呼吸系统课件：Antimycobacterial Drugs

1、 Antimycobacterial Drugs Prevalence of TB Public health campaigns in the 1920s tried to halt the spread of TB. In 2007, the prevalence of TB per 100,000 people was highest in sub- Saharan Africa, and was also relatively high in Asia. Mycobacterium tuberculosis Mycobacterium tuberculosis bacteria The

2、 bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery. Tuberculosis in China oIn China, tuberculosis has been the number 1 cause of death from infectio

3、us disease in adults. In 1990, 360,000 people in China died from tuberculosis. A new five-year initiative program, announced on 1 April 2009, aims to use innovative technologies to improve the detection and treatment of tuberculosis (TB) in China. 157810 0，000 in China About one third of the worlds

4、population is infected with tuberculosis (TB) bacteria. 10% of those infected will become sick with TB. S/S of Active Disease Signs rifampin； pyrazinamide; streptomycin; and ethambutol. First-line Isoniazidpharmacological effectspharmacological effects o Isoniazid is bactericidal to rapidly dividing

5、 mycobacteria o But isoniazid is bacteriostatic if the mycobacteria are slow- growing First-line Isoniazid Mechanism of action bacterial catalase- peroxidase enzyme isonicotinic acyl-NADH complex isonicotinic acyl with NADH synthesis of mycolic acid Kills the pathogens Destroy Cell Wall inhA First-l

6、ine IsoniazidAdverse Reactions 1. Peripheral neuropathy and CNS effects associated with the use of isoniazid and are due to vitamin B6 depletion 2. Hepatotoxicity The N-acetylhydrazine metabolite is believed to be responsible for the hepatotoxic effects seen in patients treated with isoniazid 3.Othe

7、rs rash, nausea, vomiting, abdominal pain, and appetite; anemia First-line Rifampicinmechanism of actionmechanism of action o Rifampicin inhibits bacterial DNA- dependent RNA synthesis by inhibiting bacterial DNA- dependent RNA polymerase. First-line RifampicinAdverse ReactionsAdverse Reactions o He

8、patotoxic - o Respiratory - breathlessness o Cutaneous - flushing, rash, redness and watering of eyes o Abdominal - nausea, vomiting o Flu-like symptoms - with chills, fever, headache, First-line Ethambutol EMB It is well absorbed from the gastrointestinal tract and well distributed in body tissues

9、and fluids. 50% is excreted unchanged in urine. It works by obstructing the formation of cell wall. First-line pyrazinamide，PZA o The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria o It is never used on its own. only used in combination with ot

10、her drugs such as isoniazid and rifampicin in the treatment of TB. o It has no other indicated medical uses. First-line? streptomycin o It is the first antibiotic used to treat TB. o In combination with other anti-TB drugs. o It is not the first-line treatment, except in medically under-served popul

11、ations where the cost of more expensive treatments is prohibitive. second-line o para-aminosalicylic acid, PAS： PAS is always used in combination with other anti-TB drugs. o Ethionamide: Chemically related to isoniazid. o Capreomycin: o Cycloserine: control strategy o Standard treatment regimen dire

12、ctly observed o combination of several antibiotics o A regular drug supply o treatments can be prolonged (months) drug-resistant TB o Drug-resistant TB has become a very serious problem in recent years in certain populations. o The major reason for the development of resistance is poorly managed TB care. This can result from poor patient compliance, inappropriate dosing or prescribing of medication, poorly formulated medications, and/or an inadeq