1. PROBLEMA DE SANATATE PUBLICA
HEPATITA VIRALA C –
PROBLEMA DE SANATATE PUBLICA
IN ROMANIA
Laura Iliescu
Centrul de Medicina Interna IC Fundeni

2. VHB + VHC 1 milion decese / an
0.5 miliarde pacienti cu infectie cronica 2

3. Cauze de deces boli infectioase : VHB (locul7) si VHC (locul 10)
DECESE/AN
1. Infectii ap respirator
~ 3.5 mil
2. HIV/SIDA
~ 3.0 mil
3. Boli diareice
~ 2.2 mil
4. Tuberculoza
~ 2.0 mil
5. Malarie
~ 1-3 mil
6. Boli eruptive
~ 888,000
This slide shows the 10 leading causes of infectious disease deaths worldwide. Hepatitis B is number 7 and hepatitis C is number 10. If hepatitis B and C are grouped together, viral hepatitis is nearly number 5 in terms of the risk of infectious disease death. This, of course, relates to cirrhosis and cancer deaths for both of these chronic viral hepatitis infections.
7. Hepatita B ~ 500, ,000
10. Hepatita C ~ 250,000
8. Pertussis
~ 355,000
9. Tetanos Neonatal
~ 300,000
WHO. Hepatitis B Maynard JE, et al. In: Viral Hepatitis and Liver Disease. New York: Alan R. Liss, Inc CDC. Epidemiology & prevention of vaccine-preventable diseases. The Pink Book. 8th ed. CDC. MMWR. 2001;50:RR-11. 3 3

4. Hepatita cronica VHC
Impactul la nivel global al bolilor hepatice cronice datorate VHC este substantial
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

5. Epidemiologie Hepatita cronica VHC
Infectia cronica VHC reprezinta o problema majora de sanatate pubilca, in intreaga lume existand 170 milioane persoane infectate
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

6. - VHC - 170 milioane subiecti (3%) din intreaga lume
- 5 milioane in Europa de Vest
- rata crescuta in Europa de Est
- prima cauza de transolant hepatic
- a doua cauza la nivel mondial si prima cauza in Europa de cancer hepatic 6

7. Estimari globale VHC Prevalenta Anti VHC: 7 7 7
Pozitivi, %
Taiwan
Vietnam
4-9
China
2.1
Africa
Filipine
1.6
Tailanda
2.0
Japonia
0-5.1
Coreea Sud
1.4
India
Rusia
USA
0.1
HBsAg, hepatitis B surface antigen.
This slide illustrates the prevalence of hepatitis B using global estimates by region and country. As seen on this slide, there are wide ranges of hepatitis B surface antigen (HBsAg) prevalence in different countries. However, some information on this slide may not fully reflect the current situation. For instance, in some communities in Vietnam and China, the prevalence is as high as 30%. Fortunately, in a number of countries that instituted vaccination, which will also be discussed later, there has been a declining prevalence of hepatitis B, especially in babies, infants, and young children.
Prevalenta Anti VHC:
Inalta (≥ 8%)
Intermediara (2% to 8%)
Scazuta (< 2%)
Mast EE, et al. MMWR Recomm Rep. 2006;55:1-33. Custer B, et al. J Clin Gastroenterology. 2004;38(10 suppl):S158-S168. 7 7 7

8. VHC
Epidemiologie
Genotipurile VHC au semnificatie si importanta clinica in stabilirea raspunsului la tratament si a prognosticului
Distributia geografica a genotipurilor VHC este variabila
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

9. Eastern Mediterranean
GENOTIPURI VHC
1, 2, 3 1
1, 3
1,3 3 4
4,5
Asia: 6
Europe
8.9 million
(1.03%)
The Americas
13.1 million
(1.7%)
Africa
31.9 million
(5.3%)
Southeast Asia
32.3 million
(2.15%)
Western Pacific
62.2 million
(3.9%)
Eastern Mediterranean
21.3 million
(4.6%)
It is estimated by the World Health Organization that approximately 170 million individuals, or 3.1% of the world population, are infected with HCV—more than 4 times the number of people living with HIV.
Relative Prevalence
There is, however, considerable geographic variation in the prevalence of HCV infection. In the Americas, approximately 1.7% of the population is currently living with HCV. In a survey conducted from , the prevalence of HCV in the United States was estimated to be 1.6% (95% confidence interval: 1.3% to 1.9%), corresponding to 4.1 million individuals with anti-HCV antibodies nationwide, and 1.3% or 3.2 million persons had chronic hepatitis. Areas of higher prevalence include some countries of Africa, the eastern Mediterranean, southeast Asia, and the western Pacific. In some areas, the prevalence of infection exceeds 10% in the general population. For example, in Egypt, there are some areas in which one out of every 5 individuals has chronic hepatitis C. The virus spread in Egypt drastically as a result of unsafe injection practices during a campaign to eradicate schistosomiasis. That practice has since stopped and ongoing transmission of hepatitis C has reduced dramatically in that country.
Genotip
World Health Organization. Hepatitis C: global prevalence: update Farci P, et al. Semin Liver Dis. 2000;20: Wasley A, et al. Semin Liver Dis. 2000;20:1-16. 9 9 9

