Pain Management in CKD

Transcription

1 What is Pain? Pain Management in CKD Timothy Nguyen, PharmD, BCPS Assistant Professor, Long Island University Morristown Medical Center 2012 May 19 A. Unpleasant sensory experience B. Unpleasant sensory and emotional experience C. Whatever the experiencing person says it is, existing whenever s/he says it does D. Associated with tissue damage 1 What is Pain? IASP: > Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage > Pain is always subjective Classification Acute vs. Chronic Cancer/Malignant Pain Neuropathic vs. Nociceptive Pain IASP Taxonomy. International Association for the Study of Pain Web site. efault.htm#pain. Accessed April 14, Acute vs. Chronic Pain Acute >Well-defined pattern of onset >Usually lasts <3 months >S & O signs may be present Chronic >Persists >3 months >Generally lacks objective signs Breakthrough >Usually precipitated by activity >May occur w/out identifiable cause Baumann TJ. Pain management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY:McGraw-Hill; 2005: Pain: Assessment Nociceptive vs. Neuropathic, or Both? Nociceptive > Aching, dull, throbbing, cramping, pressure Neuropathic > Tingling, burning, stabbing, or numb Baumann TJ. Pain management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY:McGraw-Hill; 2005:

2 Pathophysiology Nociceptive Pain >Arises from damage to non-neural tissue & activation of nociceptors Somatic >Skin, bone, joint, muscle >Throbbing, aching Visceral >Internal organ >Cramping, sharp Baumann TJ. Pain management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY:McGraw-Hill; 2005: Pathophysiology Neuropathic Pain >A lesion or dz of the somatosensory nervous system >Nerve damage >Burning, tingling, shooting pain > Pins & needles Baumann TJ. Pain management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY:McGraw-Hill; 2005: Large Needle Muscle cramp SOB Fluid accumulation Sit still for 4 hrs 9 10 Pain in Dialysis Pain Assessment >Assessment/INTEGRAL part of every patient >Requires UNDERSTANDING & what it FEELS like >You can NOT know unless been on dialysis >BELIEVE your pt report of pain

3 Characteristics of Pain: PQRST P Palliative factors/provocative factors What makes the pain better or worse? Movement, medications, onset Q Quality Describe the pain R Radiation Where is the pain? S Severity/Intensity How does this pain compare with other pain experienced? T Temporal factors Does the intensity of the pain change with time? How long does it last? Continuous, intermittent, breakthrough Baumann TJ. Pain management. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY:McGraw-Hill; 2005:761. General Principles >Start - lowest effective therapy >Use - simplest regimens >Substitute w/in a category b/f changing thx >ATC dosing may be superior to PRN >For continuous pain Used CR or LA dosage forms >Give PRN doses for breakthrough pain 14 Choosing an Agent Consider Duration of effect Potency Side effects Patient tolerance Allergies Dosage forms available WHO Three-Step Ladder Step 3 - Severe pain (7 10) Opioid for moderate to severe pain +/- Non-opioid +/- Adjuvant Step 2 - Moderate pain (4 6) Opioid (low) for mild to moderate pain + Non-opioid +/- Adjuvant Step 1 - Mild pain (1-3) Non-opioid +/- Adjuvant 15 The World Health Organization [Internet] [cited 2010 Jan 2]. Available from: ladder/en/ CKD & DIALYSIS Non-Opioid Agents Acetaminophen (APAP) Nonsteroidal anti-inflammatory drugs (NSAIDs) Acetylsalicylic acid (Aspirin, ASA) Tramadol (centrally acting synthetic opioid) Clinical Algorithms & Preferred Medications to Treat Pain in Dialysis Patients. Mid-Atlantic Renal Coalition (MARC). September

