Cephalosporin

1. Cephalosporin

2. What is an Antibiotics? • A substance produced by or a semisynthetic substance derived from a microorganisms and able to inhibit or kill another organisms.

3. What is Cephalosporin? • Semi-Synthetic Antibiotic • It is derived semi-synthetically from `Cephalosporin-C` which is obtained from a fungus `Cephalosporium`. • C. acermonium, a Sardinian fungus was used to isolate the 3 natural chephalosporin, Cephalosporin P, N & C by Brotzuin 1948

4. Composition of Cephalosporin • All the cephalosporin contain a β-lactam Ring which is fused with the dihydrothiazine ring and an amino acid, they form 7-aminocephalosporanic acid or cephalosporin Nucleus. • By the addition of many side chain at 7th position of the β-lactam ring or at 3rd position of dihydrothiazinering, different semi-synthetic antibiotics are made

5. Dihydrothiazine Ring Β-Lactam ring

6. Properties of Cephalosporin • Just similar to the Penicillin • Cephalosporin are more water and acid soluble. • More stable to temperature and pH • They are susceptible to the β-lactamase or cephalosporinase

7. Mechanism of Action • All cephalosporin are bacteriocidal • They inhibit bacterial cell wall synthesis by binding to different protein required for synthesis.

8. Pharmacokinetics • There is insufficeint data about the pharmacokinetics of the cephalosporin • Absorption • A few cephalosporin are acid soluble and given orally, most of the cephalosporin are given parentally • The cephalosporin given orally has 75-90% absorption

9. b) Distribution • They are distributed throughout the body tissue and fluids including lungs, kidney, placenta, soft tissue and joint fluid • Some of them can cross Blood-Brain barrier • The plasma protein binding of cephalosporinis highly variable (20-80%) • They enter milk in less concentration • c) Biotransformation • Most of cephalosporin does not undergo any biotransformation • Some of the compound are actively deactylated in liver

10. d) Excretion • The plasma half life of cephalosporin is 30-120 minutes usually but 3rd generation have longer half life. • They are excreted mainly by the kidneys in tubular secretion and glomerular filtration. • Some of the drugs (3rd generation) are also excreted in the bile.

11. Classification of Cephalosporin • Classified on the basis of chronological sequence into 4 groups; • 1st generation Cephalosporin • 2ndgeneration Cephalosporin • 3rdgeneration Cephalosporin • 4thgeneration Cephalosporin

12. a) 1stgeneration Cephalosporin • They are developed in the 1960 • They have strong activity against gram +ve bacteria • They have less activity against gram –ve bacteria • They don`t have any activity against anaerobic bacteria like Pseudomonas, Proteus and Enterococcus species • They considered 1st alternative form of penicillin

13. The 1stgeneration Cephalosporin include following drugs • Cephalothin • Injectable antibiotic, not absorbed orally • Freely soluble in Water and slightly soluble in alcohol • Cephalothin is active against penicillin G sensitive organisms like streptococcus and staphlococcus • It is resistant to Staphlococcalβ-lactamase • It is metabolized in the liver and kidney by deacetylation to desacetylcephalothin • Excreted in unchanged form

14. B) Cefazolin • Injectible semi-synthetic antibiotic, not absorbed orally • Its mechanism of action is similar to Cephalothin • It is more active against Klebsiella and E.Coli • More sensitive against Staphlococcalβ-lactamase • Its excretion period is more longer than the cephalothoin • It is preferred because of its longer half life

15. C) Cephalexin • semisynthetic antibiotic, affected orally • It is similar to cephalothin, but it is less active against β-lactamase producing staphlococci • It is less bound to plasma and present as it in blood and bile freely • Excreted mainly in unchanged form in urine • It may cause salivation and tachypnoea

16. D) Cefadroxil • Semisynthetic antibiotic, orally effective • Well absorbed after oral administration with peak plasma conc. • It is excreted mainly in unchanged form in urine and has half life of 2 hours in dogs • Mainly used in the small animals. Effective in skin infection, soft-tissue and genitourinary tract in dog • Less oral dosing due to long sustaining in body

