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Antimycobacterial drugs

Antimycobacterial drugs. Famous Aff e cted Europeans. Lesja Ukrainka Anton Tchekhov John Keats Frédéric Chopin Charlotte , Emily , and Anne Brontë Franz Kafka George Orwell. Increased Risk for TB : People with HIV People who smoke 20+ cigarettes daily.

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Antimycobacterial drugs

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  1. Antimycobacterial drugs

  2. FamousAffectedEuropeans • LesjaUkrainka • Anton Tchekhov • JohnKeats • FrédéricChopin • Charlotte, Emily, andAnneBrontë • FranzKafka • GeorgeOrwell

  3. Increased Risk for TB: People with HIVPeople who smoke 20+ cigarettes daily Man at an increased risk for TB

  4. Mordidity on tuberculosis in Ukraine

  5. AIDS in Ukraine

  6. 10-15 mlnco-infected AIDS 33 mln infected Tuberculosis 2 bln infected Multyresistant tuberculosis

  7. Ukraine • Morbidity 100/100000population • 48,000 new cases annually • Mortality 15/100000 • Every hour 1 person dies from tuberculosis • 8.3% of TB cases that are HIV + • 10 % of new cases are MDR-TB 2005 2006

  8. Ukrainian PrisonsHigher risk for developing active TB due to the following problems: • -Poor infection control • -Delays in diagnosis • -Inadequate treatment • -High prevalence of HIV • -Overcrowding and poor nutrition • TB is not unavoidable in prisons!

  9. 1993 – WHO Epidemyoftuberculosishasstartedintheworld, inthemostcountriesithasspreadfarbeyondcontrolbordersandnowitis a globaldangerforhumanity

  10. Treatment of patients with tuberculosis • Chemotherapy with tuberculostatics • Hygiene regime • Diet • Fito therapy • Sanatorium treatment • Collapse therapy • Surgical methods • Other drugs

  11. Antimycobacterial drugs • Derivatives of HINA: isoniazid, ftivazid etc. • Antibiotics: rifampicin, rifabutin, strepromycin, kanamycin, florimycin, capreomycin, cycloserine • Derivatives of pyrazin-carbonic acid: pyrazinamide • Ethambutol • Tiourens: tioacetazone (tibon), salutizone • Derivatives of tiamide-α-ethylizonicotinic acid: ethionamide, protionamide • Saltsof PASA: PASA-Naetc. • Combinatedtuberculostatics: • inabutol (isoniazid + ethambutol) • infiricine (rifampicine + isoniazide) • rifater (isoniazide + rifampicine + pyrazinamide)

  12. Classification of International Union of tuberculosis treatment

  13. 1st row: Isoniazid, Rifampicin, Ethambutol, Pirazynamid, Streptomycine 2nd row others

  14. Isoniazide • Inhibits synthesis of phospholipids and damages membranes of MBT, hurts mycolyc acids • Forms compositionswithtwo-valentions • Hurts formation of RNA and DNA • Inhibits oxidative processes • Actson MBT whichisinstateofactivedevelopment, situatedintra- andextracellularly • Penetratesthroughallorgansandtissues

  15. Metabolism in liver (acetylation)HINAinactivators (acetylators) (genetics)

  16. Side effects of isoniazide (derivatives of HINA) (5-18% of patients) • CNS – headache, euforia, insomnia, dizzyness • peripheral neuritis (derivatives of HINA – antivitamins В6), prophylaxis – 50 mg Vit В6 daily • allergy (treatment – antihistamine) • heart – tachycardia, arrhythmia • dyspeptic disorders, stomatitis • hepatitis

  17. Rifampicine • Bactericide action, wide spectrum of action • damages synthesis of proteins of MBT • influences on intra- and extracellular MBT • penetratesthroughallorgansanddamagedareas(moleculeinnotionized) • concentrationin organsis 3-4 timeshigherthaninbloodserum

  18. Rifampicine

  19. Rifampicine

  20. Side effects of rifampicine (8-22%) • hepatotoxicity • immune-allergic complications • pseudo-flue syndrome - decreasing of platelets aggregation • haemolysis • acute hepato-renal insufficiency • induction of microsomal enzymes→ decreasing of effectiveness of oral contraceptives etc. • dyspeptic manifestations, stomatitis • changes of urine, feaces,sweat, tears etc. color into orange-red

  21. Streptomycin • wide spectrum of action • influences only on MBT situated extracellularly • is not absorbed in GIT • concentration in tissues is 25-40 times lower than in blood • does not penetrate in caverns, through BBB

  22. Side effects of streptomycin • Allergic reactions • Ototoxic action • Peripheral neuritis • Nephrotoxic action

  23. Ethambutol • Influences on atypical mycobacterium • On intra- and extracellular MBT, which rapidly reproduce • Gets accumulated in erythrocytes • Penetrates into all organs and tissues, into caverns

  24. Side effects of ethambutol(1-2%) • Retro bulbar neuritis of optic nerve (disorders of color vision – green, red, inaccuracy) – shouldn’t be administered for children under the age of 12 • Bronchial spasm

  25. Pyrasinamid • Acts on MBT, which are in condition of metabolic rest • On intra- and extracellular MBT • Penetrates into all organs and tissues • Activity grows in acid medium of caseous masses

  26. Side effects of pyrasinamid • hepatotoxicity • early – 7th day • late – after 6-8 months • dyspeptic disorders • arthralgia (retains uric acid in the organism – pyrasine-carbon acid is its antagonist) • Photosensitization

  27. Ciprobai (ciprofloxacin)

  28. Abactal (pefloxacin)

  29. Nolicin (norfloxacin)

  30. Other fluoroquinolones • Lomefloxacin • Levofloxacin • Moxyfloxacin

  31. Standard regimes of anti-tuberculosis treatment according to WHO

  32. Tuberculosis treatment

  33. 3 main schemes of administration of anti-tuberculosis drugs • І. Traditional long lasting (brakeless) treatment • ІІ. Intermitting chemotherapy • 3 times a week • 1 time a week (HINAin slow acetylators) • mixed chemotherapy (interchange of one drug in a certain combination - 3-4 drugs daily from 5-6 of the administered) – 1-3 times a week the combination is changed, at nowadays – 5-6 drugs simultaneously • ІІІ. Short lasting courses of brakeless treatment

  34. FLUOROQUNOLONES

  35. І generation Ciprofloxacin * Ofloxacin * Norfloxacin * Pefloxacin * Lomefloxacin * Fleroxacin ІІ generation Grepafloxacin Sparfloxacin* Gatifloxacin Clinafloxacin Moxifloxacin* Trovafloxacin Levofloxacin * Classificatoin of fluoroquinolones

  36. Ciprolet (Ciprofloxacin)

  37. Nolicine (Norfloxacine)

  38. Drugsof І choice Acuteattackofchronicbronchitis Acuteandchronicsinusitis Malignantotitis Hospitalpneumonia Pneumoniaandbronchitisinpatientswithtuberculosis Pneumoniainpatientswithmucoviscidosis Cholecystitis/ cholangitis Chronicpielonephritis Chronicprostatitis Bacterialdiarrhea Diarrheaoftravellers Alternative drugs Acute medial otitis Community-acquired pneumonia Sepsis Intraabdominal infections Osteomyelitis Postoperative arthritis Gynecological infections Meningitis Indications for fluoroquinilones administration

  39. Side effects offluoroquinilones • photosensitization • seizures (if combined with metronidazole, NSAIDs) • dyspeptic disorders • changes of mood, insomnia, depression • allergic reactions • ulcerations of cartilages in children and teenagers

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