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46 Cards in this Set
- Front
- Back
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General Principles of Antivirals
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1.) Tend to be static and not cidal. Therefore, the host immune response is important.
2.) May blunt immune response to some degree 3.) Combo therapies are becoming more attractive 4.) Intracellular conc. of drug is what's important, but hard to measure 5.) Clinical failure may not mean resistance 6.) Usually inhibit virus specific events, but can have some human side effects |
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Factors that increase likelihood of resistance
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1.) Viral heterogeneity
2.) RNA / Retroviruses 3.) Immunosuppression 4.) High viral load 5.) Sub-therapeutic levels of the drug (may be caused by non-compliance) Generally, compliance of > 90% is needed to avoid resistance Cross-resistance b/w drugs in same family is common If failure occurs - Resistance genotyping and then add at least 2 new drugs. |
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Nucleoside Reverse Transcriptase Inhibitors ("nukes")
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Analogs of DNA substrates
Compete w/ host cell dNTPs for binding to active site of HIV reverse transcriptase. Block further elongations b/c they lack 3'OH group so they are CHAIN TERMINATORS Must be phosphorylated 3 times by the Host Cell, except for Tenofovir, which already has one phosphate group (NucleoTIDE inhibitor) |
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Mutations that can lead to resistance
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Discriminate mutation - puts a bulky group on that doesn't allow nucleoside reverse transcriptase inhibitors to bind
Thymidine analog mutation - Facilitates influx of ATP, which drives the RXN to the left, pulling off Thymidine and stopping nucleoside reverse transcriptase inhibitors |
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AZT
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Nucleoside reverse transcriptase inhibitor
Can cause anemia and neutropenia |
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D4T
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Neucleoside reverse transcriptase inhibitor (NRTI)
Can cause peripheral neuropathy (like DDI) |
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3TC
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Nucleoside reverse transcriptase inhibitor (NTI)
No real side effects Also active against Hep B |
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FTC
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Nucleoside reverse transcriptase inhibitor (NTI)
No real side effects Also active against Hep B |
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DDI
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Nucleoside reverse transcriptase inhibitor (NRTI)
Can cause peripheral neuropathy (along w/ D4T) |
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Abacavir
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Nucleoside reverse transcriptase inhibitor (NTI)
Commonly used Can cause Hypersensitivity Syndrome w/ fever, rash, abdominal pain Can test to see if person is at risk for Hypersensitivity Syndrome |
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Tenofovir
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NucleoTIDE reverse transcriptase inhibitor (NTI)
Can cause renal toxicity and phosphate wasting Often used when HIV is resistant to other NRTIs Already has one phosphate group so it is a NucleoTIDE reverse transcriptase inhibitor Also works against HepB |
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Non-Nucleoside Reverse Transcriptase Inhibitors
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Specific for HIV-1
Bind to a hydrophobic pocket and locks reverse transcriptase polymerase in open confirmation, making it much less efficient Liver metabolism = more drug interactions Resistance is likely b/c only 1-2 mutations required |
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Efavirenz
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Most common Non-Nucleoside Reverse Transcriptase inhibitor (NNRTIs)
The only TERATOGENIC HIV drug (don't give to pregnant women) Mild CNS side effects in 50% |
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Rilpivine
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Brand new Non-Nucleoside Reverse Transcriptase inhibitor (NNRTIs)
May cause Rash or hepatitis. Less CNS side effects than Efavirenz |
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Etravirine
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Non-Nucleoside Reverse Transcriptase inhibitor (NNRTIs)
The least likely NNRTI for HIV to become resistant too Can cause rash or hepatitis like Rilpivine |
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Protease Inhibitors (PIs)
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HIV antiviral
Blocks HIV protease, which prevents virion from maturing Mimics peptide bond that HIV protease cleaves P450 enzyme metabolism so numerous drug interactions Ritonavir inhibits P450 enzyme CYP3A4 so it can increase drug levels of many drugs such as other Protease Inhibitors (Called "boosting") Mutations in HIV protease gene can cause resistance |
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Saquinavir
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Protease Inhibitor (PI)
Large pill burden so often combined w/ Ritonavir for "boosting" |
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Ritonavir
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Protease Inhibitor (PI)
Used in "boosting" b/c it inhibits CYP3A4 drug metabolism Can cause significant GI intolerance Many drug interactions |
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Tipranavir
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Protease Inhibitor (PI)
Can cause GI intolerance Used for PI resistant patients |
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Darunavir
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Protease Inhibitor (PI)
Can cause Lipodystrophy syndrome Used for PI resistant pateitns |
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fosAmprenavir
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Protease Inhibitor (PI)
Can cause Lipodystrophy syndrome along w/ Darunavir Large pill burden that can be reduced by "boosting" w/ Ritonavir |
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Lopinavir
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Protease Inhibitor (PI)