17. E) Cephapirin • Injectable antibiotic, not absorbed orally • similar to chephalosporin • Its bioavailability is >95% • It is short acting injectable antibiotic • Intramammary administration is approved for the treatment of Mastitis

18. F) Cephradine • Orally and parenterally used antibiotic • Oral administration may cause diarrhea • G) Cephaloridine • Most Nephrotoxic Cephalosporin that why less used as therapeutic

19. b) 2nd Generation Cephalosporin • These drugs have braoder spectrum than the 1st generation cephalosporin • They are effective against the gram +ve and gram –ve bacteria. Some of these are also effective anaerobe • They are relatively resistant to the β-lactamase activity • Not widely used in veterinary pratice

20. The 2nd generation cephalosporin include the following; • Cefuroxime • Injectable semisynthetic antibiotic, not effective orally • They have greater activity against the gram –vebacteria as compared to 1st generation cephalosporins • Stable to β-lactamase produced by the staphlococcus and gram –ve bacteria • It also attain a good level in CSF • It is being used in treatment of meningitis caused by H. influenza

21. B) Cefaclor • Semisynthetic injectable antibiotic, not orally absorbed • Resistant to β-lactamase producing bacteria • C) Cefamandole • Semisynthetic injectable antibiotic • It contain Methyl Tetrazolethiomethyl (MTT ) group at position 3 which is associated with the hypoprothrombinaemia, inhibition of Vit. K activation

22. 3rd Generation cephalosporin • These antibiotics were introduced in 1980 • They are effective against gram –ve bacteria and have activity against the streptococcus spp. • These drug reach upto the CNS and should be administered parenterally

23. The 3rd generation cephalosporin include • Cefotaxime • Semisynthetic antibiotic, not absorbed orally • Considered as prototype of the 3rd generation cephalosporin • It is affective against gram +ve and gram –ve bacteria but no active against on anaerobes • It is used to treat meningitis caused by the gram –ve bacteria

24. B) Ceftiofur (Cefur) • Semisynthetic antibiotic, not orally absorbed • The mostly used cephalosporin in all generation • Primarly used in the treatment of Bovine Respiratory Disease e.g pneumonia and foot rot in cattle • For treatment of horse Respiratory disease caused by Strep. Zooepidimicus • Longer half life that why single dosing per day

25. C) Ceftriaxone • Semisynthetic antibiotic, not orally absorbed • After its parenterally administration, distributed in the tissue and fluids including CSF • It is excreted through the urine and bile • It is effective against severe disease like Lyme`s disease and BorreliaBurgdoferi

26. D) Ceftazidime • Most active against Pseudomonas and also effective against the Enterobacteriaceae • It remained unmetabolised and excreted in urine • E) Cefoperazone • Semi-synthetic 3rd generation antibiotic • It is more susceptible to the β-lactamse activity • It contain Methyl Tetrazolethiomethyl (MTT ) group • which may cause coagulation abnormalities

27. d) 4th Generation Cephalosporins • They are recently introduced in the market and mainly available for human use • Highly resistant to β-lactamase activity • Cefepime • It is the most broad spectrum antibiotic • Effective against the gram +ve and gram –ve bacteria not effective MRSA • It has excellent penetration power into CSF, Not be adminiterd IV

28. Bacterial Resistance against Cephalosporin • Mechanism of bacterial resistance to cephalosporin is similar to the penicillin. These include • Elaboration of β-lactamase that destroy cephalosprin • Alternation in target protein that reduce affinity for cephalosporin • Decreased permeability to cephalosporin so that drug don`t reach their site of action in sufficient quantity

29. Side Effects of Cephalosporins • Hypersensitivity reaction manifested by rashes fever, lymphadenopathy and eosinophilia • GIT disturbance causing diarrhea, vomiting and nausea • Prolonged used of cephalosporin cause nephritis, hepatitis, thrombocytopenia and neutropenia