10. Studiul ARSF : Prevalenta VHB, VHD, VHC, VHE
22 judete
HBsAg, hepatitis B surface antigen.
This slide illustrates the prevalence of hepatitis B using global estimates by region and country. As seen on this slide, there are wide ranges of hepatitis B surface antigen (HBsAg) prevalence in different countries. However, some information on this slide may not fully reflect the current situation. For instance, in some communities in Vietnam and China, the prevalence is as high as 30%. Fortunately, in a number of countries that instituted vaccination, which will also be discussed later, there has been a declining prevalence of hepatitis B, especially in babies, infants, and young children.
- 22/42 judete ( ,6 km2)
subiecti 10 10 10

11. Populatia studiata : 5678 - 4 categorii :
- populatie care se adreseaza pt evaluare medicala sau cu ALT (>x1.5N) = 5367
- risc scazut = 93 subjecti
- risc crescut = 174 subiecti
- studenti = 44 subiecti
HBsAg, hepatitis B surface antigen.
This slide illustrates the prevalence of hepatitis B using global estimates by region and country. As seen on this slide, there are wide ranges of hepatitis B surface antigen (HBsAg) prevalence in different countries. However, some information on this slide may not fully reflect the current situation. For instance, in some communities in Vietnam and China, the prevalence is as high as 30%. Fortunately, in a number of countries that instituted vaccination, which will also be discussed later, there has been a declining prevalence of hepatitis B, especially in babies, infants, and young children. 11 11 11

12. ARSF 5-7 % din populatia tarii infectata cu HVC
No.
sub
AgHBs
PCRVHB
Anti
VHC
PCR
VHD
VHE
ALT
>2N
Populatia
Generala
2.54
5.59% -
4.56%
37.69%
Risc foarte scazut
(studenti) 44
2.27% 0%
12.5%
6.82%
Risc scazut
(medici si asistente) 93
2.15%
1,2%
1.075%
13.98%
4.3%
Risc crescut
(hemodializa)
174
7.91%
39.26%
20.69%
15%
5-7 % din populatia tarii infectata cu HVC
~ 1 mil. persoane infectate (95,5% GENOTIP 1) 12

13. ARSF
Nr. subiecti
AgHBs
PCR VHB
Anti VHC
PCR VHC
Anti VHD
Anti VHE
ALT
>2N
Populatia Generala
2696
8,87% -
7,67%
37,69%
Risc scazut 93
2,15%
1,2%
1,07%
13,98%
4,3%
Risc crescut
174
7,91%
39,26%
20,69%
15%
Studenti 44
2,27% 0%
12.5%
6,82% 13

14. VHC SURPRIZE
VIRUSOLOGIC
EPIDEMIOLOGIC
CLINIC
TERAPEUTIC

15. GLOBALIZAREA INFECTIEI CRONICE VHC CONSECINTE EPIDEMIOLOGICE
milioane peroane infectate VHC
27% ciroza hepatica
25% carcinom hepatocelular
JANSEN D., DDW 2009

16. Evoluţia naturală a infecţiei VHC
primară
Clearance
viral
Infecţie cronică
Asimptomatică
75%
Infecţie
persistentă
80-95%
Ciroză
CHC
Simptomatică
25%
Clearance al
infecţiei
5-20%
Infecţie
asimptomatică
20%

17. Progresia Hepatitei Cronice C
Rata de progresie
Rapidă
Intermediară
Lentă
5-10 ani
15-30 ani
>30 ani
Ciroză
Decompensare
5-10% /an
CHC 3-5%/an
Decese 2-5%/an

18. HETEROGENITATEA SPECTRULUI ACTUAL AL INFECTIEI VHC
POOL ASTEPTAT
ANTI VHC
Calculat dupa date
prevalenta%
Infectii noi
(dupa incidenta /100000)
15-20%
ARN-VHC –
SURPRIZA
F1: 7.5%
F2/3: 89,5%
80-85%
ARN -VHC +
HUARE Mg. et al., Hepatology 2008; 48: 1737.

