HIV Flashcards
Drugs in the NRTI class
MOA
Names
inhibit HIV reverse transcriptase and inhibit DNA polymerase
abacavir, didanosine, emtricitabine, lamivudine, stravudine, tenofovir, zidovudine
What class of HIV antivirals must be phosphorylated to be active?
NRTIs
NRTIs incorporate into viral DNA chain to cause chain termination
NRTIs
Side effects (general)
NRTIs
Mitochondrial toxicity (inhibition of mitochondrial DNA polymerase)
Lactic acidosis with hepatic steatosis
abacavir
side effects
Hypersensitivity reactions and increased risk of myocardial infarction
didanosine
side effects
Pancreatitis
zidovudine
side effects
bone marrow suppression resulting in anemia or neutropenia
zidovudine and stavudine
side effects
dislipidemia and insulin resistance
NNRTIs
MOA
Names
NNRTIs
bind to HIT RT and inhibit DNA polymerase (noncompetative inhibitors that cause a conformational change in the enzyme structure)
Delavirdine, efavirenz, etravirine, nevirapine, rilpivirine
NNRTIs
Clinical Use
Drug Drug interactions
NNRTIs
Use for HIV-1 only
mutation occurs rapidly
metabolized by CYP450: delaviridine is a cyp450 inhibitor, efavirenz, etravirine, nevirapine are inducers
dizziness, drowsiness, insomnia, nightmares, and headache are all side effects of what drug?
efavirenz
rilpivirine
side effects
depression, insomnia, increased serum cholesterol, fat redistribution syndrome
which NNRTI is teratogenic?
efavirenz
Protease inhibitors (PI)
MOA
Names
PI
inhibit HIV protease by competitivily binding to the protease active site and thereby preventing the production of functional proteins.
atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, squinavir, tipanavir
“-navir”
Protease Inhibitors
Side Effects
PI
GI intolerance
Metabolic complications- lipodystrophy (cushing-like syndrome, fat accumulation, central obesity, fat around neck, between shoulders), dyslipidemia, hyperglycemia and insulin resistance
Resistance to PI also develops rapidly
which PI is an inhibitor to CYP3A4 and why do we care?
ritonavir is an inhibitor of CYP3A4 and can be used to “boost” the effects of other drugs by inhibiting their metabolism
Maraviroc
MOA
Maraviroc inhibits entry into the host cell as a CCR5 receptor antagonist. This prevents gp120 binding, fusion and entry
Maraviroc
Clinical Use
Maravirocis approved for use in combination with other antiretroviral agents in treatment experienced adult patients infected with only CCR5-tropic HIV-1
Maraviroc
Side Effects
Maraviroc
cough, hepatotoxicity
drug interactions: decrease the dose if being taken in combination with a CYP3A inhibitor
What drug is a fusion inhibitor?
MOA
enfurvirtide
binds to gp41 and prevents the fusion of viral and cellular membranes
enfuvirtide
clinical use
side effects
enfuvirtide
HIV1 treatment in patients where other treatments have failed
injection site reactions, (must be given sub q), insomnia, headache, dizziness, nausea, hypersensitivity. Very expensive
metabolism does not involve CYP450- fewer drug interactions
Integrase strand transfer inhibitors (INSTIs)
MOA
Names
INSTIs
bind to integrase with is essential for viral replication
dolutegravir, elvitegravir, raltegravir
“-gravir”
INSTIs
MOA
prevent the formation of covalent bonds between host and viral DNA
Active against both HIV 1 and HIV 2
INSTIs
Side Effects
INSTIs
headache and GI effects
less frequently you see insomnia and dizziness
Elvitegravir
administration
Elvitegravir requires boosting with additional drugs like ritonavir or cobicistat
