1. Chemotherapeutic Agents, chapter 34-39 Antibacterial compounds (procaryotes) Antifungal compounds (eucarytotes) Antiparasitic agents (eucarytotes) Antiviral compounds Anticancer compounds

2. Different living organisms

3. Antibacterial compounds, chapter 34 (- antimycobacterials) Synthitic antibacterials (chemotherapeutica) Antibiotics Product from metabolism (natural product) (also applies if compd is prepared synthetically, or is a synthetic analog of a naturally occuring antibiotic/ semisynthetic compd) Inhibit growth (bacteriostatic) or kill (bacteriocide) microorg. Effective in low conc. Antimicrobial chemotherapeutics: Antimicrobial comp ≠ Antibiotics

4. G+ and G- bacteria

5. Synthetic antibacterials (chemotherapeutica) Antibacterial sulfonamides

6. Nøytral sulfonilamid dårlig vannløselig. Urine pH ca 6: Crystallization neutral form, kidney damage Modern sulfa drugs pKa 5 – 7; better solubility Sulfametoxazol Bactrim®, Trimetoprim-Sulfa ® - Urine infections Combi. with trimethoprime

7. Trimetoprim Inhib. of folate reductase

8. Quinolones Inhib DNA-synthesis; DNA-gyrase (prokaryoter) uwounding DNA before replic.. DNA-topoisomerase (humans), anticancer compds. ex. doxorubicin Unique mecanism, no cross resistance Broad spectrum: G+ and G- ; also mycobactria, clamydia

9. Ciprofloksacin Ciprox®, Ciprofloxacin® Cilox® Ofloksacin Tarivid® (±)

10. Oxazolidones Linesolid Zyvoxid® Reg. Norge 2002, 1. antibact. drug with new mechaanism of action in 35 years Inhib. protein synthesis early No cross resist.. G+ and some G-. Resistant strains New drugs?

11. Other antibiotics

12. Antibiotics Penicillines  -Lactam-antibiotics

13. G- G+

14. Semi synthesis Stability

17. Nat. occuring P. Semisynthetic, increased acid stability Piperacillin Tazocin® Amoxicillin Amoxicillin®, Pivampicillin Pondocillin®, Ampicillin Pentrexyl®,

18. Kloksacillin Ekvacillin® Dikloksacillin Diclocil® Meticillin Acid labile, last resort drug resist. strains

19. Semisynthetic, Broad spectrum, Imines Meticillinam Selexid® Pivmeticillinam Selexid® No nucleophilic cabronyl

20.  - Lactamase Inhibitors Combination with penicillines Clavulanic acid Tazobaktam Mechanism based irreversible enzyme inactivators Suicide substrate - kcat inhibitors - Trojan horse inhib. - latent alkylating agent ≈ Pro-drug, must be activated by the enzyme

21. Carbapenems / Carbapenins Meropenem Meronem® 2. Gen. Not cleaved by DHP-1 Imipenem + cilastan Tienam®

22. Cephalosporins

24. 1. generation:Relatively broad spectrum (G+, some G-) Cleaved by  -Lactamase Cephalexin Cefalex® Keflex® Cefalotin Cefalotin® Keflin® 2. generation:More broad spectrum Not cleaved by  -Lactamase Cefoxitin Mefoxitin® Cefuroxim Cefuroxim® Zinacef®

25. 3. generation:Very broad spectrum, also Pseudomonas sp Not cleaved by  -Lactamase Acid labile Cefotaxim Cefotaxime® Claforan® Ceftazidim Fortum® Ceftriaxon Rohephalin® Oral 3. gen (not in N): R: -H, -CH=CH 2, -CH 2 OCH 3

26. Monobactams Aztreonam Azactam®

27. Aminoglycosides Bind to mRNA read wrong Transloc. blocked

29. Lincomycines

30. Tetrasyclines Chelate

31. Stability; acid / base

34. Makrolides

36. Polypeptides

38. Others