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Flashcards in Antiretrovirals Deck (39):
1

what are the six classes of antiretrovirals

-nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
-non nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs)
-Protease Inhibitors (PIs)
-Fusion Inhibitors (FIs)
-CCR5 antagonists
-Integrase Strand Transfer Inhibitors (INSTIs)

2

what drugs are used to improve the pharmacokinetic profiles of some antiretrovirals

pharmacokinetic enhancers
-ex: PIs and the INSTIs, elvitegravir

3

what does a typical antiretroviral regimen consist of

*two NRTIs
-usually abacavir + lamivudine
-or tenofivir + emtricitabine
*with a third antiretroviral from the classes NNRTIs, INSTIs, or PIs
*with a pharmacokinetic enhancer

4

what are the NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors)

TADELSZ

Tenofovir
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Zidovudine

5

mechanism of NRTIs

TADELSZ - tenofovir, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zidovudine

-enters the cells and undergoes phosphorylation to generate synthetic substrates for the HIV RNA dependent DNA polymerase enzyme aka reverse transcriptase

-phosphorylated analogue competitively inhibits incorporation of native nucleotides and prevents elongation of nascent provirus because they lack a 3' OH

-essentially prevents formation of provirus from HIV RNA

6

what are most of the adverse effects of NRTIs associated with (name them)

TADELSZ - tenofovir, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zidovudine

-some NRTIs have an affinity for human DNA polymerase-gamma, a mitochondrial enzyme --> anemia, granulocytopenia, myopathy, peripheral neuropathy, lipatrophy, lactic acidosis, and pancreatitis

7

adverse effects of abacavir and what drug should be avoided

hypersensitivity rash with fever, rash, malaise, respiratory and or GI symptoms

avoid alcohol

8

adverse effects of didanosine and what drug should be avoided

PANCREATITIS (insulin disturbance)
Peripheral Neuropahty
Retinal Changes

avoid Tenofovir because it increases the concentration of didanosine --> more likely cause side effects

9

of all the NRTIs which are nucleoside and which are nucleotide

Tenofovir is a nucleotide while the rest are nucleosides and hence need to be phosphorylated to be active

10

adverse effect of emtricitabine

hyperpigmentation of palms and soles especially in darker skinned people

11

adverse of Staduvine and what drug to avoid

FATAL LACTIC ACIDOSIS
Peripheral Neuropathy
Diabetes
Pancreatitis

avoid concurrent neuropathic drugs

12

drug interactions of Tenofovir

-lowers serum conc of atazanavir
-increases conc of didanosine
-together with didanosine --> decreased CD4 T cells

13

adverse effects of Tenofovir

Renal Toxicity
Decreased bone density
Osteomalacia

14

adverse effects of Zidovudine and what drugs should be avoided

Myelosuppression (bone marrow suppression)

avoid co-administration with doxorubicin and stavudine; also avoid other myelosuppressive drugs

15

what are the NNRTIs (non nucleoside/nucleotide reverse transcriptase inhibitors)

REN

Rilpivirine
Efavirenz
Nevirapine

16

mechanism of NNRTIs (name them)

REN - Rilpivirine, Efavirenz, Nevirapine

they non-competitively bind to reverse transcriptase distant from the active site and cause conformational changes hence reducing its activity without the need for phosphorylation

17

adverse effect of Efavirenz

DVN'T (DON'T

Difficulty concentrating
Vivid Dreams
Nightmares
Teratogenic (avoid in 1st trimester)

18

adverse effects of Rilpivirine

Insomnia
Depression

19

adverse effects of Nevirapine

Severe Hepatotoxicity
Hepatic Failure

20

what are inducers of both CYP3A4 and CYP2B6

Nevirapine and Efavirenz

21

what are the protease inhibitors

NAVIR tease a Protease LIDAN

Lopinavir
Indinavir
Darunavir
Atazanavir
Nelfinavir

22

which protease inhibitor is not a substrate for CYP3A4

Nelfinavir

23

mechanism of protease inhibitors (name them)

NAVIR tease a protease LIDAN - lopinavir, indinavir, darunavir, atazanavir, nelfinavir


competitively inhibits virus aspartyl protease hence inhibiting proteolytic cleavage of HIV gag and pol that includes enzymatic and structural component of HIV

24

adverse effects of Lopinavir, Indinavir, and Darunavir

Lopinavir - Asthenia (lack of energy) and Pancreatitis

Indinavir - increased indirect bilirubin, nephrolithiasis, cholelithiasis, rash, blurred vision

Darunavir - Rash

25

who should avoid darunavir

those with sulfa allergy

26

adverse effects of Atazanavir and Nelfinavir

Atazanavir - Hyperbilirubinemia and PR elongation

Nelfinavir - nausea and flatulence

27

in general what are adverse effects of protease inhibitors (name them)

NAVIR tease a protease LIDAN - lopinavir, indinavir, darunavir, atazanavir, and nelfinavir

disorders of fat and carb distribution - hyperglycemia, insulin resistance, hyperlipidemia, truncal obesity etc

28

what are the integrase strand transfer inhibitors (INSTIs)

Integrase RED GRAVIR

Raltegravir
Elvitegravir
Dolutegravir

29

how is raltegravir eliminated and what can increase its elimination hence decreasing its con

eliminated by glucuronidation mediated by UDP glucuronosyltransferase 1A1 aka UGT1A1


conc can be decreased by strong inducer of UGT1A1 for ex rifampin

30

adverse of INSTIs (name them)

Integrase RED Gravir - Raltegravir, Elvitegravir, Dolutegravir

increase in creatinine phosphokinase, myopathy, rhabdomyolysis, and systemic hypersensitivity reactions

31

what is the CCR5 antagonist and its mechanism

Maraviroc binds to CCR5 co receptor and prevents entry of CCR5 tropic viruses into CD4 T cells

32

what is the fusion inhibitor and its mechanism

Enfuvirtide binds to gp41 and prevents conformational change that would allow HIV virus to fuse to host cell

33

what are the pharmacokinetic enhancers

Cobicistat
Ritonavir

34

mechanism of pharmacokinetic enhancers (name them)

Cobicistat and Ritonavir

both potent inhibitors of CYP3A4 hence increasing plasma conc of antiretroviral drugs that are broken down by CYP3A4 leading to higher efficacy and less frequent dosing

35

difference between Cobicistat and Ritonavir

-Ritonavir has its own antiretroviral activity although it is not used for that but rather for its pharmacokinetic enhancing ability while cobicistat has no antiretroviral activity

-Ritonavir is mainly used with PIs while Cobicistat is used with INSTIs

36

antiretroviral drugs that should be avoided during pregnancy

-Efavirenz due to its teratogenic activity
-Nevirapine in those with CD4 greater than 250 due to its increased risk of hepatotoxicity

37

preferred regimen for occupational post exposure prophylaxis of HIV

superficial: 2 NRTIs

Deep: 2 NRTIs and one from another group
Raltegravir + Tenofovir + Emtricitabine

38

general recommended treatment for HIV patients (also be specific)

2 NRTIs and INSTI (highly effective with fewer side effects and no CYP3A4 drug interactions0
(Tenofovir + Emtricitabine + Raltegravir)
(Tenofovir + Emtricitabine + Daltegravir)


2 NRTIs and PI
(Tenofovir + Emtricitabine + Darunavir or Ritonavir)

39

what are HIV prophylactic vaccines

Strep pneumonia
Hep A and B
Influenza

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