Antiviral 1 Flashcards
Nucleoside analogues
Acyclovir Famciclovir Valacyclovir Panciclovir Ganciclovir Valganciclovir Cidofovir Trifluridine
Nucleoside analogues - MoA
Prodrugs that are converted to monophosphate by virus enzymes, and then to active triphosphate metabolites by host enzymes. Competitive inhibition of viral DNA polymerase.
Acyclovir - Clinical use
HSV, VZV Prophylaxis of CMV Chickenpox IV form: most effective treatment for serious herpesvirus infections, including herpetic encephalitis and severe HSV and VZV infections in immunocompromised patients Topical form: herpes genitalis and mild mucocutaneous infections in immunocompromised patients. In cases of herpes genitalis, however, topical form is less effective than oral form
Herpetic encephalitis
Acyclovir - Adverse effects
Well tolerated Headache, GI disturbances, rash (General for all the nucleoside analoges) IV: phlebitis + reversible renal dysfunction
Famciclovir - Clinical use
HSV VZV
Valacyclovir - Clinical use
HSV, VZV Prophylaxis of CMV , such as in bone marrow and organ transplant recipients and in persons with HIV
Panciclovir - Clinical use
Herpes labialis
Ganciclovir - Clincal use
Prevent CMV diseases, including retinitis, esophagitis, and colitis HSV: keratitis (infection of the corneal epithelium) caused by HSV-1 and HSV-2
Ganciclovir - Adverse effects
Leukopeina, thrombocytopenia Retinal detachment, liver and renal dysfunction
Ganciclovir - Interactions
Severe myelosupression with zidovudine
Valganciclovir - Clinical use
Prevent and treatment of less severe CMV infections, including those occurring in renal and heart transplant patients
Cidofovir - Clinical use
Prevent CMV diseases resistant to ganciclovir
Cidofovir - Contraindications
Contraindicated in patients taking other nephrotoxic drugs, such as aminoglycosides and amphotericin B.
Cidofovir - Adverse effects
Nephrotoxicity, neutropenia, metabolic acidosis.
Trifluridine - Clinical use
Ocular herpervirus infections, primarily herpetic epithelial keratitis and keratoconjuctivitis
Pyrophosphate derivative (HSV drug)
Foscarnet
Foscarnet - MoA
Blocks pyrophosphate-binding sites on viral DNA polymerase and prevents attachment of nucleotide precursor to DNA. Does not need activation by viral/host kinases.
Foscarnet - Clinical use
CMV, VZV, HSV CMV retinitis in AIDS patients Acyclovir-resistant HSV infections Shingles Combined with ganciclovir to treat infections resistant to either drug alone because of their synergistic effect on viral DNA polymerase
Foscarnet - Adverse effects
Renal impairment and acute renal failure, hematologic deficiencies, cardiac arrhythmias + heart failure, seizures, pancreatitis Renal toxicity can be minimized by administering intravenous fluids to induce diuresis before and during treatment
Nucleoside reverse transcriptase inhibitors (NRTIs)
Didanosine Lamivudine Stavudine Emtricitabine Zidovudine (ZDV) Abacivir (ABC) Tenofovir
Nucleoside reverse transcriptase inhibitors (NRTIs) - MoA
Triphosphate metabolites of the drug compete with nucleoside triphosphates for incorporation into viral DNA. Cause DNA chain termination. Inhibit host cell DNA polymerase somewhat.
Nucleoside reverse transcriptase inhibitors (NRTIs) - Clinical use
HIV Some are active for Epstein-Barr virus and hepatitis B virus
Nucleoside reverse transcriptase inhibitors (NRTIs) - Special considerations
Included in almost all HIV treatment regimens. Often more effective with multiple NRTIs (antimetabolites of different bases of DNA). Cross BBB. Careful with renal impairment
Nucleoside reverse transcriptase inhibitors (NRTIs) - Adverse effects
Lactic acidosis, hepatic steatosis, lipodystrophy
First line HIV drugs
Abacivir (ABC) Tenofovir Emtricitabine Lamivudine
Alternative for 1st line drugs for HIV
Stavudine Didanosine
ucleoside reverse transcriptase inhibitors (NRTIs) - For treatment of hepatitis B
Lamivudine Tenofovir
Which NRTI is used to treat HIV in pregnant women?
Zidovudine (ZDV)
Which NRTIs are not used together and why?
Zidovudine and stavudine because they appear to be antagonistic
Abacavir - Adverse effects
Hypersensitivity reactions
Which NRTIs cause Pancreatitis and Peripheral neuropathy
Didanosine and Stavudine
Tenofovir - Adverse effect (the most important)
Renal impairment
Zidovudine - Adverse effect (the most important)
Bone marrow suppression
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz Nevirapine Delavirdine
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - MoA
Direct inhibition of reverse transcriptase
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Clinical use
HIV
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Special considerations
Cross BBB Act synergistically with NRTIs and PIs against HIV. Never used alone for HIV
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Contraindications
Contraindicated for hepatic impairment
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) - Adverse effects
Moderately well tolerated Rash (can progress to Stevens-Johnson syndrome) Hepatotoxicity Drug interactions
Which is the most potent NNRTI?
Efavirenz
Efavirenz - Contraindications
Contraindicated during pregnancy
Efavirenz - Adverse effects
Teratogenic Neuropsychiatric reactions
Nevirapine - Interactions
Induces CYP3A4 + CYP2B6: Increases metabolism of certain drugs Increases metabolism of PIs, contraceptive steroids, other drugs
Nevirapine - Adverse effects
Hepatotoxicity, rash (+Stevens-Johnson syndrome)
Delavirdine - Special consideration
Usually not recommended for HIV (less potent)
Protease inhibitors (PIs) (Most important)
Ritonavir Atazanavir Darunavir
Protease inhibitors (PIs) - MoA
Bind HIV protease and inhibits proteolytic activity. Production of immature, noninfectious viral particles.
Protease inhibitors (PIs) - Clinical use
HIV
Protease inhibitors (PIs) - Adverse effects
Lipodystrophy, hyperlipidemia, insulin resistance and DM, liver dysfunction, hepatitis.
Protease inhibitors (PIs) - Interactions
Inhibits metabolism of other drugs: PIs, antiarrhythmic agents, opioids, tricyclic antidepressants Nevirapine: Increase PI metabolism.
