ANTIKOAGULANTU LIETOŠANA PACIENTAM AR HRONISKU NIERU SLIMĪBU
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1 Ramona Valante Rīgas Stradiņa universitātes TIF 1.gada rezidente Neiroloģijas specialitātē ANTIKOAGULANTU LIETOŠANA PACIENTAM AR HRONISKU NIERU SLIMĪBU
2 HRONISKA NIERU SLIMĪBA Kritēriju (1 no 2) 1. Nieru bojājums >3 mēnešus, kurš konstatēts pēc nieru struktūras vai funkciju novirzēm ar samazinātu GFĀ vai bez tā un kurš manifestējas ar kādu no: a. Morfoloģiskām pārmaiņām vai b. Nieru bojājuma marķieriem asinīs, urīnā vai vizualizācijas metodēs 2. GFĀ <60 ml/min >3 mēnešus ar vai bez nieru bojājuma pazīmēm
3 HRONISKAS NIERU SLIMĪBAS STADIJAS Stadija Apraksts GFĀ (ml/min) 1 Nieru bojājums ar normālu GFĀ >90 2 Nieru bojājums ar nedaudz samazinātu GFĀ Mēreni samazināts GFĀ Izteikti samazināts GFĀ. Apsverama nieru aizstājēj terapija 5 Termināla nieru mazspēja. Pacientiem nepieciešama nieru aizstājēj terapija <15
4 FAKTORI, KAS IETEKMĒ HEMOSTĀZI HNS GADĪJUMĀ Faktori, kas veicina asiņošanu: Trombocītu patoloģijas Defektīva ciklooksigenāzes aktivitāte Paaugstināta vaskulārā PGI2 veidošanās Izmainīts von Willebranda faktors Netiešie faktori, kas veicina asiņošanu: Urēmiski toksīni Anēmija, izmainīta asins reoloģija Eritropoetīna deficīts
5 FAKTORI, KAS IETEKMĒ HEMOSTĀZI HNS GADĪJUMĀ Faktori, kas samazina recēšanu: Ateroskleroze un difūzs endotēlija bojājums Disfunkcionāls aktivētā proteīna C metabolsms Plasmina inhibīcija, sakarā ar paaugstināto lipoproteīnu līmeni Defekts glikoproteīna GPIb ekspresijā
6 Atkarībā no darbības mehānisma visus antikoagulantus iedala 2 grupās: 1. Tiešas darbības antikoagulantos, kas ietekmē recēšanas faktorus tieši asinīs (heparīni, heparinoīdi, nātrija hidrocitrāts un hirudīni) 2. Netiešie darbības antikoagulantos, kas nomāc recēšanas faktoru (protrombīna u.c.) sintēzi aknās
7 TIEŠAS DARBĪBAS ANTIKOAGULANTI Heparīns Mazmolekulārie heparīna preparāti: Nadroparīns (Fraxiparin) Deltaparīns (Fragmin) Enoksaparīns (Clexane) Sintētiskie pentasaharīdi: Fondaparinukss (Fondaparin) Perorālie Xa faktora inhibitori: Rivaroksibans (Xarelto) Apiksabans (Eliquis) Tiešie trombīna inhibitori: Dabigatrans (Pradaxa)
8 NETIEŠAS DARBĪBAS ANTIKOAGULANTI 4-oksikumarīna atvasinājumi Varfarīns (Orfarin) Indāndiona atvasinājumi Fenindions Anisidions
9 ANTIKOAGULANTU KLĪRENSA CEĻŠ Nerenāls Daļēji renāls (<50%) Renāls (>50%) MMH Fondoparinuks Varfarīns Dabigatrāns Rivaroksibāns - - +
10 VARFARĪNS UN HNS HNS var ietekmēt medikamentu farmakokinētiku: Samazinot ne renālo klīrensu un izmainot medikameta metabolismu aknās (CYP 450) CYP2C9 aktivitāte terminālās nieru mazspējas gadījumā var būt samazināta līdz pat 50% Pacientiem ar HNS 3-4 pakāpi varfarīns jāuzsāk mazākās devās, lēnāk titrējot Nepieciešams biežāk kontrolēt INR Megan E. Kleinow et al, Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist- Managed Anticoagulation Clinic
11 MMH UN HNS MMH tiek izvadīti no organisma caur nierēm Pastāv medikamentu akumulācijas risks, pacientiem traucētu nieru darbību
