Term
| What general type of therapy is used for HIV patients? |
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Definition
Highly active antiretroviral therapy
(HAART) |
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Term
| When is HAART started for patients? |
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Definition
Patients wit AIDS-defining illness
Low CD4 counts (<350 cells/mm3)
High viral load |
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Term
| Describe the general drug regimen commonly used for HIV patients |
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Definition
- 2 NRTIs + 1 protease inhibitor
- 2NRTI + 1 NNRTI
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Term
| What are the general classes of HIV drugs? |
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Definition
- Protease inhibitors
- NRTIs
- NNRTIs
- Fusion Inhibitors
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Term
| What are some example of Protease inhibitors? |
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Definition
- Saquinavir
- Ritonavir
- Indinavir
- Nelfinavir
- Amprenavir
- Atazanavir
- Darunavir
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Term
| What is the MOA of protease inhibitors? |
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Definition
- Blocks aspartate protease, which cleaves precursor polypeptides to HIV
- Therefore, prevents maturation of new viruses
- Like preventing proinsulin from becoming insulin
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Term
| What gene is HIV-1 protease made from? |
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Definition
| Pol gene, which also works for integrase, reverse transcriptase |
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Term
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Definition
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Term
| What are the toxicities of protease inhibitors? |
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Definition
- Hyperglycemia
- Gi intolerance (nause, diarrhea)
- lipodystrophy (weight gain, atherosclerosis)
- Thrombocytopenia (indinavir)
- Diabetes II
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Term
| Which protease inhibitor produces the least insulin resistance? |
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Definition
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Term
| Which protease inhibitor increases INR? |
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Definition
(international normalized ratio, a test for extrinsic pathway for coagulation)
Ritonavir because it inhibits CP450
Don't use with drugs that need to be metabolized by CP450 like warfarin |
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Term
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Definition
| Nucleoside reverse transcriptase inhibitors |
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Term
| What are examples of NRTIs? |
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Definition
Zidovudine (ZDV, AZT, azidothymidine)
Didanosine (DDC)
Zalcitabine (DDC)
Lamivudine (3TC)
Stavidine (D4T)
Abacivir (ABC)
Entricitabine (FTC) |
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Term
| What is the MOA of NRTIs? |
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Definition
- Pro drug, used w/ protease inhibitors, that target non-specific kinases (leads to bone marrow issues)
- Competitively inhibit nucleotide binding to mess with reverse transcriptase and terminate DNA chain
- Must be phosphorylated by thymidine kinase to be active
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Term
| What are resistances formed against protease inhibitors? |
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Definition
| Point mutations in pol gene to change up structure of protease |
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Term
| What is the resistance formed against NRTIs? |
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Definition
| Mutations in pol gene coding for RT |
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Term
| What are the side effects/toxicities of NRTIs? |
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Definition
- Bone marrow suppression (can be reversed w/ g-CSF & erythropoietin)
- Peripheral neuropathy (esp zalcitabine and stavudine)
- Lactic acidosis (nucleosides)
- rash (non-nucleosides)
- Megaloblastic anemia (ZDV)
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Term
| What specific toxicities is zodivudine known for? |
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Definition
| Hematotoxicity and peripheral neuropathy |
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Term
| What specific toxicity is didanosine known for? |
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Definition
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Term
| What is lamivudine known for? |
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Definition
| Being the least toxic of the NRTIs, but therefore the least potent. Must be used in synergy with other drugs |
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Term
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Definition
Neviparine
Efavirenz
Declarividine |
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Term
| What is the MOA of NNRTIs? |
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Definition
- Not a prodrug, no myelosuppression (because doesn't require phosphorylation from kinases)
- Bind to reverse transcriptase at different site than NRTIs
- Compete for nucleotide sites
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Term
| What are the benefits of nevirapine? |
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Definition
- Dec Vertical transmission (mother to child) by 50%
- Rash
- Inc Liver function test, P450 issues
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Term
| What is efavirenz known for? |
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Definition
- Disrupting sleep
- Causing nightmares
- Insomnia
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Term
| What are the toxicities of NNRTIs? |
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Definition
- Same as NRTIs (w/o myelosuppression):
- lactic acidosis
- Peripheral neuropathy
- lactic acidosis
- rash
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Term
| What are the fusion inhibitors? |
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Definition
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Term
| What is the MOA of fusion inhibitors? |
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Definition
- Bind viral gp41 subunit
- Inhibit conformational change required for fusion w/ CD4 cells
- Blocks entry and replication
- Used in pts w/ persistant viral replication even w/ therapy
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Term
| What are the toxicities of fushion inhibitors? |
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Definition
- Hypersensitivity reactions
- reactions at subcutaneous injection site
- Inc risk of bacterial pneumonia
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Term
| What should you think when you see "D" in the acronym or name of a NRTI? |
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Definition
| Toxic, try to avoid them. |
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