4 Acetaminophen Dose: mg q4-6hrs >Max: 3000 mg/day MOA >Inhibits synthesis of PG in CNS Indications >Treatment of mild-moderate pain >Anti-pyretic effect >NO anti-inflammatory effects Acetaminophen >Onset of action: <1 hour >Duration of action: 4-6 hours >Adverse reactions Renal & hepatic toxicity Cyclooxygenase (COX) Enzymes COX enzymes >Production of PGs COX-1 >Maintenance & protection of GI tract COX-2 >Inflammation & pain COX Inhibitors Aspirin >Equipotent inhibition of COX-1 & COX-2 NSAIDs >Potency of inhibition of COX-1 & COX-2 varies with drug Celexcoxib >Selective inhibition of COX-2 Aspirin (Acetyl Salicylic Acid, ASA) Dose: mg q4-6hrs Max: 4 g/day MOA: >Irreversibly inhibits COX-1 & 2 enzymes Inhibits PG synthesis Indication: >Treatment of mild-moderate pain >Anti-inflammatory & anti-pyretic effects

5 Aspirin >Onset of action: <1 hour >Duration of action: 4-6 hrs >AEs >Dyspepsia, GI ulcerations, heartburn >Anti-platelet agent May the risk for bleeding >Take with food or large volume of water or milk to minimize GI upset >Do not crush SR or EC tablets 25 Aspirin: DI > anticoagulant effects > methotrexate levels >Enhances responses to sulfonylurea drugs > bleeding if combined w/etoh & corticosteroids 26 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) MOA Reversibly inhibits COX-1 & 2 enzymes Inhibits PG synthesis Indication Treatment of mild-moderate pain Anti-inflammatory & anti-pyretic effects 27 Ibuprofen (Motrin, Advil ) Fenoprofen (Nalfon ) Flurbiprofen (Ansaid ) Ketoprofen (Orudis, Oruvail ) Oxaprozin (Daypro ) Naproxen (Naproxyn, Naprelan, Aleve, Anaprox ) Diclofenac sodium (Voltaren ) Indomethacin (Indocin ) Sulindac (Clinoril ) NSAIDs Meloxicam (Mobic ) Nabumetone (Relafen ) Tolmetin (Tolectin ) Ketorolac (Toradol ) Etodolac (Lodine ) Piroxicam (Feldene ) Phenylbutazone (Butazolidin ) Mecomenamate sodium (Meclomen ) Mefanamic acid (Ponstel ) NSAIDs Onset of action: <1 hour Duration of action: 4-6 hrs ADRs Dyspepsia, GI ulcerations, heartburn Take with food to minimize GI upset Do not crush SR or EC tablets 29 Black Box Warning (BBW) NSAID and COX II Inhibitor CI for treatment of perioperative pain in the setting of CABG surgery Ass ed with an ed risk of serious adverse CV thrombotic events, including MI & stroke May risk of GI irritation, ulceration, bleeding & perforation 5

6 Pain in HD Patients Pain in HD Patients Pain in HD Pts: prevalence, cause, severity, & mgt. AJKD 2003;42: >Prospective cohort >N = 205 Results: 50% reported problem w/pain Causes: diverse, musculoskeletal (50.5%), PN, PVD Pain in HD Pts: prevalence, cause, severity, & mgt. AJKD 2003;42: >55% reported worst w/24 hrs >32% w/pain but NO analgesics >29% (non-opioids), 26% (wk opioids), 10% (strong) >Pain Mgt Index ~75% ineffective mgt Pain in HD Patients No reason for w/holding analgesics if needed Regularly reviewing the pts & their meds Pain in HD Patients Pain is so severe that pts consider stopping HD Need: Good Assessment Realistic goals Ongoing monitoring Discuss psychosocial/depression issues Pain in HD Patients Underestimated & undertreated ~50% w/chronic pain ~82% w/moderate & severe pain Pain in HD Patients Why so undertreated? >Renal & drug dosing >Accumulation >Multiple meds >Co-morbid dz s >Pain mgt is not well taught Pain is undertreated in ESRD Pts. RPA 2003 Annual Mting. Presented 3/23/03 & Aging 1998;12:

7 Opioid Receptor Types Mu (µ) receptors >Analgesia, euphoria, respiratory depression, miosis (contraction of pupils), reduced GI motility Delta (δ) receptors >Dysphoria (dissatisfaction, restlessness, depression, anxiety), psychomimetic effects (hallucinations) Kappa (κ) receptors >Analgesia (primarily in spinal cord), sedation >Respiratory depression and miosis less intense than mu receptor Secondary Effects of Opioids CNS effects >Euphoria, drowsiness, apathy, mental confusion, n/v Respiratory effects >Depressant Cardiovascular effects >Peripheral vasodilation, ed peripheral resistance, inhibition of baroreceptors (orthostatic hypotension and fainting) GIT effects >Inhibits peristalsis (constipation) Urinary tract effects >Urinary retention 38 Tolerance Things to be aware of >State of adaptation in which extended exposure > effects of the drug Physical Dependence >State of adaptation manifested by w/drawal syndrome: >If abrupt cessation >Rapid dose reduction >Adm of antagonist >Sweating >Rhinorrhea >Anxiety >Restlessness >Insomnia S&S of w/drawal >Mydriasis (dilated pupils) 70 yo AAM, HD x5 yrs PMH: DM, HTN, CAD, CA, Chronic pain Which pain med is best? A. Acetaminophen B. Percocet C. Naproxen D. Fentanyl Clinical Algorithms & Preferred Medications to Treat Pain in Dialysis Patients. Mid-Atlantic Renal Coalition (MARC). September

8 Clinical Algorithms & Preferred Medications to Treat Pain in Dialysis Patients. Mid-Atlantic Renal Coalition (MARC). September Clinical Algorithms & Preferred Medications to Treat Pain in Dialysis Patients. Mid-Atlantic Renal Coalition (MARC). September Fentanyl Patches >Chronic & stable pain >Initiate after IR opioid dose is established >Takes ~12-24 hrs >Need PRN Fentanyl >Clearance es in CKD Methadone >Excreted in the urine & feces >High protein-binding & MW >High protein-binding >Large Vd & low water solubility >Large Vd >May be removed by certain dialysis filters 47 >Poorly removed by dialysis 48 8

9 Methadone Hydromorphone >BBW prolong QTc/Torsade de point ++Baseline QTc & repeat EKG if >100 mg/day >Only knowledgeable prescribers >Not tolerate w/hydromorphone or fentanyl >Beware of multiple DI & adjust dose prn >Also used for detoxification >Metabolized via liver >Renally excreted >CKD: lower doses or extended dosing intervals >Water soluble >Small Vd & low MW >Dialyzable (?, plasma level es 60%) Morphine >Metabolized via liver >Renally excreted & metabolite can accumulate >Active metabolite is more potent analgesic +Contribute to resp depression & CKD +Cross BBB +CNS effects: somnolence, dizziness, hallucinations 51 Morphine >Low protein-binding >Moderate water solubility >Likely removed by HD +However, due to slow diffusion from CNS +Delays removal > Rebound effect post HD +Unpredictable analgesia & sedation 52 Hydromorphone & Hydrocodone Oxycodone >Hydrocodone is metabolized to hydromorphone via CYP2D6 +Poor metabolizers: little/no analgesia >Other metabolites: +Has no analgesic activity +Neurotoxicity +Agitation, confusion, hallucinations >Renally excreted >Water soluble; Small Vd; Low MW 53 >Metabolites +T 1/2 s in CKD +Excretion severely impaired +CNS toxicity & sedation in CKD >Large Vd >50% protein-bound >Water soluble 54 9

