Anti-Viral Drugs - Unit 2

Question 1

Can antiretroviral kill the HIV virus?

Answer 1

No

Question 2

What is the HIV infection process?

Answer 2

Virus bind and enter the cell—>HIV RNA is converted to DNA via reverse transcriptase—>integrates into host genome via integrase—>transcription—>protein is cleaved via protease—>bud off

Question 3

What are the 5 major classes of antiretroviral drugs?

Answer 3

NRTI—>nucleoside reverse transcriptase inhibitorNNRTI—>non nucleoside reverse transcriptase inhibitor Protease inhibitor Entry inhibitor Integrase inhibitors

Question 4

What is the mechanism of NRTI? and its major side effect?

Answer 4

DNA analogs (e.g. adenosine/guanine)—>termination of DNA chainLactic acidosis

Question 5

What are the side effects of tenofovir/abacavir/zidovudine?

Answer 5

Tenofovir—>nephrotoxicity Abacavir—>hypersensitivity reactionZidovudine—>anemia

Question 6

What is the mechanism of NNRTIs? and their common side effects?

Answer 6

Bind directly to reverse transcriptase—>inhibit its action Rash

Question 7

What are the side effects for efavirenz

Answer 7

Efavirenz—>CNS symptoms (vivid dream etc.)/teratogen

Question 8

What is the mechanism of protease inhibitors? and their side effects?

Answer 8

Bind to protease—>prevent it from cleaving proteins to function subunits Metabolic toxicities—->dyslipidemia/hyperglycemia/lipodystrophy

Question 9

What is Ritonavir Boosting?

Answer 9

Ritonavir is a potent CYP450 inhibitor—>use in low dose with other drugs to increase their half life

Question 10

What is the only HIV drug that is not orally administered? side effect? and when is it used?

Answer 10

Enfuvirtide—>entry inhibitor Increase rate of bacterial pneumonia When you ran out of other options

Question 11

What is the only HIV drug that targets the host cell?

Answer 11

Maraviroc—>CCR5 antagonist

Question 12

Why integrase inhibitors have become the first line treatment?

Answer 12

Very effective and low side effects

Question 13

When and who should we start ART (antiretroviral therapy) to?

Answer 13

Everyone that has HIV

Question 14

What is HAART and what is its concept?

Answer 14

HAART—>high active antiretroviral therapy (combo therapy)Combine at least 3 drugs with different mechanisms

Question 15

What is the combo of HAART?

Answer 15

2 NRTIs + something else like integrase inhibitor/PI/NNRTIsPreferably with integrase inhibitor or PI

Question 16

What are the HAART goals?

Answer 16

Reach undetectable viral load

Question 17

If the resistance is developed against one of the NRTI, can you use another NRTI instead? and is the resistance permanent? and what is the best way to reduce resistance?

Answer 17

No because of cross resistance within classIt is permanentBest way is to adhere to drug treatments—>resistance only develop during replication—>low viral load—>low rate of resistance development

Question 18

Most ppl who got Hep C clear it out or develop chronic Hep C? and is it curable?

Answer 18

Most people develop into chronic hep CIt is curable

Question 19

How is Hep C infect cells?

Answer 19

Gain entry—>translate RNA into protein—>protease cleave protein into function subunits

Question 20

What is the equivalent to viral cure for Hep C treatment? and what is the definition of SVR

Answer 20

SVR (sustained virologic response)—>Hep C remain undetectable 12 weeks after completion of the therapy

Question 21

Why is interferon and ribavirin are no longer used for Hep C treatments?

Answer 21

Lower efficacy and a lot of side effects

Question 22

What are the 3 new classes of drugs that treat Hep C? and how are they used?

Answer 22

NS (nucleoside) 5B polymerase inhibitorsNS5A inhibitors NS3/4A protease inhibitors Combo therapy like HIV

Question 23

What are the mechanisms of NS5B polymerase inhibitor and NS5A inhibitor?

Answer 23

NS5B—>compete with nucleotide and cause RNA chain termination like NRTINS5A—>inhibit viral phosphoprotein

Question 24

How does HSV replicate?

Answer 24

DNA virus enter cell—>use DNA polymerase to make mRNA

Question 25

How is foscarnet used?

Answer 25

IV use for acyclovir/ganciclovir resistance HSV/CMVLots of side effects

Question 26

What is the mechanism of acyclovir and penciclovir?

Answer 26

Need to be phosphorylated by viral thymidine kinase—>only effective in infected cells—>compete with DNA analogue—>terminate DNA chain

Question 27

Why do we use valacyclovir or famciclovir for oral therapy for HSV or VZV instead of acyclovir?

Answer 27

Valacyclovir and famciclovir are prodrug that are converted to acyclovir and penciclovir respectively—>higher bioavailability than just acyclovir

Question 28

Side effects of acyclovir?

Answer 28

CNS toxicityRenal dysfunction with high dose

Question 29

What is the PO form of ganciclovir? and side effect of ganciclovir?

Answer 29

Valganciclovir Myelosuppression

Question 30

What is the mechanism of foscarnet?

Answer 30

Directly inhibit HSV DNA polymerase/HIV reverse transcriptase

Question 31

What is the mechanism for neuraminidase inhibitors? and what is their greatest benefits of usage?

Answer 31

Inhibit neuraminidase—>prevent release of virus from host cellTo reduce rates of complications from influenza with severe disease

Question 32

When should you start neuraminidase inhibitors? and what is their major side effect?

Answer 32

Within 48 hours Neuropsychiatric events—>agitation/anxiety

Question 33

When do you test for drug resistance for HIV pt?

Answer 33

Before starting tx (transmitted resistance) and when tx fails

Question 34

Which class of HIV drugs has the least amount of cross resistance?

Answer 34

PI

Question 35

How long is HCV tx usually?

Answer 35

12-24wks