19. HETEROGENITATEA SPECTRULUI ACTUAL AL INFECTIEI VHC
Încărcătură virală pozitivă
80-85 % DIN Anti VHCpozitivI
DATE REALE SUA
Diagnostic < 25%
NON DIAGNOSTIC
75%
TRATATI 11%
NETRATATI 89%
NON RESPONDER
RECADERE %
RESPONDER
RVS 10-50%
Lista de asteptare
Post transplant
Psihopatii
Utilizatori droguri
Afectare hepatica usoara
Alte cauze :obezitate,DZ necontrolat,boli
CV , anemie,
leucopenie, trombocitopenie
ASTEAPTA
NOI
TERAPII
RETRATAMENT
Donald Jansen, DDW 2009.

20. HETEROGENITATEA SPECTRULUI ACTUAL AL INFECTIEI VHC IN ROMANIA
ANTI HCV (+)
~5%
NOI INFECTII
8.64/
1308/AN
INCARCATURA VIRALA (-)
~ 15-20%, ~
MONITORIZARE
80-85%
INCARCATURA VIRALA (+) ~
DIAGNOSTIC
~ 30000
1.81%:
TRATATI ,33%
IN TRATAMENT %
LISTA ASTEPTARE %
CONTRAIND. TRAT
Al. Oproiu

21. Modalitati de transmitere
VHC
Modalitati de transmitere
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

22. Transmitere verticala (materno-fetala) 6-8%
Transmitere VHC
Transmitere orizontala
Transfuzii<1995
droguri i.v.
Interventii chirurgicale
Stomatologie
Tatuaje, piercing
Acupunctura
Parenteral (i.m./i.v.)
Sexual (<10%)
Transmitere verticala (materno-fetala)
6-8%

23. Noi modalitati de transmitere asigurarile de sanatate din fiecare tara
VHC
Epidemiology
Noi modalitati de transmitere
Caile de transmitere variaza si s-au modificat in functie de diferiti factori pt fiecare regiune geografica in parte :
nivel socio-economic
asigurarile de sanatate din fiecare tara
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.
Alter MJ. Prevention of spread of hepatitis C. Hepatology 2002; 36:S93–98.
Dore GJ, Law M, MacDonald M, Kaldor JM. Epidemiology of hepatitis C virus infection in Australia. J Clin Virol 2003; 26: 171–84.

24. injectii cu materiale nesterile sau utilizate in comun
VHC
droguri injectabile
injectii cu materiale nesterile sau utilizate in comun
transfuzii
ocupational
perinatal
transmitere sexuala
necunoscut
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

25. Categorii de risc Ac VHC
TGP crescute
Boala hepatica neprecizata
Contacti familiali-sexuali pacienti VHC
Consumatori droguri
Hemodializati
Hemofilici
Receptori transfuzii<1991
Interventii chirurgicale, endoscopice, stomatologice-multiple
Personal medical (expunere la sange)
Contacte sexuale multiple neprotejate, BTS
Alte hepatite virale, HIV
Sarcina
ALTE

26. SIMPTOMATOLOGIE Hepatita cronica VHC este silentioasa dpdv clinic
Simptomatologie nespecifica
Majoritatea manifestarilor nu apar decat in momentul in care se dezvolta ciroza hepatica
Pacientii suspectati a avea infectie cronica VHC vor fi testati pentru Ac-anti VHC
RNA-VHC va fi determinat la:
pacientii cu Ac anti-VHC pozitivi
pacientii evaluati in vederea tratamentului antiviral, utilizand o metoda cantitativa
pacienti imunodeprimati cu afectare hepatica neexplicata, cu Ac anti-VHC negativi

27. Theresa Wright and M. Manns 2006
SURPRIZE CLINICE
1. FAZA ACUTA ASIMPTOMATICA IN 80% CAZURI
2. MANIFESTARI EXTRAHEPATICE
CRIOGLOBULINEMIE MIXTA +++
GN MEMBRANO – PROLIFERATIVA ++
ARTRALGII ++
TIROIDITA AUTOIMUNA ++
PORPHIRIA CUTANEA TARDA –
LICHEN PLANUS ++
DIABET ZAHARAT +++
OBOSEALA ++
LIMFOM NONHODGKIN ±
Theresa Wright and M. Manns 2006

28. LOCALIZARI EXTRAHEPATICE
LIMFOCITE B
LIMFOCITE T
MONOCITE
CELULE DENDRITICE
MONONUCLEARE PERIFERICE
CELULE EPITELIU INTESTINAL
SNC
CASTILLO J., PARDO M., BARTOLONE J., 2004
DEFORGE S. et al., 2004
FORTON DM et al., 2004

