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D&D Infectious Disease FINAL > Pharm - HIV pharmacotherap > Flashcards

Pharm - HIV pharmacotherap Flashcards

1
Q

what does HIV stand for

A

human immunodeficiency virus

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2
Q

what does AIDS stand for

A

acquired immuno deficiency syndrome

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3
Q

HIV is a retrovirus

what does this mean

A

has reverse transcriptase

converts vRNA to ssDNA and then to dsDNA – and then integrase enzyme integrates the dsDNA into the human genome

(both steps through reverse transcriptase)

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4
Q

is HIV an RNA or DNA virus

A

RNA

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5
Q

is HIV1 or HIV2 more common in europe/america

A

HIV1

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6
Q

true or false

HIV is a ssRNA virus

A

true

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7
Q

which 2 glycoproteins on the HIV virus are important for attachment to the membrane of host cells?

A

gp120 (docking glycoprotein)

gp41 (transmembrane glycoprotein)

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8
Q

name of the enzyme that allows viral dsDNA to integrate into the human genome to make NEW viral RNA?

A

INTEGRASE

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9
Q

Explain the structure of a retrovirus (HIV is one)

A

contains an RNA genome in a capsid, surrounded by a lipid envelope

this envelope contains receptors that mediate entry and infection into the host cell

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10
Q

true or false

we do not have drugs that kill the HIV virus

A

TRUE

only that inhibit their growth. thus, patients with HIV have to be on the meds forever

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11
Q

explain the lifecycle of the HIV virus

A

gp41 and gp140 allow for binding to CD4 receptors and CCR5 receptors (chemokine receptors) on the host cell membrane

fusion and uncoating occurs, and the viral RNA is released

reverse transcriptase converts this viral RNA into DNA, when then goes into the nucleus and is incorporated into the host genome through INTEGRASE.

then, transcription and translation of new viral proteins occurs.

the proteins assemble together into virions and mature. protease breaks down this polyprotein into smaller proteins which can assemble into a whole new virus that can then leave the host cell and infect more cells with the HIV virus

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12
Q

which receptors on the host cell are important for HIV virus to enter?

A

3:

CD4
CCR5
CXCR4

CCR5 and CXCR4 are coreceptors

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13
Q

what is the portal of entry for the HIV virus to get into the body?

A

blood, colon-rectum, and vagina — can get into bloodstream

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14
Q

HIV causes ___ and ___ infection of CD4 cells and persistent infection of cells of the ______ family, AND can disrupt _____

what is the result of these actions?

A

lytic and latent infection

monocyte macrophage family

can disrupt neurons

AIDS – also potential dementia bc affects neurons

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15
Q

which 2 cells can HIV infect

A

CD4 cells and macrophages

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16
Q

explain and differentiate between the lytic and latent phase of the HIV virus

A

latent:

HIV infects CD4 cells + macrophages. these serve as a reservoir for the virus. these cells can move to other areas of the body and cause lot of issues and cytokine release

lytic:

increased viral load in the blood causes CD4 cell to LYSE. the virus itself is released and can go to the brain – cause AIDS and dementia, and immuodeficiency,
total loss of cd4 cell functions – which causes SEVERE systemic opportunistic infections and lymphomas are common

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17
Q

once the CD4 count reaches below _____, severe immunodeficiency begins

A

below 200 cells/cubic mm

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18
Q

explain the progression of:

-viral load
-CD4 cells
-Anti-HIV antibody

throughout infection with HIV

A

at first, anti-HIV antibodies rise, CD4 numbers fall, and viral load increases substantially

after around 4 years, CD4 count continually decreases untill less than 200 (AIDS), but viral load is at zero bc of the antibodies still being produced

HOWEVER, past that mark of less than 200 T cells, viral load increases substantially and less antibodies produced

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19
Q

how do CD4 cells have a critical role in regulating human immune response?

