HIV Pharm Flashcards
Maraviroc
MOA: inhibits viral entry via binding to CCR5
-oral administration
-CYP3A4
Resistance: mutations of V3 loop of gp120
Emergence of CXCR4 tropic virus
hepatotoxic
Enfuvirtide
MOA: inhibits viral fusion via binding to gp41 preventing conformational changes
*subQ injection
Resistance: mutations in Gp41
AE: HA, Dizziness, Nausea
NTRI (nucleotide/side reverse transcriptase inhibitor)
competitive inhibition on HIV reverse transcriptase
leads to premature chain termination due to inhibition of binding with incoming nucleotide
Resistance: mutations of HIV reverse transcriptase
Impaired kinase activity to prevent phosphorylation and activation
Nucleotide Reverse Transcriptase Inhibitor
Tenofovir
Nucleoside Reverse Transcriptase Inhibitor
Abacavir, Didanosine, Lamivudine, Emtricitabine, Stavudine, Zidovudine
Abacavir
NsRTI \+lamivudine \+zidovudine serum levels increased with ethanol ingestion due to metabolism via alcohol dehydrogenase AE: HS and Skin Rash
Didanosine
NsRTI
- *Dose dependent pancreatitis
- *Retinal changes with optic neuritis
- *Increased risk with lactic acidosis
Lamivudine
NsRTI
active against HIV and HBV
Emtricitabine
NsRTI
active against HIV and HBV
long intracellular half life
**hyperpigmentation of palms/soles esp in black people
Stavudine
NsRTI
- *dose dependent peripheral sensory neuropathy
- *Dyslipidemia
- *Increased risk of lactic acidosis and hepatic steatosis with combined with didanosine
Zidovudine
NsRTI
- **macrocytic anemia
- **Neutropenia
Tenofovir
NtRTI
Active against HBV and HIV
AE: flatulance
NNRTIs
binds directly to HIV reverse transcriptase distant from active site
- binding =conformational change in enzyme and reduced activity
- non-competitive inhibitors
Resistance: HIV reverse transcriptase point mutations that alter NNRTI binding
CYP450: drug-drug interactions
Delavirdine
NNRTI
decreased potency compared to others
**skin rash
Increased aminotransferase levels
Efavirenz
NNRTI increased half life (once daily) **CNS: dizziness, drowsiness, insomnia, nightmares, HA **skin rash \+tenofovir, emtricitabine,
Nevirapine
NNRTI
–> prevents transmission of HIV from mother to child
Etravirine
NNRTI (2nd gen)
Rash, nausea, diarrhea
Rilpivirine
NNRTI (2nd gen)
**high doses associated with QT prolongation
INSTIS
integrase strand transfer inhibitors MOA: binds HIV integrase inhibits strand transfer and prevents ligation of reverse transcribed DNA into chromosome of host cell AE: headache and GI (end in suffix-"gravir")
INSTIs
Dolutegravir
Elvitegravir
Raltegravir
Dolutegravir
INSTI treatment naive patients \+ tenofovir, emtricitabine \+abacavir, lamivudine long half life
Elvitegravir
INSTI
combination pill
requires boosting with cobicistat
Raltegravir
INSTI
preferred for treatment naive patients
Protease Inhibitors
blocks HIV protease and prevents maturation of final structural proteins to make viron core
-specifically inhibits HIV aspartyl protease
- quick resistance if monotherapy
- GI intolerance, Lipodystrophy (metabolic, morphologic)
- **redistribution and accumulation of body fat
CYP3A4 metabolism of Protease inhibitors
ritonavir has the most pronounced inhibitory effect
saquinavir has the least inhibitory effect
Protease Inhibitors
Atazanivir Darunavir Ritonavir (used as a booster) Fosamprenavir Indinavir Lopinavir Nelfinavir Saquinavir Tipranavir
Atazanavir
PI
Once daily dosing
Skin rash
Darunavir
PI
HS if sulfa allergy
+ritonavir
+cobicistat
Fosamprenavir
PI
+ritonavir
HS if sulfa allergy
Indinavir
PI
Unconjugated hperbillirubinemia, nephrolithiasis
drink lots of water
Lopinavir
PI
+ritonavir
generally well tolerated
Nelfinavir
PI
Diarrhea and flatulence
Ritonavir
high rate GI side effects
CYP450 inhibitor
**primarily used as a booster
Saquinavir
less GI effects if ritonavir used as a booster
Tipranavir
indicated if resistant to other protease inhibitors
Urticarial or maculopapular rash**
HS rxn if sulfa allergy
HAART
2 NTRI +
- 1 protease inhibitor
- 1 NNRTI
- INSTI
MC: tenofovir+emtricitabine+others
