everything you ever wanted to know about tuberculosis
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- M tuberculosis organisms are characterized by what features?
-
they have a very lipid rich cell wall (60%)composed of
mycolic acids (acid-fast)
are extremely slow growing (doubles every 18 hrs, vs most double every hour)
cord factor which is found in virulent strains
sulfatides
wax D
- salfatides are an important part of virulence of TB why?
- they inhibit the fusion of the phagosome with the lysosome, making TB a facultative intracellular org, allowing for better evasion of the immune system.
- first line drugs in Tx of TB
-
RIP
rifampin
isoniazid
pyrazinamide
(all 3 are hepatotoxic, w/ isoniazid being the worst)
+ ethambutol or streptomicin - two potential populations of TB patients:
-
those with active TB
ie fever, productive cough, night sweats for 2 months
and those with latent TB, + PPD
ie >5mm in high risk pop
>10mm in moderate risk pop
and >15mm in low risk pop - how would one be classified as high/moderate/low risk?
-
high risk defined as:
HIV+,organ transplant pts, Xray evidence of healed old TB infection, and close contacts of presons with active pulmonary TB.
moderate risk: med cond that lower immune sys (diabetes, renal failure, steroid use), recent arrivals from endemic countries, iv drug users, residents/employees of high risk settings (homeless shelter, prisons, etc), recent PPD conversion ( - Tx for active pulmonary TB includes:
- isoniazide, rifampin, pyrazinamide and ethambutol (except in kids) for first 2 months, then just rifampin and isoniazide for the last 4 months...really want to see what the sensitivity tests say as well.
- Tx of PPD reactors?
-
considered preventive. You need to exclude the possibility of active disease before you decide to begin prophylactic treatment, because the two are very different!! chest x ray and sputum AFB and culture shoudl do the trick.
Tx isoniazid given for 9 months
- what is a major adverse effect of TB Tx?
- hepatotoxicity. need to monitor liver function while treating!
- what are some factors that increase the risk for hepatotoxicity occuring with isoniazid Tx?
-
age is a major risk factor; rare in younger pts, much more freq as get older.
alcohol intak ecan also increase risk of hepatotox.
if liver enzymes are elevated >5X UNL, then discontinue drug
remember, enzymes will be elevated in most pts by 2-3X normal, but still cont with Tx. - some other side effects of isoniazid include
- peripheral neuropathy and CNS toxicity. Give pyridoxine to prevent these SE!
- what percentage of patients on isoniazid will experience drug-induced hepatitis?
- ~1%
- common symptoms/signs of hepatitis are
- jaundice, nausea, vomiting, fatigue
- isoniazid inhibits what?
- CYP3A4, so for instance, inhibits the met of phenytoin, an anti-seizure med that has a narrow TI
- isoniazid MOA
- is a prodrug activated by bacterial enzyme, inhibits synthesis of mycolic acid
- the most common side effete of INH is?
- peripheral neuropathy/CNS toxicity if pyridoxine is not given prophylactically
- Rifampin does what to hepatic cytochromes?
- Revs them up!! get increased met of many drugs, including OC, warfarin, phenytoin, etc.
- adverse effects of rifampin
-
is generally well tolerated, can turn the body fluids red/orange.
hepatitis is less common than w INH - which if the first line agents is the most hepatotoxic?
- pyrazinamide
- the RIP drugs are all
-
hepatotoxic
and
bacerticidal - ethambutol is the only firts line drugs that is
- bacteriostatic
- ethambutol is really useful as an adjunct to Tx because it
- decreases the emergence of resistance
- ethambutol MOA
- inhibits arabinosyl transferase used in cell wall synthesis
- ethambutol has a couple of adverse effects. what are they?
-
optic neuritis -> loss of red-green color vision. need to monitor visual acuity and avoid giving it to kids
also causes decreased uric acid secretion...just like pyrazinamide - streptomycin
- is not used too much anymore has lots of AE, such as ototoxicity (may be permanent) and nephrotoxicity. must be given parenterally.
- acid-fast bacteria appear what color after staining
- red! think of a fast red sports car
- what is the prime defense mechanism against TB?
-
cell mediated immunity
TB is facultatively intracellular so need cell-mediated to get at them - primary infection with TB can be either
- asymptomatic/subclinical pulmonary infection, symptomatic Tb (children, elderly, HIV) or overt or manifest primary TB(really bad, draining caseating granulomas, cavitary lesions visible on CXR)
- primary infection tb
- inhale enters macros goes throughout body tcell response eventually activated, get recruitment of macros -> tissue destruction, caseating granulomas in which viable organisms can live indefinitely walled off.
- hm
- hmmmm
- secondary often starts why?
-
immunocompromise
- can i add cards now
- ???