Anti-Mycobacterial Drugs (Tuberculosis/Leprosy/MAC)

Question 1

What is the cause of Mtb-mediated tissue injury and death?

Answer 1

HOST immune response of inflammation [CASEOUS NECROSIS]
NOT the specific toxin
Inflammation and host self-death in attempt to control intracellular bacterial growth

Question 2

Most commonly recovered NON-TB, nonpathogenic Mycobacterium species __
Where is it found?

Answer 2

M. gordonae

Soil/Water

Question 3

Greatest diagnostic test to diagnose Mtb

Answer 3

NAAT - Greater sensitivity and greater specificity than the conventional smear or culture

Question 4

Difference between LTBI (latent tb infection) therapy versus active TB disease

Answer 4

LTBI - can use single or multi drug therapy

Active TB - ALWAYS use multi drug

Question 5

Which first line drug targets arabinogalactan of the MYCOBACTERIAL cell wall AND is particularly effective against fast-growing EXTRACELLULAR Mtb?

Answer 5

Ethambutol (EMB)

Question 6

3 Drugs that target mycolic acid of MYOBACTERIAL cell wall

Answer 6

FIRST-LINE: INH (isoniazid)

SECOND-LINE: PAS (p-aminosalicylic acid) + ETA (ethionamide)

Question 7

Which first line drug inhibits the large subunit of RNA polymerase and inhibits RNA synthesis (release of nascent RNA) [particularly effective against slow-growing INTRACELLULAR Mtb]?

Answer 7

Rifampin

Question 8

Which first line drug inhibits protein synthesis in DORMANT bacteria

Answer 8

Pyrazinamide

Question 9

Which two first line anti-mycobacterial drugs are used for prophylactic treatment?

Answer 9

Rifampin

Isonozaid

Question 10

Which two first line and one second-line drug are anti-mycobacterial pro-drugs? (Necessitate activation by bacteria for the drug to be effective)

Answer 10

Isoniazid
Pyrazinamide

PAS

Question 11

Active form of INH (isoniazid)?
What bacterial enzyme mediates this conversion?
What does it target?

Answer 11

INH-NAD
Conversion by bacterial KatG (catalase-peroxidase)
Targets the Fab1 (InhA) of FASII - enzyme that elongates mycolic acid of the cell wall

Question 12

Main side effect of INH _
Why? _
Management of this side effect _

Answer 12

Peripheral neuropathy
Due to pyridoxal deficiency (INH looks structurally similar to VitB6)
Management by VitB6 supplementation

Question 13

Non-toxic side effect of rifampin on excreted body fluids (urine, sweat, tears)

Answer 13

Harmless purple/red in these fluids

Question 14

Toxic side effects of rifampin

Answer 14

1) Flu-like symptoms
2) Induces CYP3A -> Increases elimination of other drugs
3) Can penetrate into CSF is patient also has meningitis

Question 15

Advantages of rifabutin + Rifapentine over rifampin (RIF)

Answer 15

1) Higher potency
2) Longer half life
3) Greater membrane permeability - can infiltrate macrophages more easily
4) Less CYP3A induction -> Less excretion of other drugs (better if the patient is taking other medications such as anti-arrhythmic agents/HIV)

Question 16

Active form of pyrazinamide __

What does the active form bind?

Answer 16

POA - pyrazinoic acid
Binds RpsA [ribosomal protein S1]
which inhibits S1 from binding tmRNA -> Prevents trans-translation mechanism -> Prevents rescue of stalled ribosomes -> Accumulation of misfolded peptides that do not get sent for degradation ->
DORMANT bacteria can not survive under these stressful conditions

Question 17

Which anti-mycobacterial first-line drug should you NOT administer to children younger than 5yrs old? Why?

Answer 17

Ethambutol

Optic neuritis + Red-green color blindness

Question 18

Treatment of MAC infection

Answer 18

MACROLIDES: Azithromycin + Clarithromycin

May also use ciprofloxacin, ethambutol and rifabutin

Question 19

Who is most at risk for Mtb progression (reactivation/reinfection)? Why?

Answer 19

HIV - immunocompromised patients who do not have CD4+ Th cells to mediate cell-mediated immunity in the Langerhan giant cells - Can not contain bacteria because they can not form the granuloma around the bacteria (tubercle bacilli)