Embed Size (px)
DESCRIPTION
Maximizing Medications for Good Outcomes. Lee H. Stringer, Pharm.D., BCPS, FASCP, CPE Clinical Pharmacist, Certified Pain Educator Montana Pain Initiative May 30, 2014. Conflict of Interest Disclosure Lee H. Stringer, Pharm.D. Has no real or apparent conflicts of interest to report. - PowerPoint PPT Presentation
Citation preview
Health Care, Education and Research www.billingsclinic.com
Maximizing Medications for Good Outcomes
Lee H. Stringer, Pharm.D., BCPS, FASCP, CPE
Clinical Pharmacist, Certified Pain Educator
Montana Pain Initiative
May 30, 2014
Conflict of Interest Disclosure Lee H. Stringer, Pharm.D.
Has no real or apparent
conflicts of interest to report.
Objectives
1. Explore principles of rational polypharmacy
2. Learn mechanisms of action of non-opioid and adjuvant analgesics
3. Recognize an appropriate analgesic trial including proper titration
Terminology
• Narcotic– A substance that causes narcosis– Heroin, cocaine, methamphetamine
• Opioid– A substance that binds to the opioid receptor– Morphine, fentanyl, oxycodone
Analgesic Classes
American Pain Society. (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (6th ed.). Glenview, IL: American Pain Society.
Non-opioidAnalgesics
Pure Opioid Analgesics
Adjuvants
APAP and NSAIDs MorphineAntidepressants and
antiepileptics
Nociceptive painNociceptive and neuropathic pain
Nociceptive and neuropathic pain
Potential end-organ damage
No end-organ damage?Potential end-organ
damage
Ceiling analgesic effect No ceiling? Ceiling dose
Key Pharmacotherapeutic Concepts in Pain
Management• Consider multimodal analgesia• Polypharmacy is the RULE, rather than the
exception• Consider the need for dose titration (up/down)• Minimize side effects through careful medication
selection• Anticipate and treat side effects• Always have a contingency plan
Werder SF, Preskorn SH. Managing polypharmacy: walking the line between help and harm. J Fam Prac 2003;2(2)Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain. Am J Phys Med Rehabil 2005;84(3Suppl):S64-76.
Considerations for Rational Polypharmacy
• Know drug mechanisms of action• Avoid overlapping mechanisms• Know drug toxicities• Avoid overlapping/additive toxicities• Understand drug pharmacokinetics
Werder SF, Preskorn SH. Managing polypharmacy: walking the line between help and harm. J Fam Prac 2003;2(2)Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain. Am J Phys Med Rehabil 2005;84(3Suppl):S64-76.
Considerations for Rational Polypharmacy, cont’d
• Maximize current regimen• Ensure an appropriate trial is given• Have convincing evidence that combination >
monotherapy• Treat “symptom clusters”
Werder SF, Preskorn SH. Managing polypharmacy: walking the line between help and harm. J Fam Prac 2003;2(2)Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain. Am J Phys Med Rehabil 2005;84(3Suppl):S64-76.
Barriers to Rational Polypharmacy
• Drug-Drug Interactions• Drug-Disease Interactions• Medication misuse• Cost (financial toxicity)• Pill burden
Werder SF, Preskorn SH. Managing polypharmacy: walking the line between help and harm. J Fam Prac 2003;2(2)Gallagher RM. Rational integration of pharmacologic, behavioral, and rehabilitation strategies in the treatment of chronic pain. Am J Phys Med Rehabil 2005;84(3Suppl):S64-76.
Polypharmacy in Pain Medicine
• Goal: achieve optimal pain/function improvement with minimal toxicity– Facilitate use of lower doses of one or more
drugs– Maintain efficacy– Synergize effect of two drugs with differing
mechanisms of action
Fishbain DA. Polypharmacy treatment approaches to the psychiatric and somatic comorbidities found in patients with chronic pain. Am J Phys Med Rehabil. 2005;84(Suppl 3):S56-63.
Mechanistic Stratification
Beydoun A, Backonja MM. Mechanistic stratification of antineuralgic agents. J Pain Symptom Manage. 2005:25;S18-30.
Pathophysiologic Stratification
• Transduction: Capsaicin, LA, NSAID/steroid, topical opioid
• Conduction (Transmission): LA, TCA
• Plasticity (Modulation)– Ectopic activity: LA, TCA, NSAID– Synaptic transmission: gabapentinoids, NMDA
antagonists, α-agonists, ziconotide– Descending modulation: TCA, SNRI, opioids
• Perception: TCA, SNRI, gabapentinoids, systemic opioid
Mao J et al. Combination drug therapy for chronic pain: a call for more clinical studies. J Pain. 2011;12:157-6.
Non-opioid Analgesics:
Acetaminophen
Benefit of APAP in combinations at “LOW” doses
Edwards JE, McQuay HJ, Moore RA. Combination analgesic efficiacy; individual patient dtat meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain. J Pain Symptom Manage. 2002:23;121-130.
Benefit of APAP in combinations at “HIGH” doses
Study Mean MED
Average baseline pain
APAP benefit > 70 MED?
