Antiviral Drugs Flashcards
Anti-herpes virus Agents
Acyclovir Valacyclovir Ganciclovir Valganciclovir Cidofovir Foscarnet Trifluridine
Anti-herpes virus Agents: Acyclovir
Anti-Metabolites: inhibit host polymerases
HSV infections
Activation by Viral Thymidine Kinase
Manage, not cure*
Anti-herpes virus Agents: Valacyclovir
Anti-Metabolites
HSV infections
Prodrug; better oral bioavailability
Manage, not cure*
Anti-herpes virus Agents:
Ganciclovir
Anti-Metabolites
CMV infections
more toxic
Ph. By viral kinase
Anti-herpes virus Agents:
Valganciclovir
Anti-Metabolites
CMV infections
prodrug; better oral bioavailability
Ph. By viral kinase
Anti-herpes virus Agents:
Cidofovir
Competitive inhibitor of Viral DNA synthesis
CMV infections (CMV retinitis)
phosphorylated; for resistant strains
nucleotide
Nephrotoxicity + Tubular Secretion: Must be administered with Probenecid
Anti-herpes virus Agents:
Foscarnet
Direct inhibition of viral polymerases
HSV and CMV infections (Ganciclovir R CMV and Acyclovir R HSV, VZV)
phosphorylated; for resistant strains
A Pyrophosphate
Anti-herpes virus Agents:
Trifluridine
Competes with TTP
inhibits DNA synthesis
primary keratoconjunctivitis and recurrent epithelial keratitis caused by HSV I and II
Activated by Host Kinase (NO viral kinase is required)
Anti-HIV Agents
Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
HIV Protease Inhibitors (“-navir”)
Fusion Inhibitor
Integrase Strand transfer Inhibitors (INSTI) (“-gravir”)
CCR5 Antagonist
HAART
Anti-HIV Agents
Nucleoside Reverse Transcriptase Inhibitors
Zidovudine/Azidothymidine (AZT)
Thymidine Analog; Substrate for/inhibitor of HIV RT
Inhibits stable infection of new cells
temporarily reduces morbidity/mortality from HIV; use in 3-4 multidrug cocktail
Resistance develops due to mutations in RT
Well absorbed from GI tract; rapidly metabolized and excreted; half-life = 1-3 hours
common, may be severe; bone marrow depression; toxicity enhanced by drugs that compete for glucuronidation (acetaminophen)
Anti-HIV Agents
Nucleoside Reverse Transcriptase Inhibitors
Lamivudine
Also used to Tx Hep B
Safe in Pregnant Women
Anti-HIV Agents
Nucleoside Reverse Transcriptase Inhibitors
Abacavir
HLA B5701
Metabolized by Alcohol Dehydrogenase
Anti-HIV Agents
Nucleoside Reverse Transcriptase Inhibitors
Tenofovir disproxil
used when you have resistance to other agents; Hep. B
Used in combo with Emtricitabine
Nucleotide
Anti-HIV Agents
Nucleoside Reverse Transcriptase Inhibitors
Emtricitabine
Flourinated Lamivudine, used with Tenofovir
Anti-HIV Agents
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Nevirapine
Non-competitive RT inhibitor, binds near but not in active side
can be active against AZT-resistant HIV
Rapid emergence of resistance - used in combo therapy
CYP3A4 substrate and inducer
severe, possibly life-threatening skin rash- SJS
Anti-HIV Agents
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Efavirenz
Non-competitive RT inhibitor, binds near but not in active side
Anti-HIV Agents
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Etravirine
Non-competitive RT inhibitor, binds near but not in active side
Anti-HIV Agents
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Rilpivirine
Non-competitive RT inhibitor, binds near but not in active side
Anti-HIV Agents
HIV Protease Inhibitors (“-navir”)
Saquinavir
Inhibits the action of HIV protease, which cleaves the translated polyprotein to yield active individual proteins
Prevent viral particle production - added, synergistic activity
DDIs; resistance develops slowly; use in combo with RT inhibitors
Extensive first-pass effect (CYP3A4)-Administered with a PK booster
altered body fat distribution, hyperlipidemia, insulin resistance (buffalo hump, gynecomastia, truncal obesity, facial wasting); Cushingoid effects
Anti-HIV Agents
HIV Protease Inhibitors (“-navir”)
Lopinavir
Prevent viral particle production - added, synergistic activity
DDIs; resistance develops slowly; use in combo with RT inhibitors
Extensive first-pass effect (CYP3A4)-Administered with a PK booster
altered body fat distribution, hyperlipidemia, insulin resistance (buffalo hump, gynecomastia, truncal obesity, facial wasting); Cushingoid effects
Anti-HIV Agents
HIV Protease Inhibitors (“-navir”)
Ritonavir, Cobicistat
“Pharmacokinetic Booster” - inhibitor of CYP3A4 to enhace the actions of these drugs
Prevent viral particle production - added, synergistic activity
DDIs; resistance develops slowly; use in combo with RT inhibitors
Extensive first-pass effect (CYP3A4)-Administered with a PK booster
altered body fat distribution, hyperlipidemia, insulin resistance (buffalo hump, gynecomastia, truncal obesity, facial wasting); Cushingoid effects
Anti-HIV Agents
HIV Protease Inhibitors (“-navir”)
Indinavir
