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28 Cards in this Set

  • Front
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Types of first line nucleoside reverse transcriptase inhibitors (NRTIs)

Abacavir (ABC)


Emtracitabine (FTC)


Lamivudine (3TC)


Tenofovir (TDF)


Zidovudine (ZDV)

Types of Alternate Nucleoside reverse transcriptase inhibitors

Didanosine (ddI)


Stavudine (d4T)

Efavirenz

First line preferred non-nucleoside reverse transcriptase inhibitors (NNRTIs)



AVOID IN PREGNANCY

Nevirapine


Etravirine

first line alternative non-nucleoside reverse transcriptase inhibitor



Use Etravirine specifically if resistance develops from other NNRTIs

Atazanavir + Ritonavir


-what is it?


-whats the alternative?

HIV protease inhibitor


alternative is Lopinavir

Darunavir + Ritonavir


-what is it?


-whats the alternative?

HIV protease inhibitor


alternative is Tipranavir

What is raltegravir?

HIV integrase strand transfer inhibitors

What are Viral fusion/entry inhibitors

CCR5 antagonist: Maraviroc


GP41 antagonist: Enfuvirtide

What are the most commonly used initial HIV treatment regimens

3 drug combinations


- 2NRTIs + NNRTI


-2 NRTIs + PI


-2 NRTIs + INSTI

Why do HIV treatments fail?

Drug resistance



HIV replicates rapidly and creates new viral genomes. The mutations can make AA substitutions which cancel the activity of HIV drugs.

Which HIV drugs get inside the brain?

NRTIs: azidothymidine and stavudine


NNRTI: nevirapine

MOA of NRTIs

Inhibition of HIV reverse transcriptase. They are prodrugs.



Host cell purine and pyrimidine kinase enzymes must convert NRTIs into nucleotide triphosphates inside HIV infected cells. the NRTI triphosphate gets blended into pools of natural dNTPs for DNA synthesis so it is used for viral DNA synthesis .


NRTI triphosphates then 1. competitively inhibit DNA polymerase and 2. irreversibly terminate DNA strand elongation.

Which NRTIs replace purines?

Guanosine: Abacavir


Adenosine: Didanosine, Tenofovir



They lack a 3' OH

Which NRTI's replace pyrimidines?

Cytosine: lamivudine, emtricitabine


Thymidine: Zidovudine, Stavudine



They lack a 3' OH

How do we pick the combination of NRTI's?

We combine 1 purine and 1 pyrimidine type.



If we need to substitute we substitute within the same time.

All NRTIs have a black box warning.. what is it?

They can cause lactic acidosis syndrome which can be potentially fatal.


Symptoms of lactic acid failure and how to reverse it

N/V, abdominal pain, weight loss, fatigue, myalgia, hepatic dysfunction features (tender hepatomegaly, peripheral edema, ascites, and encephalopathy)



IV and oral Bicarbonate, riboflavin and phosphorus and discontinue the NRTI

What is the hallmark toxicity of NRTIs

Mitochondrial toxicity


this is because HIV reverse transcripts is similar to mitochondrial DNA polymerase gamma. So you cannot make proteins needed for oxidative phosphorylation. So no ATP is made. O2 builds up which harms mitochondria and glucose is being made into lactate because of disruption of oxidative phosphorylation system, causing lactic acidosis.

Rank from WORST to less worse NRTIs

Diadnosine>Stavudine>or= Zidovudine>>>>



Tenofovir= Lamivudine = Emtricitabine = Abacavir

What are the 3 NRTIs which have high occurrence of side effects? and what are the side effects?

Stavudine: neuropathy, lactic acidosis, hepatic steatosis, lipoatrophy and lipodystrophy and PANCREATITIS


Diadnosine: same as stavudine except NO pancreatitis


Zidovudine: Lactic acidosis, hepatic steatosis, lipoatrophy and lipodystrophy

When do we discontinue NRTI

when aminotransferase levels are rapidly rising, progressive hepatomegaly, or metabolic acidosis of unknown cause

Which NRTI is known for nephrotoxicity?


why does it happen? what drug do we give instead?

Tenofovir


It has a phosphate in the parent molecule


so it is eliminated via glom filtration and active tubular secretion.


YOU DO NOT GIVE THIS TO RENAL PTs


use an alternative NRTI without renal toxicity like abacavir.

Abacavir hypersensitivity

Idiosyncratic, multisystem inflammatory reaction occurs in 5-8% of white patients. Symptoms appear within 6 weeks of starting drug.



Fever, rash, GI, respiratory symptoms, lethargy or malaise.


genetic test for HLAB57. if they have it don't give.

NRTI combinations to avoid

-Triple nucleoside analog combinations. (DO NOT GIVE 3 NRTIs) additive toxicity


-Zidovudine and Stavudine: in vivo antagonism


-Lamivudine and emtricitabine: nearly identical and will have same primary resistance mutation


-Stavudine and didanosine: overlaps in side effects


-Didanosine and tenofovir: high failure rates

What is the preferred dual NRTI pair for treatment naive patient?

Tenofovir and Emtricitabine



Because of its overall potency, favorable toxicity profile, and convenient dosing and its active vs HepB virus

What is the alternative dual NRTI pair?

ABC/3TC


Abacavir/ Lamivudine



3TC is active against HepB virus



-caution with CV risk factors

Which dual NRTI pair is the "acceptable" form and preferred in pregnancy?

ZDV/ 3TC


Zidovudine/ Lamivudine



It has more toxicities than the other two paris and you take it twice daily.


NRTI dosing in pregnancy

Monotherapy with zidovudine during pregnancy, labor and delivery, plus zidovudine in the infant reduces perinatal HIV transmission.