29. Infectia HCV: Manifestari Extrahepatice
Hematologic
. Crioglobulinemia
Anemia aplastica
Trombocitopenie
• Non-Hodgkin limfom
Ocular
Ulcer corneean
Uveite
Sindrom Sjogren
Vascular
Vasculita necrotizanta
PAN
PIF
Dermatologic
Porfiria cutanea tarda
Lichen plan
Vasculita necrotizanta cutanata
Neuromuscular
Mialgii
Neuropatie periferica
Artrite sero-/artralgii
Renal
Glomerulonefrita membranoasa
Neurologic
FENOMENE AUTOIMUNE
Sindrom CREST
Granulom nespecific
Autoanticorpi
Endocrine
Tiroidita autoimuna
Diabet zaharat
Salivar
Sialoadenite
Hadziyannis. J Eur Acad Dermatol Venereol 29

30. TEST SCREENING: antiHCV
ALT(TGP) NU!
sensibilitate redusă (multe hepatite cronice HCV evoluează cu TGP normale, dar necesita tratament)
specificitate minima (numeroase cauze de citoliza)

31. Screening
Beneficii
Costuri

32. Screening al populaţiei generale: probabil NU!...
..dar screening al persoanelor cu :
risc expunere/expunere certă la HCV: DA!
suferinţă hepatică de cauză incertă: DA!

33. Screening – Expunere HCV certă
1. Personal medical expus (ac contaminat cu sânge pacient): implicaţii medicale şi sociale – accident de muncă!
RISC = 1,5-2% după înţepătură accidentală ac contaminat

34. 2. Copiii mamelor HCV+ Screening – Expunere HCV certă
RISC = 4% (15-20% dacă mama este si HIV+)

35. Screening – Categorii la risc pentru expunere HCV
Toxicomanii – emergenţa unei categorii de risc şi în România
RISC = 10-20%
pentru fiecare an de toxicomanie

36. Screening – Categorii la risc pentru expunere HCV
Persoane cu transfuzii înainte de 1993
Hemodializaţi
Partener sexual HCV+/- comportament sexual dezordonat
RISC = 1,5-6% dintre partenerii sexuali ai celor infectaţi HCV+

37. « Valul » de pacienti prilejuit de programul national de evaluare
Screening – Afecţiune hepatică de cauză incertă
Valori crescute ale ALT
O singura data: de evaluat indicaţia în contextul stării prezente a pacientului
Doua sau mai multe determinari: obligatoriu !
« Valul » de pacienti prilejuit de programul national de evaluare

38. Testare anonimă şi gratuită în unele state, împreună cu testarea HIV +
Screening – la cerere
Aprox. 10% dintre infecţiile HCV sunt astfel descoperite
Testare anonimă şi gratuită în unele state, împreună cu testarea HIV +
Consiliere dacă test pozitiv

39. EVALUARE PACIENTI ANTI-HCV POZITIVI

40. Dacă antiHCV+, care sunt următorii paşi? Confirmarea infecţieiNU DA
Reluarea anamnezei
Consiliere
COMPLETARE BILANŢ

41. Prezenta antiHCV  infecţie HCV
Confirmarea diagnosticului de infecţie HCV
ATENŢIE!
Prezenta antiHCV  infecţie HCV

42. Confirmarea diagnosticului de infecţie HCV
antiHCV+
RNA-HCV (–) (2 în 6 luni)
RNA-HCV (+) (60-90%)
RIBA +
RIBA -
Infecţie HCV
Infecţie HCV vindecată
Test antiHCV fals pozitiv

43. Severitatea afectiunii:
Bilanţul pacientului cu hepatită HCV:
are indicaţie de terapie antivirala?
Severitatea afectiunii:
morfologic: rolul PBH pentru evaluarea fibrozei (teste noi: fibroscan, fibrotest, fibromax)
- risc carcinom hepatic: alfafetoproteina, imagistica
sindrom hipertensiune portală (varice esofagiene)
- manifestari extrahepatice (citopenii…)

44. Patologie asociată ce poate schimba conduita: - coinfecţii HBV, HIV;
Bilanţul pacientului cu hepatita HCV:
are indicaţie de terapie antivirala?
Patologie asociată ce poate schimba conduita:
- coinfecţii HBV, HIV;
- afecţiuni extrahepatice (mai ales neoplazice, cardiace, tiroidiene);
tratamente cronice care pot interfera cu terapia antiHCV

