antiviral drugs , their mechanism, side effect

1. Antiviral
Drugs
Group members
1: Mohamed Bashe
Ali
2: A/ karim Ali Osman
3: A/Qani Yusuf
Qassim
4: A/Risaq Farah Hirsi
5: Ismail A/Qani
Ibrahem
6: Mohamed Omar
7:Madar Awil Jama
Group one presentation 1

2. Antiviral Drugs
 Until recent years no
chemotherapeutic agents effective
against viruses were available. One
reason for the difficulty in finding such
agents is that the agent must act on
viruses within cells without severely
affecting the host cells. Currently
available antiviral agents inhibit some
phase of viral replication, but they do
not kill the viruses.
Group one presentation 2

3. Continue
 Viruses controlled by current antiviral
therapy include : Cytomegalo virus ,
Hepatitis virus , Herpes virus , Human
immunodeficiency virus (HIV) ,
Influenza virus ( the flu) and
respiratory syncytial virus ( RSV)
Group one presentation 3

4. Mechanism of action of antiviral
drugs
 Inhibition of early events
E.g. : Amantadine prevents uncoating of
influenza A viruses, absorption and
penetration occur normally but no viral
replication, influenza B and influenza C
are not affected
Group one presentation 4

5. Continue
 Inhibition of viral nucleic acid
synthesis
 E.g. : Idoxuridine and trifluridine,
both analogs of thymine, are
administered in eye drops to treat
inflammation of the cornea caused by
a herpes virus.
Group one presentation 5

6. Continue
 Inhibition of viral protein synthesis
 E.g : Interferons Cells infected with
viruses produce one or more proteins
collectively referred to as Interferons
When released, these proteins induce
neighboring cells to produce antiviral
proteins,
Group one presentation 6

7. Anti herpes virus agents
 acyclovir/ valacyclovir
 Famciclovir / Penciclovir
 Ganciclovir/ cidofovir
 Trifluridine /idoxuridine/ vidarabine
 Valacyclovir is prodrug of acyclovir with better
bioavailability .
 Famciclovir is hydrolyzed to Penciclovir and
has greatest bioavailability .
 Penciclovir is used only topically whereas
Famciclovir can be administered orally
Group one presentation 7

8. Group one presentation 8

9. Group one presentation 9

10. Mechanism of action of
Acyclovir
 All drugs are phosphorylated by a viral
thymidine kinase then metabolized by
host cell kinases to nucleotide analogs .
 The analog inhibits viral DNA polymerase
 Only actively replicating viruses are
inhibited
 Acyclovir is thus selectively activated in
cells infected with herpes virus uninfected
cells do not phosphorylate acyclovir
Group one presentation 10

11. Pharmacokinetics of Acyclovir
 Oral bioavailability : 20-30%
 Distribution to all body tissues
including CNS
 Renal excretion is >80%
 Half lives : 2-5 hours
 Administration : Topical , Oral , IV
Group one presentation 11

12. Administration of Acyclovir
 Oral , IV , topical formulations
 Cleared by glomerular filtration and
tubular secretion
Group one presentation 12

13. Adverse effects
 Adverse effect of acyclovir include :
 Nausea , vomiting , and diarrhea
 Nephrotoxicity , crystallluria ,
heamaturia
 Neatropenia , thrombocytopenia
Group one presentation 13

14. Clinical Uses
 Acyclovir is the drug of choice for :
 Herpes simplex virus 1 and 2
 Herpes simplex encephalitis ( type 1)
 Vericella zoster virus
 HSV genital infections
 HSV encephalitis
 HSV infections in
immunocompromised patients
Group one presentation 14

15. Mechanism of resistance
Mechanism of resistance of acyclovir :
Alteration in viral thymidine kinase .
Alteration in viral DNA polymerase .
Cross resistance with valacyclovir ,
Famciclovir and ganciclovir
Group one presentation 15