10 Codeine Meperidine >Metabolites +Renally excreted +Clearances in CKD +Accumulation, causing intoxication +Respiratory arrest +Profound narcolepsy >Large Vd & MW >Not extensively dialyzed +Accumulate to toxic levels 55 >Metabolizes to normeperidine +Toxic & long-lasting +T 1/2 ~5-10x longer than meperidine & in CKD +Excrete via kidney +Excessive accumulation + CNS hyperexcitability & seizures >Water soluble; Small MW 56 CKD & DIALYSIS >Challenging b/c risk of overdose >Altered drug clearance >Accumulation of parent &/or metabolites >Dialysis >Filter pore size >Flow rate >Efficiency of technique >Intermittent vs. continuous >Resp depession, HOTN, CNS toxicity 57 Opioid CKD Dialysis Comment Morphine Cautiously; adjust dose Hydromorphone, Hydrocodone Cautiously; adjust dose Cautiously & monitor for rebound pain effect or Do Not use Cautiously & monitor pt carefully for sx s of opioid overdose -CKD: Metabolites can accumulate causing ed therapeutic & AE s -HD: Both parent drug & metabolites can be removed with dialysis -CKD: The 3-glucuronide metabolite can accumulate & cause neuro-excitatory effects -HD: The parent drug can be removed, but metabolite accumulation is a risk Methadone Appears safe Appears safe -CKD: Metabolites are inactive -HD: Metabolites are inactive, but use caution b/c parent drug is not dialyzed. Fentanyl Oxycodone Appears safe; Appears safe however, a dose is necessary Cautiously w/careful monitoring; adjust dose Do Not Use -CKD: No active metabolites & appears to have no added risk of AE s; monitor w/long term use -HD: Metabolites are inactive, but use caution b/c poorly dialyzable -CKD: metabolites & parent drug can accumulate causing toxic & CNS-depressant effects. -HD: No data on oxycodone & its metabolites in dialysis Codeine Do Not Use Do Not Use -CKD: metabolites can accumulate causing AE s -HD: the parent drug & metabolites can accumulate causing AE s Meperidine Do Not Use Do Not Use -CKD: metabolites can accumulate causing ed risk of AE s -HD: Few data; risk of AE s 58 Opioid Allergies Allergies: generally no cross-reactivity between classes >Phenanthrenes = Morphine analogues Codeine, oxycodone, hydromorphone, hydrocodone, levorphanol >Phenylpiperidines = Meperidine analogues Fentanyl, meperidine >Diphenylheptanes = Methadone analogues Methadone Opioid Conversions Calculate 24 hr dose of current drug Translate to equianalgesic 24 hr dose of PO morphine Translate to equianagesic dose of new drug with appropriate interval & dose 60 10

11 Opioid Conversions Opioid Conversions >Hydromorphone 4 mg po q4h >How much IV to give? >Morphine 10 mg po q6h >How much hydromorphone PO to give? Mgt of Opioid AE s Acute excessive sedation, RR (low O 2 ) >Naloxone 0.4 mg/10 ml NS IV q1-2m til arouses >Monitor for return of sedation & slow RR Chronic N/V >Prochlorperazine >Haloperidol >Metochlopramide >Dimenhydrinate >Ondansetron Constipation Mgt of Opioid AE s >Docusate + Senna >Lactulose Cognitive Impairment > opioids Neuropathic Pain Gabapentin >Start 100 mg po HS & wkly by 100 mg to a max of 300 mg Occasionally up to 600 mg Pregabalin >25 mg HS & qfewdays to 100 mg >~2-4 wks; if inadequate, d/c; Start desipramine Desipramine >10 mg HS & 150 mg Adjuvant Analgesics Assists in ing pain perception Alone or in combo w/an opioid or nonopioid >Neuropathic >Musculoskeletal >Cancer >Headache

12 Adjuvant Analgesics Adjuvant Analgesics Antidepressants >TCA (amitriptyline, desipramine, nortriptyline) >SSRIs/SNRIs (duloxetine, venlafaxine) Anticonvulsants >Gabapentin >Pregabalin >Carbamazepine >Valproic acid & divalproex acid >Topiramate 67 Skeletal Muscle Relaxants >Carisoprodol, cyclobenzaprine >Baclofen, tizanidine Topical Analgesics >Lidocaine Patch, Cream, Solution >Emla cream >Corticosteroids 68 THANK YOU Timothy Nguyen, PharmD, BCPS QUESTION? Assistant Professor of Pharmacy Practice AMSCOP, Long Island University Clinical Pharmacy Specialist, Nephrology & Dialysis Mount Sinai Medical Center, NYC Adjunct Pharmacology Professor Saint Peter s College