Antiretrovirals

Question 1

What do the NRTIs do?

Answer 1

• act as faulty building blocks in production of viral DNA synthesis = competitive inhibitors
• nucleosides must be phosphorylated by host enzymes

Question 2

What drugs are NRTIs?

Answer 2

Zidovudine, Abacavir, Lamivudine, Tenofovir, Emtricitabine (TAZEL drugs Razzle your mitochondria)

Question 3

What are the general toxicities for the NRTIs?

Answer 3

mitochondrial toxicity and lactic acidosis

Question 4

What resistance would occur for the NRTIs?

Answer 4

change in RT or inability to phosphorylate prodrug

Question 5

What are all AE of NRTIs?

Answer 5

fat redistribution, hyperlipidemia, hepatomegaly (hepatic steatosis), lactic acidosis

Question 6

What are the specific toxicities for AZT (zidovudine)?

Answer 6

anemia and granulocytopenia

Question 7

What are the specific toxicities for abacavir?

Answer 7

hypersensitivity

Question 8

What are the specific toxicities for tenofovir?

Answer 8

most renal toxic of the ART drugs

Question 9

What drug is an integrase inhibitor?

Answer 9

raltegravir

Question 10

What is the action of raltegravir?

Answer 10

inhibit integrase –> virus cannot be integrated into host genome –> no viral replication

Question 11

What is the resistance to raltegravir?

Answer 11

change integrase enzyme

Question 12

What are the toxicities related to raltegravir?

Answer 12

drug interactions

Question 13

What ART drugs have drug-drug interactions?

Answer 13

Non-NRTIs, protease inhibitors, integrase inhibitor (raltegravir)

Question 14

What is the general action of the protease inhibitors?

Answer 14

bind the active site of protease –> can’t cleave gag-pol-env polyprotein

Question 15

What drugs are protease inhibitors?

Answer 15

Ritonavir, Atazanavir, Darunavir

If you are a pro at something, you’re probably pretty RAD

Question 16

What are the general toxicities associated with the protease inhibitors?

Answer 16

drug interactions, peripheral lipoatrophy and central fat accumulation

RAD to have skinny arms and fat gut

Question 17

What is the major function of Ritonavir?

Answer 17

inhibits Cyp450 –> used in conjunction with other protease inhibitors to increase their concentration

Question 18

What is the general action of the entry/fusion inhibitors?

Answer 18

block virus from entering cell by blocking host receptor or viral env proteins

Question 19

What is the major downside of entry/fusion inhibitors?

Answer 19

must be administered through injection - tough to get compliance

Question 20

What drugs are entry/fusion inhibitors?

Answer 20

Maraviroc, Enfuvirtide

Question 21

What is the action of Maraviroc?

Answer 21

CCR5 receptor antagonist that blocks viral gp120 from associated with its receptor
-is blocking HOST protein

Question 22

What must be done before Maraviroc is administered?

Answer 22

trofile assay to determine viral tropism - virus could use CXCR4 to enter cells rather than CCR5

Question 23

What is the action of Enfurvirtide?

Answer 23

inhibits conformational change in viral gp41 that is required for HIV entry

Question 24

What is the general action of NNRTIs?

Answer 24

directly bind RT and inhibit its action –> no copies of viral DNA made

• act directly on enzyme unlike NRTIs
• allosteric inhibitors, don’t bind active site

Question 25

What are the general toxicities associated with NNRTIs?

Answer 25

Rash, GI issues, Drug interactions

Question 26

What drugs are NNRTIs?

Answer 26

Efavirenz, Etravirine, Nevirapine

Question 27

What drug has the most drug interaction potential?

Answer 27

Etravirine - has tons of metabolism through Cyp450

Question 28

What is genotypic resistance testing?

Answer 28

sequence RT and protease and look for KNOWN mutations associated with resistance to drugs - cheaper, but can only detect known mutations

Question 29

What is phenotypic resistance testing?

Answer 29

isolate virus from patient and grow in the presence of different drugs to determine susceptibility to drugs - only do after previous treatment has failed