Antiviral Drugs

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Most common mechanism of action of antiviral drugs

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Inhibiting viral nucleic acid synthesis

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How antiviral nucleoside analogues function

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Incorporation of analogue terminates viral DNA or RNA replication, most current analogues have modifications to the ribose part of the molecule

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Description of prototypical anti-herpes drug

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Acyclovir- guanosine analog with an acyclic group replacing the ribose

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Mechanism of viral resistance to acyclovir

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Viral enzymes mutate and no longer add initial phosphate to the drug

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Alternative therapeutic options to acyclovir

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Foscarnet or Cidofovir

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Pregnancy and Acyclovir

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Acyclovir NOT approved for pregnancy but no birth defects have been associated with its use in pregnant women, effective in near-term women with recurrent genital herpes to prevent spread of virus to newborn

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Viruses targeted by Foscarnet or Cidofovir

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HSV or VZV (varicella zoster virus)

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Drug of choice for CMV infection

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Ganciclovir (for CMV that is life and sight-threatening), can be used prophylactically in transplant patients

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Serious Ganciclovir side effects

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Aspermatogenesis, granulocytopenia, thrombocytopenia, animal models show carcinogenesis and teratogenesis, retinal detachment in patients with CMV retinitis

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Association of resistance in Ganciclovir

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Reistance is associated with persistent infection

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Alternative drugs used with Ganciclovir-resistant CMV infection

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Foscarnet or Cidofovir

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Drug that has replaced Ganciclovir in certain cases

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Valganciclovir replaces IV and oral ganciclovir for patients with CMV retinitis that is not life or sight threatening

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In patients with AIDS, drug used to treat CMV

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Cidofovir administered IV to delay progression of CMV retinitis in AIDS patients

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Contraindication of IV Cidofovir

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Contraindicated in patients taking other nephrotoxic agents

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Infections targeted by Cidofovir

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Acyclovir-resistent HSV or VZV (varicella zoster virus)

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What clinical diseases are caused by Varicella Zoster Virus (VZV)

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Causative agent of chicken pox or shingles

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Vaccine against Varicella Zoster Virus (VZV)

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Varivax- live attenuated virus vaccine against chicken pox

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Varicella Zoster Virus vaccine for older patients

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Zostavax used in patients >60 yrs old (immunocompetent)

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Contraindications for Zostavax (VZV vaccine)

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Contraindicated for immunocompromised patients and people with a history of anaphylactic shock to gelatin, neomycin, or other components of vaccine

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Clinical use of Zostavax

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Used to prevent shingles in people >60 yrs old (immunocompetent)

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Enzyme encoded by HIV

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Reverse Transcriptase

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Effectiveness of HIV therapy measured by...

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Viral RNA load, CD4+ T cell counts

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Mechanism of action of Nucleoside Transcriptase Inhibitors (NRTI)

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Inhibit Reverse Transcriptase--> block transcription of viral RNA genome into DNA

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Adverse side effects of Nucleoside Reverse Transcriptase Inhibitors (NRTI)

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Potentiall fatal lactic acidosis, peripheral lipoatrophy, central fat accumulation, hyperlipidemia

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Nucleoside Reverse Transcriptase Inhibitor drugs that are most often seen to have adverse side effects

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Stavudine and Zidovudine

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Drug (NRTI) most often associated with lactic acidosis

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Stavudine

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Protease inhibitor site of action

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Synthesis of viral proteins

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Metabolism of HIV protease inhibitors

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HIV protease inhibitors metabolized by and are inhibitors of CYP3A4, can interfere with metabolism of other drugs

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Good HIV Protease Inhibitor for Pediatric Patients

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Indinavir

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Treatment of choice for naive HIV patients

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Lopinavir + Ritonavir

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Drugs good for HIV patients that have had extensive treatment and drug resistance problems

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Tipranavir + low dose Ritonavir

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Classification of other inhibitors of HIV reverse transcriptase

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Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

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Drugs classified as Non-Nucleoside Reverse Transcriptase Inhibitors

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Delavirdine, Nevirapine, Efavirenz

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Contraindication of Efavirenz (non-nucleoside RT inhibitor)

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Efavirenz contraindicated in pregnant women

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Drug that is an HIV Fusion Inhibitor

