Isoniazid side effects

While Mr. Jbhnson is taking isoniazid) explain what instructions the nurse should give him concerning side effects. 

Frequency 45-65% of Caucasians and African Americans 10-15% of Asians Slow inactivation of drugs such as isoniazid (for tuberculosis), dapsone (for leprosy), and hydralazine (for high blood pressure), leading to toxicity from the drug at doses well tolerated in people with rapid acetylator phenotype Clinical consequences depend on the specific side effects of the drugs... 

Administer pyridoxine (vitamin Be) 25 to 50 mg daily or 50 to 100 mg twice weekly to all HIV-infected patients who are undergoing tuberculosis treatment with isoniazid to reduce the occurrence of isoniazid-induced side effects in the central and peripheral nervous system. 

The most commonly observed side effects are GI disturbances and nervous system symptoms, such as nausea, vomiting, headache, dizziness, and fatigue. Hepatitis is a major adverse effect, and the risk is highest in patients with underlying liver diseases and in slow isoniazid acetylators the rate of hepatotoxicity is increased if isoniazid and rifampin are combined. 

Thiacetazone is active against many strains of M. tuberculosis. It is not marketed in the United States. However, because of its low cost, it is used as a first-line agent in East Africa, especially in combination with compounds such as isoniazid. The most common side effects of thiacetazone include GI intolerance and development of rashes. It causes significant ototoxicity, especially when coadministered with streptomycin. Life-threatening hypersensitivity reactions, such as hepatitis, transient marrow aplastic syndromes, neutropenia, and thrombocytopenia, have been reported. 

A. Ethambutol is associated with retrobulbar neuritis, resulting in loss of central vision and impaired red-green discrimination. Ethionamide (B) is an analogue of isonicotinic acid and is associated with GI intolerance and peripheral neuropathy, but not the optic neuritis or color vision discrimination problems. Aminosalicylic acid (C) can cause GI irritation and bleeding problems, so caution is required in peptic ulcer patients. It has no neurological side effects. Rifampin (D) is associated with red-orange discoloration of saliva, tears, and urine but not the color vision problems. Isoniazid (E) is associated with peripheral neuritis in chronic alcoholics and malnourished individuals and requires pyridoxine supplements. It is not associated with optic neuritis. 

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]. 

Hydrazines. The hydrazines have only historic significance. The entire group of MAOIs was discovered through the euphoric side effect of isoniazid (8.36, isonicotinyl-hydrazide), a successful antituberculotic drug introduced in 1952. Iproniazid (8.37) is the corresponding isopropyl derivative. All of the hydrazides are highly hepatotoxic, and are no longer available. 

Ethambutol suppresses the growth of isoniazid- and streptomycin-resistant tubercle bacilli. The most important but not common side effects are optic neuritis, decreased visual acuity, and inability to perceive the color green. 

Commonly used drugs (other than isoniazid) affected by NAT2 polymorphism were procainamide, hydralazine, dapsone, and sulfonamides with an increase of side effects in all cases. A selective substrate of NATl is -aminosalicylic acid (PAS), but its genetic variation was never clinically important (52). Because of such lack of importance, more attention is often paid to the fact that various industrial chemicals with carcinogenic potential, and mutagenic heterocyclic amines, are substrates of both N-acetyltransferases (53). The presence or absence of these transferases will determine some incidences of cancer (54). Attempts have been made to ascribe cancer incidences in different populations to acetyltransferase differences (55). 

Iproniazid 24, an alkyl analog of the antituberculous drug isoniazid 25 (Figure 2.8), surprisingly showed mood-improving activity in several depressed tuberculosis patients, which turned out to result from a monoamine oxidase (MAO) inhibitory activity. Since the compound was already registered as an antituberculosis drug and since it constituted the very first effective treatment of depression, more than 400 000 patients received it within only one year after the first announcement of its antidepressant activity [2, 33], Later it was withdrawn from therapy, due to hepatotoxic side effects. 

