Drugs for TB Flashcards
Drugs for TB are
Rifampicin/rifampin, rifabutin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin
Characteristics of mycobacteria
rod-shaped aerobic bacilli
highly lipophilic cell walls that stain poorly with gram stain
‘acid fact bacilli’
treatment for latent TB
isoniazid for 6 months
OR
isoniazid + rifampicin for 3 months
treatmment for active TB
intensive phase: reduce bac population
-RIPE for 2 months
continuation phase: destroy remaining bac
-RI for 4 months
MOA of rifampicin
-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
pharmacokinetics of rifampicin
-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
Metabolism of rifampicin/rifampin
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.
Therapeutic uses of rifampicin
- TB: used alone OR combined therapy
- Meningococcal dx & H. influenzae meningitis: act as prophylaxis
- Staph. endocarditis/osteomyelitis: with(got resistance) /without vancomycin
- Brucellosis: +doxycycline
Adverse effects of rifampin/rifampicin
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
drug interaction of rifampicin
- potent inducer of CYP enzymes, decreases half-life of drugs that depend on the metabolisation of CYP
- reduces effectiveness of oral contraceptives (rmb to inform pt)
MOA of isoniazid
-inhibits synthesis of mycolic acid, a component of bacterial cell wall
-bactericidal for rapid growers
-bacteriostatic for slow growers
Pharmacokinetics of isoniazid
-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
Adverse effects of isoniazid
peripheral neuritis/peripheral neuropathy: hence should ass pyridoxine/B6 to prevent beri-beri
MOA of ethambutol
-bacteriostatic
-inhibits arabinosyl transferase III, disrupting transfer of arabinose into arabinogalactan biosynthesis, which disrupts assembly of mycobacterial cell wall
pharmacokinetics of ethambutol
-renally excreted (used with caution in renal failure pt)
Adverse effects of ethambutol
-optic neuritis :blurred vision and red-green color blindness [drug cannot be used in children]
-increase urea concentration in blood, leading to hyperuricemia
MOA of pyrazinamide
-activated in acidic conditions
-disrupt mycobacterial cell membrane metabolism & transport function
-bactericidal
adverse effects of pyrazinamide
hepatotoxicity :check LFT
hyperuricaemia/inhibit excertion of urate: acute gout
pharmacokinetics of pyrazinamide
clearance reduced in renal failure pt, hence need to reduce dosing frequency
MOA of streptomycin
-inhibits protein synthesis by binding with 30s ribosomal subunit
-misreading of genetic code during translation
-bactericidal
*effective for extracellular bacilli
pharmacokinetics of streptomycin
-water soluble, thus poor GI absorption, given parenterally/injection
drugs for atypical TB infections
therapy for disseminated M. avium complex
1.prophylatic therapy (CD4<50): monotherapy azithromycin/clarithromycin or rifabutin
- definitive and suppressive therapy
clarithromycin/azithromycin+ ethambutol+rifabutin