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Enfuvirtide prevents HIV from entering host cell by blocking gp41

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Definition of an Integrase Inhibitor

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Integrase Inhibitor blocks integration of viral DNA into host genome

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Investigational Anti-HIV drug

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Maraviroc for patients with CCR5-tropic HIV-1

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Treatment of HIV patients (acronym)

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Highly Active Anti-Retroviral Therapy (HAART), combination therapy

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Initial combination therapy for HIV patients

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2 NRTIs + Efavirenz (NNRTI)
OR
2 NRTIs + PI combination (Lopinavir/Ritonavir)

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Combination therapy for HIV patients with advanced disease

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Darunavir or Tipranavir + Enfuvirtide

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Prevention of perinatal HIV transmission

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If not on therapy at onset of pregnancy, should wait until 10-12 weeks of gestation to begin

AZT- administer to newborn for 6 weeks

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Prevention of perinatal HIV- drugs contraindicated in pregnant women

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Stavudine and Didanosine
Enfavirenz

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Anti-Influenza Drugs

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Oseltamivir, Zanamivir treat Influenza A and B

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Mechanism of action of Oseltamivir and Zanamivir (Anti-Influenza drugs)

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Block neuraminidase activity required for release of new virus particles from infected cells

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Anti-influenza drug for patients 1 yr and older, route of administration

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Oseltamivir (oral)

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Anti-influenza drug for patients 7 yrs and older, route of administration

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Zanamivir (inhaled)

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Most effective method of preventing influenza infection

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Annual immunization against Influenza A and B most effective method of preventing infection

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2 types of influenze vaccine formulations, route of administration

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Type 1- inactivated, administered IM
Type 2- live-attenuated, intranasal

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Patient population targeted for use of Type 1 Influenza vaccine

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Use Type 1 Influenza Vaccine for:

Children aged 6-59 months
Pregnant women (any trimester)
People older than 50

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Patient population contraindicated for use of Type 2 Influenza vaccine

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Do not use Type 2 Influenza vaccine in pregnant patients, immunosuppressed patients

Patients that receive this vaccine should avoid contact with severely immunocompromised patients for 7 days

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Drugs to treat H5N1 (avian flu)

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Oseltamivir and Zanamivir best options for prophylaxis and early treatment of susceptible H5N1 strains

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Symptoms of H1N1 (swine flu)

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Vomiting, diarrhea, etc.

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H1N1 is NOT caused by...

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H1N1 is not caused by eating pork or pork products

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Mechanism of action of Foscarnet

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Foscarnet blocks viral polymerases (DNA pol, RNA pol, and reverse transcriptase) by binding to pyrophosphate site

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Diseases targeted by Foscarnet

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Foscarnet can be used to treat herpes, varicella, CMV, hepatitis B, HIV

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Clinical uses associated with Foscarnet

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Foscarnet can be used to treat acyclovir-resistant HSV in AIDS patients, acyclovir-resistant VZV, CMV retinitis in immunosuppressed patients (alternative to ganciclovir)

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Anti-Hepatitis B and C drugs

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Drugs that can treat Hepatitis B and C: Lamivudine, Adefovir Dipivoxil, Interferon alpa, Ribavarin

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Mechanism of action of Human Interferons (anti-hepatitis B and C drug)

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Human interferons are glycoproteins secreted by lymphocytes and macrophages in response to viral infections, interferons promote an antiviral state in uninfected cells

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Clinical use of Ribavarin

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Ribavarin is used in combination with Interferon alpha for treating chronic hepatitis C virus

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Patient populations for whom Ribavirin is contraindicated (and why)

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Ribavarin can stay in RBCs for month, should not be given to pregnant women because it is teratogenic and embryotoxic

Pregnant women should avoid contact with people using Ribavarin; women taking Ribavarin should not get pregnant for 6 months

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Vaccine to treat Human Papilloma Virus

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Gardasil

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Patient population for whom Gardasil is contraindicated

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Gardasil is contraindicated in pregnant women

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Description of Rotavirus disease manifestation

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Rotavirus causes gastroenteritis with fever, vomiting, diarrhea, dehydration

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Adverse side effect of HIV Protease Inhibitors

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Fat redistribution (e.g. buffalo hum) occurs with Protease Inhibitors