Penicillins and cephalosporin antibiotics.pptx

Penicillin's and cephalosporins are the important classification in antibiotics which acts as broad spectrum

1. Penicillins

2. Introduction Penicillin: a class of beta-lactam antibiotics. Penicillin was the first antibiotic discovered from the mold Penicillium notatum in 1928 by Alexander Fleming Beta-lactamases (also called penicillinases) are enzymes that deactivate penicillins by destroying the beta-lactam ring via hydrolysis. Beta-lactamases allow bacteria to be resistant to penicillin.

3. Classification of Penicillins Natural Penicillins: Benzylpenicillin (Penicillin G) Phenoxymethylpenicillin (Penicillin V) Penicillinase Resistant Penicillins Methicillin Oxacillin, Nafcillin,

4. Extended Spectrum Penicillins (Aminopenicillins) Ampicillin, Amoxicillin Anti-pseudomonal penicillins Carboxypenicillins: Carbenicillin, Ticarcillin Ureidopenicillins: Piperacillin, azlocillin

5. Mechanism of Action Beta-lactam antibiotics are bactericidal drugs. They act to inhibit cell wall synthesis by the binding of the drug to specific enzymes (penicillin-binding proteins [PBPs]) located in the bacterial cytoplasmic membrane. Inhibition of the transpeptidation reaction that cross-links the linear peptidoglycan chain constituents of the cell wall Activation of autolytic enzymes that cause lesions in the bacterial cell wall.

6. Pharmacokinetics Absorption:  The potassium salt of penicillin V (oral formulation) is resistant to inactivation by gastric acid; however, penicillin G is destroyed by stomach acid. Benzathine penicillin G has slow hydrolysis and absorption, resulting in a prolonged half-life. Distribution:  Penicillin V and penicillin G have approximately 80% and 60% plasma protein binding, respectively. Tissue levels are highest in the kidneys. The concentration of penicillin in abscesses, synovial, and peritoneal fluids is higher in the presence of inflammation. However, penicillin G does have poor distribution in polymorphonuclear leukocytes. 

7. Metabolism:  Penicillin derivatives are minimally metabolized by the liver. Organic anion transporter-3 plays a vital role in renal excretion Elimination:  These agents are rapidly excreted in the urine as they are water-soluble, and others are excreted in bile. Penicillin has a relatively short half-life of about 2 hours. Penicillin is excreted rapidly by tubular excretion, which is inhibited by probenecid.

8. Adverse Effects of Penicillins Allergy-Allergic reactions include, fever, joint swelling, haemolytic anaemia, nephritis, and anaphylaxis Gastrointestinal disturbances- nausea and diarrhea may occur with oral penicillin, especially with Ampicillin. Gastrointestinal upsets may be caused by direct irritation or by overgrowth of gram-positive organisms or yeasts. Thrombocytopenia Seizures.

9. Uses Streptococcal Infections Syphilis Neisseria gonorrhoeae Surgical prophylaxis

10. Cephalosporin The cephalosporins are B-lactam antibiotics that are closely related both structurally and functionally to the penicillins . that were originally derived from the fungus Cephalosporium acremonium Most cephalosporins are produced semisynthetically by the chemical attachment of various R1 and R2 groups to 7-aminocephalosporanic acid

11. Mechanism of Action Inhibit cell wall synthesis in a way similar to that of penicillins

12. Cephalosporins Prototypes Other Significant Agents 1 st Gen. Cefazolin Cephradine , Cephalexin, Cephadroxil 2 nd gen Cefamandole Cefaclor, Cefotetan, Cefoxitin, Cefuroxim 3 rd gen Cefoperazone Cefotaxime, Ceftazidime, Ceftriaxone, Cefixime 4 th gen Cefipime Cefpriome 5 th gen Ceftopibrole

13. Pharmacokinetics Oral & parenteral t1/2 is 1 - 4h exception ceftriaxone 8 h Wide distribution Binding to plasma protein vary from one to another 3 rd & 4 th Gen. can penetrate CNS except ( Cefoperazone & Cefixime) Cefoperazone & Ceftriaxone mainly excretion by bile

14. Clinical Uses of 1st Gen Active against Gram - positive cocci Minimal activity against Gram - negative cocci, enterococci Uses: Infection, UTI, soft tissue abscess Surgical prophylaxis

15. Clinical Uses of 2nd Gen. Less activity against G - positive Extended activity against G-negative Uses: Cefotetan, Cefoxitin in abdominal and pelvic infections caused by anaerobe bacteroides fragilitis Cefuroxim in comunity aquired pneumonia which caused by strep. pneomonia Cefemandole , Cefuroxime, Cefaclor in sinus, ear, respiratiry infection caused by H infuenzae

16. Clinical Uses of 3rd Gen. Increased activity against G-negative Most active against b-lactamase (H influenza and Neisseria) Less active against Enterobacter strains Uses: Cefoperazone , ceftazidime active against pseudomonas aeruginosae (used in Septicemia ) Ceftriaxone for Meningitis Ceftriaxone, cefixime are the drug of choice in gonorrhea Ceftriaxone in acute otitis media

17. 4th Gen Very good activity against Gram-positive including s. aureus More resistant to b - lactamases produced by (Enterobacter, Haemophilus, neisseria V. good activity against Gram-negative including p. aeruginosa Uses Nosocomial pneomonia of Enterobacter Infection caused by pseudomonas aeruginosa Febrile neutropenia UTI Intra-abdominal infections

18. 5th gen. Ceftobiprole Ceftopirole : broad spectrum, MRSA, penicillin resistance streptococcus pneumonia, pseudomonas aeruginosa and enterococci Ceftopirole : Its new drug for treatment diabetic foot infections

19. Adverse reactions Allergy :Cross-allergy with penicillin (5-10%) Thrombocytopenia, haemolytic anemia Abnormal liver function test Prothrombin deficiency with Cefamandole, Cefotetan, Cefoperazone

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