ANTIBIOTICS-1

1. ANTIBIOTICS-1

3. Bacteria Shapes (a) Round cocci (b) Rod-like bacilli (c) Spiral-shaped spirochetes

4. Principles of rational antibiotic therapy • Presence of substantiated indications for prescription of an antibiotic • Choosing of the most effective and the least toxic drug, intime administration • Introduction of optimal doses with optimal frequency, taking into consideration complexity of the disease • Choosing of the optimal way of introduction • Estimation of duration of treatment • Control after treatment • Monitoring and prophylaxis of negative side effects • Decision on expediency of combined antibiotic therapy

8. ANTIBIOTICS • Beta-lactam antibiotics: • А. Penicillins • Б. Inhibitors of beta-lactamases and combined drugs, • В. Cephalosporins • Г. Monobactams • Д. Tienamycin (carbapenems). • Macrolides, azalides, streptogramins, prystinamycines. • Linkozamides. • Tetracyclines. • Aminoglycosides. • Chloramphenicols. • Glycopeptides. • Cyclic polipeptides (polimixins). • Other antibiotics

9. ANTIBIOTICS

11. PENICILLINS Natural (biosynthetic) penicillins: • benzylpenicillin (penicillin G), phenoxymethylpenicillin (penicillin V), novocain salt of benzylpenicillin (benzylpenicillin procain), bicillin-1 (benzatyn benzylpenicillin), bicillin-3, bicillin-5. Semisynthetic penicillins: • 1antistaphylococci penicillinase resistant penicillins – izoxazolil-penicillins (oxacillin, dicloxacillin, methicillin); • 2of a spread spectrum – aminopenicillins (ampicillin, amoxicillin); • 3antipseudomonade – carboxypenicillins (carbenicillin, ticarcillin); ureidopenicillins (azlocillin, piperacillin, sulbenicillin); • 4 combined with inhibitors of beta-lactamases - “protected” penicillins (amoxicillin/clavulanate, ampicillin/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam).

13. S H2N CH3 CH3 T L O N C O OH Nucleus of penicillin molecule L – beta-lactame ring, T – thiazoline ring

14. Mechanism of penicillins action They form complexes with enzymes - trans- and carboxypeptidases (PCP), which control synthesis of peptidoglycan – component of cell-wall of microorganisms

15. Spectrum of action of biosynthetic penicllins

16. schemes on introduction of biosynthetic penicillins

18. Complications of biosynthetic penicillins • Allergic reactions (10%) • Endotoxic shock • Disorders of electrolyte balance • Neurotoxic reactions (in using of big doses) – encephalopathy (hyperreflexia, seizures, hallucinations, coma) • Daily dose of BPduring intratecal introductionshould not overcome 10000 U (5000 U – for children) • Interstitial nephritis

19. Oxacillin Antistaphylococci penicillinase-resistant semisynthetic penicillin, acid stable Administration: intramuscular, intravenously, oraly 3-6-8 g/24 hours (4-6 times of injections)

20. Spectrum of action of aminopecillins (ampicillin, amoxicillin) wide spectrum, destroyed by beta-lactamases Influence on: streptococci, Haemophilus influenzae, causative agent of wooping cough, gonococci, meningococci, proteus, Escherichia coli, salmonella, shigella .

21. Ampicillin

22. Amoxicillin

23. Differences between ampicillin and amoxicillin

24. Indications for administration of amoxicillin

25. Side effects of semisynthetic penicillins • Irritation of mucous membrane of digestive tract(diarrhea) • Disbacteriosis • Superinfection (colonizing of gut with Candida fungi, enterococci, Pseudomonas aeruginosa, clostridia) • Pain in injection area, aseptical inflammation, phlebitis • Allergic reactions • Granulocytopenia (oxacillin) • Reduction of platelets agregation (ampicillin) • Disorders of liver function • Encephalopathy (in introduction of high doses)

26. Inhibitors of beta-lactamases Clavulanic acid Sulbactam Tazobactam

27. Unasyn (ampicillin/sulbactam)

28. Inhibitor-protected (“screened”, “protected”) penicillins Amoxicillin/clavulanate (amoxyclav, augmentin) Ampicillin/sulbactam (sultamycillin, unasin) Ticarcillin/clavulanate (timentin) Piperacillin/tazobactam

29. S H2N L D N CH2 O CO CH3 O O C OH Structure of cephalosporins L – beta-lactame ring, D – dihydrothiazine ring

30. Classification of cephalosporins

31. Cefazolin-sodium (C I)

32. Cezolin (Cefazolin, C I)

33. Cefalexin ( C I)

34. Zinnat (Cefuroxime, C II)

35. Cefotaxime (C III)

36. Claphoran (cefotaxime, C III)

37. Cefobid (Cefoperazone, C III)

38. Antimicrobial spectrum of cephalosporins

39. Complications, caused by cephalosporins • Irritation of mucous membrane of digestive tract, infiltrates after intromuscular introduction , phlebitis after inrtavenous introduction • Disbacteriosis, superinfection • Allergic reactions, including cross allergy with penicillins • Granulocytopenia (in case of treatment during more than 2 weeks) • Hemorrhages (inhibition of synthesis of factors of blood coagulation in liver) – cephalosporins ІІІ • Nephrotoxicity (accumulation in epithilial cells of kidney canalicules) • Encephalopathy (hyperreflexia, seizures, coma) 

40. Cephalosporines Not recommended to combine with other nephrotoxic drugs (aminoglycosides) Contraindicated to combine with loop diuretics (furosemid, etacrinic acid)

41. Carbapenems (tienamytsin) Tienam (imipenem + cylastatin) Meropenem Thewidestspectrumofantibacterialaction mostofaerobeandanaerobeGram(+) and Gram (-) bacteria, includingthosewhich produce beta-lactamase

45. ANTIBIOTICS -2

49. Classificationofmacrolides І. Natural substances: erythromycin, oleandomycin,spiramycin, jozamycin, midecamycin. ІІ. Semi-synthetic substances: roxythromycin, clarithromycin, flurythromycin, dyrythromycin, miokamycin, rokitamycin. III. Azalides (neutrogen atom is introduced in lacton ring): azithromycin.

50. Erythromycin