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Farmacologie > Tratamentul antiviral in hepatitele cronice > Flashcards

Tratamentul antiviral in hepatitele cronice Flashcards

1
Q

Masuri generale in hepatitele cronice

A

Alimentatie echilibrata
CI consum alcool
Efort fizic moderat in forme inactive
Restrictia efortului fizic in formele active

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2
Q

Obiectivele terapiei antivirale

A 
Suprimarea replicarii virale
Scaderea infectivitatii
Normalizarea probelor hepatice
Ameliorare histologica
Prevenirea progresiei, complicatiilor
Cresterea supravietuirii
Evitarea aparitiei rezistentei virale
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3
Q

Indicatii pentru tratamentul HBV

A

Nivele serice crescute de ADN-HBV sau ALAT
CH
Risc de reactivare a infectiei (imunosupresie, chimioterapie)

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4
Q

Vindecarea functionala a HBV

A

Nivel nedetectabil al ADN-HBV

seroconversia Ag-HBs la Ac-antiHBs

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5
Q

Clase de medicamente utilizate in tratamentul HBV

A

IFN a

Analogi nucleozidici

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6
Q

Ce sunt INTERFERONII?

A

citokine cu proprietati antivirale (IFN tip I - alfa, beta; IFN tip III - lambda), imunomodulatoare (IFN tip II - gamma), antiproliferative specifice

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7
Q

IFN - mecanism de actiune

A

+ sist JAK-STAT -> efecte antivirale directe si indirecte
DIRECT: + transcriptia unor gene specifice care codifica > 20 de P antivirale
INDIRECT: + Mo, Mfg, NK, LyT citotoxice, LyB

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8
Q

IFN - farmacocinetica

A

Admin parenterala im/sc - forma pegylata (+ polietilenglicol printr-o legatura covalenta) -> abs incetinita, Cl redus, Cp mai mare => admin 1/sapt

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9
Q

IFN - indicatii

A

HBV - tratament de prima linie
Virus delta
HPV
Alte infectii virale - herpetice, CMV, transplant renal, HIV
Imunomodulare si antitumoral: neo mieloproliferative si leucemii (LMC - prima linie), MM, limfom non-Hodgkin, melanom malign, sarcom Kaposi, MS

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10
Q

IFN - RA

A 
sindrom pseudogripal
leucopenie, trombocitopenie, anemie
depresie, psihoza, coma, convulsii
hTA, aritmii, IMA, AVC, ischemie periferica
inapetenta, scadere ponderala
hepatice si metab - creste E hepatice, scade calcemia, creste potasemia
rash, alopecie
efecte autoimune
efect teratogen
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11
Q

IFN - CI

A 
Psihoza, depresie, boli neurologice
CH decompensata
boli CV simptomatice
citopenii
transplant de organe (Exceptie: FICAT)
DZ decompensat
boli autoimune
sarcina
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12
Q

Analogi nucleozidici - reprezentanti

A 
ENTECAVIR
TENOFOVIR
ADEFOVIR DIPIVOXIL
LAMIVUDINA
TELBIVUDINA
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13
Q

Entecavir - mecanism de actiune

A

analog de guanozina -> fosforilare ic => entecavir trifosfat -> - polimeraza virala => - replicarea virala

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14
Q

Entecavir - farmacocinetica

A

Admin orala - A reduse de alimente
D larga
E renala prin FG si secretie tubulara - ! ajustarea dozelor la ClCr <50 ml/min

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15
Q

Entecavir - indicatii

A

HBV la adulti si copii >2 ani (I linie)
+ tenofovir -> CH decompensata
+ antiretrovirale -> coinfectia HBV si HIV

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16
Q

Entecavir - RA

A

exacerbare acuta a hepatitei B la intreruperea tratamentului
rezistenta
cefalee, ameteli, astenie, greturi
acidoza lactica, hepatomegalie + steatoza

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17
Q

Tenofovir - forme

A

promedicament - 2 forme: dipivoxil fumarat (TDF) si alafenamida (TAF)

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18
Q

Tenofovir - mecanism de actiune

A
  • ADN polimeraza virala
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19
Q

