Antibiotics

this is the antibiotics

1. Antibiotics Presented By Mr. Surya Nath Pandey (Asst. Prof. )

2. ANTIBIOTICS The term antibiotics has its origin in the world antibiosis that is a process in which one organism may destroy another to preserve itself. We should know thi very clear “Antibiosis” means against the life. These are the chemical substances which is derived from different species of microorganisms (bacteria, fungi, etc.) that suppress the growth of other microorganisms and eventually may destroy them at low concentration. However, all chemical substances produced by living cells cannot function as antibiotics. In order to act as antibiotics, the compound must satisfy the following conditions:- It should be effective at low concentration against pathogens’ It should be product of metabolism analogue of naturally occurring antibiotics. It should be stable and should be completely eliminated from syste .

3. CLASSIFICATION They are classified as on the basis of mechanism of action and on the basis of chemical structure:- On the basis of mechanism of action:- 1. agents that inhibits the synthesis of bacterial cell walls:- penicillins , cephalosporins , vancomycin, cycloserine , bacitracin, imidazole & antifungals. 2. agents that act directly on the cell membrane of microorganisms, affecting permeability and leading to leakage of intracellular compounds:- polymyxin , polyene, nystatin, amphotericin B. 3. agents that affects the function of 30s and 50s ribosomal subunits :- tetracycline, erythromycin, chloramphenicol and clindamycin. 4. agents that binds to 30s ribosomal subunits and alters the protein synthesis: -aminoglycosides 5. agents that affects the nucleic acid metabolism:- rifampicin.

4. On the basis of chemical structure :- 1. β -lactam antibiotics 2. Aminoglycosides 3. Tetracycline 4. Polypeptide antibiotics Macrolides 6. Linomycins Beta lactam antibiotics: - these are the antibiotics which have β -lactam ring in their structure. It includes penicillins , cephalosporins , monobactams and carbapenems . They are described as follows:- Penicillins :- it was the discovered by Alexander Fleming in 1928. it was the 1 st antibiotic used clinically in 1941. it is a miracle that the least toxic drug of its kind was 1 st to be discovered. It was originally obtained from Penicillium notatum but present source is a high yielding mutant of penicillium chrysogenum . It contains thiazolidine and β -lactam ring.

5. Classification 1. Penicillinase -susceptible penicillins : - penicillin G, penicillin V, penicillin O, phonethicillin . 2. Penicillinase -resistant penicillins :- methicillin, cloxacillin , dicloxacillin . 3. Extend spectrum penicillins :- [A]. Aminopencillins :- ampicillin, bacampicillin , amoxicillin. [B]. Carboxypenicillins : - carbapenicillin . [C]. Ureidopenicillins : - piperacillin, mezlocillin . 4. β -lactamase inhibitor:- clavulanic acid, sulbactam , tazobactam , avibactam, relebactam . This is the classification of penicillins now comes to the mechanism/mode of action of penicillins . It is very easy to remember with the help of flow chart. All penicillins have similar MOA but t1/2 is different. Lets see the MOA of Penicillins :-

6. Mechanism of actions Things to remember: - all antibiotics inhibits the protein synthesis, DNA,RNA. After that the inhibition of that things the bacteria, microorganisms can not make their synthesis due to this inhibition.

7. MOA of Penicillins Penicillins Inhibits the synthesis of peptidoglycan layer containing NAG(N-acetyl glucosamine) and NAM (N-acetyl muramic acid) connected by PBP(penicillin binding protein) Acts on penicillin binding protein (PBP) Cell wall synthesis inhibition Bacteriostatic & bacteriocidal

8. Uses & adverse effects:- Uses:- streptococcal infections, pneumococcal infection, gonorrhoea, syphilis, tetnus , diphtheria, respiratory tract infection, urinary tract infection, etc. Adverse effect:- kidney failure, neurotoxicity, diarrhea , GIT disturbance, chills, fever, etc.

9. Cephalosporins These are the semisynthetic antibiotic which is derived from cephalosporin-C which is obtained from cephalosporium (fungus). The nucleus of its also have the β -lactam ring fused to dihydro -thiazine ring. Classification:- cephalosporins are categorized into four generations. They are described as follows:- 1 st generation: - cefazolin, cephalothin , cephaloridine, cephapirin , cefadroxil , cephalexin. 2 nd generation: - cefuroxime, cefoxitin , cefaclor , cefonicid , cefamandole . 3 rd generation: - ceftizoxime , cefotaxime , cefixime , ceftibuten , cefoperazone , ceftazidime , cefdinir 4 th generation: - cefepime , cefpirome . These are the classifications now comes to the mechanism of action. MOA of all drugs are similar but they have different t1/2.

