Drugs for TB

Question 1

Drugs for TB are

Answer 1

Rifampicin/rifampin, rifabutin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin

Question 2

Characteristics of mycobacteria

Answer 2

rod-shaped aerobic bacilli
highly lipophilic cell walls that stain poorly with gram stain
‘acid fact bacilli’

Question 3

treatment for latent TB

Answer 3

isoniazid for 6 months
OR
isoniazid + rifampicin for 3 months

Question 4

treatmment for active TB

Answer 4

intensive phase: reduce bac population
-RIPE for 2 months

continuation phase: destroy remaining bac
-RI for 4 months

Question 5

MOA of rifampicin

Answer 5

-not effective against dormant bacilli
-bactericidal
-binds to beta subunit of DNA-dependent RNA polymerase to form a stable drug-enzyme complex
-drug binding suppresses chain formation in DNA synthesis

Question 6

pharmacokinetics of rifampicin

Answer 6

-food decreases the rifampin maximum concentration by 1/3 hence drug cannot achieve therapeutic level, bacteria cannot be killed
-SHOULD BE TAKEN ON AN EMPTY STOMACH

Question 7

Metabolism of rifampicin/rifampin

Answer 7

It is a potent inducer of cytochrome P450-dependent drug-metabolizing enzymes. Hence any drugs that are dependent upon hepatic clearance will undergo enhanced drug metabolism & increase risk of withdrawal symptoms if the person is a drug abuser.

Question 8

Therapeutic uses of rifampicin

Answer 8

1. TB: used alone OR combined therapy
2. Meningococcal dx & H. influenzae meningitis: act as prophylaxis
3. Staph. endocarditis/osteomyelitis: with(got resistance) /without vancomycin
4. Brucellosis: +doxycycline

Question 9

Adverse effects of rifampin/rifampicin

Answer 9

hepatitis
liver failure (ask pt to take note of jaundice, vomiting, and malaise)
orange-tan discolouration of skin, urine, tears (rmb to inform pt)

!! avoid in pregnancy as rifampicin crosses placenta

Question 10

drug interaction of rifampicin

Answer 10

1. potent inducer of CYP enzymes, decreases half-life of drugs that depend on the metabolisation of CYP
2. reduces effectiveness of oral contraceptives (rmb to inform pt)

Question 11

MOA of isoniazid

Answer 11

-inhibits synthesis of mycolic acid, a component of bacterial cell wall
-bactericidal for rapid growers
-bacteriostatic for slow growers

Question 12

Pharmacokinetics of isoniazid

Answer 12

-can enter CNS
-enzyme inhibitor
-metabolised by ‘acetylation process’ hence isoniazid clearance in pt can be classified into ‘slow’ and ‘fast’ acetylators

*slow acetylators: neuropathy
*fast acetylators: treatment failure & relapse

Question 13

Adverse effects of isoniazid

Answer 13

peripheral neuritis/peripheral neuropathy: hence should ass pyridoxine/B6 to prevent beri-beri

Question 14

MOA of ethambutol

Answer 14

-bacteriostatic
-inhibits arabinosyl transferase III, disrupting transfer of arabinose into arabinogalactan biosynthesis, which disrupts assembly of mycobacterial cell wall

Question 15

pharmacokinetics of ethambutol

Answer 15

-renally excreted (used with caution in renal failure pt)

Question 16

Adverse effects of ethambutol

Answer 16

-optic neuritis :blurred vision and red-green color blindness [drug cannot be used in children]
-increase urea concentration in blood, leading to hyperuricemia

Question 17

MOA of pyrazinamide

Answer 17

-activated in acidic conditions
-disrupt mycobacterial cell membrane metabolism & transport function
-bactericidal

Question 18

adverse effects of pyrazinamide

Answer 18

hepatotoxicity :check LFT
hyperuricaemia/inhibit excertion of urate: acute gout

Question 19

pharmacokinetics of pyrazinamide

Answer 19

clearance reduced in renal failure pt, hence need to reduce dosing frequency

Question 20

MOA of streptomycin

Answer 20

-inhibits protein synthesis by binding with 30s ribosomal subunit
-misreading of genetic code during translation
-bactericidal

*effective for extracellular bacilli

Question 21

pharmacokinetics of streptomycin

Answer 21

-water soluble, thus poor GI absorption, given parenterally/injection

Question 22

drugs for atypical TB infections

Answer 22

therapy for disseminated M. avium complex

1.prophylatic therapy (CD4<50): monotherapy azithromycin/clarithromycin or rifabutin

2. definitive and suppressive therapy
   clarithromycin/azithromycin+ ethambutol+rifabutin