Pharmacology – Anti-Tuberculosis and Leprosy Drugs

Pharmacology – Anti-Tuberculosis and Leprosy Drugs

Anti-tuberculosis drugs:

Mechanism of action:

• Rifampicin: Binds to RNA polymerase, inhibiting RNA synthesis in bacteria.

• Isoniazid (INH): Interferes with mycolic acid synthesis, disrupting the synthesis of the bacterial cell wall.

• Pyrazinamide (PZA): Mycobacterium tuberculosis releases pyrazinamidase, transforming PZA into POA, which has biological activity and lowers the pH below that required for the growth of Mycobacterium tuberculosis.

• Ethambutol: Inhibits arabinosyl transferase enzyme.

• Clofazimine: Binds to DNA and inhibits replication.

Effects on Mycobacterium tuberculosis:

• Streptomycin (S): Bacteria in the lung cavities.

• INH: Bacteria in the lung cavities and macrophages.

• Pyrazinamide: Bacteria in macrophages.

• Rifampicin: Effective against all three forms (lung cavities, macrophages, bacilli) but less effective against bacilli.

Mycobacterium tuberculosis exists in the body in 3 forms:

• Lung cavities

• Macrophages

• Bacilli

Tuberculosis treatment regimens:

• Attack phase: The first stage of treatment, aimed at rapidly killing Mycobacterium tuberculosis.

• Consolidation phase for relapse prevention: The subsequent stage, aimed at preventing the recurrence of bacteria.

• Treatment regimen for children: 6 months: 2R,H,Z/ 4R,H

• Important in tuberculosis chemotherapy: Full adherence to treatment regimen to avoid treatment failure.

Side effects:

• Rifampicin: Hepatitis, bone marrow toxicity, turns body fluids red. Rifampicin can decrease the concentration of drugs such as fluconazole, iconazole, ketoconazole due to increased excretion.

• Isoniazid: Do not use with B6 if there are signs of B6 deficiency in tuberculosis treatment.

• Pyrazinamide: Inhibits uric acid excretion, joint pain, fever, nausea, vomiting.

• Ethambutol: Causes visual disturbances, inability to distinguish between blue and red if not treated promptly.

Quantification methods:

• Rifampicin: UV measurement at a wavelength of 475nm.

• Isoniazid: Iodide method (quantitative hydrolysis of released hydrazine).

Leading drugs in tuberculosis treatment:

• Pyrazinamide: Added to the treatment regimen for sensitive or resistant tuberculosis.

Besides tuberculosis treatment, Rifampicin is also used to treat:

• Leprosy

• Meningitis

Rifampicin’s effect on CYP450:

• Increases the metabolism of drugs such as chloramphenicol, corticosteroids, cyclosporine, diazepam, AZT.

Leprosy drugs:

Leprosy-causing bacteria:

• Mycobacterium leprae is also known as Hansen’s bacillus or BH.

Forms of leprosy:

• Type I (Indefinite): Indefinite form is the early stage of the disease.

• Type T (Tuberculoid): Tuberculoid form.

• Type B (borderline): Borderline form.

• Type L (Lepromatous): Lepromatous form (formerly known as malignant form).

Effective leprosy drugs:

• Dapsone (DDS), Rifampicin (RFP), Clofazimine (CLF).

Other drugs in leprosy treatment:

• Ofloxacin, Minocycline.

Side effects:

• Dapsone: Skin turns bluish-purple after a period of time due to the formation of quinolinine metabolite, which is blue.

• Clofazimine: Turns body fluids red.

Quantification methods:

• Dapsone: Nitrite measurement.

Other effects of Clofazimine:

• Besides leprosy treatment, Clofazimine also has anti-inflammatory effects (increases the phagocytosis ability of polymorphonuclear leukocytes and macrophages), and bacteriostatic effects.

Effect of Ethambutol:

• Bacteriostatic.

Note:

• This article provides general information on pharmacology – anti-tuberculosis and leprosy drugs.

• Always consult a doctor or healthcare professional before using any medication.

• Do not self-medicate or alter the dosage of medication.