TUBERCULOSIS AND LEPROSY PART-I

TUBERCULOSIS-TREATMENTS

Tuberculosis has become a more important challenging problem because of the emergence of multiple drug-resistant species of the causative microbe mycobacterium avium which also become a common infective organism in immunity compromising patients such those who have been infected with HIV virus.AIDS the pandemic disease is often associated with a marked increase in tuberculosis and infection caused by M.avium complex and M.tuberculosis.

Tuberculosis is a slowly developing chronic disease by the infection of highly heat-resisting M.avium complex.M.tuberculosis is the most drug resisting strain.

The treatment can be divided into two as follows:-

A.First-Line Treatments 

These treatments include drugs with high efficacy with an acceptable degree of toxicity.

1.Isoniazid:-

Chemically it isonicotinic acid hydrazide. It is still is considered as the primary drug of choice for T.B.

The mechanism of action is by inhibiting the synthesis of mycolic acids and thereby destructing the bacterial cell walls.

Route of administration is by oral and by injection by i.m.

The total daily dose is 5mg/kg to the maximum of 300mg/day by oral or by i.m., as both doses or identical. 

Pyridoxine can be administered with isoniazid to minimize the side effects

Kinetics

Isoniazid penetrates all body fluids, cells, and caseous material. Hence it is effective intracellularly too. It is metabolized in the liver by N-acetylation and the acetylation process is varying among human beings as in some people it as rapid as 1 hour and in some people it is as slow as 3 hours.

Drug Interaction

Isoniazid inhibits the liver enzyme cytochrome P-450 and thereby it increases the plasma levels of phenytoin, benzodiazepines, and warfarin if administered concurrently.

Side effects

1.Peripheral Neuritis: Vit-B-6 can minimize this effect.

2.Liver toxicity such as Jaundice and hepatitis

3.Rashes and skin eruptions

4.Convulsions and seizures.

In most cases Isoniazid can be given with other drugs. But as a prophylactic it should be given alone.

Pregnancy is contraindicated

2.Rifampin

Rifampin is an antibiotic.

Mechanism of Action

It inhibits the DNA dependent RNA polymerase and thereby inhibits the synthesis of RNA by blocking the chain initiation.

Kinetics

Rifampin is absorbed orally very well. It very easily penetrates into all cells, fluids, and CNS.

Rifampin is metabolized in the liver by inducing the liver enzyme cytochrome P-450 system.

Drug Interactions

Drugs like ketoconazole and warfarin need higher doses if administered concurrently as their inactivation is enhanced by rifampin by liver enzyme induction.

Side effects

1. Urine, sweat, tears and other secretions can become red-orange in color

2.Rash

3.Fever

4.Nausea and vomiting

5. A flu-like syndrome with chills, fever, and myalgia may develop in patients who use this drug once or twice weekly.

3.Pyrazinamide

This drug can be used for the short-course treatment of T.B.in combination with isoniazid or rifampin.

It is orally absorbed well.

Distributed into most of the body fluids including CNS

Side effects

1.Liver damage

2.Gout due to the inhibition of uric acid secretion.

3.Arthralgia and myalgia

4.Ethambutol

Ethambutol is almost very effective against M.tuberculosis

It is well absorbed orally and distributed in all tissue fluids including the CNS

Ethambutol is bacteriostatic.

Side effects

1.Optic neuritis

2.Gout.

5.Streptomycin

It is an aminoglycoside antibiotic.

Streptomycin is acting by binding to the 30s ribosomal subunit and causing a misinterpretation of the genetic code.

Treatment of life-threatening T.B.in combination therapy.

Side effects

1.Ototoxicity

2.Nephrotoxicity.