Isoniazid is an active ingredient in the antibiotics class of drugs and is assigned to the tuberculostatics group. The drug is used to treat and prevent tuberculosis in infected individuals.
What is isoniazid?
Isoniazid is used for the treatment and prevention of tuberculosis in infected individuals. The main causative agent of tuberculosis is Mycobacterium tuberculosis. Isoniazid is short for isonicotinic hydrazide. It is an antibiotic used primarily in combination with the antibiotic rifampicin to treat the infectious disease tuberculosis. In HIV patients, isoniazid is used in particular for tuberculosis prophylaxis. As a result, the number of tuberculosis cases and also the total number of deaths from tuberculosis in HIV patients has been greatly reduced. 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 about 30 years later. In the laboratories of the pharmaceutical companies Hoffman-La Roche and Bayer AG, researchers and chemists Herbert Fox and Gerhard Domagk and their team continued to develop the substance until it was finally ready for the market.
Pharmacological action
The bactericidal agent isoniazid is taken up by bacterial cells. Inside the bacterial cell, the enzyme catalase or peroxidase (KatG) then converts isoniazid into isonicotinic acid. This isonicotinic acid is incorporated into the NAD coenzymes by the bacteria in place of nicotinic acid. NAD play a crucial role in various metabolic processes and metabolic reactions. Due to the incorporated 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 component of the cell walls of bacteria. This makes up the resistance of the bacterium. When the cell wall is unstable due to the antibiotic, the bacteria perish.
Medical application and use
The main indication of isoniazid is for the treatment of tuberculosis. The drug is also used to treat people who have been infected with tuberculosis but have not yet become ill. Tuberculosis is an infectious disease that can be caused by various mycobacteria. However, the main pathogen is Mycobacterium tuberculosis. Every year, about 1.3 million people die from tuberculosis. Basically, tuberculosis can be divided into different stages. Severe infections occur mainly in immunocompromised people. For this reason, the antibiotic isoniazid is also used to prevent tuberculosis in HIV patients. For this purpose, the antibiotic is usually administered orally. At around 90 percent, isoniazid has good bioavailability. Acetylation in the liver is 75 percent. The drug and its metabolites are ultimately excreted by the kidneys. Isoniazid is usually administered together with other tuberculostatics. This is to prevent the development of resistance.
Risks and side effects
Medication with isoniazid may cause gastrointestinal symptoms such as nausea, vomiting, or diarrhea. Central nervous system disorders, allergies, and peripheral neuropathies are also among the possible side effects. Furthermore, intrahepatic icterus (jaundice) may occur due to some liver toxicity. Due to the impaired liver, some patients also suffer from alcohol intolerance. Vitamin B6 deficiency may develop while taking the antibiotic. This can lead to the development of polyneuritis, which is associated with various neurological symptoms such as tingling, sensory disturbances or paralysis. To prevent such polyneuritis, the treating physician may additionally administer a vitamin B6 preparation. Isoniazid shows interactions with various other preparations. When acetaminophen (paracetamol) is administered at the same time, the toxicity of this drug increases, so that severe liver damage may occur. There is also an interaction with the drug carbamazepine. Isoniazid decreases carbamazepine clearance so that the drug remains in the blood longer. In contrast, the drug levels of ketoconazole, a drug used to treat fungal infections, are decreased by isoniazid. Isoniazid increases serum levels of theophylline and valproate.Theophylline is used for the treatment of bronchial asthma and valproate for the treatment of epilepsy. Isoniazid is absolutely contraindicated in liver diseases. Thus, its use should be avoided if possible in acute hepatitis and hepatic insufficiency. Taking the antibiotic isoniazid is also not recommended in alcohol abuse and in the metabolic disease diabetes mellitus.
