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Flashcards in Treatment of TB Deck (58)
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31

What is dose intensity based on for TB in HUV patients?

CD4 counts, 2x/week for greater than 100CD4/ul and daily or 3x/week for less than 100CD4/ul

32

What is something to be cautious of in Active TB HIV patients?

DD interactions with some PIs and NNRTIs

33

How is isoniazid changed one inside the body?

it is a pro-drug that acetylated by NAT2 isoforms to its principal metabolite,

34

How is N-acetyl isoniazid excreted?

renal

35

How is N-acetyl isoniazid activated?

diffuses into mycoplasma and is activated by KatG (oxidase/peroxidase) to the nicrotinoyl radial, which reacts with NAD+ or NADP+ to produce adducts that inhibit cell-wall (enoyl-acyl carrier reductase) and nucleus acid synthesis

36

Specifically, how does isoniazid inhibit nucleic acid synthesis?

dihydrofolate reductase inhibitor

37

What is the significance of isoniazid in drug dosing?

humans vary in their acetylating capacity (called 'status')

38

What ethnicities are typically fast acetylators?

Asians (may require higher doses)

39

What is a risk for slow acetylators?

drug accumulation giving rise to lupus-like AEs

40

What endogenous molecule does isonazid deplete?

vitamin B6 (so pyridoxine supplements are often given)

41

How does isoniazid deplete vitamin B6?

CYP2E1 products bind and inactivate pyridoxine species and inhibits pyridoxine phosphokinase

42

What are some possible toxicities isoniazid?

-Hepatitis
-Peripheral neuropathy (Give vitamin B6)
-Seizures in epileptic patients (reduction of GABA)

43

Hemolysis is a possible AE of isoniazid in ____ patients

G6PD deficient

44

Isoniazid inhibits which CYP?

2C19

45

DD interactions of Isoniazid?

-Antidepressants
-PPIs
-Phenyotin

46

What are the member of the rifamycin family of drugs?

-Rifampin
-Rifabutin
-Rifapentine

47

How do rifamycin drugs work?

They inhibit bacterial RNA synthesis by forming a stable complex with DNA-dependent RNA polymerase (rpoB)

48

How are rifamycins metabolized?

via deacetylation and CYP3A hydrolysis

49

What is one thing to remember about Rifamycins?

they are CYP1A2 2C9, 2C19, and 3A4 INDUCERS (Rifampin the most) by promoting protein synthesis in the liver

50

AEs of rifamycins?

-red-man syndrome
-rare hepatotoxicity
-discoloration of contact lens

51

How does Pyrazinamide enter mycobacteria?

processed by initial
deamination within the mycobacterium and is effluxed, only to re-enter the bacillus
by simple diffusion in an acidic environment.

52

How does pyrazinamide kill TB?

1) Inhibition of fatty acid synthase type 1 inhibiting mycelia acid synthesis

2) reduction of intracellular pH

3) disruption of membrane transport by HPOA

53

Toxicities of Pyrazinamide?

-Hepatotoxicity
-Inhibition of urate excretion, causing hyperuricemia in nearly all patients

-May cause gout

54

T or F. Pyrazinamide is allowed during pregnancy

F.

55

How does Ethambutol work?

The final one of the principal drugs to consider is ethambutol. Activity is limited to
mycobacteria where it seems to work by inhibiting mycobacterial cell wall production
by inhibiting arabinosyl transferase enzyme activity.

56

AEs of Ethambutol?

-dose-related optic neuropathy (change in acuity or red-green blindness)
-hyperuricemia and elevated LFTs

57

2nd line options for TB

-Fluoroquinolones
-Amikacin, Kanamycin
-Linezolid
-many others

58

Why do seizures occur with isoniazid?

isoniazid complexes with pyridoxal-5-phosphate (and is then lost in the kidneys). Pyridoxal-5-phosphate is needed to produce GABA which normally down-regulates brain activity and thus you see seizures