremity pain –minimally invasive option that requires minimal recovery and lessens elevated risks of spine surgery in older adults –recent systematic review (2010): nucleoplasty potentially effective as a minimally invasive therapy and strongly supportive of efficacy. Need RCTs Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283 Gerges FJ, Lipsitz SR, Nedeljkovic SS. A systematic review on the effectiveness of the nucleoplasty procedure for discogenic pain. Pain Physician 2010; 13 (2): 117-32

Interventional Therapies (cont’d)  Sympathetic nerve blocks – indicated for pain due to: CRPS, herpes zoster, visceral pain in abdomen/pelvis/perineum, cancer pain  Implantable drug delivery systems – applied in cancer pain, non-malignant pain (failed back surgery syndrome, spasticity) – use opioids, local anesthetics, clonidine, ziconotide delivered to cerebrospinal fluid  Scrambler Therapy (electrocutaneous nerve stimulation device) – pilot RCT shows sig. relief compared to medications for neuropathic pain, PHN, central canal stenosis Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283 Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Marineo G, Iorno V, Gandini C, et al. Scrambler Therapy May Relieve Chronic Neuropathic Pain More Effectively Than Guideline-Based Drug Management: Results of a Pilot, Randomized, Controlled Trial. Journal Pain Symptom Management 43 (1): 2012

Interventional Therapies (cont’d)  Spinal cord stimulation – deliver electrical impulses to dorsal columns via epidural electrodes – applied for neuropathic pain (FBSS, RSD, PHN), chronic LBP, radicular pain, inoperable ischemic leg pain, refractory angina, occipital neuralgia, interstitial cystitis • elders more vulnerable to PHN, LBP, FBSS, ischemic pain – trial performed first, then implantation – rechargeable systems last approx 5-10 yrs Berstein C, Lateef B, Fine P. In: Gibson SJ, Weiner DK, eds. Pain in Older Persons. Seattle: IASP Press; 2005:263-283 Christo PJ, Li S, Gibson SJ, Fine P, Hameed H: Effective Treatments for Pain in the Older Patient. Anesthetic Techniques in Pain Management. In: Silberstein SD (ed): Current Pain and Headache Reports, Philadelphia, PA., 15 (1): 22-34; DOI 10.1007/s11916-010-0164-0 (2011).

Summary  Aging induces physiologic changes that alter the pharmacokinetics and pharmacodynamics of pain medications  Hepatic function and renal function decrease  Pharmacokinetic changes lead to prolonged plasma drug concentrations  Pharmacodynamic changes lead to unpredictable effects  Be aware of specific drugs within each category that are recommended and contraindicated in older adults  Interventional therapies may reduce drug burden and enhance quality of life