(7) Antimicrobials: Antivirals HIV (6.1-6.4) Flashcards
How are NRTIs different from endogenous molecules?
Lack 3’ hydroxyl
MOA: NRTIs: NRTIs
Incorporation into viral DNA ⇒ Premature chain termination
How are nucleoside NRTIs activated?
Phosphorylation
Adverse Effects (2) : All NRTIs
(1) Mitochondrial toxicity
(2) ⇒ Lactic acidosis
Suffix: NRTIs
“-dine”
Which NRTIs are used to treat Hepatitis B?
(1) Lamivudine
(2) Tenofovir
Is Tenofovir a nucleoside or nucleotide?
Tenofovir = Nucleotide
Which NRTI is first-line during pregnancy and breastfeeding?
Zidovudine
Adverse Effect: Zidovudine
Myelosuppression
Which NRTIs are associated with lipodystrophy?
(1) Zidovudine
(2) Stavudine
Which NRTI is associated with pancreatitis?
Didanosine
Which NRTI is most associated with hypersensitivity reactions?
Abacavir
Which HLA allele has an association with hypersensitivity reactions with Abacavir?
HLA-B 57:01
What type of hypersensitivity reaction is associated with Abacavir?
Type IV
Which NRTI is associated with hyperpigmentation of palms and soles?
Emtricitabine
Do NNRTIs require phosphorylation to be active?
No
MOA: NNRTIs
Directly bind reverse transcriptase and inhibit enzyme
Adverse Effects (2) : NNRTIs
(1) Liver failure
(2) Stevens-Johnson syndrome
Which NNRTI is most associated with CNS side effects?
Efavirenz
Which class of HIV drugs should be avoided in pregnancy?
NNRTIs
(Nevirapine is not contraindicated)
What effect do NNRTIs have on CYP450 system?
Varying – some induce and others inhibit
Which NNRTI is NOT contraindicated in pregnancy?
Nevirapine
(N in Nevirapine stands for No contraindication)
Suffix: Protease inhibitors
“-navir”
What HIV gene codes for proteases?
pol
Adverse Effects - Metabolic (3) : Protease inhibitors
(1) Insulin resistance
(2) Dyslipidemia
(3) Central adiposity
What drug used to treat HIV is associated with nephrolithiasis?
Indinavir
What protease inhibitor is the strongest inhibitor of the CYP450 system?
Ritonavir
What tuberculosis drug is contraindicated in people taking protease inhibitors?
Rifampin
MOA: HIV Protease inhibitors
Inhibits cleavage of precursor protein into active units
What does the HIV gag gene code for?
The STRUCTURAL proteins,
(1) p24
(2) p7
What does the HIV env gene code for?
The ENVELOPE proteins,
(1) gp41
(2) gp120
What HIV protein binds host CD4/CCR5?
gp120
MOA: Maraviroc
Binds CCR5 ⇒ Inhibits interaction with gp120
(Note: This is likely more effective during early infection when CCR5 receptor is preferred over CXCR4)
What HIV protein is responsible for fusion?
gp41
MOA: Enfuvirtide
Binds gp41 ⇒ Inhibits fusion
What does HIV pol gene code for?
(1) Protease
(2) Reverse transcriptase
(3) Integrase
MOA: Raltegravir
HIV integrase inhibitor
Adverse Effect: Integrase inhibitors
Rhabdomyolysis