TB and other fungi

Question 1

What type of stain do you use for TB?

Answer 1

Acid Fast staining

Question 2

How is TB spread?

Answer 2

inhalation of droplet nuclei

Question 3

What allows the TB mycobacteria to clump together?

Answer 3

Cord Factor

Question 4

what type of granules are seen in TB infections?

Answer 4

Caseating granules

Question 5

What is Pott Disease?

Answer 5

Pott Disease is TB that affects verteral bodies and presents as chronic back pain

Question 6

What is the Ghon Complex?

Answer 6

a parenchymal lesion and nodal involvement

Question 7

What is it called when the Ghon complex progresses to fibrosis and radiological calcification?

Answer 7

Ranke process

Question 8

Trigger words for TB:

Answer 8

Acid Fast Cord Factor Droplet nucleii Caseous necrosis BCG vacine PPD Gohn focus

Question 9

what type of media do you culture TB in?

Answer 9

Lowenstein-Jensen (egg based)

Question 10

What are the first line treatments of TB?

Answer 10

RIPE

Isoniazid- inhibits mycolic acid during cell wall synthesis

Rifampin- Inhibits DNA-dependent RNA polymerase

Pyrazinamide-unclear

Ethambutol Inhibits arabinogalactan during cell wall synthesis

Question 11

Isoniazid

1) MOA
2) Major Side Effects

Answer 11

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

Question 12

What is the most frequent major side effect of Isoniazid?

Answer 12

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

Question 13

convulsions, hyperirritability, peripheral neuropathy, and sideroblastic anemia are caused by a deficiency in what? This is a side effect of what drug?

Answer 13

Convulsions, hyperirritability, peripheral neuropathy, and sideroblastic anemia are caused by a deficiency in B6 (pyridoxine) caused by isoniazid

Question 14

How does isoniazid cause pyridoxine deficiency?

Answer 14

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

Question 15

What are the 4 R’s of Rifampin?

Answer 15

RNA polymerase inhibitor

Ramps up microsomal CYP450 (CYP450 inducer)

Red/Orange body fluids

Rapid resistance if used alone

Question 16

Does it matter if a person with TB is co-infected with HIV?

Answer 16

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

Question 17

What is the MOA for pyrazinamide?

Answer 17

Sucker. We don’t know.

Question 18

Mutations in what gene cause resistance to pyranzinamide?

Answer 18

pncA

pncA converts pyrazinamide to its active form pyranzinoic acid.

Question 19

Which drug(s) work in the acidic environment of the macrophages?

Answer 19

Pyrazinamide works in the acidic environment of the lysosomes of macrophages.

Question 20

gouty arthritis can be provoked by what TB drug?

Answer 20

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

Question 21

What is the mechanism of action of Ethambutol?

Answer 21

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

Question 22

What are the clinical indications for ethambutol?

Answer 22

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

Question 23

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?

Answer 23

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

Question 24

what are the second line drugs for treating TB?

Answer 24

Streptomycin

and other antibiotics

Question 25

what is the MOA for streptomycin?

How about side effects?

Answer 25

Streptomycin binds to the 30S ribosome and inhibits protein synthesis.

Streptomycin can cause ototoxicity, nephrotoxicity, and is teratogenic

Question 26

mycobactrium leprae

Treatment:

Tuberculoid form:

Lepromatous form:

Answer 26

Tuberculoid form: combination of dapsone and rifampin (6-12 month course)

Lepromatous form: dapsone, rifampin, and clofazimine (12-24 months)

Question 27

Dapsone:

MOA:

Clinical use:

Side Effects:

Answer 27

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

Question 28

Clofazimine

MOA:

Clinical Use

Side effects:

Answer 28

Clofazimine

MOA: unclear

Clinical Use: leprosy

Side effects: discoloration of skin andd conjunctiva

GI problems including abdominal pain, diarrhea, nausea, and vomiting