2. Antimycobacterial drugs

Question 1

mycobacteria

Answer 1

mycobacterium tuberculosis
non mucobatirume tuberculosis (NMT)
leprosy

Question 2

mycobacterium tuberculosis & NMT types of treatment treatment

Answer 2

First line & Second lines of treatment

Question 3

First line treatment drugs

Answer 3

all give in oral administration

Isoniazid (INH)
Rifampin
Pyrazinamide
Ethambutol

Question 4

First line treatment drug regimen

Answer 4

Initial therapy: isoniazid + rifampin + pyrazinamide + ethambutol/streptomycin for 2 months, then: isoniazid + rifampin for 4 months (4 for 2 and 2 for 4)

Question 5

Second line treatment drugs

Answer 5

for MDR tuberculosis
more toxic, and less effective

drugs... 
Streptomycin 
Para-aminosalicylic acid
Capreomycin 
Cycloserine 
Ethionamide 
Fluoroquinolones 
Macrolide 
Rifabutin

Question 6

Fluoroquinolones

Answer 6

for TBC and NTM

drugs …
Levofloxacin
Moxifloxacin

Question 7

Macrolide

Answer 7

for NTM

drugs
Azithromycin
clarithromycin

Question 8

Levofloxacin

Answer 8

Fluoroquinolones 3 generation
L- isomer of ofloxacin (2nd gen.)

Spectrum: G-ive aerobe bacteria, Proteus, E.coli, Klebsiella, H, influenzae, Nissera better G+ive (Strep pneumoniae) than 2nd generation but less pseudomonas
Clinical use: respiratory oriented | prostatitis | skin infection

Kinetics: 100% bioavailability | renal excretion
Administration: Oral and IV | ophthalmic

Adverse effect: GI, QT prolongation

Question 9

Moxifloxacin

Answer 9

Fluoroquinolones 4 generation

Spectrum: G-ive aerobe bacteria, Proteus, E.coli, Klebsiella, H, influenzae, Nissera better G+ive (Strep pneumoniae) than 3nd generation andsome anaerobes as well

Clinical use: respiratory oriented | prostatitis | skin infection | Not for UTI

Kinetics: good absorption | long half life (once a day administration) | liver excretion
Administration: IV | Ophthalmic

Adverse effect: GI, CNS, QT prolongation

Question 10

Azithromycin

Answer 10

Macrolide

in case of mycobacteria infection it is preferred for patients at greater risk for drug interactions

Spectrum: more potent against G-ive | G+ive Cocci, G-ive Cocci, borrelia burgdorferi | M.avium
Clinical use: Uretritis (chlamydia)

Administration: Oral and IV
Kinetics: longest half life and largest Vd
Distribution: Well | concentrated in neutrophils, macrophages and fibroblasts |
Elimination: Liver

Adverse effect: Less GI, no interactions

Question 11

clarithromycin

Answer 11

Macrolide

Spectrum: more potent against G+ive | G-ive | H. influenzae, H. Pylori | Chlamydia | M.avium

Kinetics: good bioavailability | renal excretion
Administration: Oral and IV, food increases absorption.
Distribution: Well
Elimination: Kidney

Adverse effect: Less GI, few interactions

Question 12

Isoniazid (INH)

Answer 12

Prodrug - activated by catalase peroxidase (KatG)
Inhibition of mycolic acid synthesis (needed for the cell wall)
Bactericidal (only for actively growing bacteria)

Spectrum: M. tuberculosis and kansasii (in high concentration)

Absorption: good but reduced with food (high fat)
Distribution: good - also to CNS and caseous material
Metabolism: N-acetylation (fast/slow acetylators) and hydrolysis | inhibits CYP450
Excretion: Glomerular

Adverse effect: Hepatitis (risk increase with age), peripheral neuropathy, SLE
*Give pyridoxine (B6) to avoid neuropathies

Question 13

pyridoxine

Answer 13

vitemin B6 to avoid adverse effects of neuropathies in isoniazid treatment

Question 14

Rifampin

Answer 14

Inhibition of RNA polymerase
Bactericidal
Long PAE

Spectrum: M. tuberculosis, NTM (kansasii, avium, leprae), G+ive (staph), G-ive (H.influenzae, N.meningitidis - prophylactic)

Distribution: good | CNS variable
Metabolism: Enterohepatic recycling
Excretion: Bille

Adverse effect: Orange discoloration of body fluid, nusea | drug inducer (CYP450 inducer)
*Always given in combination

Question 15

Pyrazinamide

Answer 15

Metabolized to pyrazinoic acid which inhibits cell membrane function (resistance by lacking metabolising enzyme)

Spectrum: M. tuberculosis (in acidic lesions and macrophages)

Distribution: good | CNS penetration

Adverse effect: Hepatotoxicity, uric acid retention

Question 16

Ethambutol

Answer 16

Inhibits arabinosyl-transferase - inhibits cell wall synthesis
Bacteriostatic

Spectrum: Mycobacterium
Distribution: good | CNS minimal
Excretion: Urine

Adverse effect: Optic neuritis (red-green color blindness) | uric acid excretion decreased

Question 17

Streptomycin

Answer 17

border line - first line in treatment of mycobacterium tuberculosis
Aminoglycoside
Bactericidal

toxic (oto and nephro), acts against extracellular mycobacteria

Question 18

Para-aminosalicylic acid

Answer 18

Inhibitor of folic acid synthesis
Only against M. tuberculosis
rarely used because of side effects

Question 19

Capreomycin

Answer 19

inhibits protein synthesis

given IM

AE: nephro and oto-toxicity

Question 20

Cycloserine

Answer 20

Cell wall synthesis inhibitor
bacteriostatic

given orally
well distributed including CNS

AE: CNS disturbances (seizures)

Question 21

Ethionamide

Answer 21

Inhibitor of mycolic acid synthesis (as INH)

well distributed including CNS

AE: Neurotoxicity, hepatotoxicity

Question 22

Inhibitor of mycolic acid synthesis

Answer 22

Ethionamide & Isoniazid (INH)

Question 23

Rifabutin

Answer 23

A derivative of rifampin
reverse transcriptase inhibitors

Preferred in patients coinfected with HIV and receiving
protease inhibitors or several of the non-nucleoside

Less potent inducer of CYP450 => less interactions

Question 24

Drugs against leprosy

Answer 24

Dapsone
Rifampin
Clofazimine

Question 25

Dapsone

Answer 25

Structurally related to sulfonamides
Inhibitor of folic acid synthesis (inhibits dihydropteroate synthetase)

Bacteriostatic (for M. leprae)
Also used in treatment of pneumonia caused by Pneumocystis jirovecii in immunosuppressed patients

Distribution: good GI penetration, well distributed, high concentration in the skin

Adverse effects: Hemolysis (especially in patients with G6PD deficiency), Methemoglobinemia, Erythema nodosum, peripheral neuropathy

Question 26

Rifampin used for

Answer 26

M. tuberculosis, NTM (kansasii, avium, leprae), G+ive (staph), G-ive (H.influenzae, N.meningitidis - prophylactic)

Question 27

Clofazimine

Answer 27

A phenazine dye, unknown mechanism (may involve binding to DNA)

Used in case of dapsone resistance

Bactericidal to M. leprae and has potential to be used for M. tuberculosis and atypical mycobacteria

Has some anti-inflammatory and anti-immune activities
This may stop the development of erythema nodosum leprosum in treated patients

Adverse effects: black and brown discoloration of the skin