51-Antimycobacterial Drugs

Question 1

Recommended Treatment regimen for active TB?

Answer 1

Preferred regimen: Daily INH, RIF, PZA, and EMB for 8 weeks then either daily or twice weekly INH and RIF for 18 weeks

Question 2

Alternative treatments for active TB

Answer 2

Alternative #1: Daily INH, RIF, PZA, and EMB for two weeks then twice weekly for six weeks. Then INH and RIF twice weekly for 18 weeks.

Alternative #2: Thrice-weekly INH, RIF, PZA, and EMB for 8 weeks. Then INH and RIF thrice weekly for 18 weeks.

Question 3

What is the most active drug in the treatment of TB (active and latent)?

Answer 3

Isoniazid (INH)

Question 4

Recommended treatment regimen for latent TB?

Answer 4

Isoniazid for 9 months (either daily or twice weekly)

Question 5

What makes Isoniazid particularly potent against TB infections?

Answer 5

It penetrates macrophages so it is effective against extracellular and intracellular organisms.
It also readily penetrates CNS.

Question 6

Isoniazid mechanism of action?

resistance?

Answer 6

Inhibits synthesis of mycolic acid for cell wall. Prodrug is activated by mycobacterial Kat G enzyme.
Resistance if mutation in Kat G or overexpression of Inh A protein involved in mycolic acid synthesis

Question 7

When does Isoniazid pose a toxicity threat?

Answer 7

In people that are slow acetylators (inactivators). It is acetylated in the liver, bowel, and kidney

Question 8

What are the most significant adverse effects of Isoniazid?

Answer 8

Liver toxicity causing hepatitis. People at an increased risk are older or alcohol dependants.
Peripheral neuropathy can occur in slow acetylators and patients who are malnourished, alcoholic, diabetic, or AIDS

Question 9

Rifampin mechanism of action?

Answer 9

inhibits RNA synthesis by binding bacterial DNA dependent RNA polymerase. (also effective at killing intracellular bacteria)

Question 10

Resistance to Rifampin?

Answer 10

point mutations in the bacterial RNA polymerase gene are very common (1 in 10^6)

Question 11

Adverse effects of Rifampin?

Answer 11

GI, nervous system.
Hepatitis (most common with underlying liver disease and slow INH acetylators (combo therapy).
Also red-orange color in secretions (harmless)

Question 12

Rifampin drug-drug interactions?

Answer 12

Induces Cytochrome P450 which metabolizes many drugs including antiretroviral drugs. Thus, in HIV infected patients use rifabutin as a substitute!

Question 13

Pyrazinamide mechanism of action?

Answer 13

Prodrug is converted by bacterial enzyme and inhibits mycolic acid synthesis. Requires an acidic environment so works well against intracellular bacteria in macrophage lysosomes.

Question 14

Resistance to Pyrazinamide?

Answer 14

mutation in the pyrazinamidase enzyme

Question 15

Adverse effects of Pyrazinamide?

Answer 15

Hepatotoxicity, hyperuricemia (small percent gouty arthritis)

Question 16

Ethambutol to treat what?

Answer 16

Used for active TB and M. avium bacteria.

Question 17

Ethambutol mechanism of action?

Answer 17

Inhibits cell wall synthesis by arabinosyl transferases. Resistance with point mutations in genes encoding arabinosyl transferases.

Question 18

Adverse reactions to Ethambutol?

Answer 18

Retrobulbar neuritis or red-green colorblindness (both reversible) and hyperuricemia

Question 19

Streptomycin
(mechanism)
(resistance)
(adverse)

Answer 19

injectable that interferes with bacterial protein synthesis at 30S ribosome
point mutations in ribosome proteins
ototoxic/nephrotic

Question 20

Rifabutin

Answer 20

used in the treatment of HIV infected patients because it doesn’t induce the CYP450 metabolism as much as rifampin.
Also has a greater efficacy against MAC organisms than rifampin

Question 21

M. avium complex (MAC) treatment

Answer 21

Macrolide antibiotic
rifampin
ethambutol
streptomycin (+ or -)

for disseminated just top 3, pulmonary consider adding streptomycin

Question 22

Treatment of leprosy

Answer 22

dapsone, clofazimine, and rifampin multidrug therapy. 1-2 years for tuberculoid, 5 years for lepromatous!

Question 23

Dapsone mechanism and adverse

Answer 23

competitive inhibitor of folic acid synthesis (PABA analog)
can induce non-hemolytic anemias in some, and acute hemolytic anemia in people with G-6-P deficiency
(half-life 1-2 days, but high concentrations can remain in skin, liver and kidney for weeks after discontinuation)

Question 24

Clofazamine

Answer 24

bactericidal dye

causes skin discoloration