Pharmacotherapy of chronic pain
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1 Pharmactherapy f chrnic pain Addictin, detxificatin and periperative management Bart Vaes Prmtr: Prf. Dr. B. Mrlin
2 Intrductin Chrnic pain = pain withut apparent bilgical value that has persisted beynd nrmal tissue healing time usually taken t be 3 mnths (IASP). Opiids: Acute pain, pstsurgical, cancer r end-f-life care Chrnic nncancer pain (CNCP) Neurpathic (e.g. pstherpetic neuralgia) Nciceptive (e.g. degenerative) ADDICTION?!
3 Opiids Mrphine (MS Direct, MS Cntin ), Hydrmrphne (Palladne ), Fentanyl (Durgesic ), Oxycdne (OxyCntin, OxyNrm ) and Methadne (Mephenn ) µ-receptr: spinal and supraspinal analgesia, reduced gastrintestinal mtility, respiratry depressin, euphria and sedatin Side-effects Cnstipatin, urinary retentin Euphria Sedatin, smnlence, dizziness Respiratry depressin, brnchspasm Hyptensin, bradycardia Misis Nausea and vmiting Others: itch, cugh suppresin, hives, rigidity Withdrawal Diarrhea, abdminal cramp, rhinrrhea, lacrimatin Dysphria, anhednia Agitatin, sleeplessness Hyperventilatin Hypertensin, tachycardia Mydriasis Nausea and vmiting Cld, pale, pilerected skin, yawning, shaking, fever
4 Dependence: Physical: withdrawal Abrupt cessatin, dse reductin, decreasing bld levels, antagnist. Psychlgical: craving : Need fr its psitive effects r t avid withdrawal Tlerance Diminutin f ne r mre f the drug s effects ver time => dse escalatin T nausea, sedatin and respiratry depressin, nt t cnstipatin and misis. Addictin: Primary, chrnic, neurbilgical disease Genetic, psychscial, and envirnmental influences 4 C s: Impaired cntrl ver drug use, cmpulsive use, cntinued use despite harm, craving.
5 Addictin Epidemilgy: Opiid use: 0.6% - 0.8% r millin piid users Addictin: 0,19% - 0,27% f patients n chrnic piid therapy UNODC, Wrld Drug Reprt 2012
6 Neurbilgy Pharmalgical effects: neuradaptatins => neurplasticity 1. Binge/intxicatin: meslimbic dpamine system (ventral tegmental area (VTA), nucleus accumbens, amygdala and prefrntal crtex ) => acute rewarding (speed f delivery!) 2. Withdrawal/negative affect: extended amygdala (negative reinfrcement, decrease in dpaminergic activity) 3. Preccupatin/anticipatin (craving): baslateral amygdala (prcessing f cnditined reinfrcement), hippcampus (memries), prefrntal crtex (executive cntrl) Kb GF, Vlkw ND. Neurcircuitry f addictin. Neurpsychpharmaclgy 2010 Jan;35(1):
7 Ballantyne JC, LaFrge KS. Opiid dependence and addictin during piid treatment f chrnic pain. Pain 2007 Jun;129(3):
8 Management f addictin 1. Detxificatin: withdrawal Slw tapering + Psychscial therapy (relapse!) Methadne (full µ-agnist) slw nset f actin (2-4h), lng eliminatin half-life (28h) Withdrawal reslves mre quickly than with buprenrphine Buprenrphine (partial µ-agnist) Sublingual (Subutex ), transdermal (Transtec, Temgesic ) Onset 1-3h, half-life 37h Safety prfile 2. Opiid maintenance therapy (OMT): reduce craving, harms en csts, avid illicit drug use, imprve QL and psychscial functining Methadne: mst effective Buprenrphine: inferir higher dses f methadne cannt be administered methadne is nt well tlerated in a primary care setting ( safety prfile)
9 Clnidine/Lfexidine (α-2 adrenergic agnists) Amelirate piid withdrawal symptms Reduce nradrenergic hyperactivity Side effects: hyptensin and sedatin Naltrexne (µ-receptr antagnist) Pst-piid detxificatin stage (blck f 48h) Reductin f reincarceratins => relapse preventin Lng-acting frmulatins: nce mnthly extended-release frmulatin (Vivitrl ) Abuse preventin (Embeda ): released by chewing r crushing Nalxne (µ-receptr antagnist) Extensive first-pass effect: lw ral, high IV biavailability Abuse preventin: cmbinatin with sublingual buprenrphine (Subxne )
10 Periperative management f the piidtlerant patient GOALS: effective analgesia, prevent withdrawal Preperative management: - Identificatin - Preperative evaluatin (baseline piid dsage!) - Multidisciplinary cmmunicatin - Educatin - Investigatin (methadn: QT prlngatin) - Multimdal pain analgesia (NSAIDs, paracetaml, gabapentine, pregabaline) => piid-sparing effect - Give regular piid dse n the mrning f the surgery
11 Intraperative management: - Give baseline piid dse, if nt recieved yet - Cntinue transdermal fentanyl patches - Risk f aspiratin - Higher piid requirements (50-300%) Heart rate, bld pressure, respiratry rate, pupil dilatin Spntaneusly breathing Fentanyl challenge test. - NOT: remifentanil, nalxne, flumazenil. - Multimdal analgesia: paracetaml, NSAIDs, COX-2 inhibitrs, ketamine, clnidine and dexmedetmidine.
12 Pstperative management: - Higher pstperative piid requirements (30-50%): apprpriate assessment and mnitring - Maintain baseline piid administratin - PCIA: basal infusin with 50% higher blus dses - PCEA: higher blus dses and shrter lck-ut intervals - Reginal anesthesia. - Cntinue multimdal analgesia.
13 CONCLUSIONS Opiids are increasingly used fr the treatment f chrnic nncancer pain (CNCP) Little is knwn abut the lng-term effects like the develpment f addictin Addictin is a primary, chrnic, neurbilgical disease, influenced by genetic, psychscial, and envirnmental factrs. Treatment include detxificatin using tapered methadne r buprenrphine, α-2 adrenergic agnists and naltrexne r nalxne In piid maintenance therapy (OMT), methadne is mst widely used Cmplete treatment shuld als include effective psychscial therapy
14 Grwing numbers f chrnic pain patients n piids are facing surgical interventins but there is limited evidence regarding the periperative management in this ppulatin Cnsensus recmmendatins include (expert pinins) Maintain baseline piid requirements Prvide higher intra- and pstperative piid needs due t tlerance Prvide additinal multimdal analgesia Use PCIA r PCEA with higher blus dses and shrter lck-ut intervals Use reginal anesthesia
15 Questins?
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