10. Mechanism of action Cephalosporins Binds to CBP (cephalosporin binding protein) or PBP-1 or PBP-3 Inhibits the synthesis of peptidoglycan layer Inhibition of cell wall synthesis

11. β -lactamase inhibitors These are a family of enzymes involved in bacterial resistance to β -lactam antibiotics. They act by breaking the β -lactam ring that allows penicillin like antibiotics to work. They includes clavulanic acid, sulbactam , tazobactam , avibactam, relebactam . MOA of clavulanic acid: -

12. Clavulanic acid Binds with serine (amino acids makes proteins) residue in β -lactamase Creates a highly active complex this complex binds with amino acids of β -lactamase Permanently inactive β - lactamse enzyme Complete protection against resistant pathogens

13. Aminoglycoside It is a molecule composed of amino modified sugars. It has a hexose ring, either streptidine and various amino sugars are attached to this ring by glycosidic linkage. Streptomycin was the 1 st antibiotic of this group . It was discovered by Waksman and his collegue in 1944, isolated from a strain of Streptomyces griseus . Waksman got the nobel prize in 1952. Neomycin was dicovered in 1949 and kanamycin was discovered in 1960. All aminoglycosides are produced by soil actinomycetes . Classification: - a) Systemic:- streptomycin, gentamycin, amikacin, kanamycin, tobramycin, sisomicin , netilmicin . b) Topical: - neomycin, framycetin . Now comes to the mechanism of action. All aminoglycosides have similar MOA but they have different t1/2.

14. MOA Aminoglycosides Binds with 30s ribosomal unit Inhibits the initiation of protein synthesis Cause misreading of genetic code on recognition region of ribosome Insertion of wrong amino acids Destruction of cell membrane

15. Tetracycline These are class of antibiotics having a nucleus of four cyclic rings. All are obtained from soil actinimycetes . Chlortetracycline was the 1 st drug which introduced in 1948. all tetracyclines are slightly bitter solids which are slightly soluble in water, but their hydrochlorides are more soluble. All TCs have the same antimicrobial activity practically. Classifications: - 1.Natural tetracyclines : - tetracycline, chlortetracycline, oxytetracycline , bromotetracycline , dexamethyltetracycline . 2. Semisynthetic tetracyclines : - doxycycline, minocycline, methacycline , sancycline . 3. Protetracycline : - rolitetracycline , lymecycine , apicycline , meglucycline . Now comes to the MOA, every drug have the similar MOA but they have different t1/2.

16. MOA Tetracyclines Binds to A(aminoacyl t-RNA) site of 30s ribosomal subunit Prevent binding of t-RNA to A site Chain fails to grow Prevent protein synthesis

17. Macrolides These are antibiotics having a macrocyclic lactone ring with attached sugars. Erythromycin was the 1 st member discovered in 1950s. Roxithromycin , clarithromycin and azithromycin, later added. Now comes to the mechanism of action which are described as follows:-

18. MOA Macrolides Binds to 50s ribosomal unit Inhibits polypeptide chain elongation & protein synthesis inhibition Results in inhibition of growth and multiplication Erythromycin (MOA): - binds to 23s rRNA molecule in 50s. Uses: - respiratory tract infection, urinary tract infection, H. pylori, pneumonia. Adverse effect:- kidney failure, GI problems, neurotoxicity.

19. Chloramphenicol It was initially obtained from Streptomyces venezuelae in 1947. it was soon synthesized chemically and commercial product now it is all synthetic. It is a yellowish white crystalline solid, aqueous solution is quite stable. The nitrobenzene moiety of this is probably responsible for antibacterial activity as well as its bitter taste. MOA

20. MOA Chloramphenicol Attaches to 50s ribosomes Near acceptor (A) site for amino acids incorporation by acting as a peptide analogue Prevents peptide bonds Inhibition of protein synthesis at peptidyl transferase reaction

21. Uses: - anaerobic infections, intraocular infections, urinary tract infections. Adverse effects: - bone marrow depression, anemia , thrombocytopenia. This is all about antibiotics. Categorywise drugs are well described in these slides. Most of the drugs are described in these slides.