Tuberculosis adverse effects

Mycobacteria are responsible for two diseases tuberculosis, mostly caused by M. tuberculosis, and leprosy due to M. leprae. The therapeutic principle applicable to both is combined treatment with two or more drugs. Combination therapy prevents the emergence of resistant mycobacteria Because the antibacterial effects of the individual substances are additive, correspondingly smaller doses are sufficient Therefore, the risk of individual adverse effects is lowered. Most drugs are active against only one of the two diseases. 

Isoniazid is bactericidal against growing M. tuberculosis. Its mechanism of action remains unclear. (In the bacterium it is converted to isonicotinic acid, which is membrane impermeable, hence likely to accumulate intracellu-larly.) Isoniazid is rapidly absorbed after oral administration. In the liver, it is inactivated by acetylation, the rate of which is genetically controlled and shows a characteristic distribution in different ethnic groups (fast vs. slow acetylators). Notable adverse effects are peripheral neuropathy, optic neuritis preventable by administration of vitamin Be (pyridoxine) hepatitis, jaundice. 

IX.b.3.4. Genetically engineered antibodies. Anti-TNF antibody treatment with infliximab or adalimumab is now accepted as of value in treating severe and fistulating exacerbations of Crohn s disease when standard treatments are not tolerated or have failed. Adverse effects which limit usefulness include the occurrence of tuberculosis and septicaemia, leucopenia and pancytopenia, and risk of exacerbation of demyelinating disease. Considerations of benefits versus risks of such treatment are complex, but probably positive. 

Geriatric Considerations - Summary Age is not a contraindication to INH prophylaxis or treatment of tuberculosis. Follow adult guidelines for treatment. INH maybe used in patient wit h stable hepatic disease. The risk of clinical hepatitis increases with age and has been reported in 2% of adults aged greater than 50. INH interferes with the metabolism of pyridoxine therefore concomitant pyridoxine therapy at 25mg/day is recommended to prevent neurotoxicity. INH is metabolized via acetylation in the liver. Older adults who are slow acetylators of the drug may require lower doses to achieve effective serum concentrations and prevent adverse effects. Food, especially high-fat meals, delays and reduces absorption therefore administer INH on an empty stomach. 

Little Is known about possible long-term effects of CS Inhalation. This is due In part to the fact that short-term experiments with experimental animals, carried out for from several days to a month and using much higher (In some cases, nearly lethal) concentrations of CS, showed that ocular, respiratory, and cutaneous alte-. rations were mild and readily reversible, whereas necropsy findings failed to reveal any evidence of systemic alterations. Retrospective studies performed by the Hlmsworth committee at the request of the British Parliament after the extensive use of CS in Northern Ireland showed that no adverse effects of CS use were observed, with respect to eye burns, residual respiratory tract injury, Increased death rate in the elderly, exacerbations of mental Illness, increased Incidence of strokes or heart attacks, or incidence of tuberculosis. At exposure concentrations reported by the Hlmsworth committee (about 90 mg-min/m ), no persistent or notably adverse health effects were observed. 

About 30% of patients develop rashes with the first 1000 mg treatment this incidence decreases to about 10% with the second infusion and progressively decreases with each course of therapy thereafter. These rashes do not usually require discontinuation of therapy although urticarial or anaphylactoid reactions, of course, preclude further therapy. Immunoglobulins (particularly IgG and IgM) may decrease with repeated courses of therapy and infections can occur, although they do not seem directly associated with the decreases in immunoglobulins. Rituximab has not been associated with activation of tuberculosis, nor with the occurrence of lymphomas or other tumors (see Chapter 55). Other adverse effects, eg, cardiovascular events, are rare. 

Serious adverse events occur in up to 6% of patients with anti-TNF therapy. The most important adverse effect of these drugs is infection due to suppression of the ThI inflammatory response. This may lead to serious infections such as bacterial sepsis, tuberculosis, invasive fungal organisms, reactivation of hepatitis B, listeriosis, and other opportunistic infections. Reactivation of latent tuberculosis, with dissemination, has occurred. Before administering anti-TNF therapy, all patients must undergo purified protein derivative (PPD) testing prophylactic therapy for tuberculosis is warranted for patients with positive test results. More common but usually less serious infections include upper respiratory infections (sinusitis, bronchitis, and pneumonia) and cellulitis. The risk of serious infections is increased markedly in patients taking concomitant corticosteroids. 

The mechanism of ethambutol (Myambutol) is not fully understood. This drug apparently suppresses RNA synthesis in susceptible bacteria, but it is not known how this occurs. Ethambutol is primarily effective against M. tuberculosis infections and is a secondary agent in the treatment of tuberculosis.61 Adverse effects associated with this drug include joint pain, nausea, skin rash and itching, and CNS abnormalities (dizziness, confusion, hallucinations). 

Besides the adverse effects just described, glucocorticoid therapy is contraindicated under the following circumstances diabetes mellitus, digitalis therapy, glaucoma, hypertension, infection, osteoporosis, peptic ulcer, tuberculosis, and viral infection. 

The most important adverse effect of infliximab therapy is infection due to suppression of the THl inflammatory response. Reactivation of latent tuberculosis, with dissemination, has occurred. 

The adverse effects of stress and depression, the effects of bereavement, unemployment and social isolation on mental and physical health have been known since antiquity. Aristotle advised physicians, "Just as you ought not to attempt to cure eyes without head or head without body, so you should not treat body without soul." One of the fathers of modem medicine put it more scientifically in the 19th century when he recommended that when attempting to predict health outcomes from tuberculosis in patients, it is just as important to know what is going on in a man s head as it is in his chest. 

Ethambutol [e THAM byoo tole] is bacteriostatic and specific for most strains of M- tuberculosis and M- kansasii. Resistance is not a serious problem if the drug is employed with other antituberculous agents. Ethambutol can be used in combination with pyrazinamide, isoniazid, and rifampin to treat tuberculosis. Absorbed on oral administration, ethambutol is well distributed throughout the body. Penetration into the central nervous system (CNS) is therapeutically adequate in tuberculous meningitis. Both parent drug and metabolites are excreted by glomerular filtration and tubular secretion. The most important adverse effect is optic neuritis, which results in... 

The severe fiver dysfunction also seemed to be more common in slow metabofizers, and it was proposed that this due to a deficiency in detoxication of a metabolite. Monitoring patients with fiver function tests is one way to avoid this adverse effect. There may be other factors as well as the acetylator phenot5rpe that are important, such as other drugs being taken at the same time. Excessive and sustained alcohol intake may also be a factor, as this is quite commonly associated with the occurrence of tuberculosis. Apart from weakening the fiver it will also increase the amount of the enzyme that produces the toxic metabolite of isoniazid. 

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