Tenofovir - farmacocinetica

A

Bd crescuta de admin cu alimente grase

reducerea dozelor la ClCr < 50 ml/min

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20
Q

Tenofovir - indicatii

A

HBV adulti si copii > 2ani (I linie)
Paciente gravide (clasa de risc B)
+ emtricitabina - HIV

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21
Q

Tenofovir - RA

A

exacerbarea acuta a hepatitei la intreruperea tratamentului
scaderea functiei renale - ! monitorizare
la gravide - scade densitatea osoasa la copil

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22
Q

Adefovir dipivoxil - mecanism de actiune

A

analog al AMP -> activat cel prin transf in difosfat => - ADN polimeraza si revers transcriptaza

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23
Q

Adefovir - farmacocinetica

A

Admin orala sub forma de promedicament
A rapida, neinfluentata de alim
hidrolizat de esteraze
E renala prin FG si secr tubulara - ! reducere doze la ClCr <50ml/min

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24
Q

Adefovir - indicatii

A

HBV - linia II

HIV (dar a fost abandonat)

25
Q

Adefovir - RA

A

NEFROTOXIC - dependent de doza, reversibil (crest Cr, hipofosfatemie, acidoza, proteinurie)
risc crescut: afectare renala preexist, trat de lunga durata, doze mari
Cefalee, discomfort abdominal, diaree, astenie
Exacerbare acuta
acidoza lactica, hepatomegalie, steatoza
clasa de risc C in sarcina

26
Q

Lamivudina - mecanism de actiune

A

Analog nucleozidic - enatiomer de dideoxitiacitidina -> tranf in lamivudina trifosfat -> - competitiv ADN polimeraza HBV si revers transcriptaza HIV => X sint P virale

27
Q

Lamivudina - farmacocinetica

A

Admin orala - A rapida, neinfl de alim, Bd mare
E renala - ! ajustare doze la ClCr < 50 ml/min
mutatii punctiforme ale genei care codif polimeraza virala => REZISTENTA - incrucisata cu emtricitabina si asoc cu rezist la famciclovir

28
Q

Lamivudina - indicatii

A

HBV - nu de prima linie dat aparitiei rezist

HIV + cu antiretrovirale

29
Q

Lamivudina - RA

A

Bine tolerata - greturi, tulb GI, cefalee, neutropenie

tratamentul limitat de aparitia rezistentei

30
Q

Telbivudina - mecanism de actiune

A

sub forma de trifosfat - ADN polimeraza virala si replicarea virusului

31
Q

Telbivudina - indicatii

A

HBV la pacienti naivi, adulti si copii >16 ani - linia II

32
Q

Telbivudina - RA

A

Bine tolerata - creste CK si miopatie, greturi, varsaturi, diaree

33
Q

Scheme de tratament HBV

A

1, PegIFNa 48 S
2. Entecavir/ tenofovir/ adefovir/ lamivudina > 1 an cu eval la 6 luni (ALAT, ADN-HBV, seroconversia HBe), durata tratamentului stabilita in functie de raspunsul la tratament

34
Q

Tratamentul HCV - indicatie si obiective

A

Indic: la TOTI pacientii cu infectie
Obiectiv: eradicarea infectiei prin rasp virusologic sustinut (RVS) = nivele nedetectabile ale ARN-HCV la 12 S dupa initierea tratamentului antiviral

35
Q

Inhibitorii de NS5B polimeraza - reprezentanti

A

SOFOSBUVIR

DASABUVIR

36
Q

Sofosbuvir - mecanism de actiune

A

analog de 5’ UMP, activat intracel -> - polimeraza virala

37
Q

Sofosbuvir - farmacocinetica si spectru

A 
Admin orala, Bd mare
Leg moderata de P plasm
M hepatic -> metabolit inactiv -> E urinar
! se poarte admin in CH decompensata
! ajustare doze la ClCr < 30 ml/min
activ pe TOATE genotipurile virale
38
Q

Sofosbuvir - indicatii

A

HCV 1/zi in combinatie cu alte antivirale

39
Q

Sofosbuvir - RA

A

bine tolerat, astenie, cefalee, greata, insomnie, prurit

40
Q

Sofosbuvir - interactiuni

A

substrat pt P-gp

+ amiodarona - monitoriz AV timp de 2 sapt pt ca pot produce bk si stop cardiac

41
Q

Dasabuvir - farmacocinetica

A

admin oral - Bd crescuta de alim bogate in grasimi
legare crescuta de alb
M CYP2C8 - ! interactiuni

