Isoniazid

Isoniazid is assigned to an active ingredient from the antibiotic class and the tuberculostatics group. The drug is used to treat and prevent tuberculosis in infected people.

What is isoniazid?

Isoniazid is used to treat and prevent tuberculosis in infected people. The main causative agent of tuberculosis is Mycobacterium tuberculosis.

Isoniazid is short for Isonicotinic hydrazide. It is an antibiotic that is mainly used in combination with the antibiotic rifampicin to treat the infectious disease tuberculosis. Isoniazid is used in particular for tuberculosis prophylaxis in HIV patients. This has greatly reduced the number of cases of tuberculosis and the total number of deaths from tuberculosis in HIV patients.

The first synthesis of the drug took place in 1912 at the University of Prague and was carried out by Meyer and Malley. However, the antibiotic effect was first recognized around 30 years later. In the laboratories of the pharmaceutical companies Hoffman-La Roche and Bayer AG, the researchers and chemists Herbert Fox and Gerhard Domagk and their team further developed the substance until it was finally ready for the market.

Pharmacological effect

The bactericidal active ingredient isoniazid is absorbed by the bacterial cells. Inside the bacterial cell, the enzyme catalase or peroxidase (KatG) converts isoniazid into isonicotinic acid. This isonicotinic acid is built into the NAD coenzymes by the bacteria instead of nicotinic acid.

NAD play a crucial role in various metabolic processes and metabolic reactions. Due to the built-in isonicotinic acid, the coenzymes can no longer perform their function, so that the synthesis of nucleic acids and the synthesis of mycolic acid are disturbed. Mycolic acid is an important part of the bacterial cell walls. This makes up the resistance of the bacterium. If the cell wall is unstable due to the antibiotic, the bacteria perish.

Medical application & use

The main indication of isoniazid is the therapy of tuberculosis. The drug is also used to treat people who have been infected with tuberculosis but have not yet fallen ill. Tuberculosis is an infectious disease that can be caused by various mycobacteria. The main pathogen, however, is Mycobacterium tuberculosis. About 1.3 million people die of tuberculosis each year.

Basically, tuberculosis can be divided into different stages. Serious infections mainly occur in people with weakened immune systems. The antibiotic isoniazid is therefore also used for tuberculosis prophylaxis in HIV patients. For this, the antibiotic is usually given orally.

Isoniazid has a good bioavailability of around 90 percent. Acetylation is 75 percent in the liver. The drug and its metabolites are ultimately excreted through the kidneys.

Isoniazid is usually given with other tuberculostatics. This is to avoid the development of resistance.

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Risks & side effects

Medication with isoniazid can lead to gastrointestinal symptoms such as nausea, vomiting or diarrhea. Central nervous system disorders, allergies and peripheral neuropathies are also possible side effects. In addition, intrahepatic jaundice (jaundice) can occur due to a certain liver toxicity.

Due to the impaired liver, some patients also suffer from alcohol intolerance. Taking the antibiotic can lead to a vitamin B6 deficiency. This can lead to the development of polyneuritis, which is associated with various neurological symptoms such as tingling, paralysis or paralysis. To avoid such a polyneuritis, the attending physician can also administer a vitamin B6 preparation.

Isoniazid interacts with several other products. If acetaminophen (paracetamol) is administered at the same time, the toxicity of this drug increases, which can lead to severe liver damage. There is also an interaction with the drug carbamazepine. Isoniazid lowers the clearance of carbamazepine so that the drug stays in the blood longer. On the other hand, isoniazid lowers the active ingredient levels of ketoconazole, a drug used to treat fungal infections. Isoniazid increases serum levels of theophylline and valproate. Theophylline is used to treat bronchial asthma and valproate to treat epilepsy.

Isoniazid is absolutely contraindicated in diseases of the liver. In the case of acute hepatitis and liver insufficiency, it should be avoided if possible. Taking the antibiotic isoniazid is also not recommended in the case of alcohol abuse and the metabolic disease diabetes mellitus.