Flashcards in Anti-Mycobacterial Drugs (Tuberculosis/Leprosy/MAC) Deck (19)
What is the cause of Mtb-mediated tissue injury and death?
HOST immune response of inflammation [CASEOUS NECROSIS]
NOT the specific toxin
Inflammation and host self-death in attempt to control intracellular bacterial growth
Most commonly recovered NON-TB, nonpathogenic Mycobacterium species __
Where is it found?
Greatest diagnostic test to diagnose Mtb
NAAT - Greater sensitivity and greater specificity than the conventional smear or culture
Difference between LTBI (latent tb infection) therapy versus active TB disease
LTBI - can use single or multi drug therapy
Active TB - ALWAYS use multi drug
Which first line drug targets arabinogalactan of the MYCOBACTERIAL cell wall AND is particularly effective against fast-growing EXTRACELLULAR Mtb?
3 Drugs that target mycolic acid of MYOBACTERIAL cell wall
FIRST-LINE: INH (isoniazid)
SECOND-LINE: PAS (p-aminosalicylic acid) + ETA (ethionamide)
Which first line drug inhibits the large subunit of RNA polymerase and inhibits RNA synthesis (release of nascent RNA) [particularly effective against slow-growing INTRACELLULAR Mtb]?
Which first line drug inhibits protein synthesis in DORMANT bacteria
Which two first line anti-mycobacterial drugs are used for prophylactic treatment?
Which two first line and one second-line drug are anti-mycobacterial pro-drugs? (Necessitate activation by bacteria for the drug to be effective)
Active form of INH (isoniazid)?
What bacterial enzyme mediates this conversion?
What does it target?
Conversion by bacterial KatG (catalase-peroxidase)
Targets the Fab1 (InhA) of FASII - enzyme that elongates mycolic acid of the cell wall
Main side effect of INH _
Management of this side effect _
Due to pyridoxal deficiency (INH looks structurally similar to VitB6)
Management by VitB6 supplementation
Non-toxic side effect of rifampin on excreted body fluids (urine, sweat, tears)
Harmless purple/red in these fluids
Toxic side effects of rifampin
1) Flu-like symptoms
2) Induces CYP3A -> Increases elimination of other drugs
3) Can penetrate into CSF is patient also has meningitis
Advantages of rifabutin + Rifapentine over rifampin (RIF)
1) Higher potency
2) Longer half life
3) Greater membrane permeability - can infiltrate macrophages more easily
4) Less CYP3A induction -> Less excretion of other drugs (better if the patient is taking other medications such as anti-arrhythmic agents/HIV)
Active form of pyrazinamide __
What does the active form bind?
POA - pyrazinoic acid
Binds RpsA [ribosomal protein S1]
which inhibits S1 from binding tmRNA -> Prevents trans-translation mechanism -> Prevents rescue of stalled ribosomes -> Accumulation of misfolded peptides that do not get sent for degradation ->
DORMANT bacteria can not survive under these stressful conditions
Which anti-mycobacterial first-line drug should you NOT administer to children younger than 5yrs old? Why?
Optic neuritis + Red-green color blindness
Treatment of MAC infection
MACROLIDES: Azithromycin + Clarithromycin
May also use ciprofloxacin, ethambutol and rifabutin