Antivirals/HIV drugs Flashcards
Mechanism of oseltamivir/zanamivir
inhibits influenza neuraminidase –> decreased release of progeny virions
Use of oseltamivir/zanamivir
treat and prevent both influenza A and B within 72 hrs
Mechanism of acyclovir, famciclovir, valacyclovir
guanosine analogs
monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells –> few adverse effects
triphosphate formed by cellular enzymes
preferentially inhibit viral DNA polymerase by chain termination
Use of acyclovir, famciclovir, valacyclovir
HSV - against mucocutaneous and genital lesions and encephalitis
VZV
weak against EBV
prophylaxis in immunocompromised patients
no effect on latent HSV or VZV
What do use for herpes zoster?
famciclovir
What is special about valacyclovir
prodrug of acyclovir and has better bioavailability
Toxicity of acyclovir, famciclovir, valacyclovir
obstructive crystalline nephropathy and acute renal failure if not adequately hydrated
Mechanism of resistance of acyclovir, famciclovir, valacyclovir
mutated viral thymidine kinase
Mechanism of ganciclovir
5’-monophosphate formed by a CMV viral kinase
guanosine analog
triphosphate formed by cellular kinase
preferentially inhibits viral DNA polymerase by chain termination
Use of ganciclovir
CMV, especially in immunocompromised pts
What is valganciclovir?
prodrug of ganciclovir with better oral bioavailability
Toxicity of ganciclovir
leukopenia, neutropenia, thrombocytopenia, renal toxicity
more toxic to host enzymes than acyclovir
Mechanism of resistance of ganciclovir
mutated viral kinase
Mechanism of foscarnet
viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
binds to pyrophosphate-binding site on enzyme
NO activation required by viral kinase
Use of foscarnet
CMV retinitis in immunocompromised pts when ganciclovir fails
acyclovir-resistant HSV
Toxicity of foscarnet
nephrotoxicity, electrolyte abnormalities (hypo- or hypercalcemia, hypo- or hyperphosphatemia, hypokalemia, hypomagnesemia) can lead to seizures
Mechanism of resistance of foscarnet
mutated DNA polymerase
Mechanism of cidofovir
preferentially inhibits viral DNA polymerase
dose not require phosphorylation by viral kinase
Use of cidofovir
CMV retinitis in immunocompromised patients
acyclovir-resistant HSV
long half-life
Toxicity of cidofovir
nephrotoxicity (coadminister with probenecid and IV saline to decrease toxicity)
What is the standard HART regimen?
2 NRTIs + 1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor
Name the protease inhibitors
“-navir”
atazanavir darunavir fosamprenavir indinavir lopinavir ritonavir saquinavir
Mechanism of protease inhibitors
assembly of virions depends on HIV-1 protease (pol genes), which cleaves the polypeptide produces of HIV mRNA into their functional parts
thus, protease inhibitors prevent maturation of new viruses
Ritonavir and p450
INHIBITS cyt p450
Toxicity of protease inhibitors
hyperglycemia
GI intolerance (nausea, diarrhea)
lipodystrophy
neuropathy, hematuria (indinavir)
Rifampin and protease inhibitors
rifampin AMPs up the cyt p450 enzymes and thus can lower protease inhibitor concentrations
Name the NRTIs
abacavir didanosine emtricitabine lamivudine stavudine tenofovir zidovudine
Mechanism of NRTIs
competitively inhibit nucleotide binding to reverse transcriptase and terminates the DNA chain (lack a 3’OH group)
Which of the NRTIs is nucleotides?
Tenofovir
What do need to do to NRTIs that are nucleosides?
need to be phosphorylated to be active
Use of zidovudine
general prophylaxis
PREGNANCY
Toxicity of NRITs
bone marrow suppression (give G-CSF and Epo) peripheral neuropathy lactic acidosis (nucleoside) anemia (ZDV) pancreatitis (didanosine)
Name the NNRTIs
Delavirdine
Efavirenz
Nevirapine
Mechanism of NNRTIs
bind to reverse transcriptase at site different from NRTIs
do NOT require phosphorylation to be active or compete with nucleotides
Toxicity of NNRTIs
rash and hepatotoxicity are common to all
Toxicity of efavirenz
rash and hepatotoxicty
vivid dreams and CNS symptoms
Contraindication of efavirenz and delavirdine
do NOT use in pregnancy
Name the integrase inhibitor
raltegravir
Mechanism of integrase inhibitor
inhibits HIV genome integration into host cell chromosome by irreversibly inhibiting HIV integrase
Toxicity of integrase inhibitor
increased creatine kinase
Mechanism of enfuvirtide
binds gp41, inhibiting viral entry
Toxicity of enfuvirtide
skin reaction at injection site
Mechanism of maraviroc
binds CCR5 on surface of T cells/monocytes inhibiting interaction with gp120
Mechanism of interferons
glycoprotein normally synthesized by virus-infect cells
exhibits antiviral and antihumoral properties
Use of interferon-alpha
chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
Use of interferon-beta
multiple sclerosis
Use of interferon-gamma
chronic granulomatous disease
Toxicity of interferons
neutropenia, myopathy
Drugs to treat hepatitis C
ribavirin, simeprevir, sofosbuvir
Mechanism of ribavirin
inhibits synthesis of guanine nucleotides by competitely inhibiting inosine monophosphate dehydrogenase
Use of ribavirin
chronic HCV, also RSV (palivizumab preferred in children)
Toxicity of ribavirin
hemolytic anemia
severe teratogen
Mechanism of simeprevir
HCV protease inhibitor
prevents viral replication
Use of simeprevir
chronic HCV in combo with ribavirin and peginterferon alfa
Can use simeprevir as monotherapy?
NO
Toxicity of simeprevir
photosensitivity reactions, rash
Mechanism of sofosbuvir
inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator
Use of sofosbuvir
chronic HCV in combo with ribavirin +/- peginterferon alfa
Can you use sofosbuvir as monotherapy?
NO
Toxicity of sofosbuvir
fatigue, headache, nausea
