Tuberclulosis Medications

Question 1

Mycobacterium

Answer 1

Slow growing, rod shaped, unique lipid-ric cell wall aerobe.
Relatively impermeable to many ABX
Mycobacteria can reside inside non-activated macrophages.
Multiple drug tx required

Question 2

Tuberculosis

Answer 2

Transmitted via airborne particles
Leading cause of death world wide
Pulmonary disease that can disseminate

Question 3

Isoniazid (INH)- MOA

Answer 3

Inhibition of cell wall synthesis by inhibiting acid synthesis
Bacteriostatic for stationary phase and bactericidal for rapid dividing phase
Penetrates host cell and drug retained within hose cell longer
Metabolized by N-acetylation and hydrolysis

Question 4

Isoniazid (INH)- Resistance and Adverse effects

Answer 4

No cross resistance to other TB drugs
AE- peripheral neuritis- pyroxidine deficiency
Inhibits phenytoin metabolism and may produce convulsions in seizure prone patients
Hepatitis/hepatotoxicity- most severe and increased with rifampin and daily ETOH

Question 5

Isoniazid (INH)- Black box Warning

Answer 5

Sever and sometimes fatal hepatitis associated with isoniazid therapy may occur & may develop even after many months of tx

Question 6

Rifamycins- Mechanism

Answer 6

Blocks transcription by interacting w. the beta subunit of bacterial DNA-dependent RNA polymerase.
Antimicrobial spectrum- Broader spectrum vs INH

Question 7

Rifamycins- Spectrum of activity

Answer 7

Bactericidal against gram (+) and (-) organisms: used prophylactically in individuals exposed to meningitis.
Rifabutin, analog of rigampin, active against mycobacterium gyium complex, but less active for TB

Question 8

Rifamycin- pharmacokinetics

Answer 8

Oral admin, distribution all body fluids and organs
Induces hepatic mixed-function oxidases increasing its own metabolism and other drugs
Eliminated via feces and urine which may have an orange-red color.
Adverse effects- nausea and vomiting.

Question 9

Pyrazinamide- MOA

Answer 9

Bactericidal
Enters M. tuberculosis by passive diffusion, concerted to pyrazinoic acid by PZase
Inhibits fatty acid synthase I
Accumulates within acidic environment of macrophages monocytes and kills tubercle bacill.

Question 10

Pyrazinamide- Adverse Effects

Answer 10

Liver injury (15%) with jaundice (2-3%), rarely fatal
Get liver function test, do not use if problems

Question 11

Ethambutol

Answer 11

Bacteriostatic
Inhibits cell wall synthesis by inhibiting synthesis of polysaccharides and transfer of mycolic acids to the cell wall.
Helps prevent emergence of RIF resistant organisms

Question 12

Ethambutol- Adverse reactions

Answer 12

Optic neuritis
Results in diminished visual acuity and loss of red/green discrimination
Decreases urate excretion= gout if predisposed.