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30 Cards in this Set

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How do you test someone for TB?
Tuberculin skin test (TST)

A "purified protein derivative" (PPD) prepared from M. tuberculosis is injected s.c. and the skin response to this immune challenge is "read" over the next few days
What does a positive PPD mean?
--It is a positive response to challenging of the immune system with TB proteins
--reflects T cell-mediated immunity against M. tuberculosis
--is characterized by a type IV, delayed HS reaction

-- CANNOT differentiate latent infection from active infection

-- means that patient has TB
What must be present for a PPD to be positive?
Induration of the tissue -- hardening of normally soft tissue due to inflammation or infiltration
What size induration does one need to have?
--greater or equal to 5mm is positive in a patient with HIV

--greater or equal to 15mm is required for a test to be positive in a person with no risk factors
If I have a TST and no one can decide if it is positive or negative, can I be retested with the PPD two weeks later?
Recent exposure to PPD will "boost" someone's response who is infected but will NOT convert someone with a negative response to a positive response if that person has never had TB

-- two separate screenings are actually recommended for health care workers who may have a latent infection
Does prior inoculation with BCG vaccine cause a patient to exhibit a positive PPD?
Reactions of 5-10mm may be seen in persons who have received BCG but unless a vaccination was very recent a reaction >10mm should NOT be attributed to a prior vaccination with BCG.
What drugs do we use to treat TB?
Rifampin
Rifabutin
Isoniazid
Pyrazinamide
Ethambutol
**RIPE**
Streptomycin
Isoniazid (INH) MOA?
-- Prodrug converted to it's active form by the mycobacterial catalase peroxidase
-- Active INH metabolite prevents synth of mycolic acid, a long-chain f.a. needed to maintain integrity of Mycobact cell wall
-- Synth of mycolic acid prevented because active INH matabolite binds covalently to acyl carrier protein and the B-ketoacyl carrier protein synthetase

--Bacteriostatic for latent Mycobact but kills bacilli which are dividing rapidly
INH therapeutic use?
- first obligatory drug therapy for TB!

- never used as single agent in treatment because of rapid development resistance

- used as a single agent to treat patients PPD+ but negative CXR

- without treatment, 5-15% will develop tubercular disease at some time in their life
INH toxicity?
- metabolized by hepatic N-acetylation and "slow" acetylarots at increased risk for hepato- and neurotoxicity
INH hepatotoxicity?
-- up to 20% patients on INH have 3-4x increase in ALT and AST, but increases in LFTs of this magnitude do NOT necessitate discontinuation of INH
--about 1% of patients can develop severe hepatitis w/ jaundice, URQ pain, n/v
--drug must be d/c to prevent death

--Risk of clinically signif hepatitis is small
--If patient is >35y.o. and date of seroconversion unknown, do NOT use INH, treat with rifampin

--EtOH intake increases hepatotoxicity
INH neurotoxicity?
--structurally similar to pyridoxine (Vitamin B6) and antagonizes reactions which use pyridoxine as cofactor
--peripheral neuropathy caused by INH closely resembles neuropathy caused by pyridoxine deficiency (axonal sensorimotor deficiency)
-- usually preceeded by paresthesias of hands and feet
-- treatment with daily dose Vitamin B6 prevents and reverses neuropathy
Rifampin and rifabutin MOA?
--inhibit RNA synth by ninding B-subunit of bacterial DNA-dep-RNA-pol (drugs do NOT bind human RNApol)
--both drugs are bactericidal and they easily penetrate tissues to kill intracellular mycobacteria as well as bugs hiding in abscessses
Rifampin therapeutic use?
***second obligatory drug for TB
--never used as single agent in treatment of active TB b/c of quick resistance development
--strong inducer of CYP450 and enhances hepatic clearance of drugs used to treat HIV infections (protease inhibitors and NNRTIs)
--drug regimens which include rifambin clear sputum of mycobact about two weeks faster than those w/o
--can be used as alternative for INH in TB prophylaxis
**also active against meningococci, pneumococci, and staph
-eliminates meningococcal carrier state
- active against MRSA
- active against PCN-resistant strep pneumo
Rifabutin therapeutic use?
Can replace rifampin when needed

**causes about 50% of the CYP induction caused by rifampin, so use in HIV patients
Rifampin toxicity?
--urine, skin, saliva, tears turn orane and soft contact lenses can be perm discolored
--flu-like syndrome
--hepatitis w/ elevated LFT but usually disappear w/ continued treatment
--DRUG-DRUG interactions - strongly induces all CYP450 isozymes so increases hepatic clearance of many other drugs
Rifampin and INH with pregnancy?
they are category C -- benefit should strongly outweigh the risk
Rifabutin toxicity?
--harmless yellow discoloration of skin
--polymyalgias
--uveitis
Pyrazinamide MOA?
unknown; but kills semidormant, intracellular bacilli in macrophages
Pyrazinamide therapeutic use?
--NEVER used as single agent in treatment - resistance

--50% of isolates resistant to INH-rifampin are resistant to PZA
--used as third drug with INH-rifampin
Pyrazinamide toxicity?
--n/v
--hepatotoxicity (1-5%)
--no clinically signif drug-drug interactions
Ethambutol MOA?
--ihnibits arabinosyl transferase, an enzyme which polymerizes arabinoglycan
--arabinoglycan is essential component of bacterial wall, so it inhibits wall synth
--"PCN" for mycobact
Ethambutol therapeutic use?
--NEVER as single agent

--used as fourth in INH-Rifampin-PZA

--up to 80% of isolates resistant to INH-rifampin are resistant to EMB
Ethambutol toxicity?
1. Ocular damage -- serious retinobulbar neuritis which results in impaired vision and abnorm red/green vision
--must have basal vision exam and follow-up exams q4-6 wks

2. No clinically signif drug-drug interactions
streptomycin MOA?
An aminoglycoside antibiotic drug, so it inhibits bacterial protein synth

Acts primarily against extracellular bacilli
Streptomycin and TB?
Given i.m. or i.v. to treat patients with mycobact meningitis or disseminated infection

Up to 80% isolates resistant to INH-rifampin are resistant to streptomycin

Streptomycin-resistant isolates may be susceptible to the generic amikacin

Streptomycin sometimes replaces EMB in the INH-rifampin-PZA regimen
Streptomycin toxicity?
--exerts greater vestibular toxicity compared to other aminoglycosides = vertigo and loss of balance
--exerts less auditory and renal toxicity
Treatment of MDR active TB?
ciprofloxacin and levofloxacin

moxifloxacin shows the greatest activity versus TB

(all of those are FQs)
How long do you treat a patient with TB?
RIPE for 9 months

All four drugs for one month while susceptibility testing
TB chemoprophylaxis?
In recent PPD converters (last two years), treatment with 300mg ING daily for 9 months reduces prob of developing active disease by 50%

--avoid EtOH intake because it increases hepatotoxicity probability