anti viral drugs Flashcards
what classes of drugs are there
- non nucleoside reverse transcriptase inhibitors
- nucleoside reverse transcriptase inhibitors
- integrase inhibitor
- protease inhibitor
what are the drugs under nucleoside reverse transcriptase inhibitors
lamivudine, tenofovir, abacavir, emtricitabine, zidovudine
what is the current standard of care for HIV treatment
use at least 3 drugs simultaneously for the entire duration
2- NRTI and a 3rd drug either a NNRTI, protease inhibitor or integrase inhibitor
how does nucleoside reverse transcriptase inhibitors work
they are analogs of native ribosides lacking 3’OH group,
causes chain termination as they are preferentially incorporated into viral DNA by reverse transcriptase as they are phosphorylated to corresponding triphosphate analog upon cell entry
Because 3’OH group not present, a3’5 phosphodiester bond between incoming nucleoside triphosphate and growing DNA chain cannot be form
DNA chain elongation terminated
how is nrti excreted
mainly renally
What are the prenancy cat for abacavir, lamivudine, zidovudine, emtricitabine, tenofovir
cat c for the first 3, cat B for the last 2
what do you not co administer with emtricitabine and why
lamivudine, because both are cytosine analogue, will reduce efficacy
what do you have to do before administering abacavir
need to find out if the patient is negative for the HLA-B*5701 allele, need to be genotyped
which is the least toxic antiretroviral drug
lamivudine
how does integrase inhibitor work
binds and inhibits catalytic site of HIV integrase, terminate integration of HIV DNA into host genome, active against HIV1 and HIV 2
how is integrase inhibitor administered
orally
how is the absorption of integrase inhibitors
decreased absorption from gut by polyvalent cations, should be take 2hrs before or 6hrs after taking cation containing antacids or supplements
what are the adverse effects of integrase inhibitors
weight gain, hypersensitivity reaction, cns effects like insomniam depression
What is ritonavir and what does it do
added as a pk booster that has an inhibitory effect on cyp450 enzyme which extends shelf life of protease inhibitor
how does protease inhibitors work
prevents viral protein from being cleaved into mature functional proteins
How are protease inhibitors metabolised
they are substrates for CYP3A4 isoenzyme, extensive hepatic metabolism
how are protease inhibitors eliminated
mostly eliminated by biliary excresion, dosage adjustment unncessary in renal impairment as very little of them are excreted unchanged in urine
what are the main problems with protease inhibitors
potent inhibitors of CYP450, drugs that rely on cyp450 isoenzyme mediated metabolism may accumulate to toxic levels
What is NNRTI not used for
HIV-2 as there is high rate of resistance
What is the mechanism of action for NNRTI
Binds to HIV reverse transcriptase at an allosteric hydrophobic site adjacent to active site, inducing conformational change that result in enzyme inhibition
what are the drug interaction of NNRTI
efavirenz induces CYP3A4, may lower concentration of CYP3A4 substrates
What cat is NNRTI
cat D
how long must prep be
continue prep 1 month after last possible exposure
how long must PEP be started after recent possible exposure to PEP
72 hours
what is acyclovir used for
HSV encephalitis and commonly used for genital herpes infection
How is acyclovir used for
IV, oral, topical
What is the mechanism of action for acyclovir
phosphorylated by viral thymidine kinase to acyclovir monophosphate, and host cell enzymes to acyclovir triphosphate form
it stops replication of herpes viral DNA by
- inhibiting viral DNA polymerase
- inactivate viral DNA polymerase
- incorporates into and terminates viral growing DNA chain
Does acyclovir have greater antiviral activity on HSV or VSV
HSV
what are the benefits of choosing valacyclovir instead of acyclovir
has greater oral bioavailability and can be dosed less frequently than acyclovir
how is acyclovir excreted
into urine occurs both by glomerular filtration and tubular
What are some adverse effects of acyclovir
local irritation from topical application
Headache, diarrhoea, nausea, vomitting
transiet renal dysfuinction occuring in high doses or in dehydrated patients receiving drug IV
What cat is acyclovir in pregnancy
cat B
what inhibitory effect does ganciclovir have. What is it most especially effective against
inhibitory effect against all herpesvirus, especially effective against CMV
What is the mechanism of action for ganciclovir
monophosphorylated intracellularly by viral thymidine kinase and viral phosphotransferase during HSV and CMV
what does food do to valganciclovir
increases its bioavailability by 25%
how can CMV become resistant to ganciclovir
1) Reduced intracellular ganciclovir phosphorylation due to mutations in viral phosphotransferase and mutation in viral DNA polymerase
Ganciclovir also less active against acyclovir resistant thymidine kinase deficient HSV strains
how can resistance occur to acyclovir
Resistance can occur due to altered or deficient thymidine kinase and DNA polymerases
