Cepham drugs.pptx-Drugs containing Cepham, Cephem Structure

Antibiotics- Consists of Penicillins, cephalosporins, Tetracyclines.

1. CEPHALOSPORINS Medicinal Chemistry Pharm.D III Yr By Dr. Rakam Gopi Krishna Department of Pharmaceutical Chemistry

2. A group of widely used broad-spectrum antibiotics, originally isolated as a product of fermentation from the fungus Cephalosporium acremonium are called Cephalosporins. Department of Pharmaceutical Chemistry

3. Cephalosporins The cephalosporins are β- lactam antibiotics isolated from Cephalosporium spp. or prepared semisynthetically . Most of the antibiotics introduced since 1965 have been semisynthetic cephalosporins. Cephalosporins are beta-lactam antimicrobials used to manage a wide range of infections from gram-positive and gram-negative bacteria. The five generations of cephalosporins are useful against skin infection, resistant bacteria, meningitis, and other infections.

4. Structure Cephalosporins have a basic structural core consisting of a 4-membered β- lactam ring attached to a 6-membered dihydrothiazine ring, and therefore are β- lactams. The two-ring combination gives the cephalosporin structure inherent resistance to β- lactamase enzymes.

5. Hi s t o r y: Cephalosporins were discovered shortly after penicillin entered into widespread product, but not developed till the 1960’s. C e pha l osp o r i n s a r e simila r t o p enici l lins b u t h a v e a 6 member dihydrothiazine ring instead of a 5 member thiazolidine ring. 7-aminocephalosporanic acid (7-ACA) can be obtained from bacteria, but it is easier to expand the ring system of 7-APA because it is so widely produced. They were isolated from cultures of Cephalosporium acremonium by italian scientist Giuseppe Brotzu in 1945. Department of Pharmaceutical Chemistry

6. 7- Amino Cephalosporanic Acid(7-ACA) Department of Pharmaceutical Chemistry

7. Cephalosporins re of 3 types C-P is a steroid antibiotic that resembles fusidic acid and obtained from Fusidium coccineum. C-N is a penicillin like structure derived from 6-APA. Identical to penicillin N. C-C is a derivative of 7- Amino cephalosporanic acid. Department of Pharmaceutical Chemistry

8. Cephalosporin C/ D-Alpha amino adipic acid Department of Pharmaceutical Chemistry

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13. Third-generation drugs exhibit the least activity against gram-positive bacteria, but most potent activity against gram-negative bacteria . They show Extended antibacterial spectrum, include Pseud. aeruginosa . These drugs have l ess activity on gram-positive bacteria than first and second generation drugs. They are m ost active on gram-negative bacteria . They have h igh stability with β-lactamase . They can e as ily penetrate to different tissues, and then have broad distribution; They possess low kidney toxicity . Department of Pharmaceutical Chemistry

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15. These are Zwitterionic compounds. They possess Good affinity for the transpeptidase enzyme. They have Low affinity for some β-lactamases. These drugs c ross the BBB and effective in meningitis . Department of Pharmaceutical Chemistry

16. Active against : Methicillin-resistant - Staphylococcus aureus Penicillin-resistant - Streptococcus pneumoniae Department of Pharmaceutical Chemistry

17. Properties of cephalosporins Broad spectrum activity : They are water soluble. The molecular weight of cephalosporins is 400-450gms. These drugs are Relatively stable to pH and temperature changes. Nucleus of cephalosporin is 7-amino cephalosporanic acid. Their activity is not reduced by serum. Nucleus Consists of dihydrothiazine ring fused to a β–lactam ring. Range from very narrow spectrum to very broad spectrum. 7-aminocephalosporanic acid has been modified by addition of different side chains to create a whole family of cephalosporin antibiotics. Department of Pharmaceutical Chemistry

18. R= OCOCH3 Degradation of Cephalosporin Esterase/acid Further breakdown leads to fragmented and inactive products

19. Mechanism of Action Cephalosporins exert bactericidal effect in manner similar to that of Penicillins . Binding to specific Penicillin Binding Proteins Inhibition of cell wall synthesis by inhibiting transpeptidation of Peptidoglycan Activation of Autolytic enzymes: Autolysins or Murein Hydrolases

20. Uses of Cephalosporins They are widely used antibiotics. Unfortunately, overuse of these agents in situations where drugs with less broad spectrum activity would be more appropriate has led to the emergence of wide array of cephalosporin resistant bacteria. Cephalosporins are effective as both Prophylactically & Therapeutically. Use as Alternative to Penicillins Used to treat Respiratory tract infections caused by Klebsiella, Enterobacter, Proteus, Providencia, and Haemophilus species. Gonorrhoea Typhoid fever Meningitis

21. Cephalosporins advantages over penicillins Increased acid stability compare to penicillins. Most of the drugs have better absorption than penicillins. Broad antimicrobial spectrum. Increased activity against resistant microorganisms. Decreased allergenicity. Increased tolerence than penicillins. Better permeability into bacterial cells. Department of Pharmaceutical Chemistry

22. MONO B A C T AMS Monobactams are monocyclic and bacterially- produced β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams. Monobactams are effective only against aerobic Gram- negative bacteria. (e.g., Neisseria , Pseudomonas ) Eg: Aztreonam Department of Pharmaceutical Chemistry