Antitubercular isoniazid

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

An interesting example of racial differences in drug conversion is seen in the metabolism of the antitubercular, isoniazid. It is inactivated by an acetylation reaction. Slow acetylation leads to toxicity (lupus, drowsiness, nausea, cyanosis). Free isoniazid also inhibits the action of phenytoin (an anticonvulsive) and results in phenytoin toxicity. Normal acetylation has a half-life of 45-80 minutes while a "slow acetylator" shows a 140-200 min half-life. The U.S. population shows a 50/50 distribution of "slow" versus "fast" acetylators. 44-55% of American Causasians and blacks are "slow". 

Acetylation is a very common metabolic reaction, which occurs with amino, hydroxyl or sulfhydryl groups. The acetyl group is transferred from acetyl-Coenzyme A, and the reaction is catalyzed by acetyltransferases. An important aspect of this kind of substitution is the genetic polymorphism of one acetyltrans-ferase in humans, who are divided into fast and slow acetyla-tors. In a few cases, the conjugates are further metabolized to toxic compounds, as is seen with isoniazid. Some evidence exists that acetylation of the antitubercular isoniazid leads to enhanced hepatotoxicity of the drug. " Acetylation followed by hydrolysis and CYP-dependent oxidation yields free acetyl... 

Control of tuberculosis, long one of the scourges of mankind, began with the introduction of effective antibacterial agents. Thus, this disease was treated initially with some small measure of success with various sulfa drugs the advent of the antibiotic, streptomycin, provided a major advance in antitubercular therapy, as did the subsequent discovery of isoniazid and its analogs. 

Fig. 5.17 Antitubercular compounds (see text also for details of antibiotics) A, PAS B, isoniazid C, ethionamide D, pyrazinamide E, prothionamide F, thiaeetazone G, ethambutol.

Irradiation of an alcoholic solution of the antitubercular drug isoniazid (261) with a low-pressure mercury lamp by Ninomiya and Yamamoto gave isolated yields of the hydrazone (262, 60%) and the hydrazide (264, 17%). Nicotinic and picolinic acid hydrazides reacted similarly, as did other alcohols. The production of (262) was easily understood since it was known that photolysis of ethanol gave acetaldehyde which would react spontaneously with the... 

Some substances, such as carbon monoxide and barbiturates, can deprive brain cells of oxygen or glucose - they produce anoxia - with potentially serious consequences for gray matter. Other substances, such as lead, hexachlorophene, and the antitubercular drug isoniazid, are capable of causing loss of myelin, a coating or sheath for the axon and dendrites that extend from the central unit (cell body) of neurons. Demyelination can occur in either the CNS or PNS. 

Isoniazid (INH) [Antitubercular Agent] Uses Rx prophylaxis of TB Action Bactericidal interferes w/ mycolic acid synth, disrupts cell wall Dose Adults. Active TB 5 mg/kg/24 h PO or IM (usually 300 mg/d) or DOT 15mg/kg... 

Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapul-monary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis. 

The first inhibitors of flavin-dependent MAO that were developed for clinical use were hydrazines and hydrazides. The chance discovery that the antitubercular drug, 4-pyridine carboxylic acid hydrazide (isoniazid, 40), was also a potent MAO inhibitor led to the development of the related drug, iproniazid (41), used for the treatment of depressive illness. Although this compound demonstrated remarkable antidepressant action, its clinical value was seriously compromised by side effects [19]. 

V-Acetylation /V-acetyl transferase Isoniazid (antitubercular) Peripheral neuropathy... 

As well as being implicated as a hepatotoxin, the antitubercular drug isoniazid may also cause peripheral neuropathy with chronic use. In practice, this can be avoided by the concomitant administration of vitamin B6 (pyridoxine). 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

HPI KC is a 50-year-old Mexican man who presents to the clinic with upper right quadrant pain and darkMycobacterium tuberculosis (MTB). He has no other significant PMH. Medications Rifampin, isoniazid, ethambutol, and pyrazinamide. 

Acnisal salicylic acid, aconiazide [inn] is an isoniazid analogue and an ANTITUBERCULAR and ANTIBACTERIAL AGENT, aconitine is an alkaloid from monk s hood or wolfsbane (Aconitum napellus) and other Aconltum spp. (Ranunculaceae). It is a NEUROTOXiN implicated in poisoning by A. spp., especially, 4. chasmanthum in India. Experimentally, it is a SODIUM-CHANNEL ACTIVATOR that binds to Na -channels, slows inactivation, shifts inactivation to a more negative value, and alters ion specificity. This results in repetitive firing of neurons, with marked effects on the heart including positive inotropism and arrhythmias. Aconitine (and the related alkaloid delphinine) were formerly used in... 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

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