Anti-Tuberculosis Drugs
Examples
Stage (Initial)
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
Stage (Continuation)
Indications
- Mycobacterium tuberculosis
Tuberculosis is treated in two stages with combinations of drugs. Treatment should be under the care of a specialist.
Contraindications
Contraindications
- Drug intolerance or allergy
- Isoniazid - drug-induced liver disease
- Rifampicin - jaundice
- Pyrazinamide - acute porphyria
- Ethambutol - optic neuritis, poor vision
Cautions
- Pre-existing liver disease or alcohol dependency
- Reduced renal function
- Epilepsy
- HIV infection
- History of psychosis
- Diabetes mellitus
- Gout (avoid in acute attacks)
- Caution should be exercised in pregnancy and when breast-feeding
Mechanism
Isoniazid is a bacteriostatic agent which, inhibits the synthesis of mycolic acid, a cell wall component of M. Tuberculosis.
Rifampicin is an inhibitor of nucleic acid metabolism via inhibition of bacterial DNA-dependent mRNA polymerase.
Pyrazinamide is a bactericidal agent, its exact mechanism of action is unknown.
Ethambutol acts by inhibition of lipoarabinomannan and arabinogalactan biosynthesis within mycobacterial cell wall.
Administration
Antituberculous treatment is usually given orally. Directly observed therapy (DOT) may be used where there are concerns about patient compliance. In this situation, treatment is given three times a week.
Adverse Reactions
The most important adverse effects with these drugs are: peripheral neuropathy (more common with other risk factors such as diabetes or HIV), hepatotoxicity, and visual disturbances with ethambutol. A range of toxicity syndromes are seen with intermittent use of rifampicin.
Interactions
Complex interactions occur with anti-tuberculous drugs. The BNF should be checked for all new drugs. Rifampicin is a powerful inducer of the hepatic P450 system, and isoniazid is an inhibitor of the same. Particular issues occur with anti-convulsants, the oral contraceptive pill and anti-virals in HIV.
Education
Patients should be advised to complete the prescribed course of antibiotic therapy. They should be warned about the signs of liver toxicity and visual changes and should seek urgent medical help if these occur.
Pharmacokinetics
Isoniazid is readily absorbed from the gastro-intestinal tract and distributed widely across body tissues and fluids including the CSF. It penetrates well into caseous tuberculous lesions. Acetylation and inactivation of the drug depends on the individual with slower inactivators enjoying a better therapeutic response. Excretion is in the urine of both the acetylated inactivated form and active drug.
Rifampicin is absorbed from the gastro-intestinal tract and widely distributed. It gives an orange tinge to saliva, sputum, tears and sweat. Excretion is partly in the urine and partly in the bile.
Pyrazinamide is well absorbed through the gastro-intestinal tract and distributed widely. Excretion is primarily renal via glomerular filtration.
Ethambutol is well absorbed when administered orally and reaches therapeutic concentrations in four hours. It is taken up by erythrocytes in the blood and released slowly. It is excreted in the urine partly metabolised.
