HIV Pharm Flashcards by Ashley McKinstry

Antiretroviral therapy treatment goals

suppress HIV RNA, restore and preserve immune function, decrease morbidity and increase survival, prevent HIV transmission

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HIV treatment interruption is associated with…

rebound viremia, worsening of immune function, increased morbidity and mortality

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Drug combinations needed to achieve HIV viral suppression

3 active drugs from >/= 2 drug classes

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How long does it take for ART to reduce viral load to below detection limit?

12 to 24 weeks

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Predictors of virologic success

low baseline viremia, high potency of ARV regimen, and tolerability, convenience, and excellent adherence to regimen

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MOA nucleoside reverse transcriptase inhibitors

binds to DNA chain and terminates production, inhibit incorporation of native nucleotides

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What does the toxicity of NRTIs depend on?

ability to inhibit HIV RT without inhibiting host cell DNA pol

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NRTIs most commonly used

emtricitabine, lamivudine, abacavir, tenofovir

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Toxicities associated with NRTI

lactic acidosis, peripheral neuropathy, pancreatitis, anemia, myopathy

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Zidovudine MOA

NRTI that interferes with thymidine incorporation

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Clinical applications zidovudine

inhibits HIV-1, HIV-2, HTLV-1 and HTLV-2, mother-to-child transmission, prophylaxis for health care workers

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Zidovudine toxicities

myalgia, nausea, anorexia, loss of limb fat, bone marrow suppression, skeletal muscle myopathy, hepatic steatosis

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MOA stavudine

NRTI that interferes with thymidine incorporation

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Clinical applications stavudine

inhibits HIV-1 and HIV-2

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Stavudine toxicities

peripheral neuropathy, lipodystrophy, lactic acidosis, and hepatic steatosis

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Emtricitabine MOA

NRTI, interferes with cytosine incorporation

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Clinical applications emtricitabine

low barrier to resistance, treats HIV-1 and HIV-2, also active against HBV

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Pharmacokinetics emtricitabine

long half life, excreted primarily unchanged in the urine

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Emtricitabine toxicities

one of the least toxic, hyperpigmentation

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Lamivudine MOA

NRTI, interferes with cytidine incorporation

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Clinical applications lamivudine

treat HIV-1 and HIV-2, active against HBV

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Pharmacokinetics lamivudine

long half life, excreted primarily unchanged as urine

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Lamivudine toxicities

one of the least toxic agents, but may have HA, fatigue, N/D, rash, neutropenia, MSK pain, fever

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Abacavir MOA

NRTI, interferes with guanosine analog

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Clinical applications abacavir

treat HIV in combination

Who should abacavir not be given to?

patients with HLA-B*5701 genotype (causes an aberrant release of TNF)

Abacavir pharmacokinetics

long half life, not CYP substrate

Abacavir toxicities

unique hypersensitivity syndrome; fever, GI distress, rash, malaise, fatigue

Tenofovir disoproxil fumarate (TDF) MOA

NRTI, nucleoTide adenosine analog

Clinical applications TDF

treat HIV in combo, treat HBV

Pharmacokinetics TDF

10-50 hr half life, excreted unchange in urine

TDF toxicity

generally well tolerated, nephrotoxicity with acute tubular necrosis, decreased bone mineral density

Tenofovir alafenamide MOA

nucleoTide, adenosine analog

Clinical applications tenofovir alafenamide

treat HIV and HBV

ART drug combos

2 NRTIs targeting different bases and a drug from a different class

NRTIs commonly combined

emtricitabine and tenofovir

NRTIs not combined

emtricitabine and lamivudine; TDF and TA

Lamivudine is given in combo with what INSTI

dolutegravir

INSTI MOA

Integrase strand transfer inhibitors, blocks integration of the viral genome

Raltegravir MOA

prevents formation of covalent bonds between viral and host DNA

Toxicity raltegravir

"remarkably little" clinical toxicity, may have some hypersensitivities associated with it

MOA Dolutegravir

prevents strand transfer, blocks chromosomal integration of viral CNA

Toxicities dolutegravir

generally well tolerated, avoid in pregnancy

INSTI metabolized by CYP3A4

elvitegravir

Bictegravir MOA

prevents strand transfer, blocks chromosomal integration

Protease Inhibitors MOA

prevents cleave of peptide and subsequent maturation of the virion; inhibit activity of aspartyl protease, which prevents proteolytic cleavage of gag and pol peptides

Pharmacokinetics protease inhibitors

highly protein-bound, hepatic clearance, substrate for P-glycoprotein

Toxicities protease inhibitors

nausea, vomiting, diarrhea; insulin resistance and lipodystrophy

Saquinavir MOA

first protease inhibitor, prevents maturation of HIV particle

Indinavir MOA

prevents maturation of HIV particle

Indinavir toxicities

unique crystaluria/renal stones

Darunavir MOA

non-peptidic protease inhibitor that prevents maturation of capsid

Darunavir toxicities

Gi distress, increase triglycerides, rash and hypersensitivity reaction because it is a sulfa drug

Atazanavir MOA

protease inhibitor that prevents maturation of capsid

Toxicities atazanavir

GI distress, increase serum cholesterol, unconjugated hyperbilirubinemia not associated with hepatitis

Lopinavir MOA

protease inhibitor that prevents maturation of HIV particle

Ritonavir MOA

protease inhibitor but only used to block CYP3A4 and increase levels of more potent PIs

Cobicistat MOA

CYP3A4 inhibitor used to boost levels of PIs

NNRTI MOA

non-nucleoside reverse transcriptase inhibitors, inhibitor binds to reverse transcriptase and denatures it

NNRTIs are only active against....

HIV-1

Nevirapine MOA

NNRTI, prevents generation of DNA from viral RNA, induces CYP3A4

Efavirenz MOA

NNRTI

Efavirenz toxicities

CNS toxicity/psych side effects, rash

Etravirine MOA

NNRTI, still works despite mutations

Rilpivirine MOA

NNRTI

Rilpivirine toxicities

more common in adolescents and children; CNS, endo and GI issues

Doravirine MOA

NNRTI

Entry inhibitor MOA

T20 peptides prevent conformational change allowing fusion of viral package to cell

Enfuvirtide MOA

peptide that inhibits formation of protein critical for membrane fusion

Enfuvirtide Clinical applications

only active against HIV-1

Pharmacokinetics enfuvirtide

must be administered parenterally

Entry blocker-CCR5 MOA

blocks CCR5, preventing fusion

Maraviroc MOA

blocks binding of GP120 to CCR5, blocks HIV entry

Maraviroc is not active against...

CXCR4 or mixed trophic viruses

Pharmacokinetics maraviroc

CYP3A4, renal elimination

Toxicities maraviroc

generally well tolerated, may experience cold-like symptoms, dizziness, GI upset

HIV RNA viral load level that prevents sexual transmission

<200 copies/mL