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(TB) remains the leading cause of death worldwide from a single infectious disease agent.
1/2 of the world's population is infected with TB. The registered number of new cases of TB worldwide roughly correlates with economic conditions: the highest incidences are seen in those countries of Africa, Asia, and Latin America with the lowest gross national products. WHO estimates that eight million people get TB every year, of whom 95% live in developing countries. An estimated 2 million people die from TB every year.
It is estimated that between 2000 and 2020, nearly one billion people will be newly infected, 200 million people will get sick, and 35 million will die from TB - if control is not further strengthened. The mechanisms, pathogenesis, and prophylaxis knowledge is minimal. After a century of decline TB is increasing and there are strains emerging which are resistant to antibiotics. This excess of cases is attributable to the changes in the social structure in cities, the human immunodeficiency virus epidemic, and failure of most cities to improve public health programs, and the economic cost of treating.
TB is an ancient infectious disease caused by Mycobacterium tuberculosis . It has been known since 1000 B.C., so it not a new disease. Since TB is a disease of respiratory transmission, optimal conditions for transmission include:
This is known as the primary infection. The patient will heal and a scar will appear in the infected loci. There will also be a few viable bacilli/spores may remain in these areas (particularly in the lung). The bacteria at this time goes into a dormant state, as long as the person's immune system remains active and functions normally this person isn't bothered by the dormant bacillus.
When a person's immune system is depressed., a secondary reactivation occurs. 85-90% of the cases seen which are of secondary reactivation type occurs in the lungs.
- The main excretory product- acetylisoniazid. This is a result of enzymatic acetylation, Very important in terms of metabolism, Isoniazid is under genetic control, There are 2 groups of people. Fast and slow acetylators
Induced Hepatitis (2% of Population) due to the buildup of toxic metabolic products of acetylisoniazid --> acetylhydrazine. This is more frequent in slow acetylators .
Hepatic reactions to Isoniazid are also age dependent
There is a 250X increase in the incidence of hepatitis over age. More frequent in the fast acetylators when measured intragroup, (Compare elderly fast acetylators patients with elderly slow patients,) Ranges from mild hepatitis to serious tissue necrosis.
Age dependency >60 2.5 55 1.75 45 1.09 35 .59 25 0.13 age % incidence
Competition between Isoniazid and Phenytoin (anticonvulsant). They both compete for drug metabolism enzymes. Phenytoin interferes with metabolism of isoniazid by reduction in excretion or enhancement of effect of isoniazid
Due to alteration of the target (DNA dependent RNA polymerase) of the drug, prevents further initiation but not elongation. The micro-organism can change the structure of the enzyme so that the drug no longer has an effect.
Rifampin does induce microsomal drug metabolizing enzymes. This will decrease the half-life of some other drugs. (ie. phenytoin, digitoxin)
WARNING! Rifampin and Isoniazid are the most effective drugs for the treatment of TB, The drug enjoys high patient compliance and acceptability. But these 2 drugs should never be given alone! They are always used in combination because resistance occurs to one drug alone very rapidly. They are used in combination with each other initially as well as other drugs. Bacilli must become resistant to two drugs in order to remain viable. Statistically, the chances are verv small of the bacilli becoming resistant to both. . Prophylaxis is with one drug usually isoniazid.
2nd Line Drugs: Not as effective and have more toxicity
The first drug used clinically for treatment of TB 1947-1952; was the only drug available at that time.
is an aminoglycoside antibiotic
acts by protein synthesis inhibitor and decreases the fidelity mRNA and garbles the message, leads to nonsense proteins.
a structural analog of PABA (p-aminobenzoic acid) is bacteriostatic inhibits de novo folate synthesis
half life = 1 hour after 4 g. dose
you can give this drug up to 12 grams per day. 80% of the drug is excreted in the urine and 50% of that is as an acetylated metabolite which is insoluble. You must make sure the patient's urine is normal or alkaline.
Pharmacokinetics: Rapidly absorbed Peak [plasma] occurs in 3-4 hours Distributed throughout all body fluids, including CSF About 50% is excreted in unchanged form in the urine during the first 12 hours. Only about 35% of the drug metabolized This drug can accumulate to toxic conc in patients with renal insufficiency
The drug of choice for chemoprophylaxis is isoniazid. Prophylaxis uses only one drug. In patients who are HIV+ and TB+ and have the disease; they are treated for a minimum of 9 months, The first 2 months using isoniazid and rifampin and for the next 7 months or longer, use only 2 or 3 of the 2nd/3rd line drugs and Isoniazid/Rifampin.
Isoniazid, Ethambutol, & Rifampin are given for 2 months.
Isoniazid & Rifampin are given for 4 months.
If you suspect resistance to isoniazid use Isoniazid, Ethambutol, Rifampin & Parazinamide. Incidence of drug resistance is 2-5% in the U.S.
Prolonged bed rest is not necessary or helpful in obtaining a speedy recovery. The patient must be seen at regular and frequent intervals to follow the course of the disease and treatment. Look for toxic effects
Positive Skin Tests for Tuberculosis (American Family Physician) http://www.aafp.org/afp/961101ap/pat_1991.html
National Tuberculosis Center http:// www.umdnj.edu/~ntbcweb/ntbchome.htm
CDC; Division of Tuberculosis Elimination http://www.cdc.gov/nchstp/tb/structure.htm
Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children American Thoracic Society Medical Section of the American Lung Association American Journal of Respiratory and Critical Care Medicine Vol 149 1994 http://aepo-xdv-www.epo.cdc.gov/wonder/PrevGuid/p0000413/p0000413.htm
Brief History of Tuberculosis http:// www.umdnj.edu/~ntbcweb/history.htm