anti viral drugs presentation
TRANSCRIPT
Group one presentation 1
Antiviral Drugs Group members 1: Mohamed Bashe
Ali 2: A/ karim Ali Osman3: A/Qani Yusuf
Qassim 4: A/Risaq Farah Hirsi 5: Ismail A/Qani
Ibrahem 6: Mohamed Omar7:Madar Awil Jama8: A/ Rahman haybe
Abdi
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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.
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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)
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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
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Continue Inhibition of viral nucleic acid
synthesisE.g. : Idoxuridine and
trifluridine, both analogs of thymine, are administered in eye drops to treat inflammation of the cornea caused by a herpes virus.
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Continue Inhibition of viral protein
synthesisE.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,
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Anti herpes virus agents acyclovir/ valacyclovirFamciclovir / PenciclovirGanciclovir/ cidofovirTrifluridine /idoxuridine/ vidarabineValacyclovir 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
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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
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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
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Administration of Acyclovir Oral , IV , topical formulationsCleared by glomerular filtration
and tubular secretion
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Adverse effects Adverse effect of acyclovir
include :Nausea , vomiting , and diarrhea Nephrotoxicity , crystallluria ,
heamaturiaNeatropenia , thrombocytopenia
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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
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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
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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 ValgancyclovirCidofovirFomivirsen
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Ganciclovir Mechanism of action : same as
acyclovir Uses : CMV , HSV , VZV and EBVSide effects : myelosuppression Valgancyclovir M.O.A : same as Gancyclovir Uses : CMVSide effects : myelosuppression
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Antiretroviral Agents 1: Nucleoside Reverse Transcriptase
inhibitors (NRTIs)2: Nonnucleoside Reverse
Transcriptase inhibitors ( NNRTIs)3: Protease inhibitors
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Reverse transcriptase inhibitors Zidovudine ( AZT)Didanosine ( causes
pancreatitis )Lamivudine ( causes pancreatitis)Stavudine (causes peripheral
neuropathy)Zalcitabine ( causes peripheral
neuropathy)
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Zidovudine (AZT)Mechanism of action : enters
the cell via passive diffusion , competitively inhibits deoxythymidine triphosphate for the reverse transcriptase enzyme and cause chain termination .
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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
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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
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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
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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 CYP3A4
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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
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Protease inhibitors Indinavir Ritonavir SaquinavirNelfinavirAmprenavirThe protease enzyme cleaves precursor
molecules to produce mature infectious virions .
These agents inhibit protease and prevents the spread of infection
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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.
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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
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Anti-Hepatitis Agents Lamivudine ( nucleoside reverse transcriptase
inhibitors ) for chronic hepatitis BAdefovir ( nucleotide inhibitor) for chronic
hepatitis BInterferon 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
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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
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RibavirinRibavirin : 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
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Continue Oral bioavailability is 50%Half life >10 days
Adverse effects Anemia , bone marrow
depression , hemolysisTeratogenic , bronchospasm
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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 .
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Mechanism of action of Interferons 1: protein kinase : which inhibits
protein synthesis2: 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
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Pharmacokinetics of Interferons Oral bioavailability <1%Administered :IVDistribution in all body tissues
except CNS and Eye.Half live : 1-4 hours
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Clinical uses of Interferons Therapeutic uses of Interferons :Chronic hepatitis B and C Hairy cell leukemia Aids related Kaposi sarcoma
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Side effects of Interferons Common side effects of
Interferons are :Headaches and muscle aches.FatigueFever.Hair lossBonne marrow suppression Impairment of fertility
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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.
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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 disease , gastric ulcer and pregnancy
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Continue Amantadine side effects:
nausea , anorexia , insomnia , lack of mental concentration
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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
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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
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