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2020 CPR II Pulm Exam 2 > PHARM Tuberculosis (Iszard) > Flashcards

PHARM Tuberculosis (Iszard) Flashcards

1
Q

What 4 drugs are the standard first-line agents for tx of TB?

A
  • Rifampin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol

*RIPE*

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2
Q

Which 3 first-line agents for TB can cause liver damage as an AE?

A
  • Isoniazid
  • Rifampin
  • Pyrazinamide
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3
Q

What is the MOA of isoniazid?

A

Inhibits mycolid acid synthesis

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4
Q

What are 2 major AE’s associated with Isoniazid?

A
  • Hepatotoxicity
  • Peripheral neuropathy can be ↓ w/ pyridoxine (B6)
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5
Q

Which second-line TB drug has same pharmacokinetics as isoniazid, but can be used in its place when resistance to isoniazid develops?

A

Ethionamide

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6
Q

What is the strategy for treating PPD reactors w/ active TB rules out (aka latent TB)?

A
  • Isoniazid for 9 months
  • Rifampin for 4 months or combo of 1x/week isoniazid + rifapetine for 3 months
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7
Q

What is the MOA of Rifampin?

A

Binds β subunit of bacterial DNA-dependent RNA polymerase –> inhibits RNA synthesis

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8
Q

Which first-line TB agent readily penetrates most tissues and phagoytic cells, allowing for bactericidal action in abscesses and lung cavities?

A

Rifampin

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9
Q

Resistance to rifampin may devlop by mutation in what gene?

A

rpoB

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10
Q

After oral administration where is majority of rifampin excreted and enters into where?

A

Mainly via liver –> bile and undergoes enterohepatic circulation

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11
Q

What are the major AE’s associated with Rifampin?

A
  • Orange/red color to urine, sweat, and tears
  • Rashes, thrombocytopenia and nephritis
  • Hepatitis and cholestatic jaundice
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12
Q

What is the MOA of Ethambutol?

A

Inhibits mycobacterial arabinosyl transferases, needed for polymerization of arabinoglycan essential for cell wall

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13
Q

Overexpression/mutuation of which gene may cause resistance to Ethambutol?

A

emb CAB

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14
Q

Higher does of ethambutol may be used to tx tuberculosis infections where?

A

Tuberculosis meningitis; crosses the BBB at high doses

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15
Q

Most common AE associated with Ethambutol and should not be given to whom?

A
  • Retrobulbar neuritis –> ↓ visual acuity and red-green color blindness
  • Don’t give to children too young to permit assessment of visual acuity and color discrimination!
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16
Q

What is the MOA of Pyrazinamide and where does it exert its effects?

A
  • Converted to pyrazinoid acid (active form) inside lysosome by mycobacterial pyrazinamidase
  • Disrupts mycobacterial cell wall membrane metabolism and transport functions
17
Q

What are 2 ways in which resistance to Pyrazinamide may occur?

A
  • Impaired uptake of pyrazinamide into lysosome
  • Mutations in pncA which encodes enzyme necessary for conversion to active form PZA
18
Q

Which 1st line agent for TB is the “sterilizing agent” and what does adding this agent to the regimen do?

A
  • Pyrazinamide
  • Shortens regimen from 9 months –> 6 months!!!
19
Q

Major AE’s of Pyrazinamide?

A
  • Hepatotoxicity
  • Hyperuricemia may precipitate gout
20
Q

Which first-line TB agent diffuses readily into ALL tissues and body fluid, including the CNS?

A

Isoniazid

21
Q

How does the 6 month regimen of first-line agents for active TB work (i.e., which drugs given and when)?

A
  • 2 months INTENSIVE phase w/ RIPE
  • Then 4 months of isoniazid and rifampin

*Remember 4 for 2; then 2 for 4

22
Q

Which class does Streptomycin belong to and its MOA?

When would it be used for TB?

A
  • Aminoglycoside –> protein synthesis inhibitor
  • Used when IV or IM route is desired and in cases where there is resistance
23
Q

Ethionamide has the same MOA, resistance, and AE’s as what other TB agent?

A

Isoniazid

24
Q

What is the MOA of Capreomycin?

A

Protein synthesis inhibitor

25
Q

Which 2nd-line TB agents can be used for streptomycin-resistant strains?

Which is specifically used if an IV or IM route is desired?

A
  • Capreomycin –> can be given IV or IM
  • Kanamycin and Amikacin –> only amikacin used in US!
26
Q

What is the MOA of Cycloserine?

A

Structural analog of D-alanine inhibits alanine racemase and D-alanyl-D-alanine ligase –> cell wall synthesis inhibitor

27
Q

Cycloserine is given via which route and is cleared by which organ?

A

Oral dose and is cleared renally

28
Q

What are the most serious AE’s associated w/ Cycloserine?

A
  • CNS dysfunction
  • Peripheral neuropathy –> can be ↓ w/ pyridoxine (B6)
29
Q

What is the MOA of Aminosalicylic Acid as 2nd-line against TB?

A

Structural analog of PABA = folate synthesis inhibitor

30
Q

What is unique about how Aminosalicyclic Acid is packaged for use and is given how?

A

Packet of delayed-release granules that are given by sprinkling over food such as applesauce or yogurt

31
Q

What are the common and serious AE’s associated with Aminosalicyclic Acid?

A
  • GI sx’s = common; may be ↓ by giving with food
  • Peptic ulceration + hemorrhage
  • Hypersensitivity rxn occurring 3-8 wks after beginning tx
32
Q

What is the MOA of the fluoroquinolones and which 2 are used most?

A
  • DNA gyrase inhibitors (topoisomerase II and IV)
  • Moxifloxacin = Most active against TB; and Levofloxacin
33
Q

What are the 5 major AE’s of the fluoroquinolones?

A
  • GI effects = most common
  • Achilles tendon RUPTURE
  • QT prolongation (Moxifloxacin)
  • C. difficile colitis
  • CNS effects
34
Q

What is MOA of linezolid and when is it used for TB?

A
  • Protein synthesis inhibitor; bind 50s subunit and prevent fMET tRNA
  • Used in rare case when resistance to both 1st and 2nd line agents
35
Q

What are 2 major AE’s associated with Linezolid?

A
  • Bone marrow suppression
  • IRREVERSIBLE peripheral and optic neuropathy
36
Q

What is the MOA of Rifabutin and Rifapentine?

A

Bind β-subunit of bacterial DNA-dependent RNA polymerase and inhibits RNA synthesis (same as Rifampin)

37
Q

What are the uses of Rifabutin and Rifapentine for TB?

A
  • Rifabutine used in place of rifampin for tx of TB in pt’s w/ HIV on HAART, due to being less potent inducer of CYP450
  • Rifapentine: sometimes used in combo w/ isoniazid for latent TB
38
Q

What are the 3 most common AE’s associated w/ Bedaquiline; what is the black-box warning associated with this drug?

A
  • Nausea + arthralgia + HA = common
  • BBW = QTc prolongation w/ assoc. mortality
39
Q

If resistance to TB develops what are the recommendations for adding new drugs (i.e., amount)?

A

NEVER add single agent, ALWAYS add 2 to prevent further resistance

2020 CPR II Pulm Exam 2 (28 decks)

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