Isoniazid

Isoniazid is an antibiotic used to treat infection with mycobacteria (tuberculosis bacteria). In combination with other antimycobacterial drugs, it is most commonly used to treat tuberculosis.

Although the active ingredient was synthesized as early as 1912, its antibiotic effect was not recognized until after World War II, and the drug was introduced to the market in the early 1950s.

Since a deficiency of vitamin B6 can occur during therapy, the antibiotic should be administered together with a vitamin B6 preparation in order to counteract neurological side effects.

Pharmacodynamics

Isoniazid has a bactericidal (killing) effect on rapidly multiplying mycobacteria and a bacteriostatic (growth-inhibiting) effect on slowly multiplying ones. The antibiotic is administered as an inactive precursor and must first be activated by the bacterial enzyme KatG. Instead of nicotinic acid, the active isonicotinic acid is now incorporated into the cofactor NAD. This inhibits the synthesis of mycolic acids, which are an essential component of the bacterial cell wall.

During treatment, the active ingredient interferes with the body's own pyridoxine (vitamin B6) metabolism, affecting the build-up or formation of neurotransmitters such as GABA, serotonin or catecholamines.

Isoniazid should be used only in combination with other drugs, since the antifungal agent develops 46-89% resistance after two to three months of therapy alone and virtually 100% resistance of the pathogens after six to eight months.

Pharmacokinetics

Isoniazid is absorbed primarily in the small intestine after oral administration. The absorption and bioavailability of the active ingredient are reduced when taken concomitantly with food; therefore, the drug should be taken in a single dose on an empty stomach.
Der Stoffwechsel findet primär in der Leber statt, wo Isoniazid durch Acetylierung und Hydrolyse zu inaktiven Zwischenprodukten abgebaut wird. Die genetisch festgelegte Geschwindigkeit, mit der das Antibiotikum acetyliert wird, bestimmt die Plasmakonzentration sowie die Halbwertszeit. Letztere beträgt je nach Acetylierungsrate 0,5-1,6 Stunden bzw. 2-5 Stunden.
Der Großteil einer Isoniazid-Dosis wird innerhalb eines Tages mit dem Urin ausgeschieden.

Contraindications

Isoniazid should not be used in hypersensitivity, peripheral nervous system disorders, severe bleeding tendencies, and liver dysfunction (hepatitis, cirrhosis).

Drug interactions

Interactions may occur with drugs such as barbiturates, phenytoin, carbamazepine, primidone, rifampicin, valproic acid, acetaminophen, ketoconazole, theophylline, disulfiram, and levodopa.

During use, foods containing histamine and thyramine and alcohol should be avoided, and caffeine intake should be limited.
Isoniazid sollte getrennt von Antazida (Magensaftneutralisierende Medikamente) eingenommen werden.

Side effects

Side effects include:

• skin rashes, itching
• Muscle aging
• elevated liver enzymes
• hepatitis (inflammation of the liver)
• Gastrointestinal disorders (including diarrhea, constipation, vomiting)
• Peripheral nervous system disorders (when taken without vitamin B6)

Toxicological data

LD50 (human, oral): 100 mg/kg