Isoniazid Health Dictionary

An infectious disease, commonly called , caused in humans by the bacterium MYCOBACTERIUM TUBERCULOSIS. is usually transmitted in airborne droplets expelled when an infected person coughs or sneezes. An inhaled droplet enters the lungs and the bacteria begin multiplying. The immune system usually seals off the infection at this point, but in about 5 per cent of cases the infection spreads to the lymph nodes. It may also spread to other organs through the bloodstream, which may lead to miliary tuberculosis, a potentially fatal form of the disease.

In about another 5 per cent of cases, bacteria held in a dormant state by the immune system become reactivated months, or even years, later. The infection may then progressively damage the lungs, forming cavities.

The primary infection is usually without symptoms. Progressive infection in the lungs causes coughing (sometimes bringing up blood), chest pain, shortness of breath, fever and sweating, poor appetite, and weight loss. Pleural effusion or pneumothorax may develop. The lung damage may be fatal.

A diagnosis is made from the symptoms and signs, from a chest X-ray, and from tests on the sputum. Alternatively, a bronchoscopy may also be carried out to obtain samples for culture.

Treatment is usually with a course of 3 or 4 drugs, taken daily for 2 months, followed by daily doses of isoniazid and rifampicin for 4–6 months. However, bacteria are increasingly resistant to the drugs used in treatment, and others may have to be used and treatment carried out for a longer period. If the full course of drugs is taken, most patients recover.

can be prevented by BCG vaccination, which is offered routinely at birth or age 10–14.

Any contacts of an infected person are traced and examined, and, if infected, are treated early to reduce the risk of the infection spreading.... tuberculosis

In?ammation of the LIVER which damages liver cells and may ultimately kill them. Acute injury of the liver is usually followed by complete recovery, but prolonged in?ammation after injury may result in FIBROSIS and CIRRHOSIS. Excluding trauma, hepatitis has several causes:

Viral infections by any of hepatitis A, B, C, D, or E viruses and also CYTOMEGALOVIRUS (CMV), EPSTEIN BARR VIRUS, and HERPES SIMPLEX.

Autoimmune disorders such as autoimmune chronic hepatitis, toxins, alcohol and certain drugs – ISONIAZID, RIFAMPICIN, HALOTHANE and CHLORPROMAZINE.

WILSON’S DISEASE.

Acute viral hepatitis causes damage throughout the liver and in severe infections may destroy whole lobules (see below).

Chronic hepatitis is typi?ed by an invasion of the portal tract by white blood cells (mild hepatitis). If these mononuclear in?ammatory cells invade the body (parenchyma) of the liver tissue, ?brosis and then chronic disease or cirrhosis can develop. Cirrhosis may develop at any age and commonly results in prolonged ill health. It is an important cause of premature death, with excessive alcohol consumption commonly the triggering factor. Sometimes, cirrhosis may be asymptomatic, but common symptoms are weakness, tiredness, poor appetite, weight loss, nausea, vomiting, abdominal discomfort and production of abnormal amounts of wind. Initially, the liver may enlarge, but later it becomes hard and shrunken, though rarely causing pain. Skin pigmentation may occur along with jaundice, the result of failure to excrete the liver product BILIRUBIN. Routine liver-function tests on blood are used to help diagnose the disease and to monitor its progress. Spider telangiectasia (caused by damage to blood vessels – see TELANGIECTASIS) usually develop, and these are a signi?cant pointer to liver disease. ENDOCRINE changes occur, especially in men, who lose their typical hair distribution and suffer from atrophy of their testicles. Bruising and nosebleeds occur increasingly as the cirrhosis worsens, and portal hypertension (high pressure of venous blood circulation through the liver) develops due to abnormal vascular resistance. ASCITES and HEPATIC ENCEPHALOPATHY are indications of advanced cirrhosis.