A

they mediate the release of cytokines and the delayed-type hypersensitivity toward intracellular pathogens

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20
Q

loss of CD4 cells due to HIV has many negative results.

name them

A

loss of macrophage activation and thus (thru t cell release of IFN Y) delayed type hypersensitivity reactions – and thus loss of control of bacterial, fungal, and viral infections

also, no more growth and control of B cells, CD8 cells, and NK cells (CD8 cells and NK cells - IL2) - resulting in tumors and tumor progression

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21
Q

as mentioned, the receptor for HIV virus is CD4

tropism (early) is primarily for which coreceptor? how does this change into the advanced stages)

A

early - CCR5

advanced - switch to CXCR5 concurrently with CD4 cell loss

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22
Q

an issue with HIV pharmacotherapy is the rapid emergence of..

A

DRUG RESISTANCE (if the agents aren’t used properly)

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23
Q

true or false

discontinuing HIV drugs could be fatal

A

TRUE

have to be on forever

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24
Q

method to decrease HIV antiretroviral resistance

A

use combination therapy for which the virus is more susceptible

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25
Q

when administering HIV therapy, when should we get to an undetectable viral load? what is considered an undetectable viral load?

A

in 6 months

less than 50 copies of the viral RNA/plasma mL

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26
Q

standard HIV therapy consists of how many drugs

A

2+

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27
Q

all current HIV drugs do not affect what viral stage?

A

latent viral stage

(when viral DNA is already integrated with the host)

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28
Q

name 5 toxicities from HIV drugs

A

-HIV lipodystrophy syndrome (fat redistribution, hyperlipidemia, insulin resistance)

-CV toxicities (ie -QT prolongation)

-alltergies (sulfa)

-effect on CYPS

-accelerated inflammatory reactions (immune reconstitution inflammatory syndrome - IRIS)

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29
Q

name 5 NRTIs

A

abacavir
emtricitabine
lamivudine
tenofovir
zidovudine

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30
Q

what does NRTI stand for

A

nucleoside/nucleotide reverse transcriptase inhibitors

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31
Q

what is cobicistat

A

NOT an nrti/nnrti

its a pharmacokinetic enhancer - used in combination to inhibit CYPs and increase the half life of the antiviral drug

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32
Q

of the 5 NRTIs listed, (abacavir, lamivudine, emtricitabine, tenofovir, and zidovudine)

which is the ONLY nucleotide? (all the others are nucleosides)

A

TENOFOVIR

remember - FO - has phosphate

33
Q

of the 5 NRTIs, name which resemble guanine/adenine/thymine/
cytosine

A

thymine - zidovudine

adenine - tenofovir

cytosine - emtricitabine, lamivudine

guanine - abacavir

34
Q

true or false

ALL the NRTIs are prodrugs

A

TRUE

35
Q

name the 2 enzymes that are part of HIV reverse trancriptase

A

polymerase and nuclease (breaks nucleotide bonds in DNA/RNA)

36
Q

explain the MOA of NRTIs

A

1st, the NRTI has to be metabolized to become a TRIPHOSPHATE. competes with native nucelotides to incorporate into DNA strand

this then incorporates into the DNA strand and causes CHAIN TERMINATION in HIV reverse transcriptase enzyme

37
Q

true or false

NRTIs are noncompetitive inhibitors

A

FALSE - competitive inhibitors

compete with native nucleotides for incorporation into the DNA strand

38
Q

what is the backbone of HIV therapy

A

NRTIs

given with other drugs as well as other NRTIs

39
Q

what is the most potent NRTI

A

abacavir

40
Q

do NRTIs have side effects?
why or why not?

A

yes bc they also have affinity for human polymerase y in the mitochondria

this gives side effects like anemia, LACTIC ACIDOSIS (rare but serious), granulocytopneia, myopathy, peripheral neuropathy, and pancreatitis

41
Q

between all of the NRTIs, which has the worst oral bioavailability

A

tenofovir (it’s the only nucleotide!)

all the others have good oral bioavailability

42
Q

which 2 NRTIs have very little renal excretion of the parent drug

A

abacavir and zidovudine

43
Q

abacavir is a synthetic ____ analog

how is it administered?

A

guanosine

orally

44
Q

very important counseling point for abacavir

A

NO ALCOHOL!!!

