Flashcards in Pharm antivirals Deck (59)
are antiretrovirals virustatic or virucidal?
what are the five major classes of antiretroviral medications?
1. nucleoside reverse transcriptase inhibitors (NRTI's) and nucleotide RTI's (tenofovir))
2. non-nucleoside reverse transcriptase inhibitors (NNRTI's)
3. protease inhibitors
4. entry inhibitors
5. integrase inhibitors
what are the NRTI's?
zidovudine, lemivudine, emtricitabine, abacavir, tenofovir
what is the mechanism of NRTI's?
viral DNA chain termination via inhibition of viral reverse transcriptase. Tenofovir is a nucleoTide, the others are nucleosides and need to be phosphorylated to be active
what does zidovudine mimic? lemivudine? emtricitabine? abacavir? tenofovir?
zidovudine = thymidine.
lemivudine = cytosine.
emtricitabine = cytosine.
abacavir = guanine.
tenofovir = adenosine.
which NRTIs can also be used for HBV?
lamivudine, emtricitabine, tenofovir
zidovudine side effects
granulocytopenia, anemia, nausea, vomiting
lamivudine and emtricitabine side effects
headache, nausea, vomiting, rash, neutropenia, pancreatitis (NOT SERIOUS)
abacavir side effects
hypersensitivity reaction - associated with HLA-B5701 mutation
tenofovir side effects
what are the NNRTI's?
efavirenz, nevirapine, rilpivirine, etravirine
inhibit reverse transcriptase through direct enzyme inhibition (do not require phosphorylation to be active) - NONCOMPETITIVE!
what are NNRTI's and NRTI's used to treat?
NNRTIs side effects
rash and hepatotoxicity - efavirenz also has vivid dreams and CNS symptoms (stop when ax wielding elves appear in dream!), teratogenic, P450 metabolism
what are the HIV protease inhibitors?
-navir (NA VIRUS! NO NEW VIRUS!)
ritonavir, fosamprenavir, atazanavir, darunavir, lopinavir
HIV protease inhibitors (-navir) mechanism
prevent cleavage of protein chain into functional subunits
which HIV protease inhibitor has "good" drug interactions? how?
ritonavir "boosts" other drug concentrations by inhibiting cytochrome P-450
HIV protease inhibitors (-navir) side effects
GI intolerance (n/v, diarrhea), metabolic toxicities!! (dyslipidemia, hyperglycemia, lipodystrophy)
what are the 3 steps of HIV attachment and fusion?
1. HIV gp120 binds CD4 molecule
2. conformational change occurs in gp120 and then binds the coreceptor CCR5 or CXCR4
3. further conformational changes in gp120 expose gp41 protein which mediates fusion of the viral and cell membranes
what are the HIV entry inhibitors?
enfuvitide and maraviroc
binds gp41, inhibiting viral entry
enfuvirtide side effects
skin reaction at injection sites
binds CCR-5 on surface of Tcells/monocytes, inhibiting interaction with gp120 - TARGET IS ON HOST CELL!
maraviroc side effects
hepatotoxicity (rare) - cough, fever, URI, rash, musculoskeletal symptoms, ab pain, dizziness
what are the integrase inhibitors?
-tegravir (GRAB the HIV before it integrates!)
raltegravir, elvitegravir, dolutegravir
integrase inhibitors mechanism
inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
integrase inhibitors (-tegravir) side effects
myopathy and rhabdo - headache, neausea, diarrhea, pyrexia
what are the common HAART regimen combinations?
3 active agents together; typically 2 NRTIs + integrase inhibitor, PI, or NNRTI
what is commonly prescribed as initial therapy in HIV? disadvantage of this class?
NNRTI based regimen because of advantage of lower pill burden (preserve PI for later use). disadvantage is only one single mutation is needed to confer resistance and cross resistance develops for entire class