TB therapeutics Flashcards

1
Q

What are the 3 main principles of TB treatment?

A

1) multi drug therapy
2) focus on increasing adherence
3) adequate duration of therapy

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2
Q

What is the first line drug for active pulmonary TB?

A

isoniazid HCl (INH)

but not used as a single drug - used in combination

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3
Q

What is the MOA of INH?

A

prodrug activated by catalase peroxidase (the TB katG gene) then targets the inhA gene product

it is CIDAL for replicating orgs and STATIC for resting orgs

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4
Q

Name two mechanisms for INH resistance?

A

1) mutations in katG gene (cannot activate INH)

2) mutations in inhA gene (cannot impair cell wall synthesis)

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5
Q

How is INH metabolized?

A

acetylated in liver (degree of acetylation varies with one’s genetics)

non acetylated drug is excreted in urine

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6
Q

true or false: INH distributes to the CNS

A

TRUE

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7
Q

What are 3 toxicities of INH?

A

1) hepatotoxicity (especially bad with rifampin)
2) neurotoxicity
3) hypersensitivity rxns

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8
Q

What can rifampin NOT be used alone?

A

rapid development of resistance

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9
Q

What are the main mechanisms of resistance for rifampin?

A

rpoB mutations

rpoB encodes RNA polymerase

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10
Q

What are 3 common toxicities of rifampin?

A

1) red discoloration of body fluids
2) influenza syndrome
3) thrombocytopenia

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11
Q

What is a huge pitfall of rifampin?

A

drug interactions!! accelerates clearance and reduces effective conc of many drugs

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12
Q

What is the MOA of ethambutol?

A

inhibits TB arabinosyl transferase encoded by embB gene (affects cell wall synthesis)

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13
Q

What are the 2 big toxicities?

A

1) optic neuritis

2) peripheral neuropathy

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14
Q

What TB drug has known optic toxicity?

A

ethambutol

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15
Q

What is the P in RIPE TB therapy?

A

pyrazinamide (PZA)

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16
Q

When do you use PZA?

A

the first two months of therapy

17
Q

What is the MOA of PZA?

A

it is a prodrug activated by TB pyrazinamidase encoded by pncA

(resistance comes in the form of pncA mutations)

18
Q

Which TB drug is only used in the initial stages of TB?

A

PZA

19
Q

What is a big toxicity of PZA?

A

hepatitis

20
Q

What is the second line TB drug?

A

streptomycin

21
Q

What are the two types of TB resistance?

A

primary (acquired at infection by getting a drug resistant bug)

secondary (developed during therapy due to ineffective therapy design or adherence)

22
Q

What is the rationale for treatment with multiple drugs for TB

A

decrease the odds of evolution of resistance

23
Q

How do you calculate the risk f evolution of resistance to two drugs?

A

the product of the risk of development of resistance to each drug

24
Q

Define multi drug resistant TB

A

resistance to BOTH INH and rifampin

25
Q

Why is rifampin resistance so concerning?

A

eliminates the option of short course (6 month) therapy and instead requires 18-24 month therapy

26
Q

Define extensively drug resistant TB

A

resistance to ALL of the following

  • INH and rifampin
  • fluoroquinolones
  • one of three injectable antibiotics
27
Q

The initial phase of TB treatment is ______ while the continuation phase is ___

A

RIPE

RI

28
Q

True or False: intermittent therapy (2-3x week) is ONLY with daily observance

A

True

6 month therapy can be successful on if adherence is high, sputum cultures convert by 2 months and there is no major cavitary lung problems