Exam 3: HIV Flashcards
What are the 4 mechanisms for HIV drugs?
1) Reverse transcriptase inhibitors
2) protease inhibitors
3) Fusion inhibitor
4) Integrase inhibitor
What are the 5 drugs that are nucleoside analogue reverse transcriptase inhibitors (NRTI)?
- Zidovudine
- Emtricitabine
- Tenofovir
- Lamivudine
- Abacavir
What is the first choice combination of NRTI?
Emtricitabine and tenofovir
What is the 2nd choice combination for NTRI?
Lamivudine and abacavir
What is the MOA of NRTIs?
Nucleoside analogue that requires 3 phosphorylations, is incorporated into DNA and inhibits viral reverse transcriptase
Which HIV drug is useful in AIDs dementia? Why?
Zidovudine because it has good CNS penetration
What is Zidovudine normally combined with? Why?
Lamivudine because zidovudine Monotherapy develops resistance quickly.
What is the use of Zidovudine?
- Maintain CD4 count and lessen opportunistic infections
- Safe in pregnancy
What are the toxicities associated with zidovudine?
- Headache, nausea, vomiting, insomnia
- Lactic acidosis or hepatotoxicity
- Myelosuppression: neutropenia and anemia (caution with other drugs that may cause this)
How can you combat the neutropenia and anemia caused by Zidovudine?
- Epogen can increased RBCs
- Neupogen can increase WBCs
What it is the MOA for Tenofovir and Emtricitabine?
Nucleoside analogue that inhibits reverse transcriptase
What is the first line treatment of HIV?
Tenofovir and Emtricitabine
What is the MOA for Lamivudine?
Cytosine analogue that inhibits HIV reverse transcriptase and HBV polymerase
What is the MOA of Abacavir?
Guanosine analogue that is used in combination with lamivudine OR Zidovudine
What are the toxicities associated with Abacavir?
- Serious hypersensitivity
- HLA-B27 patients may develop SJS
- If hypersensitivity reaction occurs, DO NOT GIVE DRUG AGAIN
What are the serious side effects that can occur with any of the NRTIs?
Lactic acidosis and Hepatotoxicity
What are the two non-nucleotide reverse transcriptase inhibitors (NNRTIs)?
Efavirenz and Rilpivirine
What is the MOA of the NNRTIs?
- Bind directly to inhibit viral reverse transcriptase and prevent conversion of RNA to DNA
- Does not require phosphorylation
Which of the NNRTIs is the DOC that is used in initial therapy of HIV?
Efavirenz
What are the side effects of Efavirenz?
- Drug interactions- CYP34A inducer
- Teratogenic
What is the use of Rilpivirine?
Used instead of efavirenz in pregnant patients
If a drug ends in “avir” what class does it belong in? What is the exception to this?
-Protease inhibitors, except Abacavir is the NRTI
What is the MOA of protease inhibitors?
-Bind to protease and inhibit their function of digesting long viral polypeptides into smaller, mature functional proteins.
Viral particles are unable to mature and become infectious
How are protease inhibitors metabolized?
CYP34A
Why are protease inhibitors given with ritovanir?
Ritovanir is a potent inhibitor of CYP34A, which is important because protease inhibitors are given with NNRTIs, which are CYP34A inducers. Without the inhibitor, the protease inhibitors would be metabolized too quickly
What are the common toxicities associated with protease inhibitors?
- Altered body fat distribution
- insulin resistance
- increases serum cholesterol
- spontaneous bleeding in patients with hemophilia A or B
What should ritonavir never be combined with?
Saquinavir because they both cause QT prolongation
-drugs with disulfiram reactions (metronidazole and cephalosporins) because the formulation of Ritonavir contains ethanol
Why is ritonavir often combined with other protease inhibitors?
Because it inhibits CYP3A4 and protease inhibits are metabolized by CYP3A4 -Keeps drug from metabolizing too quickly.
What is the DOC of the protease inhibitors?
Darunavir
Who should Darunavir never be used for?
People with sulfa allergy
What are the common side effects seen with atazenavir?
- Less effect on body fat distribution than other protease inhibitors
- Increase in bilirubin
- Diarrhea, rash, nausea
What is Lopinavir always combined with?
Ritonavir to increase bioavailability
What are the common side effects seen with Indinavir?
Nephrolithiasis and hyperbilirubinemia (aggressive hydration recommended)
When is tipranavir used?
In combination with Ritonavir, Indicated for use in treatment-experienced HIV infected patients who harbor strains resistant to other protease inhibitors
When should tipranavir not be used?
- Patients with head trauma because it increases risk for intracranial hemorrhage
- Patients with sulfa allergy
What are the two fusion inhibitor HIV drugs?
Enfuvirtide and maraviroc
What is the MOA of Enfuvirtude (fuzeon)?
Binds to the gp41 subunit of the viral envelope glycoproteins, prevents conformation change required for membrane fusion and viral entry
What is the only parenteral antiretroviral agent?
Enfuvirtide (Fuzeon)
What is the MOA of Maraviroc?
-Inhibits fusion of virus by binding to the CCR5 receptor of the CD4 T-Cell.
When is Maraviroc used?
-ONLY in patients with a CCR5-tropic HIV infection in which other treatment has not been effective
What kind of drug is Dolutegravir?
Integrase inhibitor
-DOC in combination with NRTIs
When in Dolutegravir used?
Treatment-resistant patients where other drugs are no longer working
