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Flashcards in Tuberculosis and HIV Deck (28):
1

HIV life cycle

gp 120 and gp 41 attach to CD4 T cells --> CXCR 4 or CCR 5 --> into cell --> viral RNA to DNA by reverse transcriptase --> integrase puts DNA into cell host DNA --> transcription and translation --> protease puts viral replicated into cell wall and spreads

2

Maraviroc

binds to CXCR 4 and CCR 5 so HIV cannot bind and enter cell --> need genetic testing of HIV virus to make sure which receptor it uses

3

Enfuvirtide

binds to gp41 on HIV virus, not allowing gp41 the facilitation of viral entry

4

Abacavir
Zidovudine
Lamivudine
Emtricitabine

NRTI (nucleoside)
completely inhibits reverse transcriptase, inserts into viral DNA and causes termination
Requires phosphorylation by cellular enzymes to be active
S.E.: general hepatic toxicity
- Z ->granulocytopenia
- L/E -> best tolerated

5

Tenofovir

NRTI (nucleotide)
completely inhibits reverse transcriptase, inserts into viral DNA and causes termination
Requires phosphorylation by cellular enzymes to be active
S.E.= N/V, diarrhea, renal failure

6

Efavirenz
Etravirine

NNRTI
Inhibits reverse transcriptase at separate site from NRTI, doesn't require phosphorylation
S.E. = rashes and hepatic cy-P450

7

Atazanavir
Ritonavir
Darunavir

Protease Inhibitors
inhibit protease activity that is required for full maturation of virus --> don't become infectious
S.E. = GI, hepatotoxicity, hyperglycemia, insulin resistance
lots of cyp-450 interactions

8

Raltegovir

Integrase Inhibitor
binds integrase --> prevents strand transfer (the final step in provirus integration)

9

Rifampin

inhibits DNA-dependent RNA polymerase
Ramps up CYP-450 (be careful with HIV patients and meds)
Red/orange body fluids
Hepatotoxicity

10

Isoniazid

decreases synthesis of mycolic acids (needs bacterial catalse-peroxidase to convert to active metabolite)
only drug used prophylaxis for TB
Some people are rapid acetylators (slow acetylators --> liver damage) --> monitor liver function
S.E. = neurotoxicity, hepatotoxicity, B6 deficiency (use pyridoxine)

11

Pyridoxine

used for Isoniazid toxicity (PLP transamination)

12

Aminoglycosides

Streptomycin
inhibits formation of initiation complex by irreversibly binding 30S subunit --> causes misreading of mRNA
nephrotoxic, neurotoxic, ototoxic, teratogen
Can be inactivated by acetylation or phosphorylation
Does not enter cell --> used for extracellular treatment of TB

13

Pyrazinamide

unknown mechanism --> maybe intracellular acidity?
hyperuricemia, hepatotoxic

14

Ethambutol

decreases carbohydrate polymerization of mycobacterium cell wall
optic neuropathy --> color blindness (dose related)
don't use in kids!

15

Sensitivity

TP/ TP+FN

16

Specificity

TN/TN+FP

17

PPV

TP/TP+FP

18

NPV

TN/TN+FN

19

HIV confirmation

Negative ELISA is good enough for any population
Positive ELISA --> 5% chance that it was false positive --> perform Western blot (99%)

20

Lung nodule's

Neoplasm
Granuloma
Abscess, pneumonia, pulmonary infarct
Likelihood of malignancy is proportional to nodule size, pts age, history of smoking

21

Significance of calcification of lung nodule

calcification --> generally not malignant cancer
- could be granuloma, abscess, hamartoma, etc

22

Significance of cavitation of lung nodule

a lucency within a zone of pulmonary consolidation, a mass, or a nodule; hence, a lucent area within the lung that may or may not contain a fluid level and that is surrounded by a wall
- most likely indicates necrosis

23

Mycobacterium tuberculosis

Rod-shaped, spore forming, obligate aerobe, acid-fast bacilli
High content of mycolic acids
VF : Lipoarabinomannan -> pathogen-host interactions, facilitates survival in macrophages
CatG -> protects against oxidative stress (also required for isoniazid to work)
Cord Factor -> inhibits macrophage maturation and induces TNF-alpha
SLOW GROWER

24

Active TB Clinical Picture

SYMPTOMATIC --> CONTAGIOUS
can be either primary or secondary
Sx = cough, dyspnea, hemoptysis, weight loss, fever, chills

25

Latent TB Clinical Picture

ASYMPTOMATIC --> NOT CONTAGIOUS
can see findings of (+) mantoux or CXR
Mycobacterium are sitting in the granuloma

26

PPD (TB skin test)

subdermal injection
Th1 cells recruit macrophages --> induration and redness (test is for induration, not redness!)
Immunocompromised >5 mm (+)
High Risk >10 mm (+)
Normal Healthy >15 mm (+)

27

Reason for combo therapy for TB?

Using the combo therapy of 4 drugs GREATLY reduces the chance for drug resistance

28

Why add a low dose of Ritonovir to AIDS regimen?

Used at low doses, it increases the serum concentrations of the other protease inhibitors (Ritonovir inhibits cyp3A4 which metabolizes the other PIs)