1. Antibiotics Introduction
4th Year
2016

27. Chemical structure of penicillin
Beta lactam

30. Stereochemistry of Penicillins
It contains three chiral carbon atoms at C3, C4 & C6. L- configuration , C3 & C6 chiral centers are trans to each other.

31. Synthesis of Penicillin

32. Chemical degradation of penicillin a- Acidic hydrolysis

34. Mechanism of action
Like all β-lactam antibiotics , inhibit the synthesis of bacterial cell wall .
Through inhibition transpeptidase enzyme
They are bactericidal on the actively growing bacteria.

38. Combination therapy Penicillin + Beat lactamase
Many baterial β-lactamases are inhibited by clavulaic acid ± amoxicillin (co-amoxiclav)  antibiotic is effective against penicillinase-producing organisms.
Co-amoxiclav indicated in resp and UT infections, which are confirmed to be resistant to amoxicillin

39. SAR Conclusions Amide and carboxylic acid are involved in binding
Carboxylic acid binds as the carboxylate ion
Mechanism of action involves the b-lactam ring
Activity related to b-lactam ring strain (subject to stability factors)
Bicyclic system increases b-lactam ring strain
Not much variation in structure is possible
Variations are limited to the side chain (R)

40. Another strategy for complete protection of the β-lactam ring is introduction of 6 α-OCH 3, which is bulky enough to prevent β - lactamase attack from the back side. y Important example is temocillin, which is 6 α-methoxyticarcillin.

41. Metabolism & Excretion
Not metabolised
Excreted unchanged in urine
Probenecid blocks their secretion
Nafcillin is mainly cleared by biliary route
Oxacillin by both kidney & biliary route.

42. Aminopenicillins(Ampicillin &Amoxicillin)
Therapeutic uses
1)H.influenza
2)E.coli
3)Salmonella&Shigella infections only ampicillin
4)Prophylaxis of infective endocarditis
5) Urinary tract infections
6) Effective against penicillin –resistant pneumococci

43. Adverse effects Hypersensitivity reactions
High dose in renal failure ---seizure
Naficillin (neutropenia)
Oxacillin (hepatitis)
Methicillin(nephritis)
B.S.P.(pseudomembraneous colitis )
Secondary infections