ALCOHOL WILL INCREASE THE SERUM LEVELS OF ABACAVIR

45
Q

how is abacavir metabolized

A

hepatic - glucuronidation and carboxylation

46
Q

resistance mechanism to abacavir

A

mutations in reverse transcriptase

47
Q

important consideration before starting abacavir

A

there is hypersensitivity in 8% of patients

before starting, do HLAB5701 testing to identify hypersensitivity potential

48
Q

**some patient on abacavir have higher risk of…

A

myocardial infarction!

49
Q

emtricitabine is a ____ analog of ____

A

fluorinated analog of cytosine

50
Q

when is emtricitabine CONTRAINDICATED

A

in renal or hepatic failure

ALSO — do NOT use with lamivudine

51
Q

can emtricitabine be used for prophylaxis?
why or why not??

A

YES

can be used in combo for prophylaxis - has very long half life

52
Q

true or false

emtricitabine is active against both HIV and HBV

A

TRUE

53
Q

some rare AE of emtricitabine

A

lactic acidosis/severe hepatomegaly wiht steatosis

fat redistribution, IRIS (immune reconstitution inflammatory syndrome)

54
Q

lamivudine is a ____ analog

A

cytosine

55
Q

true or false

lamivudine, like emtricitabine, is also active against both HIV and HBV

A

true

56
Q

true or false

lamivudine cannot be given to pregnant women

A

FALSE

it can!!! recommended for pregnant women

57
Q

what happens with lamivudine is administered with chlorpropamide

A

increase glucose levels (use alternative!)

58
Q

which 2 NRTIS are recommended for use in pregnancy

what 3 are alternates?

A

lamivudine and zidovudine

alternates - abacavir, emtricitabine, tenofovir

59
Q

which NNRTI is recommended for use in pregnancy

A

nevirapine

60
Q

are protease inhibitors okay to give during pregnancy?

A

YES
recommended ones are lopinavir, ritonavir, and atazanavir

alternate is saquinavir

61
Q

tenofovir is an acyclic ______

A

nucleotide

62
Q

which base does tenofovir structurally mimic

A

adenosine

63
Q

how many steps of phosphorylation are needed for tenofovir

A

2

64
Q

can tenofovir be given for prophylaxis

A

YES

has long t 1/2

65
Q

4 major side effects of tenofovir

A

loss of renal function (fanconi syndrome)

bone mineral density decrease

lactic acidosis

liver damage

66
Q

zidovudine is a ______ analog

A

deoxythymidine

67
Q

what was the first HIV drug approved by the FDA

A

zidovudine

68
Q

AE of zidovudine

A

myelosuppression
lactic acidosis and severe hepatomegaly
lipoatrophy

69
Q

name 5 NNRTIS

A

efavirenz
etravirine
nevirapine
rilpivirine
doravirine

‘VIR”

70
Q

true or false

NNRTIS are NOT prodrugs

A

TRUE

71
Q

explain the MOA of NNRTIS

A

they DO NOT BIND THE ENZYMATIC/CATALYTIC SITE OF RT LIKE NRTIS!!!!!

they bind a distant, allosteric site on the enzyme which affects the enzyme’s structural transformation, and it’s activity decreases

72
Q

true or false

NNRTIS are reversible, competitive antagonists

A

FALSE

reversible, NON competitve
bind the ALLOSTERIC SITE

73
Q

true or false

NNRTIs do NOT need intracellular phosphorylation

A

TRUE - THEY ARE NOT PRODRUGS!!!!!!!!!!!!!!

74
Q

true or false

NNRTIs are active against both HIV1 and HIV2

A

FALSE

only HIV1

75
Q

true or false

NNRTIs do NOT target host DNA polymerase

A

TRUE

this is good bc less side effects

76
Q

very important DDI consideration with NNRTIS

A

they have HIGH hepatic metabolism by CYP3A4!!! therefore, considerable drug drug interactions

77
Q

explain NNRTI resistance and is there any cross resistance with NRTIS

A

NNRTIs are susceptible to resistance by a SINGLE mutation

however, there is no cross resistance with NRTIs

since these agents are highly suceptible to resistance, they are combined with AT LEAST 2 OTHER ACTIVE AGENTS to avoid resistance. they are still highly potent and effective

78
Q
A

D&D Infectious Disease FINAL (21 decks)

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