Treatment of cirrhosis is to tackle the underlying cause, to maintain the patient’s nutrition (advising him or her to avoid alcohol), and to treat any complications. The disorder can also be treated by liver transplantation; indeed, 75 per cent of liver transplants are done for cirrhosis. The overall prognosis of cirrhosis, however, is not good, especially as many patients attend for medical care late in the course of the disease. Overall, only 25 per cent of patients live for ?ve years after diagnosis, though patients who have a liver transplant and survive for a year (80 per cent do) have a good prognosis.

Autoimmune hepatitis is a type that most commonly occurs in women between 20 and 40 years of age. The cause is unknown and it has been suggested that the disease has several immunological subtypes. Symptoms are similar to other viral hepatitis infections, with painful joints and AMENORRHOEA as additional symptoms. Jaundice and signs of chronic liver disease usually occur. Treatment with CORTICOSTEROIDS is life-saving in autoimmune hepatitis, and maintenance treatment may be needed for two years or more. Remissions and exacerbations are typical, and most patients eventually develop cirrhosis, with 50 per cent of victims dying of liver failure if not treated. This ?gure falls to 10 per cent in treated patients.

Viral hepatitis The ?ve hepatic viruses (A to E) all cause acute primary liver disease, though each belongs to a separate group of viruses.

•Hepatitis A virus (HAV) is an ENTEROVIRUS

which is very infectious, spreading by faecal contamination from patients suffering from (or incubating) the infection; victims excrete viruses into the faeces for around ?ve weeks during incubation and development of the disease. Overcrowding and poor sanitation help to spread hepatitis A, which fortunately usually causes only mild disease.

Hepatitis B (HBV) is caused by a hepadna virus, and humans are the only reservoir of infection, with blood the main agent for transferring it. Transfusions of infected blood or blood products, and injections using contaminated needles (common among habitual drug abusers), are common modes of transfer. Tattooing and ACUPUNCTURE may spread hepatitis B unless high standards of sterilisation are maintained. Sexual intercourse, particularly between male homosexuals, is a signi?cant infection route.

Hepatitis C (HCV) is a ?avivirus whose source of infection is usually via blood contacts. E?ective screening of blood donors and heat treatment of blood factors should prevent the spread of this infection, which becomes chronic in about 75 per cent of those infected, lasting for life. Although most carriers do not suffer an acute illness, they must practise life-long preventive measures.

Hepatitis D (HDV) cannot survive independently, needing HBV to replicate, so its sources and methods of spread are similar to the B virus. HDV can infect people at the same time as HBV, but it is capable of superinfecting those who are already chronic carriers of the B virus. Acute and chronic infection of HDV can occur, depending on individual circumstances, and parenteral drug abuse spreads the infection. The disease occurs worldwide, being endemic in Africa, South America and the Mediterranean littoral.

Hepatitis E virus (HEV) is excreted in the stools, spreading via the faeco-oral route. It causes large epidemics of water-borne hepatitis and ?ourishes wherever there is poor sanitation. It resembles acute HAV infection and the patient usually recovers. HEV does not cause chronic infection. The clinical characteristics of the ?ve hepatic

viruses are broadly similar. The initial symptoms last for up to two weeks (comprising temperature, headache and malaise), and JAUNDICE then develops, with anorexia, nausea, vomiting and diarrhoea common manifestations. Upper abdominal pain and a tender enlarged liver margin, accompanied by enlarged cervical lymph glands, are usual.

As well as blood tests to assess liver function, there are speci?c virological tests to identify the ?ve infective agents, and these are important contributions to diagnosis. However, there is no speci?c treatment of any of these infections. The more seriously ill patients may require hospital care, mainly to enable doctors to spot at an early stage those developing acute liver failure. If vomiting is a problem, intravenous ?uid and glucose can be given. Therapeutic drugs – especially sedatives and hypnotics – should be avoided, and alcohol must not be taken during the acute phase. Interferon is the only licensed drug for the treatment of chronic hepatitis B, but this is used with care.

Otherwise-?t patients under 40 with acute viral hepatitis have a mortality rate of around

0.5 per cent; for those over 60, this ?gure is around 3 per cent. Up to 95 per cent of adults with acute HBV infection recover fully but the rest may develop life-long chronic hepatitis, particularly those who are immunode?cient (see IMMUNODEFICIENCY).

