First Line Antitubercular Drugs

Describe First Line Antitubercular Drugs.
Or
Write Short Note On First Line Antitubercular Drugs.
Answer:

The following are the first-line drugs for the treatment of tuberculosis:

First-Line Antitubercular Drugs Isoniazid

Isoniazid is the most widely used antitubercular agent.
It is very effective orally, cheap, and has high tuberculocidal activity.
The drug is active for both intracellular and extracellular bacilli.
It is used for chemoprophylaxis of tuberculosis.
Isoniazid is a prodrug that enters inside mycobacteria and becomes active. It inhibits the synthesis of mycolic acid and acts as a bactericidal.

Isoniazid Adverse Effects

Hepatotoxicity: In chronic alcoholics, old people and rapidacetylators risk of hepatic damage is high. The effect is reversible on discontinuation of the drug.
Peripheral neuritis: Dose-related toxicity is present. The drug promotes the excretion of pyridoxine.
Various other side effects are fever, skin, rash, anemia, arthralgia, gastrointestinal disturbances, psychosis and rarely it causes convulsions.

First-Line Antitubercular Drugs Rifampin

Rifampin is bactericidal to M. tuberculosis.
Bactericidal action covers all subpopulations of TB bacilli but acts best on slowly or intermittently dividing ones, as well as on many atypical mycobacteria.
It has good sterilizing and resistance-preventing actions.
Rifampin inhibits DNA-dependent RNA synthesis.
It is well absorbed orally, and widely distributed in the body— penetrates cavities, caseous masses, placenta, and meninges.
It is metabolized in the liver to an active deacetylated metabolite which is excreted mainly in bile, some in urine also.

Rifampin Adverse Effects

Hepatitis, a major adverse effect, generally occurs in patients with preexisting liver disease.
Respiratory syndrome—breathlessness which may be associated with shock and collapse.
Flu-like symptoms, i.e. fever with chills, headache, and muscle and joint pain.
Gastrointestinal disturbances, i.e. nausea, vomiting, and abdominal discomfort.
Skin rashes, itching, and flushing
Purpura, hemolysis, shock, and renal failure.

First-Line Antitubercular Drugs Pyrazinamide

It is weakly tuberculocidal but more active in an acidic medium.
It is more lethal to intracellularly located bacilli and to those at sites showing an inflammatory response (pH is acidic at both these locations).
It is highly effective during the first 2 months of therapy when inflammatory changes are present.
By killing the residual intracellular bacilli it has good ‘sterilizing’ activity.
It inhibits mycolic acid synthesis, but by interacting with a different fatty acid synthase encoding gene.
Pyrazinamide is absorbed orally, widely distributed, has good penetration in CSF, is extensively metabolized in the liver, and excreted in the urine.

Pyrazinamide Adverse Effects

Hepatotoxicity is the most important dose-related adverse effect.
Hyperuricemia is common
Other adverse effects are arthralgia, flushing, rashes, fever, and loss of diabetes control.

First-Line Antitubercular Drugs Ethambutol

Ethambutol is selectively tuberculostatic and clinically as active as S. Fast-multiplying bacilli are more susceptible as are many atypical mycobacteria.
Ethambutol inhibits arabinose transferases involved in arabinogalactan synthesis and interferes with mycolic acid incorporation in the mycobacterial cell wall.
It is used in combination with other antitubercular drugs to prevent the emergence of resistance and for faster sputum conversion.
On oral administration it is well absorbed and is widely distributed inside the body, it is metabolized in the liver, crosses the blood-brain barrier in meningitis, and is excreted in the urine.
Patient acceptability of ethambutol is very good and side effects are few.

Ethambutol Adverse Effects

Loss of visual acuity/color vision, and field defects due to optic neuritis are the most important dose and duration of therapy-dependent toxicity.
Ethambutol produces a few other symptoms—nausea, rashes, fever, and neurological changes are infrequent.
Hyperuricemia is due to interference with urate excretion.

First-Line Antitubercular Drugs Streptomycin

It was the first clinically useful antitubercular drug.
It is tuberculocidal, but less effective than rifampin; acts only on extracellular bacilli. Thus, host defense mechanisms are needed to eradicate the disease.
It penetrates tubercular cavities, but does not cross to the CSF, and has poor action in an acidic medium.
Resistance developed rapidly when streptomycin was used alone in tuberculosis—most patients had a relapse.

Streptomycin Adverse Effects

Most atypical mycobacteria are unaffected by streptomycin popularity of streptomycin in the treatment of tuberculosis had declined due to the need for IM injections.
Ototoxicity and nephrotoxicity, especially in the elderly and in those with impaired renal function.

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