Anti TB drugs Flashcards
Frontline TB drugs
- Isoniazid
- Rifampin
- Ethambutol
- Pyrazinamide
Anti-TB drugs should be discontinued if what?
serum bilirubin is > or equal to 3 mg/dL
or
Serum transaminases are more than 5 times the upper limit of normal
Goals of TB treatment
- eradicate M. Tuberculosis infection
- Prevent emergence of drug resistance
- Prevent relapse of infection
Describe the therapy necessary got TB to achieve the goals
prolong multi drug regimen
How long do you use all 4 first line TB drugs and what phase is this
8 weeks . . intensive phase
What drugs do you use after 8 weeks? and what phase is this
Isoniazid and Rifampin . . . continuation phase
What is the purpose for the use of 4 drugs?
resistance
Route of administration for TB drugs
oral
What PARENTERAL drug is sometimes used in hospital setting in patients who cannot tolerate P.O. drugs
Streptomycin (aminoglycoside)
Isoniazid is bactericidal in what type of TB?
growing
isoniazid works by disrupting what?
mycolic acid synthesis
What mycobacterial enzyme converts isoniazid into its active metabolite?
this then blocks what?
Catalase peroxidase (KatG)
InhA and KasA
Isoniazid resistance mechanisms
- depletion of katG
- overexpression/mutation of InhA and KasA
What ethnicity are the fast acetylators of isoniazid
Asians
What ethnicity are “slow acetylators” of isoniazid?
- caucasians
- Blacks
- Hispanics
What hepatic enzyme acetylates isoniazid
NAT
2 Major adverse reactions to Isoniazid?
Hepatic
- Elevated liver enzymes
- Jaundice
- Hepatitis
Neurologic
- Peripheral neuritis (paresthesias)
- convulsions
Which acetylators get increased exposure to N-acetylhydrazine causing more hepatotoxicity
slow ones
Isoniazid reacts convalently with ______ which depletes pools of what neurotransmitter leading the neuropathy
pyridoxal-5-phosphate
GABA
What does Rifampin inhibit?
DNA dependent RNA polymerase
Describe the characteristic of Rifampin effectiveness?
bacericidal even on SLOW GROWING bacteria
Which Tb drug has high intracellular penetration?
Rifampin
What TB drug stains things red/orange like urine, sweat, and contact lenses
Rifampin
Which TB drug is a strong inducer of CYP enzymes and can increase clearance of oral contraceptives and can cause unplanned pregnancy/
Rifampin
What drug would you substitute for Rifampin in HIV/AIDS patients
Rifabutin
Which drug is narrow spectrum and is used for mycobacteria tuberculosis at ACIDIC pH
Pyrazinamide (PZA)
What enzyme does Ethambutol inhibit?
Arabinosyl transferases and cell wall synthesis
Adverse effects of ethambutol?
- Visual (optic neuritis, color disturbance)
- Renal (gout)
What TB drug blocks tubular secretion of urate leading to hyperuricemia and urate crystals
Ethambutol
Treatment for Latent TB
isoniazid daily for 9 months
What 3 drugs for TB are considered safe for pregnancy in the USA
- isoniazid
- Rifampin
- ethambutol
What is the leading killer of people who are HIV infected?
TB
How do you go about treating a patient with TB and HIV
- initiate TB treatment first, then HIV
- Avoid weekly INH-rifapentine
- Avoid twice weekly INH-rifampin if CD4 count <100
What 2 drugs is multi drug resistant TB resistant to?
isoniazid and rifampin
What are the second line drugs that can be used to treat MDR-TB
Fluoroquinolones - moxifloxacin and levofloxacin
Injectables - Amikacin, kanamycin, capreomycin, streptomycin
Add on or core 2nd line - Ethionamide, p-aminosalicyclic acid (PAS), cycloserine
MOA of bedaquiline
inhibits mycobacterial ATP synthase