45. Contraindicaţii terapie
Afectare Hepatică severa:
Afectări Extrahepatice: anemie, trombocitopenie severe
Alte afecţiuni ce pot fi agravate: coronariene, tiroidiene severe, boli autoimune, neoplazii
+ REFUZUL PACIENTULUI – informare corectă

46. TERAPIA: condusă de specialist Interferon pegilat + ribavirină

47. Tratamentul Hepatitei Cronice C Criterii de includere in terapie
ALT crescute/normale
Ac anti HVC+
ARN-VHC DETECTABIL
PBH- modificari evolutive (Metavir>A2F1)
FibroScan / FibroMax
Varsta – nu exista limita varsta; fara comorbiditati majore
Manifestari extrahepatice (Vasculita crioglobulinemica, Glomerulonefrita cu virus C )

48. Nedecontate de CNAS:
FIBROTEST- Inflamatia(A) si Fibroza(F)
FIBROSCAN- Fibroza

49. In ultima perioda s-au obtinut progrese importante in tratamentul
Gross AASLD NP-PA SCU
8/7/ :52 AM
In ultima perioda s-au obtinut progrese importante in tratamentul
hepatitei cronice VHC 49

50. Interferon/ ribavirin
Tratmentul HC VHC
PI + PegIFN/RBV
(6-12 mos)[8-10]
100
70-75 80
PegIFN/ribavirin
(6-12 mos)[6,7]
Interferon/ ribavirin
(6-12 mos)[3,4]
50-60 60
PegIFN monotherapy
(6-12 mos)[5,6]
SVR (%)
Standard interferon
(12-18 mos)[2,3]
38-43 40
Standard interferon
(6 mos)[1]
25-30
15-20 20
8-12
1991
1995
1998
2001
2011
1. Carithers RL Jr., et al. Hepatology. 1997;26(3 suppl 1):83S-88S. 2. Zeuzem S, et al. N Engl J Med. 2000;343: Poynard T, et al. Lancet. 1998;352: McHutchison JG, et al. N Engl J Med. 1998;339: Lindsay KL, et al. Hepatology. 2001;34: Fried MW, et al. N Engl J Med. 2002;347: Manns MP, et al. Lancet. 2001;358: Poordad F, et al. N Engl J Med. 2011;364: Jacobson IM, et al. N Engl J Med. 2011;364: Sherman KE, et al. N Engl J Med. 2011;365: 50

51. NOI MEDICAMENTE ANTIVHC MOLECULE MICI
TERAPIA ANTIVHC
NOI MEDICAMENTE ANTIVHC MOLECULE MICI
inhibitori proteaza (PI)
inhibitori polimeraza (Pol I)
Mai avem nevoie de IFN RBV?
IFN protejeaza impotiva aparitiei rezistetei la PI
RBV scade rate recaderilor

52. Concluzii
1. In ciuda progreselor obtinute in preventie si terapie, virusurile hepatitice reprezinta o problema majora de sanatate publica si trebuie sa fie o prioritate in fiecare tara
2. In ultimii 10 ani au aparut modificari importante in epidemiologia virusurilor hepatitice
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

53. Concluzii
3. Incidenta si prevalenta infectiei VHC raman ridicate in anumite regiuni datorita absentei unui vaccin si a unui tratament antiviral care sa determine eradicarea intr-un procent ridicat
4. Sunt necesare programe noi mai eficiente de preventie, de screening , de cresterea adresabilitatii si nu in ultimul rand de tratament
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

54. Concluzii
5. Pentru anumite situaţii/categorii de risc testarea antiHCV este obligatorie: toxicomani, expunere profesională, copii mame infectate, tratamente injectabile multiple , partener HCV pozitiv
6. Un test anti HCV pozitiv nu inseamna infecţie actuală cu HCV: trebuie evaluat!
7. Consilierea pacienţilor cu HCV este un element important al îngrijirii lor corecte
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.

55. 10. Nu exista loc sigur unde sa ne ascundem de virusuri !
Concluzii
8. Tratamentul antiviral este regula îngrijirii acestor pacienţi, abţinerea de la tratament – excepţia.
9. Pacientul care nu a răspuns / nu a putut urma tratamentul trebuie monitorizat în continuare pentru riscul de evoluţie severă / în aşteptarea unor antivirale noi.
10. Nu exista loc sigur unde sa ne ascundem de virusuri !
Slide 2
Moxonidine (4-chloro-N-(imidazolidine-2-ylidene)-6-methoxy-2-methyl-5-pyrimidinamine) is a centrally acting antihypertensive drug.
The blood pressure-lowering effect of moxonidine is due to a highly selective action in the rostral ventrolateral medulla, which leads to a reduction in overactivity of the sympathetic nervous system.