As per original post: Of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) for the management of tuberculosis:
Step 1 level:
1) Which are notably hepatotoxic? --> RIP (Rest In Peace); rifampin more so, which is why isoniazid is the monoprophylaxis for TB (9 months) over rifampin (although this can sometimes be given as monoprophylaxis for 4 months)
2) Which are known to cause gout? --> pyrazinamide, ethambutol
3) Which causes innocuous orange secretions/urine? --> rifampin ("rusty" contact lenses, orange urine/sweat)
4) What are the MOAs of all four drugs? --> Rifampin: DNA-dependent RNA polymerase; INH: inhibits mycolic acid synthesis; pyrazinamide: inhibits fatty acid synthase I; ethambutol: inhibits arabinosyl transferase
5) Which one is toxic to the visual system? What signs/symptoms are seen? --> ethambutol; red-green color blindness, central scotoma, optic neuritis
6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency? --> INH causes B6 (pyridoxine) deficiency; seizures, peripheral neuropathy, paresthesias (yes, B6 deficiency causes other things, but this is the stuff seen with INH use, notably in USMLE questions)
7) Why does the drug in #6 cause this vitamin deficiency? --> Inhibits pyridoxal kinase (enzyme normally phosphorylates and activates B6)
8) Why does that vitamin deficiency cause those symptoms/signs? --> B6 is a cofactor for decarboxylase reactions; glutamic acid --> GABA via glutamic acid decarboxylase; so decreased GABA is thought to contribute
9) Which drug works best against TB that's
already been phagocytosed? And why? --> pyrazinamide is best drug within the acidic pH of phagolysosomes, meaning it works best against TB already phagocytosed by alveolar macrophages
10) What type of hypersensitivity is the PPD test? --> IV; T-cell-mediated
11) Which drug upregulates P-450; which inhibits it? --> rifampin induces; INH inhibits
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Step 2CK level (19 and 21 overlap with Step 1):
12) When do you give prophylaxis versus full-on Tx? And what are the durations of drug therapy? --> a + PPD but negative CXR indicates latent disease and the need for prophylaxis; full-on Tx is if the PPD was + then you went on to do the CXR and that also was positive, meaning active disease; prophylaxis is 9 months INH generally; Tx is 2 months RIPE then an additional 4 months of just rifampin + INH; if the pt has TB osteomyelitis, miliary TB, TB meningitis, or is pregnant, extend the 6 months to 9 months by continuing RI 3 more months
13) Which is the preferred monoprophylaxis? How long do you give it for? --> As per above, INH for 9 months is standard; rifampin can also be used for 4 months, but isn't first-line
14) If you get a + PPD test, what's the next thing you do? --> CXR always; rarely the BCG vaccine can cause false positives if in close temporal proximity, so if the pt has had a BCG then the interferon gamma release assay is a good way to pick up TB exposure; IFN-g release assay is unaffected by the BCG.
15) If you get a - PPD test, what's the next thing you do? --> repeat it 1-2 weeks later
if the patient has risk factors (e.g., known exposure or emigration from endemic area); the immune system can sometimes show attenuated response to TB over time in someone who's had exposure
16) When is a PPD test considered positive? --> firstly, if a PPD is +, a second test is never correct; a + PPD means the person has had exposure; one measures the induration (elevation) secondary to the PPD, not the erythema; guidelines for what is considered a + test have varied; what is known however is that using a cutoff of 15 mm brings sensitivity to ~98%; at 10 mm the sensitivity is ~90%; at 5 mm the sensitivity is 50-60% (those figures are all from UpToDate); therefore one has to consider the risk factors as very substantial; the USMLE is geared toward: someone with absolutely no risk factors, 15+ mm is +; in healthcare workers, prisoners, immigrants, and those with chronic disease (e.g., COPD, renal disease), 10+ is +; in someone with recent exposure, calcifications on CXR, or significant immunosuppression (e.g., chronic steroid use, HIV/AIDS, organ transplant recipient), 5+ is +. Once again, these cutoffs vary depending on the source you read, and one should subjectively consider a patient's risk factors.
17) What's the TB vaccine called and when is it given? --> BCG; generally in endemic areas; if given before the age of 1, it will almost never cause a false-positive PPD in someone over age 10; if given after age 1, the false-positive rate varies; that's why IFN-g release assay is good in prior BCG recipients
18) If a person previously vaccinated against TB has a + PPD later on, what do you do? --> you generally hear that prior BCG should not impact the interpretation of the PPD; but now that we have the IFN-g release assay, which is not affected by the BCG, we'd do that. CXR is always the answer though any time a PPD comes back +
19) Which pneumoconiosis notably increases the risk of TB? --> silicosis; supposedly SiO2 disrupts alveolar macrophage function
20) How many people in the world have been exposed to TB? --> two billion; I know, the number sounds outrageous and absurdly high/wrong, so just so anyone doesn't freak out I've gone to UpToDate to quote it here: "GLOBAL BURDEN — More than two billion people (about one-third of the world population) are estimated to be infected with
M. tuberculosis [
2]. The global incidence of tuberculosis (TB) peaked around 2003 and appears to be declining slowly [
3]. According to the World Health Organization (WHO), in 2013, 9 million individuals became ill with TB and 1.5 million died [
4]." --> So whilst two bilion have been exposed, those who actually develop active disease are probably ~9-10 million per year.
21) There are certain drugs that can increase the risk of TB - which class notably? --> TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab); abatacept (CD80/86 inhibitor)
