Pharmacology: Anti-retroviral Agents Flashcards Preview

Hematology-Oncology Exam 2 > Pharmacology: Anti-retroviral Agents > Flashcards

Flashcards in Pharmacology: Anti-retroviral Agents Deck (46):
1

What are 4 goals of chronic disease management for HIV patients?

1. Achieve durable virologic suppression
2. Stabilize or restore immune function
3. Maintain or improve the patient's quality of life
4. Reduce HIV related mortality and morbidity

2

What leads to increases in the CD4 cell counts of over 100-200 cells/mm/year?

HAART therapy

3

Regimens of how many agents are used in HAART therapy?

3 or more

4

What are 4 examples of FDA approved agents for Drug Therapy for HIV?

1. Nuceloside reverse transcriptase inhibitors (NRTIs)
2. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
3. Protease Inhibitors (PIs)
4. Fusion Inhibitors (FIs)

5

What is the key viral enzyme that converts viral RNA to DNA?

Reverse transcriptase (catalyzes viral RNA to viral DNA)

6

What does reverse transcriptase allow for?

Selective toxicity

7

What does reverse trascriptase have to do before HIV can be inserted into the host cell's genetic material?

Convert viral RNA into proviral DNA

8

What kind of cells do NRTIs protect?

Only newly infected cells

9

What is the MOA of NRTIs?

They target the early/essential step in HIV replication by acting as substrates for reverse transcriptase...
THEY INHIBIT REVERSE TRANSCRIPTASE BY INCORPORATING FALSE NUCLEIC ACIDS INTO THE NEWLY PRODUCED PROVIRAL DNA
-These agents lack a 3' hydroxyl group, thus incorporation into DNA terminates chain elongation

10

How do NNRTIs work?

They inhibit reverse transcriptase activity by binding adjacent to the enzyme's active site and inducing conformational changes

11

What kind of cells do NNRTIs protect?

Newly infecting cells

12

What strain of HIV are NNRTIs effective against?

Only HIV-1

13

What kind of metabolism do NNRTIs have?

Hepatic...many potential drug interactions

14

True or False: There is no need for phosphorylation in NNRTIs

TRUE

15

What stage of infection do NRTIs and NNRTIs work?

They only protect NEWLY INFECTED CELLS

16

What is an essential enzyme for viral survival and infectivity?

HIV PROTEASE

17

What does HIV protease do?

Cleaves viral polyprotein into active viral enzymes (reverse transcriptase, protease, and integrase)

18

Where do protease inhibitors bind?

Reversibly to the active site of the HIV protease

19

What happens to the viral particles with a protease inhibitor?

They become immature and non-infectious

20

What cells do protease inhibitors inhibit viral replication in?

Any infected cells

21

What is a unique indication for enfuvirtide (fusion inhibitor)?

Advanced HIV-1 infection patients
(They have ongoing viral replication despite antiretroviral therapy)

22

What types of drugs are given in a PI-based HAART regimen?

Protease inhibitor and 2 NRTIs

Example: Iopinavir/ritonavir + (sidovudine or stavudine) + Lamivudine

23

What are 3 advantages of PI-based HAART Regimen?

1. Standard of care
2. Longest data record including data on survival benefit
3. Effective and durable

24

What are 3 disadvantages of PI-based HAART Regimen?

1. Metabolic complications
2. CYP3A4 metabolizes all the PIs and PIs inhibit it
3. Complex regimens

25

What are 3 advantages of NNRTI-based regimens over PI-based regimens as HAART?

1. Simple regimens
2. Less fat maldisritbution dyslipidemia than PI-based regiments (well tolerated)
3. Save PI options for future use

26

What are 2 significant tests to be done to determine the severity of HIV infection?

1. Plasma HIV RNA levels
2. CD4 T-cell counts

27

What do Plasma HIV RNA levels show?

Indicates the magnitude of HIV replication and its associate rate of CD4 T-cell destruction

28

What do CD4 T-cell counts show?

Indicated the extent of HIV-induced immune damage already suffered

29

When do HIV RNA levels stabilize after diagnosis?

6-9 months

30

True or False: HIV RNA level changes are predictable?

FALSE... they are unpredictable

31

What is the best measure of the activity of antiretroviral therapy in HIV-infected persons?

HIV RNA levels

32

What is the goal with antiretroviral therapy in HIV-infected persons?

To decrease HIV RNA levels to undetectable (this may take up to 16-24

33

What is the most prominent AE to Zidovudine (AZT)?

BM suppression (myelosuppression)

34

What is the most prominent AE to Stavudine (d4T)?

Peripheral neuropathy (20-30%)

35

What is the most prominent AE to Didanosine (ddl)?

Pancreatitis, peripheral neuropathy

36

What are 2 indications that drug failure has occurred with anti-retroviral agents?

1. Inadequate viral suppression
2. Unsatisfactory increase in CD4 count

37

What enzyme metabolizes all PIs?

CYP3A4- Metabolizes all PIs and PIs inhibit it

38

What population shouldn't receive efavirenz?

PREGGERS

39

Which 2 NRTIs are preferred for treatment of HIV?

1. Emtricitabine
2. Tenofovir

40

What are 4 disadvantages of NNRTI-based regimens over PI-based regimens as HAART?

1. Not all NNRTI are equipotent to PI
2. Low genetic barrier to resistance
3. Cross-resistance among NNRTIs
4. Skin rash

41

What can increase HIV RNA levels?

Immunizations or infections

42

What AE are common to Zidovudine, Stavudine, and Didanosine?

Cause lactic acidosis with hepatic steatosis

43

What AE can Abacavir cause?

HS (can be fatal, so stop drug), nausea, HA

44

What AE can Zalcitabine cause?

Peripheral neuropathy or pancreatitis

45

What is a major AE to anti-retrovirals (especially NNRTIs and PIs)?

Hepatotoxicity

46

How do you monitor and define hepatotoxicity from anti-retrovirals?

Serum transaminases- The hepatotox is defined as a 3-5 fold increase