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Hematology > HIV and Anti-Retrovirals > Flashcards

HIV and Anti-Retrovirals Flashcards

1
Q

What Virus is the major cause of AIDS world wide ?

A

HIV-1 It is a member of the Retrovirde family and Lintevirus Subfamily

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2
Q

How does the HIV virus particle target the T cell ?

A

Gp120 and Gp41 target the chemokine and CD4 receptors.

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3
Q

How do the fusion inhibitors work ?

A

They Bind gp41 of the viral envelope preventing its conformational change and impedes the fusion of the viral and host cell membranes.

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4
Q

How can cells develop resistance to the HIV viral inhibitors ?

A

Gp41 mutations may develop when drug is given at suboptimal doses as monotherapy.

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5
Q

What are the two fusion inhibitors

A

Enfuvirtide and Miraviroc

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6
Q

How is Enfuvirtide administered and cleared ?

A

It is administered Sub-Q, highly protein bound, and metabolized by proteolytic hydrolysis. **No CYP-450 involvement.

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7
Q

What are the adverse effects of Enfvirtide ?

A

Injection site reactions, bacterial Pneumonia and Hypersensitivity.

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8
Q

What is the CCR5 receptor ?

A

For HIV to enter the Human the infection begins when Gp120 binds to CD4 molecules on the surface of the human T cell molecules macrophages and dendritic cells. This attachment of GP120 to CD4 requires CCR5

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9
Q

How does Maraviroc work ?

A

Maraviroc binds to the transmembrane chemokine receptor CCR5 and blocks viral attachment. **CYP450 activity will have to be adjusted.

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10
Q

How does Enfvirtide work ?

A

It binds to gp41 of the viral subunit glycoprotein preventing the conformational change required for fusion.

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11
Q

What are the kinetics of Enfvirtide ?

A

It is taken orally, substrate for CYP34A and P-Glycoprotein 1/2 life is 14-18 hours.

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12
Q

What is an indication for Miraviroc use ?

A

It should be used in combination for patients who are failing other retroviral therapy.
**Co-Receptor Tropism Assay should be performed when a CCR5 antagonist is being considered. Plasma HIV should be over 1000 copies.

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13
Q

What are the 4 classes of reverse transcriptase inhibitors ?

When should these be used ?

A
  1. Analoges of Pyrimidine Nucleoside T
  2. Analogs of Pyrimidine nucleoside C
  3. Analogs of Pyrimidine nucleoside A-G
  4. Analoges of Purine Nucleoside G
    ***Notice they are all nucleoSIDE analogs.
    These drugs are commonly used in combination with other drugs to combat retroviral therapy.
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14
Q

What two drugs are analogs of pyrimidine nucleotide T ?

A

Zidovudine and Stavudine (Z-S-T)

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15
Q

What are the two analogs of the nucleoside C ?

A

Lamivudane and Emtricitabine (L,E,C)

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16
Q

What drug is an analog fo the purine nucleoside (AG) ?

A

Didanosine

17
Q

What drug is an analog of purine nucleosides G ?

A

Abacavir

18
Q

What are some of the unique toxicities associated with Zidovudine ?
Any unique advantages ?

A

Marrow supression and Lypodystromy- Concurrent administration with any of the antineoplastics for heme cancers should be avoided.
It can prevent viral spread in utero.

19
Q

What is a unique toxicity associated with Abacavir ?

A

Hypersensitivity reaction due to genetic predisposition. HLA-B 5701 screening is necessary

20
Q

What are some adverse effects of Didanosine ?

A

Early virologic failure results in combination with lamivudine (or emtricitabine) + Tenofovir

21
Q

How are the NRTI’s excreted ?

What is a common toxicity ?

A

They are all excreted unchanged in the kidney except for AZT which is metabolized by glucourinide and Abacavir which is metabolized by alcohol dehydrogenase.

They all cause GI distress and lactic acidosis

22
Q

What is a nucleotide reverse transcriptase inhibitor ?

A

Tenofovir

  • *Not a CYP450
  • *Separate dosing from didanosine by 1-2 hours
  • *Increase in Liver enzymes
23
Q

What are the adverse effects of Stavudine ?

A

Extreme Lactic Acidosis, peripheral neuropathy and pancreatitis.

24
Q

What are some of the advantages of NNRTI’s ?

A

They do not require phosphorylation to be effective. They do not bind to the active site. They bind to a hydrophobic pocket and induce a conformational change in the RT enzyme1````````

25
Q

What are the three NNRTI’s ?

A

Delavirdine, Nevirapine and Efavirenz

Hematology (12 decks)

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