Tina Guna Gaja Leban Žiga Sotler. Modul: Na dokazih temelječa medicina 14. skupina Ljubljana,
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1 Tina Guna Gaja Leban Žiga Sotler Modul: Na dokazih temelječa medicina 14. skupina Ljubljana,
2 nevropatska bolečina= bolečina, ki je posledica strukturne okvare živčevja ali njegovega motenega delovanja najpogostejše: bolečina pri diabetični nevropatiji, postherpetična nevralgija in trigeminalna nevralgija Katera zdravila so najučinkovitejša pri zdravljenju periferne nevropatske bolečine? Ali so varna, v kakšnih odmerkih jih predpišemo?
3 bolnikov z nevropatsko bolečino v Sloveniji je med deset tisoč in nekaj deset tisoč incidenca boleče distalne simetrične polinenevropatije v sklopu DM je približno 5000, vsako leto dodatno še 600 do 900 bolnikov s postherpetično bolečino nevropatsko bolečino zelo redko povsem umirimo, velik dosežek pri zdravljenju je že, če jo zmanjšamo za 50% zdravila prvega izbora: antidepresivi, in sicer TCA (amitriptilin) in SNRI (duloksetin, venlafaksin), ter antikonvulzivi (gabapentin, pregabalin)
4 1. Zaletel M. Sodobni pristop k diagnosticiranju in zdravljenju nevropatske bolečine. In: Kersnik J, Turk H, urednika. 6. Kokaljevi dnevi: Poškodbe v osnovnem zdravstvu. Zbornik predavanj; 2006 Apr 6-8; Kranjska Gora, Slovenija. Ljubljana: Združenje zdravnikov družinske medicine SZD; p (Združenje zdravnikov družinske medicine Slovenije) 2. Plested M, Budhia S, Gabriel Z. Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review. BMC Neurology 2010; 10:116 (PubMed) 3. Watson CPN, Gilron I, Sawynok J. A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain. Pain Res Manage 2010; Vol 15 No 3 May/June: (PubMed)
5 4. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the Treatment of Neuropathic Pain. Basic & Clinical Pharmacology & Toxicology 2005; 96: (PubMed) 5. Dworkin RH, O'Connor AB, Audette J, et al. Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clin Proc. 2010; 85(3)(suppl): S3-S14 (PubMed) 6. Quilici S, Chancellor J, Löthgren M, et al. Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain. BMC Neurology 2009; 9:6 (PubMed) 7. Chou R, Carson S, Chan BKS. Gabapentin Versus Tricyclic Antidepressants for Diabetic Neuropathy and Post-Herpetic Neuralgia: Discrepancies Between Direct and Indirect Meta-Analyses of Randomized Controlled Trials. J Gen Intern Med 2008; 24(2): (PubMed)
6 Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review raziskava je vključevala 17 študij med , in sicer 9 s pregabalinom, 7 z lidokainskim obližem in 1 z duloksetinom. nobena od raziskav ni primerjala zdravil direktno med seboj, številne druge slabosti pregabalin se je izkazal za učinkovitejšega od duloksetina v zdravljenju periferne nevralgične bolečine, signifikantno izboljšanje kakovosti življenja
7 A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain pregled 27 raziskav zdravljenja večinoma diabetične in postherpetične nevralgije od , 17 jih je primerjalo učinkovitost različnih analgetikov, 10 jih je preučevalo razlike med zdravili iz iste analgetične skupine primerjava NNT (number needed to treat) in NNH (number needed to harm), kakovosti življenja niso upoštevali
8 Amitriptilin: NNT , NNH 14,7 Duloksetin: NNT 4.1-5, NNH je višji od amitriptilina Venlafaksin: NNT 4.5 Gabapentin: NNT 3.2-5, NNH 26,1 Pregabalin: NNT 3,4
9 Antidepressants in the Treatment of Neuropathic Pain pregled izsledkov več randomiziranih kliničnih študij namen: primerjava učinkovitosti različnih skupin antidepresivov pri zdravljenju nevropatske bolečine med sabo in z drugimi skupinami zdravil TCA so učinkovitejši od gabapentina, tramadola in oksikodona, njim primerljiva je učinkovitost SNRI, medtem ko so SSRI manj učinkoviti. (Primerjava učinkovitosti antidepresivov: NNT TCA 2,3, NNT SNRI 4,6, SSRI 6,8) (Primerjava učinkovitosti z drugimi zdravili: NNT gabapentin 4,3, NNT oksikodon 2,6, NNT tramadol 3,5-4,8) kontraindikacije in stranski učinki TCA favorizirajo uporabo SNRI kljub nekoliko slabši učinkovitosti, obetajoči so izsledki raziskav za bupropion
10 Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update pregled izsledkov več randomiziranih kliničnih študij namen: oblikovanje smernic za farmakološko zdravljenje nevropatske bolečine zdravila prve izbire: TCA (nortriptilin, desipramin), SNRI (duloksetin, venlafaksin), vezalici alfa(2)-delta podenote kalcijevih kanalčkov (gabapentin, pregabalin), lokalna aplikacija lidokaina zdravila druge izbire: opioidni analgetiki, tramadol novejša zdravila: lokalna infiltracija z botulinum toksinom, lokalna aplikacija kapsaicina, lakozamid, SSRI, kombinacija učinkovin večinoma smernice izdelane na študijah zdravljenja PHN in DPN
11 Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain metaanaliza večih študij kriterij učinkovitosti: zmanjšanje bolečine v 24h, občutek pacienta o izboljšanju, stranski učinki občutek o izboljšanju preferira pregabalin 24h zmanjšanje bolečine: enako vrtoglavica kot stranski učinek duloksetin
12 Gabapentin Versus Tricyclic Antidepressants for Diabetic Neuropathy and Post-Herpetic Neuralgia: Discrepancies Between Direct and Indirect Meta-Analyses of Randomized Controlled Trials primerjava med gabapentinom in TCA proti placebu metaanaliza gabapentin je slabši pri lajšanju bolečine (50% manjša verjetnost za lajšanje bolečine) še posebej pri diabetični nevropatični bolečini
13 najučinkovitejši TCA, čeprav najnovejša priporočila poudarjajo, da gre za citiranje starejših študij iz osemdesetih in devetdesetih let, s številnimi metodološkimi pomanjkljivostmi potreba po RCT
14 TCA najučinkovitejši pri zdravljenju periferne nevropatske bolečine, če pa upoštevamo še kakovost življenja sta na 1. mestu gabapentin oz. pregabalin stranski učinki: SNRI < TCA, antikonvulzivi so relativno varni Amitriptilin: zdravilo I. izbora, učinek je odvisen od plazemske koncentracije, neželeni učinki: suha usta, omotična zaspanost, potenje, ortostatska hipotenzija, konstipacija, utrujenost, retenca urina kontraindikacije: motnje srčnega ritma, srčno popuščanje, epilepsija velika variacija med posamezniki
15 SNRI: manj učinkoviti od TCA, a imajo manj stranskih učinkov (slabost, bruhanje, dispepsija) titriranje je enostavnejše, nimajo večjih kontraindikacij in so bolje tolerirani Gabapentinoidi: podoben analgetičen učinek kot TCA gabapentin in pregabalin redko vstopata v interakcije z drugimi zdravili, stranski učinki omotice in sedacije so odvisni od odmerka (titriranje), potrebna je prilagoditev odmerka pri ledvični bolezni kombinacija zdravil: TCA ali venlafaksin in gabapentin in opiodi (razen tramadola), odsvetuje se kombinacija različnih antidepresivov in kombinacija antidepresivov in tramadola
16
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