Antiviral drugs Flashcards
Foscarnet - what is indicated for?
Used for CMV retinitis in immunocompromised who have failed ganciclovir therapy
Also used for acyclovir-resistant HSV
Foscarnet- what is the mechanism?
Pyrophosphate analog, inhibits viral DNA polymerase, does NOT require activation by viral kinase
Resistance via mutated DNA polymerase
Foscarnet - what is the toxicity?
Nephrotoxicity (reversible w hydration and decreased dosage)
Electrolyte abnormalities -> mental status changes, paresthesias, seizures
NRTIs (Nucleoside Reverse Transcriptase Inhibitors) - what are examples and what are they indicated for?
Examples: Abacavir (ABC), didanosine (ddl), emtrictabine (FTC), lamivudine (3TC), stavudine (d4T), tenofovir (TDF), zidovudine (ZDV, formerly AZT)
Use: antiretroviral drugs to treat HIV
NRTIs (Nucleoside Reverse Transcriptase Inhibitors) - what is the mechanism of action?
Competitively inhibit nucleotide binding to reverse transcriptase and terminate elongating DNA chain
*must be activated in the cell and requires phosphorylation
What NRTI is used for HIV prophylaxis and pregnant women who are HIV positive?
Zidovudine (ZDV)
NRTI toxicity
Bone marrow suppression-> anemia, rash, neuropathy, pancreatitis (especially w EtOH), lactic acidosis
What can be given to reverse bone marrow suppression toxicity?
EPO and G-CSF (granulocyte colony-stimulating factor)
NNRTIs (Non-nucleoside reverse transcriptase inhibitor) - what are examples and what are they indicated for?
Ex: Delavirdine, efavirenz, nevirapine
Use:HIV and AIDS
NNRTIs (Non-nucleoside reverse transcriptase inhibitor) - what is their mechanism?
Inhibits reverse transcriptase at different site from NRTIs
*do NOT require intracellular activation or phosphorylation
NNRTIs (Non-nucleoside reverse transcriptase inhibitor) - what is their toxicity and contraindication?
Side effects: Rash, Hepatotoxicity, CNS symptoms and vivid dreams
Contraindicated: pregnancy, especially delavirdine and efavirenz are teratogenic
Protease inhibitors - what are examples and what are they indicated for?
“-navir” Ritonavir, indinavir
Indicated for HIV/AIDS and Hepatitis C
Protease inhibitors - what are their mechanism of action?
Inhibits viral protease -> virus cant cleave polyproteins into functional proteins -> inhibits maturation of new viruses
What are the side effects of protease inhibitors?
GI distress,
nephropathy (indinavir)
lipodystrophy (usually in face, and can cause buffalo hump),
hyperglycemia (can progress to DM type II)
P450 inhibition
Enfuvirtide - what is it used for? what is the mechanism? what are the side effects?
Used for HIV
Mechanism: fusion inhibitor, prevents penetration; binds to gp41 (HIV protein that penetrates host cell membrane) and interferes with ability to fuse with CD4+ cells -> inhibits viral entry
Side effect: skin rxn at injection site
Maraviroc - what is it used for? what is the mechanism?
Oral medication, Used for HIV
Mechanism: fusion inhibitor, prevents attachment; binds to CCR5 (chemokine receptor) on CD4+ T-cells and prevents interaction with gp120 -> inhibits HIV entry into host cell
What are Integrase inhibitors used for and what are their mechanism of action and side effects?
“-gravir” raltegravir
Used for HIV
Mechanism: blocks insertion of viral genome, inhibit actions of integrase (enzyme used by virus to integrate viral genome)
side effects: hypercholesterolemia, insomnia
When is HAART (highly-active antiretroviral therapy) indicated?
Used for patients with:
AIDS defining illness OR CD4+
What drugs are included in HAART (highly-active antiretroviral therapy)
3 drugs:
2 NRTIs
+ 1 NNRTI or protease inhibitor or integrase inhibitor
What is Cidofovir indicated for? What is its mechanism of action and side effects?
indicated for CMV retinitis in immunocompromised and acyclovir-resistant HSV
Mechanism: inhibits viral DNA polymerase, does not require phosphorylation by viral kinase, long half life
Side effect: dose-dependent nephrotoxicity (decreased when co-administered with probenecid and IV saline)
Ribavirin - what is it indicated for? what is the mechanism and side effects?
Indicated for Hep C, viral hemorrhagic fevers and severe RSV (respiratory syncitial virus) (off-label)
Mechanism: inhibits inosine monophosphate dehydrogenase -> depletes GTP
Side effects: hemolytic anemia, teratogen
Oseltamivir, zanamivir - what is their mechanism of action and clinical use?
Tamiflu!
Mechanism: inhibits influenza neuraminidase -> cant release progeny
Use: treatment and prevention of influenza A and B
Acyclovir, famciclovir, valacyclovir- what is there mechanism of action and clinical use? what are their side effects?
Mechanism: guanosine analogs. Monophosphorylated by HSV/VZV thymidine kinase -> inhibits viral DNA polymerase by chain termination
Use: HSV and VZV mucocutaneous and genital lesions as well as encephalitis. Prophylaxis in immunocompromized. Famciclovir for herpes zoster
Toxicity: obstructive crystalline nephropathy and acute renal failure if not hydrated
Ganciclovir - what is it used for? what is the mechanism and toxicity?
Mechanism: guanosine analog, monophosphorylated by CMV viral kinase -> inhibits viral DNA polymerase by chain termination
Use: CMV, especially in immunocompromised
Toxicity: leukopenia, neutropenia, thrombocytopenia and renal toxicity. More toxic than acyclovir
