B lactum antibiotics by JITENDRA BHANGALE

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penicillin and Cephalosporins

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B lactum antibiotics by JITENDRA BHANGALE

  1. 1. 8/5/2012 By- Jitendra Bhangale Assistant Professor & Head, Department of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad 1 © 2010 Delmar, Cengage LearningThese are antibiotics having a B-lactam ring.The two major groups are penicillins and cephalosporins.Monobactams and carbapenems are relatively newer additions. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2 © 2010 Smt N. M. Padalia 1
  2. 2. 8/5/2012 By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad3 © 2010 Smt N. M. PadaliaIt was originally obtained from the fungus Penicillium notatum, but thepresent source is a high yielding mutant of P. chrysogenum. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad4 © 2010 Smt N. M. Padalia 2
  3. 3. 8/5/2012In gram-positive microorganisms, the cell wall is 50 to 100 molecules thick, but it is only 1 or 2 molecules thick in gram-negative bacteria.The peptidoglycan is composed of glycan chains, which are linear strands of two alternating amino sugars (N-acetylglucosamine and N- acetylmuramic acid) that are cross-linked by peptide chains. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad5 © 2010 Smt N. M. PadaliaThe cell walls of bacteria are essential for their normal growth and development.Peptidoglycan provides rigid mechanical stability by virtue of its highly cross- linked latticework structure. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad6 © 2010 Smt N. M. Padalia 3
  4. 4. 8/5/2012The final stage involves completion of the cross-link.This is accomplished by a transpeptidation reaction that occurs outside the cell membrane.The transpeptidase itself is membrane-bound.The terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the pentapeptide (D-alanine), releasing the fifth residue (also D-alanine).It is this last step in peptidoglycan synthesis that is inhibited by the b-lactam antibiotics. By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad7 © 2010 Smt N. M. PadaliaThere are additional, related targets for the actions of penicillins and cephalosporins; these are collectively termed penicillin- binding proteins (PBPs). All bacteria have several such entities By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad8 © 2010 Smt N. M. Padalia 4
  5. 5. 8/5/2012Penicillin GAcid resistance to Penicillin G (Semisynthetic) Penicillin VPenicillinase-resistant penicillins Methicillin, Nafcillin, Oxacillin, Cloxacillin & DicloxacillinExtended spectrum penicillins Aminopenicillins: Ampicillin, Bacampicillin, Amoxicillin Carboxypenicillins: Carbenicillin, Ticarcillin Ureidopenicillins: Piperacillin, Mezlocillin, AzlocillinB-lactamase inhibitors: Clavulanic acid, Sulbactam, Tazobactam By Jitendra Bhangale Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad9 © 2010 Smt N. M. PadaliaAntibacterial spectrumPnG is a narrow spectrum antibiotic primarily to gram-positivebacteria Bacilli: Gram-positive bacilli-Cocci: B. anthracis, Streptococci Corynebacterium diphtheriae Pneumococci, Clostridia Staphylococcus aureus ListeriaGram negative cocci- spirochetes Nelsseria gonorrhoeae But Bacteroides fragilis is largely N. meningitidis resistant. By Jitendra Bhangale 10 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 5
  6. 6. 8/5/2012PharmacokineticsAbsorptionPenicillin G is acid labile-destroyed by gastric acid.Absorption of sod. PnC from i.m. site is rapid and complete.DistributionIt is distributed mainly extracellularly; reaches most body fluids, but penetration in serous cavities and CSF is poor.ExcretionVery rapid renal excretion By Jitendra Bhangale 11 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAdverse reaction Immediate type ofThrombophlebitisMental confusion hypersensitivity-Muscular twitchings AngioedemaConvulsionsComa BronchospasmHypersensitivity rash serum sicknessItchingUrticaria Contact dermatitisFever Jarisch-Herxheimer reactionWheezingAngioneurotic (shivering, fever, myalgia,Edema exacerbation of lesions, evenSerum sicknessExfoliative dermatitis vascular collapse) By Jitendra Bhangale 12 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 6
  7. 7. 8/5/2012Therapeutic uses GonorrhoeaStreptococcal infections SyphilisPneumococcal infections DiphtheriaMeningococcal infections Tetanus and gas gangrene By Jitendra Bhangale 13 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAcid-resistant alternative to Penicillin-G.This is nothing but Phenoxymethyl penicillin.It is acid stable therefore oral absorption is better.The antibacterial spectrum of penicillin V is identical to PnG, gram negative bacteria and anaerobes.It is used only for streptococcal pharyngitis, sinusitis, otitis media, prophylaxis of rheumatic fever By Jitendra Bhangale 14 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 7
  8. 8. 8/5/2012Side chains of this class of penicillin protect the B-lactam ring fromattack by staphylococcal penicillinase.Examples: Methicillin Nafcillin Oxacillin Cloxacillin Dicloxacillin By Jitendra Bhangale 15 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaIt is highly penicillinase resistant but not acid resistant-must be injected.MRSA have emerged in many areas.The drug of choice for these organisms is vancomycin/linezolid, but ciprofloxacin can also be used.Adverse effect: Haematuria Albuminuria Reversible interstitial nephritisIt has been replaced by cloxacillin. By Jitendra Bhangale 16 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 8
  9. 9. 8/5/2012It has an isoxazolyl side chain and is highly penicillinase as well as acid resistant.Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl penicillins, similar to cloxacillin, but not marketed in India.Nafcillin is another parenteral penicillinase resistant penicillin. By Jitendra Bhangale 17 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Examples: Ureidopenicillins: Aminopenicillins: Piperacillin Ampicillin Mezlocillin Bacampicillin Azlocillin Amoxicillin Carboxypenicillins: Carbenicillin Ticarcillin By Jitendra Bhangale 18 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 9