One of the early modern medications seen to have psychiatric side effects is the antibiotic isoniazid (also known as INH). Tuberculosis (TB) is usu-... 

ISONIAZID ANTIVIRALS-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS t adverse effects with didanosine and possibly stavudine Additive side-effects Monitor closely for the development of peripheral neuropathy, but no dose adjustment is required... 

Slow acetylator Isoniazid Hydralazine, procainamide Phenelzine, sulfasalazine Increased incidence of peripheral neuropathy SLE-like syndrome and more prone to phenytoin toxicity Increased incidence of SLE-like syndrome More prone to side effects... 

Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. Eur Respir J 1996 9(10) 2026-30. 

Vegt PD, van der Meijden AP, Sylvester R, Brausi M, Holtl W, de Balincourt C, Andriole GL. Does isoniazid reduce side effects of intravesical Bacillus Calmette-Guerin therapy in superficial bladder cancer Interim results of European Organization for Research and Treatment of Cancer Protocol 30911. J Urol 1997 157(4) 1246-9. 

Dutt AK, Moers D, Stead WW. Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis. Am Rev Respir Dis 1983 128(3) 419-24. 

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxic-ity, peripheral neuropathy, optic neuritis, and Gl side effects. All four agents can potentially be hepatotoxic, but this side effect is most frequently associated with isoniazid and rifampin. Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators include people of Asian or American Indian descent and are less predisposed to these adverse effects. 

The discovery of the mood-elevating effect of MAO inhibitors was a classic example of serendipity in drug research. In 1951, isoniazid and its isopropyl derivative, iproniazid, were successfully introduced for the treatment of tuberculosis. In contrast to isoniazid, iproniazid was found to produce undesirable stimulation in some patients. In 1952, Zeller and his co-workers demonstrated that iproniazid was capable of inhibiting MAO, whereas isoniazid was ineffective (Zeller and Barsky 1952 Zeller et al. 1952). In 1956, Crane analyzed the psychiatric side-effects of iproniazid and came to the conclusion that it might be beneficial in the treatment of depression (Crane 1956). In 1957 Kline introduced it as a psychic energizer (Kline 1958). At the same time Kuhn discovered the antidepressant effect of imipramine (Kuhn 1957). This opened the way to the most powerful antidepressant therapy to date. 

Ethionamide, which has bacteriostatic actions against M. tuberculosis (0.5 to 1 g/day in divided doses) is indicated in the treatment of tuberculosis where first-line drugs such as isoniazid and rifampin have failed. The side effects of ethionamide may include nausea and vomiting, diarrhea, metallic taste, hepatitis, jaundice, stomatitis, depression, drowsiness, asthenia, peripheral neuritis, olfactory disturbances, diplopia, blurred vision, optic neuritis, convulsions, postural hypotension, thrombocytopenia, gynecomastia, impotence, menorrhagia, or diabetes mellitus. 

Drug Interactions Contraceptive effects are decreased when "the pill" is taken with ANTIDIOTICS (ampicillin, isoniazid, neomycin, pen V, rifampin, sulfonamides, tetracycline) or CNS AGENTS (barbiturates, benzodiazepines, phenytoin). Contraceptives increase the effects of corticosteroids and worsen side effects of tricyclic antidepressants. Oral contraceptives decrease the effectiveness of oral anticoagulants, anticonvulsants, and oral hypoglycemic agents. 

Other clinical applications of SNP reflect correlation between phenotype and reaction to therapy (pharmacogenomics). SNP is the basis for ushering in the personalized medicine. For example, an SNP in the gene for iV-acetyl transferase is correlated with peripheral neuropathy (weakness, numbness and pain in the arms, legs, hands and feet) as the side effect of treatment for tuberculosis with isoniazid (isonicotinic acid hydrazide). Therefore patients with this SNP are given alternative treatment. 

---