Can cause Lipodystrophy syndrome Only used w/ Ritonavir |
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Atazanavir
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Protease Inhibitor (PI)
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Lipodystrophy Syndrome
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Seen w/ HIV Protease Inhibitors
Central / thorasic fat accumulation, elevated LDL and triglycerides |
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Integrase Inhibitors
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HIV drug that inhibits the final integration of HIV DNA into the host chromosome
Few side effects and few drug interactions |
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Raltegravir
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The lone Integrase Inhibitor for HIV treatment
No interaction w/ liver metabolized drugs |
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Mariviroc
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HIV entry inhibitor
Binds CCR5 and blocks the interaction w/ HIV Only works if patient's HIV is purely CCR5 Does not work if CXCR4 is present |
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Nucleoside and nucleotide analogs for Herpes
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dNTP analogs that compete for the active site in herpes polymerase (similar to HIV NRTIs)
Different from HIV NRTIs b/c the virus itself takes care of the first phosphorylation Ganciclovir and Penciclovir are not technically chain terminators Ganciclovir and Valganciclovir attack host polymerase so can cause neutropenia and anemia Renal metabolism Resistance commonly caused by mutation in molecule that causes first viral phosphorylation (Tyrosine Kinase) |
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Acyclovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Seizures and renal toxicity at high doses Active against HSV-1 and HSV-2 High dose activity against VZV |
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Valacyclovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Seizures and renal toxicity at high doses Active against VZV and EBV |
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Penciclovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Seizures and renal toxicity at high doses Active against VZV and EBV |
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Ganciclovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Can cause anemia and neutropenia Active against CMV |
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Valganciclovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Oral Ganciclovir Can cause anemia and neutropenia Active against CMV |
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Cidofovir
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Nucleoside and nucleotide analogs for Herpes Viruses
Doesn't need Tyrosine Kinase primary phosphorylation High incidence of renal toxicity |
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Foscarnet
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Herpes drug that blocks pyrophosphate lysis needed to drive polymerase
Can cause Renal toxicity like Cidofovir Active against all human herpresviruses |
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Pegasyn
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PEG-Interferon used to treat Hep C
Induces an "antiviral state" - inhibits viral RNA transcription, induces cytotoxic T cell and NK activity Pegylated form has longer half life, more effective, and less toxic Can cause fever, chills, myalgia, depression |
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Nucleoside and Nucleotide analogs for Hep B
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Like in HIV, compete for dNTPs
Don't work against Hep C b/c Hep C is an RNA virus Many of these drugs are the same as the ones used to treat HIV 3TC / Lamivudine - Easy to be resistant so NEVER start treatment w/ Lamivudine (3TC) Entecavir - use w/ lamivudine resistant Adefovir Tenofovir Telbivudine Few side effects |
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Ribavirin
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Hep C med, but has affects on many other viruses including Influenza
Guanosine analog that after triphosphorylation by host cell interferes w/ host IMPDH in Hep C, which results in low levels of GTP Clearly enhances interferon effects and is ALWAYS paired w/ PEG-Interferon Can cause anemia and bone marrow suppression Teratogen so contraindicated in pregnancy |
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Telaprivir and Bocepavir
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New Hep C drugs that show significant increase in positive treatment outcomes when combined w/ PEG-interferon and Ribavirin
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M2 Ion Channel Inhibitors
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Only effective against Influenza - A
Blocks acidification needed for virus uncoating and release from the endosome Resistance is common via mutation in M2 protein Can shorten duration of symptoms by a few days, but only if started by 2 days of symptom onset |
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Amantadine
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M2 Protein inhibitor
Can cause CNS problems (insomnia) |
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Rimantadine
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M2 Protein inhibitor
Less CNS problems than Amantadine |
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Neuraminadase Inhibitors
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Blocks release of the virus by blocking Neuraminadase cleavage of sialic acid
Resistance is less common than M2 blockers Can shorten duration of symptoms by a few days, but only if started by 2 days of symptom onset |
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Zanamivir
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Neuraminadase inhibitor
Inhaled solution Can cause bronchospasm |
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Oseltamivir
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Neuraminadase inhibitor
Typically active against H1N1 |
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Endings for families of drugs
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"T" - Nucleoside Reverse Transcriptase Inhibitor
"-ine" - Non-Nucleoside Reverse Transcriptase inhibitor "-navir" - Protease Inhibitor "-gravir" - Integrase Inhibitor "-clovir" - Herpes Nucleotide Analog "-mantadine" - M2 Channel Blocker for Influenza "-amivir" - Neuraminadase Inhibitor for Influenza |
