Antimycobacterials

Question 1

What are the risk factors associated with TB?

Answer 1

• low socioeconomic status
• TB-endemic areas
• travel
• immunocompromised

Question 2

What are common challenges for treating TB?

Answer 2

• Only active form is susceptible to drug therapy
• Slow growing, long drug therapy
• Harder to treat longer it’s been around
• limited compliance with long treatment

Question 3

What are the most common first-line drugs for treating TB?

Answer 3

Isoniazid, Rifampin, Ethambutol, Pyrazinamide, and Steptomycin

Question 4

How is isoniazid selective to TB?

Answer 4

Isoniazid is a prodrug and is activated by TB-produced catalase-peroxidase (KATG), which the active form targets enoyl-acyl carrier protein - preventing fatty acid elongation and formation of myocolic acid (InhA).

Question 5

What are the different ways Isoniazid is used?

Answer 5

Used in combination with other drugs to treat an active infection.
Used independently to treat latent TB

Question 6

How can polymorphisms effect metabolism of Isoniazid?

Answer 6

N-acetylation metabolism - slow metabolizers can have increased side effects and rapid metabolizers might need a higher dose.

Question 7

What are common side effects of Isoniazid?

Answer 7

Neurotoxicity - peripheral neuritis

Hepatotoxicity - increased with age and other TB drugs

Question 8

What antibiotic inhibits DNA-dependent RNA polymerase?

Answer 8

Rifampin - Bactericidal

Question 9

What is a major problem with using Rifampin?

Answer 9

Potent inducer of cytochromes, causes significant drug interactions. Always used in combination with others in therapies. Hepatotoxicity worse in older population.

Question 10

What drug can cause an orange color to urine, feces, tears, and sweat?

Answer 10

Rifampin

Question 11

What antibiotic is TB-static and blocks synthesis of cell wall?

Answer 11

Ethambutol

Question 12

What is the mechanism of Ethambutol?

Answer 12

Interferes with arabinosyl transferase blocking cell wall synthesis. Bacterial-static

Question 13

What are the side effects of Ethambutol?

Answer 13

Optic neuritis - causing visual effects, unable to differentiate red from green
–Not Hepatotoxic–

Question 14

What drug is only typically used in short term therapy?

Answer 14

Pyrazinamide

Question 15

How does Pyrazinamide work?

Answer 15

Blocks synthesis of mycolic acid by inhibiting fatty acid synthase I. Bacteriacidal

Question 16

What is a problem with using Pyrazinamide in combination with other drugs, especially Rifampin?

Answer 16

Hepatic Damage, increased severity when used with other drugs like Rifampin

Question 17

What drug is typically reserved for serious TB infections only?

Answer 17

Streptomycin due to causing Ototoxicity and Nephrotoxicity

Question 18

How does Streptomycin work against TB?

Answer 18

Binds to the 30S/50S complex, stops intiation and causes misreading

Question 19

What are the typical guidelines for treating an active TB uncomplicated?

Answer 19

Isoniazid + Rifampin for ~6 months, sometimes with Pyrazinamide for 2 months

Question 20

What would be the course if the TB was disseminated?

Answer 20

Isoniazid + Rifampin 9months-years, and Pyrazinamide and Ethambutol for first 2 months

Question 21

What single agent drug would be used to prevent MAC infection in an AIDS patient?

Answer 21

Rifabutin - similar to Rifampin, except less hepatotoxicity and induction of cytochromes

Question 22

What two drugs can be used to treat a MAC infection in an AIDS patient?

Answer 22

Clarithromycin in combination and Rifabutin in combination

Not used together

Question 23

What drug has a similar mechanism as sulfa-drugs that is used to treat Leprosy?

Answer 23

Dapsone - inhibits folic acid synthesis

Question 24

What drug can also prevent and treat Pneumocysitis jiroveci in AIDS patients?

Answer 24

Dapsone

Question 25

What are common side effects of Dapsone?

Answer 25

Hemolytic Anemia and Methloglobinemia

Question 26

What leprosy agent typically causes a build up of brown-red pigmentation?

Answer 26

Clofazimine

Question 27

What drug is typically used with Dapsone to treat Laprosy?

Answer 27

Rifampin