HIV Pharm

Question 1

Maraviroc

Answer 1

MOA: inhibits viral entry via binding to CCR5
-oral administration
-CYP3A4
Resistance: mutations of V3 loop of gp120
Emergence of CXCR4 tropic virus
hepatotoxic

Question 2

Enfuvirtide

Answer 2

MOA: inhibits viral fusion via binding to gp41 preventing conformational changes
*subQ injection
Resistance: mutations in Gp41
AE: HA, Dizziness, Nausea

Question 3

NTRI (nucleotide/side reverse transcriptase inhibitor)

Answer 3

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

Question 4

Nucleotide Reverse Transcriptase Inhibitor

Answer 4

Tenofovir

Question 5

Nucleoside Reverse Transcriptase Inhibitor

Answer 5

Abacavir, Didanosine, Lamivudine, Emtricitabine, Stavudine, Zidovudine

Question 6

Abacavir

Answer 6

NsRTI
\+lamivudine
\+zidovudine
serum levels increased with ethanol ingestion due to metabolism via alcohol dehydrogenase
AE: HS and Skin Rash

Question 7

Didanosine

Answer 7

NsRTI

• *Dose dependent pancreatitis
• *Retinal changes with optic neuritis
• *Increased risk with lactic acidosis

Question 8

Lamivudine

Answer 8

NsRTI

active against HIV and HBV

Question 9

Emtricitabine

Answer 9

NsRTI
active against HIV and HBV
long intracellular half life
**hyperpigmentation of palms/soles esp in black people

Question 10

Stavudine

Answer 10

NsRTI

• *dose dependent peripheral sensory neuropathy
• *Dyslipidemia
• *Increased risk of lactic acidosis and hepatic steatosis with combined with didanosine

Question 11

Zidovudine

Answer 11

NsRTI

• **macrocytic anemia
• **Neutropenia

Question 12

Tenofovir

Answer 12

NtRTI
Active against HBV and HIV
AE: flatulance

Question 13

NNRTIs

Answer 13

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

Question 14

Delavirdine

Answer 14

NNRTI
decreased potency compared to others
**skin rash
Increased aminotransferase levels

Question 15

Efavirenz

Answer 15

NNRTI
increased half life (once daily)
**CNS: dizziness, drowsiness, insomnia, nightmares, HA
**skin rash
\+tenofovir, emtricitabine,

Question 16

Nevirapine

Answer 16

NNRTI

–> prevents transmission of HIV from mother to child

Question 17

Etravirine

Answer 17

NNRTI (2nd gen)

Rash, nausea, diarrhea

Question 18

Rilpivirine

Answer 18

NNRTI (2nd gen)

**high doses associated with QT prolongation

Question 19

INSTIS

Answer 19

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")

Question 20

INSTIs

Answer 20

Dolutegravir
Elvitegravir
Raltegravir

Question 21

Dolutegravir

Answer 21

INSTI
treatment naive patients
\+ tenofovir, emtricitabine
\+abacavir, lamivudine
long half life

Question 22

Elvitegravir

Answer 22

INSTI
combination pill
requires boosting with cobicistat

Question 23

Raltegravir

Answer 23

INSTI

preferred for treatment naive patients

Question 24

Protease Inhibitors

Answer 24

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

Question 25

CYP3A4 metabolism of Protease inhibitors

Answer 25

ritonavir has the most pronounced inhibitory effect | saquinavir has the least inhibitory effect

Question 26

Protease Inhibitors

Answer 26

``` Atazanivir Darunavir Ritonavir (used as a booster) Fosamprenavir Indinavir Lopinavir Nelfinavir Saquinavir Tipranavir ```

Question 27

Atazanavir

Answer 27

PI Once daily dosing Skin rash

Question 28

Darunavir

Answer 28

PI HS if sulfa allergy +ritonavir +cobicistat

Question 29

Fosamprenavir

Answer 29

PI +ritonavir HS if sulfa allergy

Question 30

Indinavir

Answer 30

PI Unconjugated hperbillirubinemia, nephrolithiasis drink lots of water

Question 31

Lopinavir

Answer 31

PI +ritonavir generally well tolerated

Question 32

Nelfinavir

Answer 32

PI | Diarrhea and flatulence

Question 33

Ritonavir

Answer 33

*high rate GI side effects CYP450 inhibitor ***primarily used as a booster

Question 34

Saquinavir

Answer 34

less GI effects if ritonavir used as a booster

Question 35

Tipranavir

Answer 35

indicated if resistant to other protease inhibitors Urticarial or maculopapular rash** HS rxn if sulfa allergy

Question 36

HAART

Answer 36

2 NTRI + - 1 protease inhibitor - 1 NNRTI - INSTI MC: tenofovir+emtricitabine+others