TB and other fungi Flashcards
What type of stain do you use for TB?
Acid Fast staining
How is TB spread?
inhalation of droplet nuclei
What allows the TB mycobacteria to clump together?
Cord Factor
what type of granules are seen in TB infections?
Caseating granules
What is Pott Disease?
Pott Disease is TB that affects verteral bodies and presents as chronic back pain
What is the Ghon Complex?
a parenchymal lesion and nodal involvement
What is it called when the Ghon complex progresses to fibrosis and radiological calcification?
Ranke process
Trigger words for TB:
Acid Fast Cord Factor Droplet nucleii Caseous necrosis BCG vacine PPD Gohn focus
what type of media do you culture TB in?
Lowenstein-Jensen (egg based)
What are the first line treatments of TB?
RIPE
Isoniazid- inhibits mycolic acid during cell wall synthesis
Rifampin- Inhibits DNA-dependent RNA polymerase
Pyrazinamide-unclear
Ethambutol Inhibits arabinogalactan during cell wall synthesis
Isoniazid
1) MOA
2) Major Side Effects
Isoniazid
1) MOA: inhibits mycolic acid during cell wall synthesis
2) Major Side Effects: Hepatotoxicity, SLE-like syndrome; vitamin B6 deficiency (peripheral neuropathy sideroblastic anemia) CYP450 inhibitor
What is the most frequent major side effect of Isoniazid?
The most frequent major toxic effect of isoniazid is hepatitis. Symptoms include a loss of appetite, nausea, vomiting, jaundice, and RUQ pain.
Patients should be monitored monthly and isoniazid should be discontinued if symptoms of drug induced hepatitis develop
convulsions, hyperirritability, peripheral neuropathy, and sideroblastic anemia are caused by a deficiency in what? This is a side effect of what drug?
Convulsions, hyperirritability, peripheral neuropathy, and sideroblastic anemia are caused by a deficiency in B6 (pyridoxine) caused by isoniazid
How does isoniazid cause pyridoxine deficiency?
1) pyridoxine metabolites directly attach to and inactivate pyridoxine
2) isoniazid inhibits the enzyme pyridoxine phosphokinase which is necessary to catalyze the synthesis of pyridoxal 5’ phosphate from phridoxine. pyridoxal 5’ phosphate is a co-factor in many reactions
What are the 4 R’s of Rifampin?
RNA polymerase inhibitor
Ramps up microsomal CYP450 (CYP450 inducer)
Red/Orange body fluids
Rapid resistance if used alone
Does it matter if a person with TB is co-infected with HIV?
Yes. HIV patients are susceptible to active TB infections.
The first line drug, rifampin, is a strong CYP450 inducer and will decrease the concentration of anti-HIV drug levels (NNRTIs and PI)
Use Rifabutin instead- it has the same MOA, but is a less potent CYP450 inducer
What is the MOA for pyrazinamide?
Sucker. We don’t know.
Mutations in what gene cause resistance to pyranzinamide?
pncA
pncA converts pyrazinamide to its active form pyranzinoic acid.
Which drug(s) work in the acidic environment of the macrophages?
Pyrazinamide works in the acidic environment of the lysosomes of macrophages.
gouty arthritis can be provoked by what TB drug?
Pyranzinamide causes hyperuricemia (high serum uric acid levels) which may provoke acute gouty arthritis
Ethambutol also causes hyperuricemia by decreasing renal uric acid excretion but this is to a much lesser degree than pyranzinamide
What is the mechanism of action of Ethambutol?
Ethambutol inhibits mycobacterial arabinosyl transferases (those encoded by the embB gene).
Arabinosyl transferases are involved in arainogalactan polymerization which as an essential component of the mycobacterial cell wall.
Resistance to Ethambutol occurs when there are mutations resulting in overexpression of the embB gene or overexpression of its products
What are the clinical indications for ethambutol?
Ethambutol can be used in combination with isoniazid or rifampin (+/-) pyrazinamide for treatment of active TB.
Higer doses can be used for tuberculosus meningitis and can also be used for atypical mycobacterial infections
A TB patient has been taking a drug for 6 months. He has recently had trouble distinguishing the colors red and green. What drug is he taking?
Ethambutol
Ethambutol can cause optic neuritis causing a loss of visual acuity and red-green color blindnes. It is relatively contraindicated for use in young children
what are the second line drugs for treating TB?
Streptomycin
and other antibiotics
what is the MOA for streptomycin?
How about side effects?
Streptomycin binds to the 30S ribosome and inhibits protein synthesis.
Streptomycin can cause ototoxicity, nephrotoxicity, and is teratogenic
mycobactrium leprae
Treatment:
Tuberculoid form:
Lepromatous form:
Tuberculoid form: combination of dapsone and rifampin (6-12 month course)
Lepromatous form: dapsone, rifampin, and clofazimine (12-24 months)
Dapsone:
MOA:
Clinical use:
Side Effects:
Dapsone:
MOA: inhibits folate synthesis by targeting the enzyme dihydropteroate synthase
Clinically used in hte treatment of mycobacterium leprae, prevent and treat pneumonitis jiroveci and pneumonia in AIDS patients
Dapsone is well tolerated. Do not use in pts with sulfa drug allergies. May cause hemolytic anemia in patients with a G6PD deficiency
Clofazimine
MOA:
Clinical Use
Side effects:
Clofazimine
MOA: unclear
Clinical Use: leprosy
Side effects: discoloration of skin andd conjunctiva
GI problems including abdominal pain, diarrhea, nausea, and vomiting
