Flashcards in Antivirals Deck (34):
4 targets for antivirals in HIV drugs
entry, reverse transcriptase, integrase, protease
mechanism of action for NRTI's
viral DNA chain termination via inhibition of reverse transcriptase enzyme. pose as pieces of DNA and get picked up and stop the enzyme!
NRTI class side effects
lactic acidosis (much less common with newer agents). GI side effects.
zidovudine, stavudine, didanosine, tenofovir, abacavir, zalcitabine, lamivudine, emtricitabine
NNRTI mechanism of action
bind directly to reverse transcriptase and inhibit its actions
efavirenz, nevirapine, etravirine, rilpivirine
NNRTI side effects
cause a rash. may cause CNS effects like vivid dreams, drowsiness.
protease inhibitor agents
norvir, lexiva, kaletra, reyataz, prezista
protease inhibitor mechanism of action
bind within active pocket of protease, inhibiting binding of the virus. without protease cleavage, virus cannot cause infection!
what is curious about ritonavir?
ritonavir at low doses enhances blood levels of other protease inhibitors! give together to increase clinical effectiveness and require less doses of other drugs!
protease inhibitor class toxicities
GI: N/V, diarrhea
Metabolic: dyslipidemia, hyperglycemia, lipodystrophy
enfuvirtide mechanism of action
messes with GP41, which makes the connection for CD4 binding. messes with HIV attachment and fusing
enfuvirtide adverse effects
local injection sight reaction. increased rate of bacterial pneumonia. hypersensitivity.
HIV often uses CCR5 as a co-receptor necessary to enter T cells. Maraviroc is only agent. Only drug that acts on the host cell, all others act on HIV molecules.
CCR5 adverse effects
hepatotoxicity. cough, fever, URI, rash, musculoskeletal, ab pain, dizziness
integrase inhibitor agents
raltegravir, elvitegravir, dolutegravir.
integrase inhibitor mechanism of action
inhibit viral enzyme integrase. necessary for insertion of viral DNA into human genomic DNA
integrase inhibitor adverse effects
generally few adverse effects. commonly seen: Nausea, headache, diarrhea, pyrexia. myopathy seen sometimes
basics of HAART
use at least 3 active agents representative of 2 classes of agents
goals of HAART
suppress viral load, restore immune function, improve quality of life, reduce HIV related morbidity and mortality, minimize risk for antiretroviral resistance
NS5B polymerase inhibitors agents
NS5B polymerase inhibitors mechanism of action
inhibitor of Hep C NS5B RNA dependent RNA polymerase. competes with natural viral nucleotides to cause chain termination
NS5A inhibitor agents
ledipasvir, daclatasvir, ombitasvir
NS5A inhibitor mechanism of action
inhibits hep C NS5A, a viral phosphoprotein required for viral replication.
NS3/4A protease inhibitor agents
simeprevir, boceprevir, telaprevir
NS3/4A protease inhibitor mechanism of action
prevent viral maturation through the inhibition of protein synthesis
acyclovir mechanism of action
after phosphorylation by cellular enzymes, acyclovir triphosphate competes with DNA analogues to cause viral DNA chain termination. needs viral thymidine kinase to become active
other drugs like acyclovir
valacyclovir, peniciclovir, famciclovir
acyclovir toxicity concerns
CNS: malaise, headache, confusion.
N/V, diarrhea. renal dysfunction seen in high doses of IV therapy due to drug crystallizing in kidneys
active mainly against Cytomegalovirus. (CMV). Use the prodrug when you need to give orally, as the actual drug has bad bioavailability. biggest side effect is myelosuppression
inhibitory effect on herpesvirus and HIV. directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase.
foscarnet tox issues
nephrotox, electrolyte/metabolic abnormalities, CNS side effects, myelosuppression. only used when people have resistance to other herpes drugs
oseltamivir, zanamivir, peramivir. inhibit enzyme critical in penetration of respiratory tract mucus and in the release of virus from infected cells. active against flu A and B