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Farmacologie > Tratamentul antiviral in hepatitele cronice > Flashcards

Tratamentul antiviral in hepatitele cronice Flashcards

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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

Study These Flashcards
A

HBV - linia II

HIV (dar a fost abandonat)

25
Adefovir - RA
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
Lamivudina - mecanism de actiune
Analog nucleozidic - enatiomer de dideoxitiacitidina -> tranf in lamivudina trifosfat -> - competitiv ADN polimeraza HBV si revers transcriptaza HIV => X sint P virale
27
Lamivudina - farmacocinetica
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
Lamivudina - indicatii
HBV - nu de prima linie dat aparitiei rezist | HIV + cu antiretrovirale
29
Lamivudina - RA
Bine tolerata - greturi, tulb GI, cefalee, neutropenie | tratamentul limitat de aparitia rezistentei
30
Telbivudina - mecanism de actiune
sub forma de trifosfat - ADN polimeraza virala si replicarea virusului
31
Telbivudina - indicatii
HBV la pacienti naivi, adulti si copii >16 ani - linia II
32
Telbivudina - RA
Bine tolerata - creste CK si miopatie, greturi, varsaturi, diaree
33
Scheme de tratament HBV
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
Tratamentul HCV - indicatie si obiective
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
Inhibitorii de NS5B polimeraza - reprezentanti
SOFOSBUVIR | DASABUVIR
36
Sofosbuvir - mecanism de actiune
analog de 5' UMP, activat intracel -> - polimeraza virala
37
Sofosbuvir - farmacocinetica si spectru
``` 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
Sofosbuvir - indicatii
HCV 1/zi in combinatie cu alte antivirale
39
Sofosbuvir - RA
bine tolerat, astenie, cefalee, greata, insomnie, prurit
40
Sofosbuvir - interactiuni
substrat pt P-gp | + amiodarona - monitoriz AV timp de 2 sapt pt ca pot produce bk si stop cardiac
41
Dasabuvir - farmacocinetica
admin oral - Bd crescuta de alim bogate in grasimi legare crescuta de alb M CYP2C8 - ! interactiuni
42
Dasabuvir - indicatii
HCV genotipul 1 12 sapt in asociere cu RITONAVIR+PARITAPREVIR+OMBITASVIR
43
Inhibitori de NS5A proteaza
``` DACLATASVIR LEDIPASVIR VELPATASVIR OMBITASVIR ELBASVIR ```
44
Daclatasvir
- potential crescut de interactiuni medicamentoase | Indic: HCV genotip 1 si 3 (I linie in genotipul 3 + sofosbuvir), CH (+ribavirina)
45
Ledipasvir
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
Velpatasvir
Combinatie in doza fixa cu sofosbuvir Indicatie: HCV orice genotip + ribavirina in CH Interactiuni
47
Ombitasvir
Combinatie in doza fixa cu RITONAVIR (- CYP3A) si PARITAPREVIR (- NS3 proteaza) Indicatie: HCV genotip 1 si 4
48
Elbasvir
Combinatie in doza fixa cu grazoprevir Indicatie: HCV genotipuri 1 si 4, coinfectie HIV, IR Interactiuni
49
Inhibitori de NS3 proteaza
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
Simeprevir - mecanism de actiune
previne clivarea complexului de replicare virala => previne formarea ADNului viral
51
Simeprevir - indicatii
HCV genotipurile 1 si 4 + sofosbuvir, 12 S | Nu la pacientii cu CH decompensata
52
Simeprevir - RA
cefalee, oboseala, greata, fotosensibilizare, rash, prurit cut, cresterea BT ! interactiuni
53
Paritaprevir
Combinatie in doza fixa cu ritonavir si ombitasvir I: HCV genotipul 1 si 4 CI: CH decompensata ! interactiuni
54
Grazoprevir
Combinatie in doza fixa cu elbasvir | I: HCV genotipurile 1 si 4, coinfectie HIV, IR
55
Ribavirina - mecanism de actiune
analog al guanozinei efect antibiral direct -> - sint ARN viral efect imunomodulator - restab balanta Th1 - Th2 in fav Th1, influenteaza sint citokine, potenteaza IFNa
56
Ribavirina - indicatii
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
Ribavirina - RA
Anemia prin dublu mecanism: hemolitic si supresie medulara efect teratogen rah, prirot, astenie, tuse, inapetenta, greata, insomnie, depresie inhalator - iritaite conjunctiv, tuse, wheezing
58
Ribavirina - CI
anemire, IRC in stadiu terminal, boli cardiace severe, sarcina
59
Scheme de tratament aprobate pentru HCV
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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