Infection is best prevented by good living conditions. HVA and HVB can be prevented by active immunisation with vaccines. There is no vaccine available for viruses C, D and E, although HDV is e?ectively prevented by immunisation against HBV. At-risk groups who should be vaccinated against HBV include:

Parenteral drug abusers.

Close contacts of infected individuals such as regular sexual partners and infants of infected mothers.

Men who have sex with men.

Patients undergoing regular haemodialysis.

Selected health professionals, including laboratory sta? dealing with blood samples and products.... hepatitis

been recognised from earliest times. Evidence of the condition has been found in Egyptian mummies; in the fourth century BC Hippocrates, the Greek physician, called it phthisis because of the lung involvement; and in 1882 Koch announced the discovery of the causative organism, the tubercle bacillus or Mycobacterium tuberculosis.

The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.

The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.

Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.

Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.

Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.

Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.

Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.

The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.

Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has

One of the early antituberculous (see TUBERCULOSIS) antibiotics. It tended to cause DYSPEPSIA and has been replaced by newer antituberculous drugs with fewer side-effects. The ?rst-line drugs for tuberculosis are now rifampicin, isoniazid, and ethambutol.... para-amino salicylic acid

An antituberculous drug used in combination, usually with RIFAMPICIN and ISONIAZID, as the treatment regime for TUBERCULOSIS. It penetrates the MENINGES so is valuable in treating tuberculous MENINGITIS. The drug is sometimes associated with liver damage and liver function tests should be done before using it.... pyrazinamide

see isoniazid.... inh

An antibiotic derived from Streptomyces mediterranei, rifampicin is a key component of the treatment of TUBERCULOSIS. Like ISONIAZID, it should always be included unless there is a speci?c contraindication. It is also valuable in the treatment of BRUCELLOSIS, LEGIONNAIRE’S DISEASE, serious staphylococcal (see STAPHYLOCOCCUS) infections and LEPROSY. It is also given to contacts of certain forms of childhood MENINGITIS.

Rifampicin is given by mouth; during the ?rst two months it often causes transient disturbance of LIVER function, with raised concentrations of serum transaminases, but usually treatment need not be interrupted. In patients with pre-existing liver disease more severe toxicity may occur, and liver function should be carefully monitored both before starting and during rifampicin treatment. It induces hepatic enzymes which accelerate the metabolism of various drugs including ANTICOAGULANTS, SULPHONYLUREAS, PHENYTOIN SODIUM, CORTICOSTEROIDS and OESTROGENS. The e?ectiveness of oral contraceptives is reduced and alternative family-planning advice should be o?ered.

Rifampicin should be avoided during pregnancy and breast feeding, and extra caution should be applied if there is renal impairment, JAUNDICE or PORPHYRIAS. Adverse effects include gastrointestinal symptoms, in?uenza-like symptoms, collapse and SHOCK, haemolytic ANAEMIA, acute ?ushing and URTICARIA; body secretions may be coloured red.... rifampicin

A group of watersoluble vitamins comprising thiamine (vitamin B1), riboflavin (vitamin B2), niacin, pantothenic acid, pyridoxine (vitamin B6), biotin (vitamin H), and folic acid. Vitamin B12 is discussed above.

Thiamine plays a role in the activities of various enzymes involved in the utilization of carbohydrates and thus in the functioning of nerves, muscles, and the heart. Sources include whole-grain cereals, wholemeal breads, brown rice, pasta, liver, kidney, pork, fish, beans, nuts, and eggs.

Those susceptible to deficiency include elderly people on a poor diet, and people who have hyperthyroidism, malabsorption, or severe alcohol dependence. Deficiency may also occur as a result of severe illness, surgery, or injury.

Mild deficiency may cause tiredness, irritability, and loss of appetite. Severe deficiency may cause abdominal pain, constipation, depression, memory impairment, and beriberi; in alcoholics, it may cause Wernicke–Korsakoff syndrome. Excessive intake is not known to cause harmful effects.

