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Respiratory Medicine-Unit 2 > TB Pharmacology (Fitz) > Flashcards

TB Pharmacology (Fitz) Flashcards

1
Q

What are the front line drugs for TB?

A

Isoniazid
Rifampin
Ethambutol
Pyrazinamide

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2
Q

What FQs can be used for TB?

A

Levo/moxafloxacin

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3
Q

What injectables can be used for TB?

A

Amikacin
Capreomycin
Kanamycin
Streptomycin

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4
Q

What drugs are used during the intensive phase for standard therapy for Active TB? What about the continuation phase?

A

Isoniazid
Rifampin
Ethambutol
Pyrazinamide

Continuation phase –> INH and Rifampin

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5
Q

What is the MOA of INH?

A

Disrupts mycolic acid synthesis

Gets converted to active metabolic (4-diazenyl-carbonyl pyridine) by katG enzyme

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6
Q

What are INH resistance mechanisms

A

Deletion of katG enzyme
Overexpression/mutation of InhA, KasA
Insufficient active metabolite

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7
Q

How is INH metabolized?

A

In the liver

N-Acetylation

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8
Q

What are adverse rxns to INH?

A

Hepatic –> elevated liver enzymes, jaundice, hepatitis

Neuro –> peripheral neuritis, convulsions

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9
Q

What by-product of INH are hepatotoxic?

A

N-acetyl-hydrazine`

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10
Q

This can be given to counter the neuropathy seen in INH neurotoxicity:

A

Pyridoxal-5-phosphate

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11
Q

What is the MOA of Rifampin?

A

Inhibits prokaryotic gene transcription and downstream events. It is bactericidal even on slow growing bacteria

RNA polymerase B subunit is the target

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12
Q

___ can stain red/orange such as urine, sweat, contact lenses

A

Rifampin

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13
Q

What are some drug interactions of Rifampin?

A

Strong inducer of CYP450

Increases metabolism of other drugs

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14
Q

Starting __ can increase clearance of oral contraceptives (estrogen) metabolized by CYP isoenzymes. Heightened risk for unplanned pregnancy

A

Rifampin

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15
Q

You should substitute for this drug, rather than Rifampin, in HIV/AIDS pts with TB

A

Rifabutin –> Rifampin can increase clearance of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in HIV/AIDS pts

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16
Q

This anti-tb drug has a narrow spectrum against mycobacteria TB at acidic pH

A

Pyrazinamide

17
Q

What is the MOA of PZA? Metabolism? Toxicity?

A

MOA: uncertain- mycolic acid biosynthesis; Rquires activation by/in mycobacteria; resistance develops if used alone

Metabolism: Hepatic pyrazinamide –> pyrazinamide acid 5-hydroxymetabolites (CYP450)

Toxicity: Hepatotoxic; Renal –> Gout

18
Q

When is PZA bactericidal?

A

Only at acidic pH

19
Q

What is the MOA of ethambutol? Resistance?

A

Inhibits arabinosyl transferase and cell wall synthesis

Resistance by mutation of arabinosyl transferase

20
Q

What are some adverse effects of ethambutol?

A

Visual –> optic neuritis, color disturbance

Renal –> gout

21
Q

How should you tx latent TB?

A

INH –> 9 months, daily

INH and Rifapentine –> 3 months, once weekly

22
Q

How should you tx TB in pregnancy?

A

INH, rifampin, ethambutol –> PZA not recommended for use during pregnancy

WHO –> 4 drugs recommended: INH, rifampin, pyrazinamide, and ethambutol are not teratogenic

23
Q

How should you tx TB in AIDS/HIV infx pt?

A

Initiate TB tx first, then HIV

Avoid weekly INH-rifapentine

Avoid twice weekly INH-rifampin if CD4 count < 100

24
Q

What do you need to add for tx of MDR-TB (resistance to 2 first line drugs INH and rifampin?

A

Tx for 20 months with regimen that includes 2nd line anti-TB drugs –> FQs; Injectables; Add on or core 2nd line such as Ethionamide, p-Aminosalicylic acid, Cycloserine

25
Q

What is the inhibition mechanism of Quinolones? Ethionamide? PAS?

A

Quinolones: Topoisomerase

Ethionamide: Mycolic acid

PAS: Folate pathway

26
Q

What is the inhibition mechanism of cycloserine? Injectables?

A

Cycloserine: cell wall synthesis

Injectables: protein synthesis

27
Q

In dec of 2012, the FDA approved __ “as part of combo therapy to tx adults with MDR-pulmonary TB when other alternatives are not available

A

Bedaquiline –> targets mycobacterial ATP synthase which leads to bactericidal effects for both replicating and non-replicating tubercle bacilli

Respiratory Medicine-Unit 2 (5 decks)

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