1. ANTIBIOTICS Dr.Tawfeq A. Al-Howiriny Associate Professor talhowiriny@yahoo.com

2. Properties and stability of pen G - Water insoluble, not used as such, used as salts “ water soluble salts “ !! - - In case of adequate renal function, K + will not be retained in the body, excreted in urine - In case of renal insufficiency or uremia, K + will retain in the body, may be cardiotoxic - All nitrogen atoms in pen G are neutral

3. Properties and stability of pen G - Ring system in all penicillins is called “ penam “ - Pen G is active only in this stereochemical form, any modification in the side chain may lead to : - Modify activity - Modify activity - modify antimicrobial spectrum - modify antimicrobial spectrum - modify stability - modify stability

4. Properties and stability of pen G - Pen G is acid unstable, used only orally - Pen G is unstable in the presence of water - Preparations must be stored in dry from, reconstituted immediately before use - Why pen G is acid unstable, and how can we find an acid stable alternative?

5. Properties and stability of pen G - The intermolecular reaction is slow and accounts for 20% of acid instability - The intramolecular reaction is fast and accounts for 80% of acid instability - Electron with drawing group, increase acid stability, orally active - Electron donating group, decrease acid stability

6. History cont. ► 70 ’ s - 80 ’ s Semisyn. : - Amoxicillin - Amoxicillin - Doxycycline - Doxycycline  80 ’ s – 90 ’ s Syn : - Aztreonam - Aztreonam  Antibiotic like compds : Highly potent, very low MIC Highly potent, very low MIC Fluoroquinolones Fluoroquinolones