Antimycobacterial Drugs - (TB and Leprosy) Flashcards
AE of Isoniazid
Lupus-like syndrome and Peripheral neuritis
MOA of Isoniazid
Prodrug is activated by KatG (mycobacterial catalase peroxidase) –> targets InhA and KasA –> decreased mycolic acid synthesis –> decreased cell wall synthesis
Isoniazid is a synthetic analog of ?
Pyridoxine; must supplement patient with Vitamin B6
True or False: Isoniazid is safe in pregnancy.
True
Name the Rifamycins
Rifampin, Rifabutin
MOA of Rifamycins
Bind to beta subunit of bacterial RNA polymerase –> block transcription and therefore RNA synthesis
AE of Rifamycins
Orange body fluids, proteinuria
PK/PD of Rifamycins
CYP450 inducers
PK/PD of Isoniazid
CYP450 inhibitor
True or False: Rifampin is safe in pregnancy.
True
Which forms of Mycobacteria are Rifamycins used against?
M. kansasaii, M. tuberculosis
DOC for Tuberculosis in HIV patients because of reduced CYP450 effects
Rifabutin
Resistance mechanisms against Rifamycins
rpoB gene mutations, decreased permeability
Indications of Rifamycins
Meningitis prophylaxis, latent TB in patients who cannot tolerate Isoniazid, combined with Vancomycin for MRSA
MOA of Ethambutol
Inhibits arabinosyl transferase
AE of Ethambutol
Reversible red-green colorblindness, hyperuricemia, neuritis
Resistance mechanisms against Ethambutol
emb gene mutations
Indictations of Ethambutol
combination therapy with Pyrazinamide, Isoniazid, Rifampin
Which forms of Mycobacteria is Ethambutol used against?
M. tuberculosis and M. kansasaii
AE of Pyrazinamide
Non-gouty polyarthralgia, hyperuricemia
Resistance mechanisms against Pyrazinamide
Resistant strains lack Pyrazinamidase, increased efflux
MOA of Pyrazinamide
Enzymatically hydrolyzed to Pyrazinoic acid
Is Pyrazinamide safe for use during pregnancy?
Yes, if benefits outweigh risk
What are the first line drugs for TB?
Isoniazid, Rifamycins (Rifampin and Rifabutin), Pyrazinamide, Ethambutol
What are the second line drugs for TB?
Amikacin (Aminoglycoside), Streptomycin (Aminoglycoside), Levofloxacin (3rd gen. Fluoroquinolone), Ethionamide
True or False: 2nd line drugs for TB are safe for use in pregnancy.
False; all 2nd line Antimycobacterial drugs are teratogenic!
MOA of Dapsone
Inhibits Dihydropteroate synthase –> decreases folic acid synthesis (like Sulfonamides)
Besides Leprosy, which other disease can Dapsone be used to treat?
PCP
Repository form of Dapsone
Acedapsone
AE of Dapsone
Hemolytic Anemia (b/c it is sulfa-related), Erythema nodosum (treat with Steroids or Thalidomide)
PK/PD of Dapsone
CYP450 Inhibition
Phenazine dye that is bactericidal against M.leprae
Clofazimine
MOA of Clofazimine
Binds DNA –> inhibits replication; may generate ROS
AE of Clofazimine
Red-brown skin discoloration, Eosinophilic enteritis
Treatment for pauci-bacillary skin lesions
Rifampin + Dapsone for 6 months
Treatment for multi-bacillary skin lesions
Rifampin + Dapsone + Clofazimine for 12 months
Treatment for latent TB
Isoniazid (6-9 months) + Rifampin (4 months)
Treatment against M.kansasaii
Isoniazid + Rifampin + Ethambutol
Treatment against M.marinum
2 drug combo: Rifampin, Ethambutol, Clarithromycin, Minocycline, Doxycycline, Sulfonamides
Treatment against M.chelonae
Clarithromycin monotherapy
M.avium complex
Clarithromycin + Ethambutol +/- Rifampin
M. fortuitum
Amikacin, Cefoxitin, Levofloxacin, Sulfonamides, Imipenem
