anti viral drugs presentation

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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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