16. continue
 Trifluridine : inhibits viral DNA synthesis
same as acyclovir used for HSV 1 and 2 (
topically)
 Vidarabine : inhibits viral DNA polymerase
 Anti cytomegalovirus Agents
 Gancyclovir
 Valgancyclovir
 Cidofovir
 Fomivirsen
Group one presentation 16

17. Ganciclovir
 Mechanism of action : same as
acyclovir
 Uses : CMV , HSV , VZV and EBV
 Side effects : myelosuppression
 Valgancyclovir
 M.O.A : same as Gancyclovir
 Uses : CMV
 Side effects : myelosuppression
Group one presentation 17

18. Antiretroviral Agents
1: Nucleoside Reverse Transcriptase
inhibitors (NRTIs)
2: Nonnucleoside Reverse Transcriptase
inhibitors ( NNRTIs)
3: Protease inhibitors
Group one presentation 18

19. Reverse transcriptase
inhibitors
 Zidovudine ( AZT)
 Didanosine ( causes pancreatitis )
 Lamivudine ( causes pancreatitis)
 Stavudine (causes peripheral
neuropathy)
 Zalcitabine ( causes peripheral
neuropathy)
Group one presentation 19

20. Group one presentation 20

21. Zidovudine (AZT)
 Mechanism of action : enters the cell
via passive diffusion , competitively
inhibits deoxythymidine triphosphate
for the reverse transcriptase enzyme
and cause chain termination .
Group one presentation 21

22. Clinical Uses of Zidovudine
 Mainly used for the treatment of HIV
decreases rate of progression and
prolongs survival .
 Prevents mother to newborn
transmission of HIV .
 Available in IV and Oral formulations
Group one presentation 22

23. Side effects of Zidovudine
 Myelosuppression including anemia
and neutropenia .
 GI intolerance , headaches and
insomnia
Mechanism of resistance of
Zidovudine :.
Due to mutations in the reverse
transcriptase gene.
More frequent after prolonged therapy
in persons with HIV Group one presentation 23

24. Nucleotide inhibitors
 Tenofovir
 M.O.A : competitively inhibits HIV
reverse transcriptase and cause chain
termination after incorporation into
DNA
 Uses : in combination with other
antiretroviral for HIV 1 suppression
Group one presentation 24

25. Nonnucleoside reverse
transcriptase inhibitors
 Nevirapine
Delavirdine
Efavirenz
NNRTIs : result in blockade of RNA and
DNA dependant DNA polymerase
activity.
Do not require phosphorylation
This drugs cannot be given alone
Substrate and inhibitors of CYP3A4Group one presentation 25

26. Continue
 Nevirapine : prevents transmission of HIV
from mother to newborn.
 Delavirdine : teratogenic therefore cannot be
given during pregnancy .
 Efavirenz : teratogenic therefore cannot be
given during pregnancy
Group one presentation 26

27. Protease inhibitors
 Indinavir
 Ritonavir
 Saquinavir
 Nelfinavir
 Amprenavir
The protease enzyme cleaves precursor
molecules to produce mature infectious virions
.
These agents inhibit protease and prevents the
spread of infection Group one presentation 27

28. Indinavir and ritonavir
 M.O.A : specific inhibitors of the HIV-1
protease enzyme.
 M.O.R : expression of multiple and
variable protease amino acid
substitution
 Side effect: hyperbilirubinemia
 Contraindications : inhibitors for
CYP3A4 , do not give with antifungal
azoles.
Group one presentation 28

29. Nelfinavir and Amprenavir
 M.O.A : specific inhibitor of the HIV-1
protease enzyme.
 M.O.R : expression of multiple
variable protease amino acid
substitution .
 Side effect : diarrhea and flatulence
 Contraindication : inhibitors of
CPY3A4
Group one presentation 29

30. Anti-Hepatitis Agents
 Lamivudine ( nucleoside reverse transcriptase
inhibitors ) for chronic hepatitis B
 Adefovir ( nucleotide inhibitor) for chronic
hepatitis B
 Interferon Alfa (for chronic hepatitis B and C)
 Ribavirin (chronic hepatitis C)
 Pegylated interferon Alfa
 Primary for hepatitis B : Lamivudine, Adefovir
and tenovir
 Primary for hepatitis C : interferon alpha and
Ribavirin
Group one presentation 30

