PENICILLINS

3. PENICILLINS • One of the most important groups of antibiotics. • They are still widely used . • Drugs of choice for a large number of infectious diseases.

5. S CH3 O C CH3 R C N C C A B C N C COOH O A-Thiazolidine ring B-Beta-Lactam ring CH2 R= Penicillin G

6. CLASSIFICATION OF THE PENICILLINS • Natural penicillins (Pen G and V) • Penicillinase-resistant penicillins • Aminopenicillins • Carboxypenicillins • Ureidopenicillins • Combinations with -lactamase inhibitors

7. PENICILLIN G AND V • Antimicrobial activity-NON-PENICILLINASEproducing strains of most cocci, gram positive bacilli and spirochetes.

8. DISTRIBUTION • Widely distributed throughout body spaces.

9. INFLAMED MENINGES CSF CONC’N OF PEN G NORMAL MENINGES Pen G injected HOURS

10. METABOLISM AND EXCRETION • Only a small amount is metabolized. • Pen G is eliminated rapidly and primarily by active renal tubular secretion with a short half-life.

11. REPOSITORY PREPARATIONS • Penicillin G procaine and Penicillin G benzathine (IM).

12. Pen G (IM) Pen V (Oral) Pen G (Oral) Procaine Pen G Benzathine Pen G Blood Level 2 4 6 12 18 24 Time (hrs)

13. THERAPEUTIC USES • Penicillin G is the first choice for most infections due to bacteria sensitive to penicillin.

15. Acute pneumococcal pneumonia

16. THERAPEUTIC USES • Syphilis (Benzathine Pen G)

17. Bacteroides fragilis

18. PROPHYLACTIC USES • Streptococcal infections. • Recurrences of rheumatic fever. • Syphilis.

19. PENICILLIN V • Continued treatment of infections initially treated with parenteral Pen G. • Prophylaxis of streptococcal infections (e.g.rheumatic fever).

20. SEMISYNTHETIC PENICILLINS

21. PENICILLINASE RESISTANT PENICILLINS-PROPERTIES • Resistant to hydrolysis by staphylococcal penicillinase. • Less active vs other penicillin-sensitive organisms.

22. THERAPEUTIC USES • Drugs of choice for infections caused by penicillinase-producing Staph. aureus.

23. OCH3 OCH3 METHICILLIN RESISTANT TO PENICILLINASE ORAL ABSORPTION IS POOR NARROW SPECTRUM

24. METHICILLIN-RESISTANT STAPH. (MRSA) INFECTIONS • Most commonly identified antibiotic-resistant pathogen in US hospitals. • MRSA has spread beyond health care facilities emerging in the community, where it is rapidly becoming a dominant pathogen. • Resistant to several antibiotics including penicillins and cephalosporins.

25. TREATMENT OF HA-MRSA • Vancomycin is the treatment of choice.

29. CA-MRSA • Patients with serious CA-MRSA infections should be hospitalized and treated with IV vancomycin, linezolid or daptomycin. • For less serious CA-MRSA skin or soft tissue infections, oral TMP/SMX, minocycline, doxycycline, clindamycin or linezolid could be tried.

31. ISOXAZOLYL PENICILLINS • Acid stable and adequately absorbed after oral administration. • Orally for infections of moderate severity and for prolonged outpatient treatment of chronic infections (e.g. osteomyelitis). • Parenterally for serious staph infections.

32. OC2H5 NAFCILLIN GI ABSORPTION IS VARIABLE

33. AMINOPENICILLINS • Increased activity against many gram - organisms. • Metabolized by -lactamases from both gram + and – bacteria. • Not substitutes for penicillin G or V. • Includes AMOXICILLIN, AMPICILLIN and congeners.

34. C C AMINOPENICILLINS O H HO NH AMOXICILLIN Good oral absorption

35. AMOXICILLIN-THERAPEUTIC USES • Sinusitis and other upper respiratory infections. • Bacterial endocarditis prophylaxis-DOC for prophylaxis in patients at risk while undergoing dental, oral or upper respiratory tract procedures.

36. ANTIPSEUDOMONAL PENICILLINS • Extended antibacterial range compared to amoxicillin. • Hydrolyzed by penicillinases. • Carboxypenicillins and ureidopenicillins.

37. TICARCILLIN (Ticar) • Must be given parenterally. • Gram negative infections caused by Pseudomonas and Proteus. • For most serious systemic pseudomonal infections use an antipseudomonal penicillin plus an aminoglycoside.

38. UREIDOPENICILLINS- MEZLOCILLIN AND PIPERACILLIN • Given parenterally.

39. THERAPEUTIC USES • Serious gram negative infections, especially pseudomonas.

40. COMBINATIONS WITH BETA LACTAMASE INHIBITORS • Penicillin plus a beta lactamase inhibitor.

42. BETA-LACTAMASE INHIBITOR COMBINATIONS • Inhibitor has only weak intrinsic activity. • Combination has a broader spectrum than penicillin alone.

43. THERAPEUTIC USES • Useful in infections caused by - lactamase producing bacteria, certain anaerobic infections and other infectionsusually not sensitive to penicillin.

44. SUMMARY OF THE USES OF THE DIFFERENT PENICILLINS

45. SUMMARY OF THE USES OF THE DIFFERENT PENICILLINS

47. ADVERSE REACTIONS TO THE PENICILLINS

48. HYPERSENSITIVITY REACTIONS • Cross allergenicity among all the penicillins. • Result from a previous treatment.

50. HYPERSENSITIVITY REACTIONS • Occur with almost any dosage form of penicillin. Oral penicillins have a lower risk than parenterals. • Usually clear with elimination of the penicillin.