Antimycobacterials

Question 1

First line antimycobacterial drugs:

Answer 1

ethambutol, isoniazid, pyrazinamide, rifampin, rifabutin, refapentine

Question 2

Mycobacteria morphology

Answer 2

rod-shaped bacteria with unusually waxy cell walls containing mycolic acid (fatty acids)

Question 3

What do mycobacteria infections result in?

Answer 3

slow-growing, granulomatous lesions that cause tissue destruction and become resistant to antibiotics easily

Question 4

T/F mycobacteria are resistant to most antibiotics

Answer 4

true

Question 5

What are characteristics of mycobacteria?

Answer 5

grow slowly, can be dormant, cell wall impermeable to many drugs, intracellular pathogens, can develop resistance

Question 6

What is the most widely encountered mycobacterial infection? (and leading cause of death from infection)

Answer 6

tuberculosis

Question 7

What action of tuberculosis is responsible for pulmonary tissue distruction?

Answer 7

granulomatous lesions

Question 8

What mycobacterium condition is treated in a similar way to tuberculousis?

Answer 8

leprosy

Question 9

What organism causes tuberculosis and where is the most common site of infection?

Answer 9

Mycobacterium tuberculosis, lungs

Question 10

How long does it take to treat tuberculosis?

Answer 10

months to years, partially because of delayed diagnosis

Question 11

Why does TB become resistant quickly?

Answer 11

prior treatment and pt failure to adhere to protocol

Question 12

What is characteristic of a latent TB infection?

Answer 12

no symptoms, noninfectious, positive TB skin test, should be treated

Question 13

What is characteristic of an active TB infection?

Answer 13

patient is sick (chest pain, cough, weakness, fatigue, weight loss), can be spread, more aggressive treatment

Question 14

How many people worldwide are infected with TB and how many die each year?

Answer 14

1/3 of the world’s population, 2 million die

Question 15

What are strategies for addressing drug resistance of TB?

Answer 15

multi-drug therapy that is continued well beyond the disappearance of clinical disease

Question 16

What is directly observed therapy?

Answer 16

patient reports to doctor’s office for medication, increases compliance and decreases mortality rates

Question 17

Which agent is the most potent?

Answer 17

isoniazid

Question 18

What is Isoniazid’s MOA?

Answer 18

bactericidal, inhibits mycolic acid synthesis in the cell wall (resistance develops quickly if used alone)

Question 19

Describe the development of resistance to isoniazid

Answer 19

associated with several chromosomal mutations (cross resistance does not occur)

Question 20

What is isoniazids pharmacokinetics?

Answer 20

readily absorbed orally but impaired with food, effective against intracellular bacteria, metabolized by P450 (liver), excreted by kidney

Question 21

What are the adverse effects of isoniazid?

Answer 21

hepatitis/idiosyncratic hepatotoxicity, peripheral neuropathies, mental abnormalities, convulsion, optic neuritis, hypersensitivity

Question 22

Why does isoniazid create hepatitis?

Answer 22

when broken down in the liver, the metabolite is toxic and incidence increases with age and those who drink alcohol daily

Question 23

What peripheral neuropathies does isoniazid cause?

Answer 23

paresthesia (numbness) of hands and feet

Question 24

What are the three rifamycins?

Answer 24

rifampin, rifabutin, rifapentine

Question 25

Which drugs are considered the first line therapy for mycobacterium?

Answer 25

rifamycins

Question 26

T/F rifamycins can be given alone

Answer 26

false, never given as a single agent

Question 27

Do rifamycins have broader or narrower antimicrobial activity than isoniazid?

Answer 27

broader

Question 28

What is the MOA of rifamycins?

Answer 28

interact with bacterial RNA polymerase to block transcription

Question 29

What does rifampin treat?

Answer 29

gram -/+ bacteria, mycobacteria, leprosy, prophylactic meningitis

Question 30

How is resistance to rifampin created?

Answer 30

mutation decreasing affinity of RNA polymerase for the drug or decreased permeability of the drug

Question 31

How is rifampin excreted?

Answer 31

liver metabolism and excretion!!

Question 32

What are drug considerations with rifampin?

Answer 32

may require dose adjustments, it is a potent inducer of CYP450 enzymes and can shorten the half-life of many drugs

Question 33

Which drug creates orange-red secretions?

Answer 33

rifampin

Question 34

What are the adverse effects of rifampin?

Answer 34

nausea, vomiting and rash

Question 35

How is rifabutin different than rifampin?

Answer 35

less CYP450 induction which leads to fewer drug interactions

Question 36

What is a unique side effect to rifabutin not in rifampin?

Answer 36

uveitis

Question 37

Which rifamycin is preferred for HIV patients?

Answer 37

rifabutin

Question 38

Which rifamycin has the longest half life?

Answer 38

rifapentine (weekly dosing after 2 months)

Question 39

What is the MOA of pyrazinamide?

Answer 39

bactericidal to actively dividing organisms, lowers intracellular pH and inhibits growth

Question 40

What are adverse effects of pyrazinamide?

Answer 40

liver dysfunction (when combined w/ isoniazid or rifampin) and hyperuricemia (precipitate gout)

Question 41

What is the MOA of ethambutol?

Answer 41

interferes with cell wall synthesis probably by inhibition of mycolic acid synthesis

Question 42

T/F resistance is not a problem with ethambutol when given with other drugs

Answer 42

true

Question 43

What are the adverse effects of ethambutol?

Answer 43

unilateral optic neuritis with decreased vision and loss of R/G, reversed upon discontinuation