Chapter 9: Antiviral drugs
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| How do the antiviral drugs work? | many of them get phosphorylated to eventually create a triphosphorylated form, mimicking specific nucleotide triphosphates, interfering with viral DNA synthesis and/or viral transcription processes, and blocking DNA replication.
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| what is the mechanism of action of Amantadine work? | it binds to Influenza A's M2 matrix (required for the fusion between the viral capsid and cellular lysosomal membranes) that will allow for capsid destruction.
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| what type of influenza virus does Amantadine treat? | influenza A only
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| Amantadine is only effective if used within this time period after onset of influenza symptoms | 48 hours
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| what drug works similarly to Amantadine? | Rimantadine
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| why have Amantadine and Rimantadine fell out of favor for drug use? | CNS side effects (nervousness, anxiety, hallucinations) and growing resistance
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| how does interferon work? | induces host cell responses that inhibit viral RNA translation and also induces MHC 1 expression, increasing macrophage sensitivity towards the ability to eradicate virally infected cells.
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| interferon is the DOC for what? | chronic HCV infections, and is used in monotherapy for chronic HBV infections. also used in hairy cell leukemia and kaposis sarcoma.
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| inferferon is often conjugated to what in order to increase its duration of action (and decrease dosing)? | polyethylene glycol.
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| PEG interferon is commonly used in the chronic treatment of what? | chronic HCV
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| how does ribavarin work? | sequentially phosphorylated to eventually become ribavarin triphosphate, looking much like guanosine triphosphate (one of the building blocks of DNA and RNA). It interferes with transcription.
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| Ribavarin is the drug of choice for what? | chronic and acute HCV.
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| what is the standard of therapy for HCV infection? | PEG ingerferon plus Ribavarin
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| how does Acyclovir work? | it gets sequentially phosphorylated to eventually become acyclovir triphosphate, which looks much like GTP. It is a replication inhibitor.
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| the phosphorylation process of acyclovir can only be accomplished via what? | thymidine kinase.
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| thymidine kinase is found in what viruses? | HSV1, HSV2 EBV
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| thymidine kinase is not found in what? | CMV.
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| does acyclovir penetrate the BBB? | no
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| what drug is similar to Acyclovir? | valacyclovir, but has longer half life, requiring less frequent dosing.
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| what is the MOA of vidarabine | undergoes sequential phosphorylation to imitate ATP. it becomes incorporated into DNA, inhibiting DNA synthesis.s
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| vidarabine can be used to treat what? | all herpes group viruses, especially herpes encephalitis (HSV infection of the brain) VZV (chickenpox or herpes zoster)
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| describe the MOA of ganciclovir | similar to that of acyclovir, except viral thymidine kinase is not requred for phosphorylation process, so CMV is effectively treated with this.
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| ganciclovir is the DOC for what? | CMV retinitis.
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| what is a common side effect for Ganciclovir? | bone marrow suppression, resulting in neutropenia and aplastic anemia
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| AZT is alos known as what? | zidovudine
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| how does AZT work? | it is triphosphorylatd by human thymidine kinase, becoming a TTP analog. it inhibits viral DNA synthesis after being incorporated into the growing viral DNA chain.
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| AZT is used to treat what? | HIV.
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| does AZT cross the BBB? | yes
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| AZT belongs to what class of drugs? | pharmacologic nucleosides, AKA nucleoside reverese transcriptaswe inhibitors. they all become vonverted to nucleotides and all inhibit viral DNA synthesis.
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| what do protease inhibitors do? | inhibit cleavage of the "giant protein" gag-pol-env that HIV must cut apart in order to have the functional components of thta protien.
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| protease inhibitors are used to treat what? | HIV
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| give some examples of protease inhibitors | saquinavir, ritonavir, indinavir, nelofinavir, fosamprenavir
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| how do non-nucleoside reverse transcriptase inhibitors work? | directly inhibit reverse transcriptase, and are used in management of HIV infection.
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| how do fusion inhibitors work? | prevent the fusion between the HIV virion and the cell. it binds to gp41 and prevents viral fusion with the cell's cell membrane, thereby preventing entry into the cell.
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| fusion inhibitors increase the risk of what? | bacterial pneumonia
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| what are the most common side effects of fusion inhibitors? | insomnia, headache, nausea
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| how do integrase inhibitors work? | inhibit HIV viral integrase enzyme. thereby preventing integration and insertion of HIV DNA into human DNA.
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| what are some side effects of integrase inhibitors? | may cause life threatening drug-drug interactions. instances of hypersensitivity, sevens johnsons syndrome, toxic epidermal necrolysis, hepatic failure, rhabdomyolysis.
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| what is the mechanism of action of chemokine co-receptor antagonists? (CCR5 antagonists) | block the CCR5 co-receptor located on white blood cells targeted by HIV. the drug prevents entry of the virus into the cell.
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| CCR5 antagonists are approved for what? | CCR5 tropic HIV-1
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| what is a drug in the CCR5 antagonist class? | maraviroc.
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| what is one side effect of maraviroc? | stevens johnson syndrome
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| how does Foscarnet work | it is a direc tinhibitor of both DNA polymerase and reverse transcriptase.
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| foscarnet is used as an alternative to what? | ganciclovir in the treatment of CMV, and is also useful in cases of ganciclovir resistant CMV. it is also used in the treatment o facclovir and ganciclovir resistant VZV and HSV. also effective against HIV
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| how does valganciclovir work | used in combination therapy with the drug of choice (ganciclovir) for the treatment of CMV retinitis. may cause bone marrow supression (myelosuppression)
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| how does trifluridine work | mimics TTP to be able to become incorporated into viral DNA and therefore ultimately inhibit viral DNA synthesis. it doe snot require virla thymjidine kinase to become triphosphorylated (active) and so is active against HSV
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| trifluridine is the DOC for what? | herpes keratititis
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| what is the MOA of cidofovir | alternative treatment of CMV retinitis. it is also the DOC for the treatment of smallpox and is the dru of choice for treatment of severe adenovirus infections. very nephrotoxic and at high doses cn cause fanconi syndrome
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| cidofovir is typically given with what other drug to minimize the dose while maximizing the side effects? | probenacid
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| is cidofovir teratrogenic? | yes
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