Download 39- Antituberculosis drugs

Antituberculosis drugs
1. First-line drugs: Isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin
Second-line drugs : Aminosalicylic acid（PAS）, kanamycin
2. Isoniazid : 1952, the most active drug for the treatment of tuberculosis
（1）Mechanism of action
Inhibit the synthesis of mycolic acid which is essential components of mycobacterial cell
walls
（2）Antimicrobial activity
High activity against both extracellular and intracellular tubercle bacilli
（3）Pharmacokinetics
Diffuse readily into all body fluids and tissues/ Metabolized by acetylation
（4）Clinical uses: First choice for all types of tuberculosis
（5） Adverse reactions
 Peripheral neuropathy
 CNS toxicity: memory loss, psychosis, seizures
 Hepatoxicity: the most frequent, increase in aminotransferase, hepatitis
 Allergic reactions
3. Rifampicin
（1）Antimicrobial activity
Mycobacteria, some G+ and G- cocci, chlamydiae and some virus
（2）Mechanism of action
Bind to β -subunit of bacterial DNA-dependent RNA polymerase and inhibit RNA
synthesis
（3）Clinical uses
 Tuberculosis and leprosy
 Infections caused by stapylococci and other rifampicin-susceptible bacteria
（4）Adverse reactions
 Gastrointestinal disturbance
 Liver toxicity: cholestatic jaundice, hepatitis
4. Ethambutol
（1）Mechanism: interfering with synthesis of RNA by combination with Mg2+
（2）Used in combination with INH or rifampicin
（3）Adverse effect: Loss of visual acuity, optical neuritis, red-green color blindness
5. Streptomycin
Penetrate into cell poorly, active mainly against extracellular tubercle bacilli
6. Pyrazinamide
 No cross-resistance with other antituberculosis drugs
 In conjunction with INH and rifampicin in short-course regimens to prevent relapse
7. Rationale for the use of antituberculosis drugs
 Use as early as possible
 Drug combination
 Appropriate doses
 Use regularly and enough time
8. Drugs used in leprosy
Rifampicin/ Sulfones: dapsone/ Thalidomide/ clofazimine