1. 1 PROTEIN SYNTHESIS INHIBITORS

2. 2 These antibiotics exert their actions by targeting the bacterial ribosome which has components that differ structurally from mammalian cytoplasmic ribosome. Bacterial ribosome is smaller 70 s as compared to the mammalian cytoplasmic ribosome - 80 s

3. 3 Very broad spectrum. Aerobic gm +/- Many anaerobes SE: Toxicity Nephro- Oto-toxic Very broad spectrum. Many gm +, some gm – Pen allergic pt SE: GI distress Gm+/- bacteria Spirochetes, Rickettsiae Resistant organisms SE: GI distress Photosensitivity Impair teeth & bone growth Chloramphenicol: many Gm -/+ bacteria Serious infxn. SE: Bone marrow aplasia Clindamycin: Most Gm +, some Gm – Alternative use. SE: colitis - PMC (C. difficile) Ethionamide: TB SE: GI distress Azithromycin (Zithromax) p. 554

4. 4 Aminoglycosides Susceptible organisms allow aminoglycosides to diffuse through their porin channels in their outer membranes. These organisms have oxygen dependant system that transports the drug across cell membrane.

5. 5 They bind to the 30s ribosomal subunit interfering with the assembly of functional ribosomal apparatus. They synergise with beta lactAM ANTIBIOTICS BECAUSE OF THE LATTERS ACTION ON CELL WALL SYNTHESIS, WHICH ENHANCES DIFFUSION OF THE AMINOGLYCOSIDES INTO THE BACTERIUM.

6. 6 THEY ARE BACTERICIDAL. THAY ARE EFFECTIVE ONLY AGAINST AEROBIC ORGANISM, AS ANEROBES LACK THE OXYGEN REQUIRING TRANSPORT SYSTEM. STREPTOMYCIN IS USED TO TREAT TB, PLAGUE & TULAREMIA.

7. 7 Resistance Porin channels are absent Altered 30 s subunit Plasmid associated synthesis of enzymes

8. 8 Aminoglycosides Route : parenteral Exception : neomycin –topical and sometimes oral for hepatic coma. Distribution : low conc. in CSF, Crosses placenta Excretion : Glomerular filtration HIGH CONCENTRATIONS ACCUMULATE IN THE RENAL CORTEX, ENDOLYMPH AND PERILYMPH OF INNER EAR.

9. 9 Aminoglycosides - SE OTO TOXICITY DEAFNESS, VERTIGO NEPHRO – TOXICITY RENAL TUBULAR NECROSIS NEURO MUSCULAR PARALYSIS- Ach RX – mostly calcium gluconate or neostigmine can reverse the situation CONTACT DERMATITIS –neomycin

10. 10 TETRACYCLINES Consist of 4 fused rings with a system of conjugated double bonds. THEY BIND TO THE 30S SUBUNIT OF THE BACTERIAL RIBOSOME AND BLOCK ACCESS OF THE AMINO ACYL-TRNA TO THE MRNA-RIBOSOME COMPLEX. THUS THEY INHIBIT BACTERIAL PROTEIN SYNTHESIS.

11. 11 TETRA CYCLINES ROUTE : ORAL,DECREASED BY MILK ANTACIDS IRON SUPPLEMENTS DISTRIBUTION :CROSSES BBB but not that good. Minocycline readily crosses placenta. High levels in calcium tissues- bones, teeth, some tumors Excretion :renal, exception – doxycycline ( In bile )

12. 12 They are useful in the treatment of chlamydial infection, rocky mountain spotted fever, lyme disease, mycoplasma pneumonia, cholera.

13. 13

14. 14

15. 15 TETRA CYCLINES - SE MC : GIT- epigastric discomfort CALCIUM DEPOSITION : GROWTH –STUNTED, TEETH – SMALL, DISCOLORED PHOTO TOXICITY HEPATO TOXICITY VERTIGO – MINOCYCLINE ICT –INCREASED CI : WOMEN – preg, lactating, children

16. 16 Macrolides Macrolides are a group of antibiotics with a macrocyclic lactone structure to which one or more deoxy sugars are attached. Macrolides bind to 50 s subunit of the bacterial ribosome thus inhibiting the translocation steps of protein synthesis. Erythromycin Same like penicillin G Indication – used in pt. with allergy to penicillins

17. 17 Clarithromycin Spectrum : Erythromycin - Haemophilus INFLUENZA Azithromycin Spectrum : Clarithromycin - Moraxella & respiratory pneumonias

18. 18 Macrolides Route : oral IV – thrombo phlebitis Distribution : CSF – poor. Prostate – good Excretion : liver ( in bile) Exception – clarithromycin – renal also

19. 19 Macrolides - SE MC : GIT OTO TOXICITY CHOLESTATIC JAUNDICE CI : LIVER FAILURE

20. 20 chloramphenicol BINDS TO THE 50 S RIBOSOMAL SUBUNIT AND INHIBITS PROTEIN SYNTHESIS AT THE PEPTIDYL TRANSFERASE REACTION. RESISTANCE IS BECAUSE OF R FACTOR WHICH CODES FOR ACETYL CO-A

21. 21 Broad spectrum antibiotic Active against rickettsiae Excellent against anaerobes Can be bactericidal or bacteriostatic.

22. 22 CHLORAMPHENICOL ROUTE : ORAL / IV DISTRIBUTION : CROSSES BBB, WITHOUT INFLAMMATION EXCRETION : RENAL SE GRAY BABY SYNDROME- under developed renal function. Accumulation leads to interference with function of mitochondrial ribosomes. HEMOLYTIC ANEMIA : G 6 PD DEFICIENCY

23. 23 CLINDAMYCIN INDICATION BACTERIODES FRAGILIS ROUTE : ORAL EXCRETION : RENAL & HEPATIC SE : PSEUDOMEMBRANOUS COLITIS

24. 24 Quinipristin/dalfopristin Mixture of two streptogramins in a ratio of 30 to 70. Each component of this combination binds to a separate site on 50 s bacterial ribosome. the combination drug is bactericidal. Active against mrsa resistant to vancomycin.

25. 25 Linezolid Methicillin and vancomycin resistant staphylococcus aureus. Inhibits formation of 70 s initiation complex and thus inhibits protein synthesis.