Tuberculosis

Question 1

Why are Mycobacteria resistant to most antibiotics?

Answer 1

• grow more slowly than other bacteria
• dormant, lipid-rich cell wall is impermeable to many agents
• intracellular pathogens residing in macrophages
• combinations of two or more drugs are required

Question 2

First- line agents

Answer 2

• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol

Question 3

Most active drugs

Answer 3

Isoniazid and Rifampin

Question 4

4 drugs which are usually combined

Answer 4

Isoniazid
Rifampin
Pyrazinamide - when this is combined it allows the duration of treatment to last 6 months
Ethambutol

Question 5

Isoniazid

• mechanism of action (4)
• basis of resistance

Answer 5

• bactericidal against growing tubercle bacilli
• penetrates into macrophages and is active against both extracellular and intracellular organisms
• penetrates caseous lesions
• inhibits synthesis of mycolic acid
• prodrug

-katG mutants express high level isoniazid resistance

Question 6

Isoniazid

• pharmacokinetics (3)
• drug interactions

Answer 6

• readily absorbed from GI tract; diffuses readily into all body fluids and tissues
• acetylation by liver N-acetyl transferase
• rapid and slow acetylators

-reduce the metabolism of phenytoin (increase its blood level and toxicity)

Question 7

Isoniazid

-unwanted effects

Answer 7

• hepatitis
• peripheral neuropathy
• CNS toxicity

Question 8

Rifampin

• mechanism of action
• basis of resistance

Answer 8

• binds to beta subunit of bacterial DNA dependent RNA polymerase and thereby inhibits RNA synthesis
• reduced binding to RNA polymerase

Question 9

Rifampin

• pharmacokinetics (3)
• drug interactions

Answer 9

• well absorbed

- strongly induces most cytochrome P450 isoforms, increases the elimination of numerous drugs

Question 10

Rifampin

-unwanted effects

Answer 10

-orange color to urine, sweat and tears

Question 11

Ethambutol

-mechanism of action

Answer 11

-inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon; arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall

Question 12

Ethambutol

• pharmacokinetics
• unwanted effects

Answer 12

• well absorbed, 50% excreted in urine in unchanged form

- retrobulbar neuritis

Question 13

Pyrazinamide

• mechanism of action
• basis of resistance

Answer 13

• converted to pyrazinoic acid by mycobacterial pyrazinamidase
• pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions

-no cross-resistance with other antimycobacterial drugs

Question 14

Pyrazinamide

• pharmacokinetics
• unwanted effects

Answer 14

• well absorbed

- hepatotoxicity, hyperuricemia

Question 15

Streptomycin

• mechanism of action
• pharmacokinetics

Answer 15

• aminoglycozide

- used when an injectable drug is needed or desirable and in the treatment of infections resistant to other drug

Question 16

Streptomycin

-unwanted effects

Answer 16

• ototoxic

- nephrotoxic