Antiretrovirals

Question 1

Drug that interferes with entry of HIV-1 into cells. HIV enters a cell by attachment of gp120 to the CD4 receptor, followed by binding to either the CCR5 or CXCR4 receptor. This drug binds to the CCR5 receptor preventing the interaction between HIV-1 gp120 and CCR5 receptor

Answer 1

Maraviroc

Question 2

Maraviroc

Answer 2

Interferes with entry of HIV-1 into cells by binding to the CCR5 receptor preventing the interaction between HIV-1 gp120 and CCR5 receptor

Question 3

Dosing adjustments: Maraviroc

Answer 3

No dose adjustment for renal/hepatic insufficiency, but avoid in significant renal dysfunction

Question 4

Drug-Drug Interactions: Maraviroc

Answer 4

No significant effect on other drugs, but inhibitors of CYP3A increase maraviroc levels (Protease inhibitors) and Inducers of CYP3A decrease maraviroc levels (Efavirenz/Etravirine, rifapentine, and St. John’s wort)

Question 5

Toxicity: Maraviroc

Answer 5

Allergic reactions, rash, hepatotoxicity

Question 6

Drug that interferes with entry of HIV-1 into cells. Inhibits fusion of viral and cellular membranes. Binds to the first heptad repeat in the gp41 subunit of the virus

Answer 6

Enfuvirtide

Question 7

Delivery and dosing adjustments: Enfuvirtide

Answer 7

Subcutaneous injection. Catabolism to constituent amino acids. No dose adjustment for renal/hepatic insufficiency

Question 8

Drug-Drug Interactions: Enfuvirtide

Answer 8

No drug-drug interactions

Question 9

Toxicity: Enfuvirtide

Answer 9

Injection site reactions. Bacterial pneumonia. Hypersensitivity ? 1%

Question 10

Nucleoside (Thymidine) analog(s) reverse transcriptase inhibitor(s) (NRTI)

Answer 10

Zidovudine

Question 11

Excretion and dosing adjustments: Nucleoside analog reverse transcriptase inhibitors (NRTIs)

Answer 11

Renal excretion. Dose adjustment for renal insufficiency except for abacavir. Adjustment for abacavir in hepatic insufficiency

Question 12

Nucleoside (Guanosine) analog(s) reverse transcriptase inhibitor(s) (NRTI)

Answer 12

Abacavir

Question 13

Abacavir can cause what unique side effect

Answer 13

A hypersensitivity reaction

Question 14

Nucleoside (Cytidine) analog(s) reverse transcriptase inhibitor(s) (NRTI)

Answer 14

Lamivudine & Emtricitabine

Question 15

Tenofovir can cause what unique side effect

Answer 15

Renal insufficiency

Question 16

Toxicities: Nucleoside analog reverse transcriptase inhibitors (NRTIs)

Answer 16

Mitochondrial toxicity with lactic acidosis (Onset over months. Vague GI symptoms, malaise. Can progress to multiorgan failure and death), Hepatotoxicity (Onset over months to years), Steatosis

Question 17

NucleoTide (Adenine) analog(s) reverse transcriptase inhibitor(s) (NRTI)

Answer 17

Tenofovir

Question 18

What, if administered with didanosine (a guanosine analog reverse transcriptase inhibitor), wil increase didanosine levels

Answer 18

Tenofovir

Question 19

Zidovudine antagonizes phosphorylation of what

Answer 19

Stavudine, a nucleoside (thymidine) analog(s) reverse transcriptase inhibitor (NRTI)

Question 20

Drug that requires no intracellular metabolism for activation. Reversible non-competitive inhibitor of HIV reverse transcriptase. Binding to reverse transcriptase blocks RNA- and DNA-dependent DNA polymerase action of the enzyme

Answer 20

Efavirenz (non-nucleoside reverse transcriptase inhibitor: NNRTI)

Question 21

Metabolism and dosing adjustments: Efavirenz

Answer 21

Metabolized by cytochrome P450 (CYP3A4). No dose adjustment for renal insufficiency. Caution with hepatic insufficiency (more so when taking related drug nevirapine)

Question 22

Drug-Drug Interactions: Efavirenz

Answer 22

It is both metabolized by and an inducer of CYP3A4. Simultaneous use of protease inhibitors (Inducers of P450 3A4) may require dose adjustment. Avoid sedatives such as midazolam and alprazolam (these are metabolized by CYP3A4 and will not function properly when administered with efavirenz)

Question 23

Toxicity: Efavirenz

Answer 23

Can cause some CNS side effects and it may be teratogenic. Skin Rash with onset in days to weeks. Stevens-Johnson Syndrome/Toxic Epidermal necrosis, Hepatotoxicity (all worse with nevirapine, a different NNRTI )

Question 24

Drug that interferes with HIV-1 integrase. Prevents insertion of linear HIV-1 DNA into host DNA. Prevents formation of HIV-1 provirus

Answer 24

Raltegravir (Integrase Inhibitor)

Question 25

Metabolism and dosing adjustment: Raltegravir

Answer 25

Metabolized by hepatic UGT1A1 glucuronidation. No dose change

Question 26

Drug-drug interaction: Raltegravir

Answer 26

Increase dose when taken w/rifampin

Question 27

Toxicities: Raltegravir

Answer 27

Nausea, headache, diarrhea, Fever, increased CPK (muscle pain/inflammation), Rare rash, hypersensitivity

Question 28

Drug(s) that block protease cleavage of viral gag and gag-pol polyproteins. Immature noninfectious viral particles. No intracellular metabolism. Active in resting and infected cells

Answer 28

Protease Inhibitors (Atazanavir and Darunavir)

Question 29

Dosing adjustment: Protease Inhibitors (Atazanavir and Darunavir)

Answer 29

No dose adjustment for renal insufficiency. Caution with hepatic insufficiency. Not recommended if significant liver impairment

Question 30

Drug-drug interaction: Protease Inhibitors (Atazanavir and Darunavir)

Answer 30

Protease inhibitors are metabolized by cytochrome P450 3A4. In general avoid rifampin and other rifamycins. Avoid sedatives such as midazolam and alprazolam. Avoid fluticasone nasal spray with all ritonavir-boosted PI regimens (Adrenal suppression and Cushing's syndrome). Avoid proton pump inhibitors with atazanavir (Lowers absorption significantly)

Question 31

Toxicities: Protease Inhibitors (Atazanavir and Darunavir)

Answer 31

Increased bleeding episodes in hemophiliacs, Hepatotoxicity, Possible Lipodystrophy (fat redistribution), Premature coronary artery disease, Hyperlipidemia, Osteonecrosis