42
Q

Dasabuvir - indicatii

A

HCV genotipul 1 12 sapt in asociere cu RITONAVIR+PARITAPREVIR+OMBITASVIR

43
Q

Inhibitori de NS5A proteaza

A 
DACLATASVIR
LEDIPASVIR
VELPATASVIR
OMBITASVIR
ELBASVIR
44
Q

Daclatasvir

A
  • potential crescut de interactiuni medicamentoase

Indic: HCV genotip 1 si 3 (I linie in genotipul 3 + sofosbuvir), CH (+ribavirina)

45
Q

Ledipasvir

A

Combinatie in doza fixa cu sofosbuvir
Nu necesita ajustarea dozelor in IH sau IR
Indic: HCV genotipuri 1,4,5,6 +/- coinfectie HIV, CH decompensata
Interactiuni

46
Q

Velpatasvir

A

Combinatie in doza fixa cu sofosbuvir
Indicatie: HCV orice genotip + ribavirina in CH
Interactiuni

47
Q

Ombitasvir

A

Combinatie in doza fixa cu RITONAVIR (- CYP3A) si PARITAPREVIR (- NS3 proteaza)
Indicatie: HCV genotip 1 si 4

48
Q

Elbasvir

A

Combinatie in doza fixa cu grazoprevir
Indicatie: HCV genotipuri 1 si 4, coinfectie HIV, IR
Interactiuni

49
Q

Inhibitori de NS3 proteaza

A

Gen 1: TELAPREVIR, BOCEPREVIR - activi pe genotipurile 1 si 2, admin 3/zi
Gen 2: SIMEPREVIR, FALDAPREVIR, PARITAPREVIR, ASUNAPREVIR - spectru mai larg, admin 1/zi

50
Q

Simeprevir - mecanism de actiune

A

previne clivarea complexului de replicare virala => previne formarea ADNului viral

51
Q

Simeprevir - indicatii

A

HCV genotipurile 1 si 4 + sofosbuvir, 12 S

Nu la pacientii cu CH decompensata

52
Q

Simeprevir - RA

A

cefalee, oboseala, greata, fotosensibilizare, rash, prurit cut, cresterea BT
! interactiuni

53
Q

Paritaprevir

A

Combinatie in doza fixa cu ritonavir si ombitasvir
I: HCV genotipul 1 si 4
CI: CH decompensata
! interactiuni

54
Q

Grazoprevir

A

Combinatie in doza fixa cu elbasvir

I: HCV genotipurile 1 si 4, coinfectie HIV, IR

55
Q

Ribavirina - mecanism de actiune

A

analog al guanozinei
efect antibiral direct -> - sint ARN viral
efect imunomodulator - restab balanta Th1 - Th2 in fav Th1, influenteaza sint citokine, potenteaza IFNa

56
Q

Ribavirina - indicatii

A

HCV in asociere cu antivirale directe (creste rata RVS), reducerea dozelor in IR sau CH decompensata
Febra hemoragica cu sdr renal
Infectii cu adenovirus, vaccinia, virus gripal si paragripal la imunocompromisi
Infectii severe cu VRS

57
Q

Ribavirina - RA

A

Anemia prin dublu mecanism: hemolitic si supresie medulara
efect teratogen
rah, prirot, astenie, tuse, inapetenta, greata, insomnie, depresie
inhalator - iritaite conjunctiv, tuse, wheezing

58
Q

Ribavirina - CI

A

anemire, IRC in stadiu terminal, boli cardiace severe, sarcina

59
Q

Scheme de tratament aprobate pentru HCV

A

Ombitasvir+Paritaprevir+Ritonavir+/- Dasabuvir - 12 S
Sofosbuvir + Ledipasvir - 12 S inclusiv CH decompensata
Grazoprevir + elbasvir - 12 S
La pacienti naivi, fara comorbiditati - 8 s
La pacienti cu ciroza - 24 s

Farmacologie (8 decks)

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