How is isoniazid metabolized in the body?

How is isoniazid metabolized in the body?

It is metabolized by the liver, with the rate of metabolism determined genetically by acetylator phenotype. Peripheral neuropathy and hepatotoxicity are the most common adverse effects associated with isoniazid use. It is routinely administered with pyridoxine to prevent neurotoxicity.

Which enzyme is responsible for metabolism of isoniazid?

NAT2
NAT2 is the primary enzyme that contributes to INH metabolism. NAT2 deficiency increases the risk of INH-induced liver injury.

How is vitamin B3 metabolized?

Vitamin B3, in the form of the dinucleotides, plays a central role in energy metabolism, in oxidative phosphorylation, and in the redistribution of electron equivalents from catabolism redirected toward biosynthetic pathways.

How is NAD synthesized from niacin?

NAD is produced by two pathways: one requires dietary tryptophan, and the other requires dietary niacin (Figure 2). The NAD de novo synthesis pathway catabolizes tryptophan through the kynurenine pathway, and the NAD salvage pathway converts niacin and other precursors into NAD (independent of KYNU and HAAO).

How does isoniazid cause anion gap metabolic acidosis?

Isoniazid produces acute toxic effects by competing with brain pyridoxal 5-phosphate for the enzyme glutamic acid decarboxylase. This results in lower levels of gamma-aminobutyric acid (GABA), which leads to uninhibited electrical activity manifested as seizures2.

What is isonicotinic acid hydrazide?

Isoniazid is used with other medications to treat active tuberculosis (TB) infections. It is also used alone to prevent active TB infections in people who may be infected with the bacteria (people with positive TB skin test). Isoniazid is an antibiotic and works by stopping the growth of bacteria.

How is niacinamide metabolized?

All tissues in the body convert absorbed niacin into its main metabolically active form, the coenzyme nicotinamide adenine dinucleotide (NAD). More than 400 enzymes require NAD to catalyze reactions in the body, which is more than for any other vitamin-derived coenzyme [1].

Does vitamin B3 convert to NAD?

Summary. Niacin or vitamin B3 is a water-soluble vitamin used by the body to form the nicotinamide coenzyme, NAD+.

How NAD+ is formed?

Nicotinamide adenine dinucleotide (NAD+) is a molecule formed from vitamin B3 and ATP that acts as a carrier molecule for electrons and hydrogen. NAD+ becomes NADH when two electrons and a hydrogen are added to the molecule. One molecule of glucose can form 10 molecules NADH.

What is the difference between niacin and NAD?

Niacin is an oxidated form of nicotine that the body can convert into NAD. Nicotinamide is an amide of niacin that is more similar to NAD and has fewer side effects. Nicotinamide riboside is a synthetic form of nicotinamide that has different attributes.

How does isoniazid produce hepatic necrosis?

Chronic INH hepatotoxicity results in the induction of hepatocyte apoptosis, with associated disruption of mitochondrial membrane potential and DNA strand breaks. The most likely biochemical mechanism is that the metabolism of INH produces reactive metabolites that bind and damage cellular macromolecules in the liver.

What is metabolised by CYP1A2?

CYP1A2 metabolises many clinical drugs, such as phenacetin, caffeine, clozapine, tacrine, propranolol, and mexiletine. CYP1A2 also metabolises certain precarcinogens such as aflatoxins, mycotoxins, nitrosamines, and endogenous substances such as steroids. The regulation of CYP1A2 is influenced by many factors.

Why is CYP1A2 important?

CYP1A2 has been shown to be important for dosing of several antipsychotics and for assessing both drug efficacy and adverse drug reactions. CYP1A2 is the main CYP isoform involved in clozapine metabolism [16]. Case studies have shown ultrarapid metabolizers of clozapine that presented as resistant to treatment.

Where is niacin metabolized?

Ingested niacin is absorbed primarily in the small intestine, but some is absorbed in the stomach [1-3]. Even when taken in very high doses of 3–4 g, niacin is almost completely absorbed. Once absorbed, physiologic amounts of niacin are metabolized to NAD.

For which metabolic process niacin vitamin is required?

Niacin, vitamin B3, refers to both nicotinic acid and nicotinamide. Niacin is present in all body cells and is involved in many metabolic processes, including glycolysis, fat synthesis and tissue restoration.

Does resveratrol increase NAD?

Resveratrol Increases Intracellular NAD+ Levels Through Up regulation of The NAD+ Synthetic Enzyme Nicotinamide Mononucleotide Adenylyltransferase.