Flashcards in Micro - Antimicrobials (HIV therapy) Deck (25):
What does HAART stand for? What are the criteria for it to be initiated?
Highly active antiretroviral therapy (HAART): initiated when patients present with AIDS-defining illness, low CD4 cell counts (<500 cells/mm^3), or high viral load.
What makes up the HAART regimen?
Regimen consists of 3 drugs to prevent resistance: [2 nucleoside reverse transcriptase inhibitors (NRTIs)] + [1 non-nucleoside reverse transcriptase inhibitors (NNRTI) OR 1 protease inhibitor OR 1 integrase inhibitor]
What are 7 examples of protease inhibitors? What is common to all of them?
(1) Atazanavir (2) Darunavir (3) Fosamprenavir (4) Indinavir (5) Lopinavir (6) Ritonavir (7) Saquinavir; All protease inhibitors end in -navir; "NAVIR (never) TEASE a PROTEASE"
Explain how protease inhibitors work against HIV.
Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
What effect can Ritonavir have on other drug concentrations, and how?
Ritonavir can "boost" other drug concentrations by inhibiting cytochrome P-450.
What are 3 toxicities associated with protease inhibitors in general?
(1) Hyperglycemia (2) GI intolerance (nausea, diarrhea) (3) Lipodystrophy
What are 2 toxicities associated with Indinavir?
(1) Nephropathy (2) Hematuria (Indinavir)
What are 7 examples of NRTIs?
(1) Abacavir (ABC) (2) Didanosine (ddI) (3) Emtricitabine (FTC) (4) Lamivudine (3TC) (5) Stavudine (d4T) (6) Tenofovir (TDF) (7) Zidovudine (ZDV, formerly AZT)
What is the mechanism of NRTIs?
Competitively inhibits nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group).
What kind of molecules are most NRTIs? What is required for their activation? What is the exception to this rule?
Tenofovir is a nucleoTide; the others are nucleosides and need to be phosphorylated to be active
What is ZDV? In what 2 contexts is it used?
ZDV is used for general prophylaxis and during pregnancy to lower risk of fetal transmission; Think: "haVE YOU DINED (vudine) with my NUCLEAR (NUCLEOsides) family?"
What are 6 toxicities associated with NRTIs? Where applicable, clarify which toxicities apply to which NRTIs.
(1) Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin) (2) Peripheral neuropathy (3) Lactic acidosis (nucleosides) (4) Rash (non-nucleosides) (5) Anemia (ZDV) (6) Pancreatitis (didanosine)
How can NRTI-induced bone marrow suppression be reversed?
Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin)
What are 3 examples of NNRTIs?
(1) Efavirenz (2) Nevirapine (3) Delavirdine
What is the mechanism of NNRTIs? How do they differ from NRTIs?
Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides.
What is 2 toxicities are common to all NNRTIs?
Rash and hepatotoxicity are common to all NNRTIs
What are 2 toxicities common to efavirenz?
Vivid dreams and CNS symptoms are common with Efavirenz.
What 2 NNRTIs are contraindicated in pregnancy?
Delavirdine and Efavirenz are contraindicated in pregnancy
What is the name of a specific Integrase inhibitor?
What is the mechanism of Raltegravir?
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
What toxicity is associated with Raltegravir?
What are 2 examples of Fusion inhibitors?
(1) Enfuvirtide (2) Maraviroc
What is the mechanism of Enfuvirtide, and what effect does it have?
Binds gp41, inhibiting viral entry
What is the mechanism of Maraviroc, and what effect does it have?
Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.