  10. 10. 8/5/2012Antibacterial spectrumIt is active against all organisrn sensitive to PnG; in addition many gram-negative bacilli, e.g. H. Influenzae, E-Coli, Proteus and Shigella UsesAmpicillin is not degraded by Urinary tract infections: gastric acid. Respiratory tract infections:Oral absorption is incomplete. Meningitis:Food interferes with Gonorrhoea absorption. Typhoid fever: Cholecystitis By Jitendra Bhangale 19 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaIt is an ester prodrug of ampicillin which is nearly completely absorbed from the g.i.t. Talampicillin, Pivampicillin, Hetacillin are other prodrugs of ampicillin By Jitendra Bhangale 20 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 10
  11. 11. 8/5/2012 Oral absorption is better Food does not interfere with absorption Incidence of diarrhoea is lower. Uses: Bronchitis, urinary infection and gonorrhoea. By Jitendra Bhangale 21 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia CarboxypenicillinsThe special feature of this penicillin congener is its activity against pseudomonas aeruginosa and indole positive proteus which are not inhibited by PnG or aminopenicillins.It is inactive orally and is excreted rapidly in urineHigh doses have also caused bleeding by interferring with platelet function TicarcillinIt is more potent than carbenicillin against Pseudomonas. By Jitendra Bhangale 22 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 11
  12. 12. 8/5/2012PiperacillinThis antipseudomonal penicillin is about 8 times more active than carbenicillin.It has good activity against Klebsiella and is used mainly in neutropenic/immunocompromised patients having serious gram-negative infections, and in burns.MezlocillinIt has activity similar to ticarcillin aqainst Pseudomonns and inhibits Klebsiella as well.It is given parenterally primarily for infections caused bv enteric bacilli. By Jitendra Bhangale 23 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaB-lactamases are a family of enzymes produced by many gram- positive and gram-negative bacteria that inactivate B-lactam antibiotics by opening the B-lactam ring.Examples: Clavulanic acid Sulbactam and. Tazobactam By Jitendra Bhangale 24 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 12
  13. 13. 8/5/2012Clavulanic acid is obtained from Streptomyces clavuligerus, it has a b-lactam ring but no antibacterial activity of its own.It inhibits a wide variety (class II to class V) of B-lactamases.Clavulanic acid is a progressive inhibitor.It is also called a suicide’ inhibitor, it gets inactivated after binding to the enzyme.It permeates the outer layers of the cell wall of gram negative bacteria and inhibits the periplasmically located B- lactamase.Sulbactam and Tazobatam are semisynthetic B lactamase inhibitor. By Jitendra Bhangale 25 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia By Jitendra Bhangale 26 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 13
  14. 14. 8/5/2012It was originally obtained from the fungus Cephalosporium acremonium. By Jitendra Bhangale 27 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Third Generation CephalosporinsFirst Generation Cephalosporins Parenteral Parenteral Cefotaxime Cephalothin Ceftizoxime Cefazolin Ceftriaxone Oral Ceftazidime Cefadroxil Cefoperazone Cephalexin Oral Cephradine Cefpodoxime proxetilSecond generation Cefdinircephalosporins Ceftibuten Parenteral Ceftamet pivoxil Cefuroxime Cefixime Cefoxitin Forth generation cephalosporins Oral Parenteral Cefuroxime axetil Cefepime Cefaclor Cefpirome By Jitendra Bhangale 28 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 14
  15. 15. 8/5/2012 Oral Parenteral Cefadroxil Cephalothin Cephalexin Cefazolin Cephradine By Jitendra Bhangale 29 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAntibacterial spectrum for Ist generation cephalosporinsIt is a narrow spectrum antibiotic primarily to gram-positive bacteria Streptococci Gonococci Meningococci C. diphtheriae H. influenzae Clostridia Actinomyces Klebsiella E. coli By Jitendra Bhangale 30 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 15
  16. 16. 8/5/2012 Parenteral Oral Cefuroxime Cefuroxime axetil Cefoxitin Cefaclor By Jitendra Bhangale 31 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAntibacterial spectrum for II generation cephalosporinsIt is a narrow spectrum antibiotic primarily to gram-negativebacteria E coli H. influenzae Pr. mirabills C. diphtheriae H. Influenzae None inhibits P. aeruginosa By Jitendra Bhangale 32 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 16
  17. 17. 8/5/2012 Parenteral Oral Cefotaxime Cefpodoxime proxetil Ceftizoxime Cefdinir Ceftriaxone Ceftibuten Ceftazidime Ceftamet pivoxil Cefoperazone Cefixime By Jitendra Bhangale 33 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAntibacterial spectrum for III generation cephalosporinsIt is primarily active against gram-negative bacteria. E coli Pseudomonas H. Influenzae Not active on anaerobes (particularly Bact. fragilis), Staph. aureus and Ps. aeruginosa By Jitendra Bhangale 34 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 17
  18. 18. 8/5/2012 Parenteral Oral Cefepime Not invented yet Cefpirome By Jitendra Bhangale 35 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. PadaliaAntibacterial spectrum for IV generation cephalosporins Similar to III generation cephalosporins. Highly resistance to B lactamase By Jitendra Bhangale 36 Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 18
  19. 19. 8/5/2012 Pain Diarrhoea Hypersensitivity reactions Nephrotoxicity Bleeding Neutropenia and thrombocytopenia By Jitendra Bhangale 37Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia Respiratory, urinary and soft tissue infections Penicillinase producing staphylococcal infections Septicaemias Surgical prophylaxis Meningitis Gonorrhoea Typhoid By Jitendra Bhangale 38Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 19
  20. 20. 8/5/2012 By Jitendra Bhangale 39Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad © 2010 Smt N. M. Padalia 20

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