AntiMycobacterium

Question 1

Pulmonary; intestinal mucosa & lymph nodes;
fatal dissemination in AIDS patients
Caused by

Answer 1

M. avium-intracellulare

Question 2

CHALLENGING ASPECTS OF ANTIMYCOBACTERIAL THERAPY

Difficult to kill

Answer 2

• Difficult to grow, identify, and do susceptibility testing
• Requires very lengthy therapy
• Chronic disease
• Intracellular forms

Question 3

Mycobacterial have Spontaneous resistance … thus we must use

Answer 3

multi-drug therapy

Question 4

Goals of Therapy

Answer 4

• Convert cultures to negative in shortest possible time
• Prevent emergence of drug resistance
• Assure complete cure without relapse

Question 5

____________ is the pathologic agent in 90% of the cases; ___________ for 10% of others

Answer 5

M. tuberculosis

M. avium- intracellulare (MAI)

Question 6

has become a serious problem in AIDS patients
• More common in aged, dialysis patients, AIDS patients, immunocompromised,
immigrants, drug addicts, the homeless

Answer 6

M.avium-intracellulare

Question 7

Diagnosis for Tuberculosis

Answer 7

• Tuberculin skin test (positive prior to symptoms)
• X-ray
• Acid-fast stain/culture

Question 8

Bactericidal for actively growing bacilli, bacteriostatic for “resting cells”

Answer 8

Isoniazid

Question 9

Isoniazid works by inhibiting synthesis of ________which are important branched hydroxy fatty
acids of mycobacterial cell walls

Answer 9

mycolic acids,

Question 10

isoniazid is a prodrug which is
activated by ______________of the tubercle bacillus;
the activated drug’s target is the enoyl-acyl carrier protein reductase (InhA)

Answer 10

the catalase-peroxidase (KatG protein)

Question 11

isoniazid is a prodrug which is

activated by the catalase-peroxidase (KatG protein) of the tubercle bacillus; the activated drug’s target is the ….

Answer 11

enoyl-acyl carrier protein reductase
(enough of this Acsinice shit)
enony-acycl for isoniazid

Question 12

Resistant strains of Isoniazid often result from mutations in

Answer 12

KatG or InhA

Question 13

Most important primary TB drug; all patients with INH-sensitive strains should
receive INH if possible

Answer 13

Isoniazid

Question 14

For treatment, Isoniazid is always given i

Answer 14

n combination with other agents

Question 15

Isoniazid is for tuberculosis but may also be effective against some strains of

Answer 15

M. bovis and M. kansasii

Question 16

For prophylaxis, Isoniazid can be used alone for

Answer 16

(6–9 months)

Question 17

• For latent TB (infected, no active disease), CDC recommends

Answer 17

isoniazid (9 months) or isoniazid + rifapentine (3 months)

Question 18

Isoniazid has Oral or parenteral admin but should be administered with

Answer 18

aluminum-containing antacids interfere with absorption

Question 19

Isoniazid is rapidly absorbed; readily distributes in tissue fluids, some into CSF; penetrates into caseous lesions; intracellular and extracellular levels are similar
• N-acetylation is under

Answer 19

genetic control (slow acetylators, t1/2 ~ 2–5 hr; rapid 
acetylators, t1/2 ~ 70 min)

Question 20

Toxicity of Isoniazid:

Answer 20

Neurotoxicity, esp. peripheral neuritis — d/t thyimine defieiccy… alcoholics
• Hepatotoxicity

Question 21

What causes neurotoxicity from Isoniazid

Answer 21

— thymine or B6 deifience

Question 22

Rifampin, a macrolide for TB and it’s mechanism is:

Answer 22

Inhibits bacterial DNA-dependent RNA polymerase, no RNA made

Question 23

Rifampin is a macrolide for TB that is bactericidal or bacteriostatic

Answer 23

bacteriacidal

Question 24

Isoniazid Resistance: 1 in 10 to 7th or 10 to the 8th

cells have spontaneous mutation in

Answer 24

RNA polymerase

Question 25

Very effective when used with isoniazid or other agents; never used alone

Answer 25

Rifampin

Question 26

Adverse side effects of Rifampin

liver, orange, inducer

Answer 26

Hepatotoxicity, may be severe in alcoholics, elderly, existing hepatic damage
• Potent inducer of multiple CYPs thereby increasing metabolism of other drugs
• Orange-red color to urine, feces, saliva, sputum, tears, sweat

Question 27

Drug causes hepatotoxicity, potent inducer of multiple CYPs to increase metabolism of drugs and orange red color to feces

Answer 27

Rifampin

Question 28

Interferes with arabinosyl transferase, blocking cell wall synthesis and is tuberculostatic

Answer 28

Ethambutol

ariba ariba, ethambutol! Ethambutol

Question 29

Ethambutol’s mechanism

Answer 29

Interferes with arabinosyl transferase, blocking cell wall synthesis

Question 30

Absorption/excretion of Ethambutol

Answer 30

• Well-absorbed; distributes throughout body, adequate levels in CSF
• Metabolized to an aldehyde and a dicarboxylic acid derivative
• Two-thirds excreted unchanged in urine; t1/2 ~3–4 hr

Question 31

Ethambutol’s side effects

Answer 31

Optic neuritis,
decrease of visual acuity
can’t tell red from green

Question 32

Blocks mycolic acid synthesis by inhibiting fatty acid synthase I
• bactericidal

Answer 32

Pyrazinamide is a nicotinamide analog

Question 33

Pyrazinamide mechanism

Answer 33

Blocks mycolic acid synthesis by inhibiting fatty acid synthase I
• bactericidal

Question 34

Use of Pyrazinamide

Answer 34

Used in combination therapy; important component of short-term multi-drug therapy

Question 35

TB drug that is well absorbed and distributes into the CSF

Answer 35

Pyrazinamide

Question 36

Side affect of Pyrazinamide

Answer 36

Hepatic damage, up to 15% incidence; may be severe/potentially fatal (esp. when
combined with rifampin)

Question 37

binds to several ribosomal sites, usually at 30S/50S interface; restricts polysome
formation (i.e. stops initiation) and causes mRNA misreading

Answer 37

Streptomycin (bacteriacidal)

Question 38

Usually reserved for the most serious forms of TB (e.g. disseminated disease)

Answer 38

Streptomycin

Question 39

Admin route of Streptomycin for TB

Answer 39

Administration: parenteral (I.M.)

Question 40

Side affects of Streptomycin

Answer 40

Ototoxicity, affecting both balance and hearing

Nephrotoxicity

Question 41

Key for Multi-Drug Regimens for Treating Active TB

Answer 41

ALWAYS use at least two drugs to which strain is sensitive (since sensitivity testing
takes a very long time, three or more drugs are often used initially)

Question 42

Examples of bactericidal intracellular and extracellular TB drugs

Answer 42

isoniazid
rifampin
pyrazinamide

Question 43

Example of bacteriacidal and extracellular TB drugs

Answer 43

Streptomycin

Question 44

example of intra/extra bacteriostatic TB drugs

Answer 44

ethambutol

p-aminosalicylic acid