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Hailey - IHO > HIV/AIDS > Flashcards

HIV/AIDS Flashcards

1
Q

Key molecules of HIV replicative cycle

A 
RT
cDNA
mRNA
tat
RnaseH
gp120
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2
Q

tat

A

Protein that regulates viral Tx

Affects rate of replication

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3
Q

gp120

A

Envelope glycoprotein

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4
Q

1983

A

HIV isolated (took two years)

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5
Q

1987

A

Zidovudine available to USA

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6
Q

1993

A

AIDS leading cause of death of young adults in US

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7
Q

1996

A

HAART

Development of resistance and SE

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8
Q

2003

A

New class: fusion inhibitors

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9
Q

Goals of HIV Tx

A 
Maximally inhibit viral replication
Fully undetectable levels of virus
Lower the viral RNA --> lower rate of accumulation of drug resistance --> longer therapeutic effect
Avoid drug interactions
Encourage complicance
Drug combinations
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10
Q

General Tx strategy:

A 
COMBINATIONS
One of (NNRTI, PI, IntegraseI) + TWO NRTI
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11
Q

NRTIs (nucleoSide)

A

Zidovudine (azidothymidine or AZT)
Lamivudine
Emtricitabine
Abacavir

“Emtrici, you and Aba go feed Zido some Lami on the back Side of the house.”

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12
Q

NRTI (nucleoSide) mech

A

Competitiveliy inhibit RT
Incorporate into vDNA chain and cause termination
REQUIRES PHOSPHORYLATION by cellular enzymes to become active

Resistance to one –> resistance to another

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13
Q

NRTI (nucleoSide) SE

A

FATAL: LACTIC ACIDOSIS WITH HEPATIC STEATOSIS probably due to mitochondrial toxicity
Fat redistribution
Hyperlipidemia
Drug drug interactions

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14
Q

Zidovudine SE

A 
Granulocytopenia and anemia (45% treated patients)
CNS disturbances:
severe HA
nausea
insomnia
malaise
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15
Q

Lamivudine and Emtricitabine SE

A

Best tolerated of NRTIs

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16
Q

Abacavir SE

A

Hypersensitivity

17
Q

NRTIs (nucleoTide)

A

Tenofovir

“Best ride on the Tide is a Ten*”

18
Q

NRTI (nucleoTide) mech

A

Competitively inhibit RT
Incorporate into vDNA chain and cause termination
DOES NOT REQUIRE PHOSPHORYLATION

19
Q

NRTI (nucleoTide) SE

A 
Nausea
Vomiting
Diarrhea
Potential for renal failure
FATAL: LACTIC ACIDOSIS WITH HEPATIC STEATOSIS
20
Q

NNRTIs (non-nucleoSide)

A

Efavirenz
Etravirine

Efa plus Etra (mobsters) kill Vir with NNRTIs (weapons)

21
Q

NNRTIs mech

A

Bind directly to RT at side distinct from NRTI
RT can no longer produce vDNA
DOES NOT REQUIRE PHOSPHORYLATION

NO CROSS RESISTANCE WITH NRTIs or PIs

22
Q

NNRTIs SE

A

GI intolerance
Skin rash
Drug interactions: CYP450

23
Q

Efavirenz

A 
QD
CNS effects (vivid dreams, nightmares, hallucinations)

Efa: once daily gets weird dreams

24
Q

Etravirine

A

Rash
Nausea
Peripheral neuropathy

Etra: Nausea, Neuropathy, Rash (NNRti)

25
Q

Protease Inhibitors (PI)

A

Atazanavir
Ritonavir
Darunavir

“Darun Ate all the Rits crackers at the super bowl Party Intermission.”

26
Q

PI mech

A

Prevents protease action required for MATURATION of fully assembled virus
*WITHOUT THIS CLEAVAGE THE VIRUS IS NOT INFECTIOUS
Prevents post-Ts cleavage of Gag-Pol polyproteins

27
Q

PI SE

A 
GI disturbances
Hepatotoxicity
Hyperglycemia and insulin resistance
Dyslipidemia
Cardiac conduction abnormalities
Peripheral lipoatrophy and central fat accumulation
CYP3A4 hepatic
28
Q

Ritonavir boosting

A

high doses of PI ritonavir are POORLY TOLERATED
Used at lower doses TO INCREASE SERUM CONC OF OTHER PIS and DECREASE DOSAGE FREQ OF OTHER PIs

potent inhibitor of CYP3A4 (increases affectiveness of PIs)

29
Q

Fusion Inhibitors (FI)

A

EnfuvirTide (T-20)

“Catching Enough (e nfu) Tides? No? Do this workout: FIT-20!”

30
Q

FI mech

A

Binds to gp41 and prevents the conformational change necessary for fusion of viral an host cell membranes to allow virus into cell

31
Q

Enfuvirtide

A

SubQ BID
local reactions with pain, erythema, induration, nodules, cysts

Active against other HIV-resistant antiretrovirals

32
Q

Integrase Inhibitors (INSTI)

A

Raltegravir

“Walt’s favorite: INSTant (insti) gravy”
Ralt = Walt, gravi = gravy

33
Q

INSTI mech

A

Binds integrase
Inhibits strand transfer, the final step of provirus integration
INSTI: integrase Strand Transfer Inhibitors

Fewer drug drug Intxns

34
Q

CCR5 Antagonist

A

Maraviroc

35
Q

CCR5/CXCR4 antagonist mech

A

Binds specifically and selectively to host CCR5

CCR5: receptor HIV-1 uses to get into host cell

36
Q

CCR5 Ant SE

A

Pyrexia
Rash
Postural dizziness

37
Q

HAART

A

Highly active antiretroviral therapy
RTIs in combo with PI
HAART associate lipodystrophy

38
Q

HAART associated lipodystrophy

A 
25-50% patients affected
Wasting of suQ fat
Central adiposity
Hyperlipidemia, insulin resistance, diabetes mellitus
Most often seen with use of NRTIs and PI
39
Q

If reitonavir given in combo with darunavir, would you expect an increase, decrease, or no chance in serum conc. of daruavir computer to mono therapy with darunavir?

A

Would expect an increase in serum darunavir because ritonavir inhibits CYP450, which metabolizes PIs (darunavir).

Hailey - IHO (5 decks)

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