Prevent viral particle production - added, synergistic activity
DDIs; resistance develops slowly; use in combo with RT inhibitors
Extensive first-pass effect (CYP3A4)-Administered with a PK booster
altered body fat distribution, hyperlipidemia, insulin resistance (buffalo hump, gynecomastia, truncal obesity, facial wasting); Cushingoid effects
Anti-HIV Agents
HIV Protease Inhibitors (“-navir”)
Darunavir
Only Ad. With sub-therapeutic dose of Ritonavir
Prevent viral particle production - added, synergistic activity
DDIs; resistance develops slowly; use in combo with RT inhibitors
Extensive first-pass effect (CYP3A4)-Administered with a PK booster
altered body fat distribution, hyperlipidemia, insulin resistance (buffalo hump, gynecomastia, truncal obesity, facial wasting); Cushingoid effects
Anti-HIV Agents
Fusion Inhibitor
Enfuvertide
interferes with the entry of HIV-1 into host cells by inhibiting the fusion of the virus and cell membranes
reserved for individuals who have advanced disease or show resistance to current HIV tx
cysts, nodules as site of inj
Anti-HIV Agents
Integrase Strand transfer Inhibitors (INSTI) (“-gravir”)
Raltegravir
inhibits the catalyic activity of integrase
prevents integration of the proviral gene into human DNA
Metabolized by UGT1A1
Anti-HIV Agents
Integrase Strand transfer Inhibitors (INSTI) (“-gravir”)
Elvitgravir
inhibits the catalyic activity of integrase
prevents integration of the proviral gene into human DNA
Anti-HIV Agents
Integrase Strand transfer Inhibitors (INSTI) (“-gravir”)
Dolutgravir
inhibits the catalyic activity of integrase
prevents integration of the proviral gene into human DNA
-Eliminated via UGT1A1
Anti-HIV Agents
CCR5 Antagonist
Maraviroc
Selectively and reversibly binds to the CCR5 coreceptors located on human CD4 cells; inhibits gp120 conformational change required for fusion/entry
used in combo with other agents in pts with evidence of HIV-1 strains resistant to multiple antiretroviral therapy
Anti-HIV Agents
HAART
2 nucleoside reverse transcriptase inhibitors + either INSTI (-gravir), NNRTI, or PI (-navir) (with a pharmacokinetic booster-Ritonavir, Cobicistat)
pts are prone to opportunistic infections; numerous DDIs
Anti-Opportunistic Infx in AIDS pts
For Pneumocystic jiroveci (PJP) infx
TMP/SMX
prevention/treatment
Anti-Opportunistic Infx in AIDS pts
For MAC infx
Clarithromycin plus ethambutol
Anti-Opportunistic Infx in AIDS pts
For Toxoplasmosis
Pyrimethamine/sulfadiazine plus folinic acid
Anti-Opportunistic Infx in AIDS pts
For Cryptococcal meningitis
Amphotericin B/Flucytosine
Anti-Opportunistic Infx in AIDS pts
For CMV
Ganciclovir (Valgancyclovir)
Anti-Opportunistic Infx in AIDS pts
For Candidiasis
Fluconazole
Anti-Opportunistic Infx in AIDS pts
For HSV
Acyclovir (Valacyclovir)
Anti-Opportunistic Infx in AIDS pts
For Herpes Zoster
Acyclovir (Valacyclovir)
Inhibitors of Viral Nucleic Acid Synthesis
Ribavirin
anti-metabolite; blocks GMP formation
Effective as aerosol for RSV Tx; tx of hepatitis C(+ Peg IFN)
human teratogen; dose-dep. myelosuppresion
Influenza Drugs
Viral Neuraminidase Inhibitors (“-amivir”)
Oseltamivir
Inhibit viral NA
Prevents viral release, infection of additional cells
all common influenza (A, B and C) virus strains
oral; prodrug; activated in gut and liver
well-tolerated, some n/v
Influenza Drugs
Viral Neuraminidase Inhibitors (“-amivir”)
Zanamivir
Inhibit viral NA
Prevents viral release, infection of additional cells
effective early in infection (before 2 days)
oral inhalation
bronchospasm in asthmatics
Influenza Drugs
Viral Neuraminidase Inhibitors (“-amivir”)
Peramivir
Inhibit viral NA
Prevents viral release, infection of additional cells
tx of acute, uncomplicated influenza in adults who have been symptomatic <2 days
single IV dose
Influenza Drugs
Inhibitors of Uncoating
Amantadine
Block viral uncoating by blocking M2 proton channel; disrupts endocytosis and viral disassembly
protects against and treats only Influenza A
give in first 48 hours of contact; oral
GI intolerance, CNS effects
Influenza Drugs
Inhibitors of Uncoating
Rimantadine
Block viral uncoating by blocking M2 proton channel; disrupts endocytosis and viral disassembly
protects against and treats only Influenza A
give in first 48 hours of contact; oral
GI intolerance, CNS effects
Hepatitis C Drugs
Peg-Interferon alpha
Standard of Care for HCV
Hepatitis C Drugs
Ribavirin
inhibits RNA Polymerase
Standard of Care for HCV
Hepatitis C Drugs
Sofosbuvir
nucleotide analog, inhibits an HCV RNA-dependent RNA polymerase
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Hepatitis B Drugs
Lamivudine-NRTI
Anti-retroviral nucleoside/nucleotide analog polymerase inhibitors
Hepatitis B Drugs
Tenofovir-NRTI
Anti-retroviral nucleoside/nucleotide analog polymerase inhibitors