31. Lamivudine
 Lamivudine : an inhibitor of both hepatitis B
DNA polymerase and HIV reverse
transcriptase .
 It is the first line drug for chronic Hepatitis B
 Mechanism of action : it must be
phosphorylated by host cellular enzymes to
the triphosphate active form , this compound
competitively inhibits HBV DNA polymerase at
concentration that have negligible effects on
host DNA polymerase
Group one presentation 31

32. Group one presentation 32

33. Ribavirin
 Ribavirin : has broad spectrum
antiviral activity for influenza A and B ,
respiratory syncytial virus ( in children
only)
 Oral Ribavirin is commonly used in
chronic hepatitis C
 Mechanism of action : inhibit viral
RNA synthesis
Group one presentation 33

34. Continue
 Oral bioavailability is 50%
 Half life >10 days
 Adverse effects
 Anemia , bone marrow depression ,
hemolysis
 Teratogenic , bronchospasm
Group one presentation 34

35. Interferons
 Interferons : are natural proteins produced
by the cells of the immune systems in
response to challenges by foreign agents
such as viruses , bacteria , parasites and
tumor cells
 Three classes of Interferons are : ALPHA ,
Beta and Gamma .
Group one presentation 35

36. Mechanism of action of
Interferons
 1: protein kinase : which inhibits
protein synthesis
 2: oligo adenylate synthase which
leads to degradation of viral MRNA
 Phosphodiesterase which inhibit
tRNA the action of these enzymes
leads to an inhibition of translation
Group one presentation 36

37. Pharmacokinetics of
Interferons
 Oral bioavailability <1%
 Administered :IV
 Distribution in all body tissues except
CNS and Eye.
 Half live : 1-4 hours
Group one presentation 37

38. Clinical uses of Interferons
 Therapeutic uses of Interferons :
 Chronic hepatitis B and C
 Hairy cell leukemia
 Aids related Kaposi sarcoma
Group one presentation 38

39. Side effects of Interferons
 Common side effects of Interferons
are :
Headaches and muscle aches.
Fatigue
Fever.
Hair loss
 Bonne marrow suppression
 Impairment of fertility
Group one presentation 39

40. Interferons Resistance
 Interferon plays a critical role in the
host's natural defense against viral
infections and in their treatment. It is
the only therapy for hepatitis C virus
(HCV) infection; however, many virus
isolates are resistant. Several HCV
proteins have been shown to possess
properties that enable the virus to
evade the interferon-mediated cellular
antiviral responses.
Group one presentation 40

41. Anti-Influenza virus agents
 Amantadine
 Mechanism of action : These drugs block
the M2 ion channel thereby inhibiting
uncoating.
 Pharmacokinetics : well absorbed orally and
excreted in urine over 2-3 days.
 Uses: prophylaxis of influenza A2 during
epidemic , treatment of influenza A2 ,
reduction in fever and parkinsonism.
 Contraindication : Epilepsy and CNS
Group one presentation 41

42. Continue
 Amantadine side effects: nausea ,
anorexia , insomnia , lack of mental
concentration
Group one presentation 42

43. Continue
 Oseltamvir and zanamivir are also used
for the treatment and prevention of
influenza. They belong to a class of
drugs called neuraminidase inhibitors.
 These drugs are effective against both
influenza A and B viruses in contrast to
Amantadine which is effective only
against influenza A viruses
Group one presentation 43

44. respiratory syncytial virus (
RSV)
 respiratory syncytial virus : is the leading
cause of severe respiratory infection in
infants and children .
 It is the most common cause of bronchitis
or pneumonia during first RSV infection
 Treatment : Ribavirin is specific antiviral
drug proved to be effective when given as
small particle aerosol
Group one presentation 44

45. Group one presentation 45