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BrookeNH10
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4 Drugs that block viral entry and attachment
Enfuvirtide (HIV), Maraviroc (HIV), Docosanol (HSV), Palivizumab (RSV)
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Herpesviruses (HSV, VZV, CMV) have what type of genetic material?
dsDNA
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Retroviruses (HIV) have what type of genetic material?
ssRNA
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Orthomyxoviruses (Influenza A, B) have what type of genetic material?
(-)ssRNA
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Hepadnaviruses (HBV, HCV) have what type of genetic material?
HBV, HCV (Hep B & C)
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Includes watery blisters in the skin or mucous membranes of the mouth, lips, or genitals
HSV-1 and HSV-2
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Acyclovir is most effective against
HSV (Herpes Simplex Virus)
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Why is CMV resistant to Acyclovir?
It lacks a thymidine kinase or is the virally encoded thymidine phosphate is unable to phosphorylate acyclovir.
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Name 3 prodrugs
Valacyclovir, Penciclovir, Famciclovir
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Acylovir molecules entering the cell are converted to? By?
- Acyclovir monophosphate
- By virus-induced thymidine kinase
(Host cell enzymes add 2 more phosphates. Acyclovir triphosphate is them transported to the nucleus)
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Acyclovir monophosphate takes the place of _______ in the viral DNA. It stops chain elongation because it lacks _____
- 2'-deoxyguanosine monophosphate
- 3'-OH group
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Major adverse drug rxn of Acyclovir
- Reversible renal toxicity
- Neurologic effects (tremors, delirium, seizures)
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Acyclovir resistant mutants are sensitive to _____ because they do not require viral ______ for activation.
- Foscarnet
- Thymidine kinase
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Ganciclovir is much more effective against ____ than acyclovir
CMV
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Adverse drug rxn w/ Ganciclovir
- CNS toxicity (can cause myelosuppression)
- Hepatotoxicity
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What drug can cause myelosuppression (particularly after IV adminstration)
Ganciclovir
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Myelosuppression of Ganciclovir (CMV) may be additive in patients receiving concurrent ?
- Ziovudine
- Azathioprine
- Mycophenolate mofetil
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Primary drugs for Influenza A? How do they work?
Prevent RNA uncoating and thus release of genetic material
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Which two drugs are used to treat Influenza A & B?
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Which drug inhibits RNA polymerase of the influenza virus?
Ribavirin
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Analogs of sialic acid
Oseltamivir, Zanamivir
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Tricyclic amines of adamantane
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GI and CNS are more likely to occur in? (Rimantadine or Amantadine)
Amantadine
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Which drug is not recommended for patients with underlying airway disease?
Zanamivir
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Resistance to oseltamivir may be associated w/ point mutations in the viral ____ or ____ genes.
Hemagglutinin, neuraminidase
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Viral point mutations in hemagglutinin or neuramindiase and provide resistance to
Oseltamivir
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In contrast, to the tx of patients w/ chonric HBV infection, the primary goal of tx in patients with HCV infection is _____
eradication
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Goal of HBV therapy
Sustain suppression (prevent complications, slow progression of hepatic disease, reduce the need for liver transplantation)
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Major mechanism of action of IFN-a
Inhibition of translation
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What is the most powerful tx against HBV and C?
IFN-a (antiviral properties)
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What drug should not be administered w/ didanosine? Why?
IFN-a, because of risk of hepatic failure
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IFN-a potential drug-drug interactions
Theophylline and methadone levels may be increased
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Two drugs used in combination with IFN-a
- Lamivudine (HBV)- also used to treat HIV
- Ribavirin (HCV)
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Lamivudine w/ coinfection w/ HIV increase the risk of
pancreatitis
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Name 2 Entry Inhibitors
- Enfuvirtide (T-20)
- Maraviroc
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Binds specifically and slectively to host protein CCR5. Treats HIV-1 infection in those who are experiencing virological failure due to resistance to other antiretroviral
Maraviroc
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Maraviroc binds to ___ and treats____
CCR5, HIV-1 infxn that exhivits resistance to other antiretrovirals
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Resitance to what drug is associated w/ one or more mutations in the V3 loop of gp120?
Maraviroc
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Maraviroc is contraindicated in pts. w/ ?
- Severe or end-stage renal impairment who are taking concurrent CYP3A inhibitors or inducers
- Pts. w/ increased cardiovascular risk (has been known to cause myocardial ischemia/infarction)
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1st drug to be approved, well absorbed and distributed to most tissues (including CSF)
Zidovine (Nucleoside and Nucleotide Reverse Transcriptase Inhibitor)
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Nucleoside and Nucleotide Reverse Transcriptase Inhibitor
Zidovine
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Non-Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Delavirdine, Etravirine, and Nevirapine
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Delavirdine, Etravirine and Nevirapine treat? How?
Treat HiV-1 by binding directly to HIV-1 reverse transcriptase and result in allosteric inhibition of RNA- and DNA- dependent DNA polymerase activity
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Drug that binds directely to HIV-1 reverse transcriptase and is contraindicated in pregnancy
Delavirdine
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Drug that binds directely to HIV-1 reverse transcriptase and can also cause an elevation in serum cholesterol, tiglyceride, and glucose?
Which drug has a minimal effect on serum lipids?
Etravirine
Raltegravir
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Which Non-Nucleoside and Nucleotide Reverse Transcriptase Inhibitors are extensively metabolized by the CYP3A and CYP2D6 enzymes. It also inhibits CYP3A4 and 2C9
Delavirdine
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Which Non-Nucleoside and Nucleotide Reverse Transcriptase Inhibitors is a substrate as well as an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19?
Etravirine
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Results in decreased levels of methadone and indinavir
Nevirapine
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Inhibits viral integrase enzyme that is essential for replication of HIV-1, -2
Raltegravir
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In combination w/ rifampin, a strong inducer of ____________, the dose of ________ should be increased from 400 to 800 mg twice daily.
- UDP-glucuronosyl transferase 1A1 (UGT1A1)
- Raltegravir
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Protease inhibitor
Indinavir
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