12 NADROPRIN Nadroparīna ekskrēcija galvenokārt notiek caur nierēm, tādēļ pacientiem ar nieru darbības traucējumiem pastiprinās nadroparīna iedarbība Pacienti ar nieru darbības traucējumiem ir pakļauti paaugstinātam asiņošanas riskam un ir jāārstē piesardzīgi. Pacientiem, kuriem GFĀ ir robežās no 30 līdz 59 ml/min, ir nepieciešama devas samazināšana
13 NADROPARIN Pastāv korelācija starp nadroparīna klīrensu un GFĀ. Pacientiem ar mēreniem nieru darbības traucējumiem (GFĀ ml/min) vidējā medikamenta koncentrācija plazmā palielinās par 52% eliminācijas pusperiods paaugstināts par 39%, salīdzinot ar veseliem brīvprātīgajiem. Pacientiem ar smagiem nieru darbības traucējumiem (GFĀ ml/min) vidējā medikamenta koncentrācija plazmā palielinās par 95% eliminācijas pusperioda ilgums palielinās par 112%, salīdzinot ar veseliem brīvprātīgajiem. Bazineta A, Almanrica K, et al, Dosage of enoxaparin among obese and renal impairment patients, Thrombosis Research (2005) 116, 41 50
14 NADROPARIN Trombembolisku traucējumu profilakse pacientiem ar viegliem nieru darbības traucējumiem (ja kreatinīna klīrenss ir 60 ml/min vai lielāks) preparāta deva nav jāsamazina. Vidēji smagi un smagi nieru darbības traucējumi ir saistīti ar nadroparīna iedarbības pastiprināšanos. Šādi pacienti ir pakļauti paaugstinātam trombembolijas un asiņošanas riskam. Pacientiem ar vidēji smagiem nieru darbības traucējumiem (ja GFĀ ir robežās no 30 ml/min līdz 59 ml/min) ir vēlams samazināt devu, tā jāsamazina par 25-33% Pacientiem ar smagiem nieru darbības traucējumiem (ja GFĀ ir <30 ml/min), deva jāsamazina par 25-33% Bazineta A, Almanrica K, et al, Dosage of enoxaparin among obese and renal impairment patients, Thrombosis Research (2005) 116, 41 50
15 DABIGATRAN Uzsākot Dabigatrāna terapiju, pacientam jānosaka nieru funkcionālais stāvoklis, tas periodiski jākontrolē arī terapijas laikā Pacientiem ar smagiem nieru darbības traucējumi ( GFĀ < 30 ml/min) terapija ar Pradaxa ir kontrindicēta Par pacientiem ar vidēji smagiem nieru darbības traucējumiem (GFĀ ml/min) klīniskā pieredze ir ierobežota. Šo pacientu ārstēšanā jāievēro piesardzība. Ieteicamā deva ir 110 mg 2 reiz dienā
16 NIERU DARBĪBAS TRAUCĒJUMU IETEKME UZ DABIGATRĀNA FARMAKOKINĒTIKU Nieru funkcija GFĀ (ml/min) Koncentrācija plazmā pēc vienas devas Maksimālā koncentrācija Normāla >90 1x 1x 13 Nedaudz samazināta ,5x 1,1x 15 Vidēji izteikti traucējumi Smagi nieru darbības traucējumi ,2x 1,7x ,3x 2,1x 27 T ½ (h) John W Eikelboom, Explaining the RE-LY Trial Can J Hosp Pharm Jul- Aug; 63(4):
17 RIVAROXIBAN Rivaroxiban koncentrācija plazmā ir palielināta pacientiem ar 4-5 stadijas HNS Nieru funkcionālie rādītāji visiem pacientiem ir jākontrolē 1x gadā un vismaz 2x gadā pacientiem ar nieru darbības traucējumiem
18 RIVAROXIBAN Guidance on the use of rivaroxaban for stroke prevention in atrial fibrillation (AF) - %20formatted.pdf
19 PALDIES PAR UZMANĪBU!
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