Riboflavin is necessary for the activities of various enzymes involved in the breakdown and utilization of carbohydrates, fats, and proteins; the production of energy in cells; the utilization of other B vitamins; and hormone production by the adrenal glands. Liver, whole grains, milk, eggs, and brewer’s yeast are good sources. People who are susceptible to riboflavin deficiency include those taking phenothiazine antipsychotic drugs, tricyclic antidepressant drugs, or oestrogen-containing oral contraceptives, and those with malabsorption or severe alcohol dependence. Riboflavin deficiency may also occur as a result of serious illness, surgery, or injury.

Prolonged deficiency may cause soreness of the tongue and the corners of the mouth, and eye disorders such as amblyopia and photophobia.

Excessive intake of riboflavin is not known to have any harmful effects.

Niacin plays an essential role in the activities of various enzymes involved in the metabolism of carbohydrates and fats, the functioning of the nervous and digestive systems, the manufacture of sex hormones, and the maintenance of healthy skin. The main dietary sources are liver, lean meat, fish, nuts, and dried beans. Niacin can be made in the body from tryptophan (an amino acid). Most cases of deficiency are due to malabsorption disorders or to severe alcohol dependence. Prolonged niacin deficiency causes pellagra. Excessive intake is not known to cause harmful effects.

Pantothenic acid is essential for the activities of various enzymes involved in the metabolism of carbohydrates and fats, the manufacture of corticosteroids and sex hormones, the utilization of other vitamins, the functioning of the nervous system and adrenal glands, and growth and development. It is present in almost all vegetables, cereals, and animal foods. Deficiency of pantothenic acid usually occurs as a result of malabsorption or alcoholism, but may also occur after severe illness, surgery, or injury. The effects include fatigue, headache, nausea, abdominal pain, numbness and tingling, muscle cramps, and susceptibility to respiratory infections. In severe cases, a peptic ulcer may develop. Excessive intake has no known harmful effects.Pyridoxine aids the activities of various enzymes and hormones involved in the utilization of carbohydrates, fats, and proteins, in the manufacture of red blood cells and antibodies, in the functioning of the digestive and nervous systems, and in the maintenance of healthy skin. Dietary sources are liver, chicken, pork, fish, whole grains, wheatgerm, bananas, potatoes, and dried beans. Pyridoxine is also manufactured by intestinal bacteria. People who are susceptible to pyridoxine deficiency include elderly people who have a poor diet, those with malabsorption or severe alcohol dependence, or those who are taking certain drugs (including penicillamine and isoniazid). Deficiency may cause weakness, irritability, depression, skin disorders, inflammation of the mouth and tongue, anaemia, and, in infants, seizures. In very large amounts, pyridoxine may cause neuritis.

Biotin is essential for the activities of various enzymes involved in the breakdown of fatty acids and carbohydrates and for the excretion of the waste products of protein breakdown. It is present in many foods, especially liver, peanuts, dried beans, egg yolk, mushrooms, bananas, grapefruit, and watermelon. Biotin is also manufactured by bacteria in the intestines. Deficiency may occur during prolonged treatment with antibiotics or sulphonamide drugs. Symptoms are weakness, tiredness, poor appetite, hair loss, depression, inflammation of the tongue, and eczema. Excessive intake has no known harmful effects.

Folic acid is vital for various enzymes involved in the manufacture of nucleic acids and consequently for growth and reproduction, the production of red blood cells, and the functioning of the nervous system. Sources include green vegetables, mushrooms, liver, nuts, dried beans, peas, egg yolk, and wholemeal bread. Mild deficiency is common, but can usually be corrected by increasing dietary intake. More severe deficiency may occur during pregnancy or breastfeeding, in premature or low-birthweight infants, in people undergoing dialysis, in people with certain blood disorders, psoriasis, malabsorption, or alcohol dependence, and in people taking certain drugs. The main effects include anaemia, sores around the mouth, and, in children, poor growth. Folic acid supplements taken just before conception, and for the first 12 weeks of pregnancy, have been shown to reduce the risk of a neural tube defect.... vitamin b complex