TB meds-Table 1 Flashcards
What is mycobacterium?
Slow-growing, slender rod shaped aerobic with a lipid rich cell wall
Can remain dormant in the host for long periods of time
What does mycolic acid do?
Makes up60% of the cell wall of mycobacterium and makes it relatively impermeable to many abx
Where can mycobateria reside?
Inside non activated macrophages
What is the importance of living in the macrophages?
Creates another permeability barrier
What is the defining pathologic feature of TB?
Granuloma mass enclosed by mono, lympho, and neutrophils recruited by an inflammatory response around the foamy macrophages within a fibrous cuff
What is the MOA of isoniazid (INH)?
Inhibition of cell wall synthesis by inhibiting mycolic acid synthesis through the formation of reactive oxygen radicals and isonicotinic acid
Is INH cidal or static?
Static in the stationary phase and cidal in the rapid dividing phase
What metabolizes INH?
N-acetylation and hydrolysis
Is there cross-resistance in INH?
No cross resistance to other TB drugs
What are the ADRs of INH?
Peripheral neuritis ( B6 def, make sure you supplement)
Hepatitis/hepatotoxic
Inhibits phenytoin met and may produce convulsions in pts prone to seizures
What is the most severe side effect of INH? What increase this effect?
Hepatitis/ hepatotoxicity- rifampin and EtOH
What is the Black Box warning associated with INH?
Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of tx
What are the rifamycins?
Rifampin, rifabutin, rifapentin
What is the mechanism of rifampin?
Blocks transcription by interacting with the Bsub unit of bacterial DNA-dependent RNA polymerase
Is INH or rifampin have a greater antimicrobial spectrum?
Rifampin
Is rifampin static or cidal?
Cidal against gram + and –
When is rifampin used prophylactically?
Individuals exposed to meningitis
What is rifabutin?
Analog of rifampin active against mycobacterium avium complex but less active against TB
What is rifapentin?
Newer, induces 3A4
How are the rifamycins administered?
Orally to get to all body fluids and organs
What doe the rifamycins induce?
Hepatic mixed function that oxidases increasing its own metabolism as well as other drugs like OCPs
How are the rifamycins eliminated?
Feces and urine- may give orange red color
What should you warn contact lens wearers about?
Tears may permanently stain soft lenses orange red
What are the ADRs of rifamycins?
Minor- N/V
What is the MOA of pyrazinamide?
Bactericidal.
1) Enters Mtub by passive diffusion, converted to POA by nicotinamidase/pyrazinamidas (PZase)
2) Inhibits fatty acid synthase I- stops mycolic acid biosynthesis
3) Accumulates w/in acidic environment of macrophages and monocytes and kills tubercle bacilli – help prolong therapy
What are the ADRs of Pyrazinamide?
Liver injury with jaundice- rarely fatal
What should you do if tx with pyra?
Get liver fxn tests! Shouldn’t tx if they have preexisting liver dysfxn
What is the MOA of ethambutol?
Static
Inhibits cell wall synthesis by inhibiting synthesis of polysaccharides and transfer of mycolic acids to the cell wall
What is the role of ethambutol?
Helps to prevent the emergence of RIF resistant organisms when primary resistance to INH may be present
What are the ADRs of Ethambutol?
Optic neuritis – most imp
Diminished visual acuity and loss of green red discrimination – do visual exams
Decreases urate excretion – careful if gout
