Antimycobacterial Drugs Flashcards
what is the most common site of mycobacterial infection?
lungs
in which patients is multi-drug resistance TB seen?
HIV/AIDS +
asymptomatic, no radiographic abnormalities, and all bacteriological studies are negative
latent TB
what is the cell wall of mycobacteria made of? (3)
peptidoglycan
arabinogalactan
mycolic acid
single most important anti-T drug that inhibits synthesis of mycolic acid, destroying the cell wall
isoniazid (INH)
when is isoniazid the most potent?
during initial 2-5 days of therapy
6 ADRs of isoniazid?
“the sons are so neurotoxic (muscle twitching, insomnia), that they cause hepatotoxicity and hemolysis”
neurotoxic
muscle twitching
insomnia
hepatotoxicity
hemolysis
what enzyme does isoniazid induce in alcoholics?
CYP2E1
in which patients is hemolysis to occur when taking isoniazid?
those with G6PD deficiency (protects RBCs from damage)
what should be added when a patient is taking isoniazid? why?
vit B6
INH blocks metabolic activation of pyridoxine (vit B6)
which enzyme does isoniazid INHIBIT?
CYP450
which 4 drugs have increased side effects in patients who are slow acetylators (AKA have an absence or deficiency in the N-acetyltransferase 2 enzyme)? why?
Sulfapyridine
Hydralazine
Isoniazid
Procainamide
they all go through N-acetyltransferase 2 pathway
what effect does sulfapyridine have on slow acetylators?
liver damage
what effect do hydralazine and procainamide have on slow acetylators?
lupus-syndrome
what effect does isoniazid have on slow acetylators?
peripheral neuropathy
Rifa-
rifamycins
block RNA polymerase from initiating transcription by binding to and inhibiting it
rifamycins (rifa-)
4 ADRs of rifamycins?
“Rifa has alot of HOGS”
Hepatotoxicity
Orange
GI
Skin rash
ADR from weekly high doses of a rifamycin?
flu-like syndrome
which enzyme do rifamycins INDUCE?
CYP450
which rifamycin should be used in a patient with TB + co-infection with HIV? why?
rifabutin
less DDI
since rifamycin have biliary excretion and enterohepatic recirculation, which drug’s effectiveness will be decreased?
oral contraceptives
bacteriostatic agent that inhibits arabinosyl transferase (who is required for synthesis of arabinogalacatan, which links mycolic acid to mycobacterial cell wall)
ethambutol
what is a dose dependent ADR of ethambutol?
visual disturbances
ADR d/t prolonged high dose of ethambutol?
retinal damage
6 ADRs of ethambutol?
optic neuritis
red-green colorblindness
headache
confusion
peripheral neuropathy
hyperuricemia
bactericidal agent against semi-dormant form of TB in macrophage
pyrazinamide
4 ADRs of pyrazinamide?
“the pyraz’s want to HASH it out”
Hepatotoxicity
Arthralgia
Skin rash
Hyperuricemia
name the most frequently used 2nd line Rx for TB
IM streptomycin
amikacin/kanamycin
aminoglycosides that inhibit protein synthesis
streptomycin
amikacin/kanamycin
ADR of streptomycin + amikacin?
nephrotoxicity
ototoxicity
in which patients should streptomycin and amikacin be avoided in?
pregnant patients
which 3 fluoroquinolones can be used to treat TB?
“Moxi and Levo need their Cipro to treat their TB”
Moxi-
Levo-
Cipro-
7 ADRs of fluoroquinolones?
Skin rash/sun sensitivity
Prolonged QT/Peripheral neuropathy
Ruptured tendon
Increased risk of C. diff
Neurotoxic
GI intolerance
+Weak cartilage
2nd line tx for TB that inhibits mycolic acid synthesis
ethionamide
2nd line tx for TB that inhibits protein synthesis
capreomycin
2nd line treatment for TB that interferes with proton pump for ATP synthase
bedaquiline
2nd line tx for TB that inhibits mycobacterial cell wall synthesis; similar to INH
delamanid
2 ADRs for bedaquiline and delamanid?
increased QT
CYP3A4
used to treat persistent and latent TB
pretomanid
what should pretomanid be used with to treat extensively drug-resistant TB? (2)
bedaquiline + linezolid x 6mo
8 ADRs for combination treatment: pretomanid + bedaquiline + linezolid
nerve damage
hepatotoxicity
prolonged QT
lactic acidosis
myelosuppression
acne
headache
N/V/D
what drugs should be used during the first 2 months of tx for TB? AKA the intensive phase
Rifamycins
Isoniazid
Pyrazinamide
Ethambutol
what drugs should be used for the 2nd phase of TB? AKA the continuation phase
Rifamycin
Isoniazid
what is the monotherapy #1 for TB prophylaxis?
isoniazid daily x 6 months
what is the monotherapy #2 for TB prophylaxis?
isoniazid x 9 months
what is the monotherapy #3 for TB prophylaxis?
rifampin daily x 4 months
what is the monotherapy #4 for TB prophylaxis, especially for latent TB with HIV?
isoniazid daily + weekly rifapentine x 3 months
vaccine for TB that protects children but not adults
bacile calmette guerin
what is the most common pattern of resistance in TB treatment?
isoniazid resistance
treatment for resistant TB disease?
what is an alt?
what is added in severe disease?
rifampin + pyrazinamide + ethambutol
alt: streptomycin in place of etham.
quinolone for severe
what is the treatment rule for multi-drug resistant TB?
at least 4 drugs x 18-24 months
3 PO, 1 injection
what should be included for treatment of mycobacterium avium complex?
azithromycin OR clarithromycin
