Flashcards in HIV Drugs Deck (36):
What's the goal of therapy in HIV?
maximally inhibit viral replication and reduce viral RNA to undetectable levels
After therapy is initiated, an increase in viral load may indicate what?
What's the general strategy in terms of drug combo in adults who have never been treated for HIV before?
one of these: NNRTI, protease inhibitor, or integrase inhibitor
plus a dual combo of NRTIs
What are the four nucleoside reverse transcriptase inhibitors we know?
What's the mechanism of the NRTIs?
they competitively inhibit reverse transcritase and can be incoporated into viral DNA chain and cause termination
What do the NRTIs need in order to become active?
they need to be phosphorylated by cellular enzymes to the trphosphate form in order to be active
What are the general adverse affects of the NRTIs?
you can get a potentially fatal syndrome of lactic acidosis with hepatis steatosis
this is likely due to mitochodnrial toxicity
they're also associated with fat redistribution and thus, hyperlipidemia
What are th emore specific side effects for zidovudine?
granulocytopenia and anemia - in up to 45% of patient!
also CNS disturbances: severe headache, insomnia, malaise
What's the specific side effect for abacavir?
What's the one NUCLEOTIDE reverse transcriptase inhibitor
What's the mechanism of action for tenofovir?
same as the nucleosides - chain terminator
What's the adverse effects of tenofovir?
nausea, vomiting, diarrhea and potential for renal failure
fatal lactic acidosis has been reported
WHat are the two non nucleoside reverse transcriptase inhibitors?
efavirenz and etravirine
What's the mechanism for efavirenz and etravirine?
they bind directly to the reverse transcriptase enzyme at a distinct side and render it unable to produce viral DNA
True or false: the non nucleoside reverse transcriptase inhibitors do not require phosphorylation like the nucleoside RT inhibitors do.
Are the NNRTIs more effective against HIV1 or 2?
What are the general adverse effects of the NNRTIs?
metabolized by cyp450 - drug interactions
Which NNRTI has the specific side effect of vivid dreams, nightmares and hallucinations?
What are the more specific side effects for etravirine?
rash, nausea, peripheral neuropathy
What are the three protease inhibitors?
What's the mechanism of the protease inhibitors?
they ihibit protease, so the pre-proteins don't get cleaves to the necessary proteins for the virus
this means the virus is no longer infectious because new viral particles cannot mature
What are the adverse effects of the protease inhibitors?
peripheral lipoatrophy and central fat accumulation
metabolized by/inhibit CYP3A4
Which protease inhibitor is poorly tolerated at high doses, so it's given to increase the serum concentrations of other protease inhibitors, thus decreaseing their dosage frequency?
HOW does ritonavir increase the serum concentrations of the other protease inhibitors?
it's a potent inhibitor of CYP3a4, which metabolizes the other proteases to decrease their effectiveness
What drug is the fusion inhibitor
How does efuvirtide work?
It binds to gp41 and prevents the conformational change necessary for HIV to fuse with the host cell membrane
How is efuvirtide administered?
What are the adverse effects of efuvirtide? What infection does it increase the risk for?
you have high incidence of local reactions - pain, erythema, induration, nodules, cysts
higher incidence of bacterial pneumonia
Why is efuvirtide such a great drug to have in our aresenal?
it works against HIV that is resistant to all other classes of antiretrovirals
What's the integrase inhibitor?
How does raltegravir work?
It inhibits integrase, so you don't get the DNA strand transfer necessary for provirus integration
WHat drug acts as a CCR5 antagonist?
What are the common side effects of maraviroc?
pyrexia, rash, postural dizziness
What term do we use for combo therapy with two RTIs and a PI?
highly active antiretroviral therapy = HAART
Long term use of HAART is associated with what adverse secodnary effect?