No difference in pain control
Axelsson et al (2003) 70 mg 2 No 43%
Axelsson et al (2008) 90 mg 4 No 68%
Stockler et al (2004) 200 mg 3.1 Yes 26.7%
Israel et al (2010) 225 mg - No 68%
Non-opioid Analgesics:
NSAIDs
COX Selectivity
Antman E, DeMets D, Loscalzo. Cyclooxygenase Inhibition and Cardiovasular Risk. Circulation. 2005:112;759-70.
NSAID Chemical Class
• Salicylic acid derivatives: ASA, diflunisal, salsalate
• Propionic acids: naproxen, ibuprofen, ketoprofen
• Indolacetic acids: indomethacin, sulindac, etodolac
• Pyrrolacetic acid: ketorolac
• Anthranilic acid: mefenamic acid
• Phenylacetic acid: diclofenac
• Enolic acids: piroxicam, meloxicam
• Naphthylaklanone: nabumetone
• COX-2 inhibitor: celecoxib
American Pain Society. (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (6th ed.). Glenview, IL: American Pain Society.
NSAIDs and CV Risk
• Danish study 99,187 post-MI patients
Olsen AM et al. Curr Opin Cardiol. 2013;28:683-8.Olsen AM et al. Circulation.2012;126:1955-63.
Risk of Death Associated with NSAID use after MI
Year Post-MI No. of Events Hazard Ratio
1 1086 1.59 [1.49-1.69]
2 712 1.84 [1.69-1.70]
3 546 1.81 [1.66-1.99]
4 468 1.83 [0.66-2.01]
5 377 1.73 [1.56-1.93]
>5 963 1.63 [1.52-1.74]
NSAID Risk Stratification
Risk Category Therapeutic Recommendation
LowAge < 65No CV risk factorsNo concurrent aspirin or anticoagulants
Traditional NSAID for shortest duration and lowest dose
IntermediateAge > 65No history of complicated GI ulcerationLow CV riskConcurrent ASA for primary prophylaxis
Traditional NSAID + cytoprotectant (PPI, H2RA, misoprostol)Once daily celecoxib + cytoprotectant
HighElderly, frail, hypertensive, renal/liverHistory of complicated GI ulcerationHistory of CV disease or on antiplatelet for secondary prophylaxisHistory of heart failure
Substitute with acetaminophenAvoid chronic NSAID use if possibleNaproxen + cytoprotectant Once daily celecoxib + cytoprotectantConsider a topical
Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther. 2013;15(Suppl3):S2.
NSAIDs- Issues Often Overlooked
• Protein binding and drug-drug interactions– Traditional NSAID 2 hours before ASA
• Available topically
• Available OTC (knowyourdose.org)
• Combination with a steroid?
• Combination with APAP?
Adjuvant Analgesics
NNT for Neuropathic Pain
Tricyclic Antidepressants
• Secondary amines: Nortriptyline or desipramine
• Tertiary amines: Amitriptyline et al.
SedationAnti-cholinergic
Hypo-tension
Cardiac effects
Weight gain Seizure risk
Tertiary +++ +++ +++ +++ ++ ++
Secondary +/0 + + ++ + +
Selecting a First-line Drug for PN
• Glaucoma, orthostasis, cardiac issues, HTN, suicidal ideation, weight gain concern: avoid TCAs
• Hepatic insufficiency: avoid duloxetine
• Peripheral edema: avoid pregabalin
• Cost concern: avoid duloxetine, pregabalin
• Erectile dysfunction: use venlafaxine
• Insomnia: sedating TCA
• Depression: SNRI, TCA
TitrationMedication Starting Dose Titration Maximum Dose Duration of
Adequate Trial
NortriptylineDesipramine
10 mg qHS Increase by 10-15 mg q3-7 days as tolerated
150 mg/day 6-8 weeks with at least 2 weeks at max tolerated dose
Duloxetine DR 30 mg daily Increase to 60 mg after 1 week
120 mg/day 4 weeks
Venlafaxine ER 37.5 mg daily Increase to 75 mg after 1 week
225 mg/day 4-6 weeks
Gabapentin 100-300 mg TID Increase by 100-300 mg/dose every 1-7 days as tolerated
3600 mg/day (reduce for renal)
3-8 weeks for titration with 2 weeks at max tolerated dose
Pregabalin 50 mg TID or 75 mg BID
Increase to 300 mg/day after 3-7 days then by 150 mg every 3-7 days as tolerated
600 mg/day (reduce for renal)
4 weeks
Lidocaine pathch 5%
1-3 patches daily for 12 hours
3 patches/day 3 weeks
Medications in Disguise
Medications in Disguise
Conclusions
1. Opioids as the adjuvant
2. Rational polypharmacy is the rule, not the exception
3. Understanding mechanisms of action will facilitate safe and effective polypharmacy
4. Give an appropriate trial and don’t forget to titrate
QUESTIONS?
Lee H. Stringer, Pharm.D., BCPS, FASCP, CPE
406-238-5590
