1. PENICILLINS Beta- lactam antibiotics Derivatives of 6- aminopenicillanic acid Alteration of the side group resulted in cpds with : Broader spectrum of activity Broader spectrum of activity Resistance to penicillinase Resistance to penicillinase Stability in acid PH Stability in acid PH Most widely effective antibiotics Least toxic drugs known

3. MECHANISM OF ACTION They act by inhibition of bacterial cell wall synthesis Thus exposing the osmotically less stable membrane This cause lysis of bacterial cell wall These agents are bactericidal Active against multiplying and not resting bacteria Inactive against mycobacteria, protozoa, fungi and viruses

4. Classifications of penicillins 1.Penicillin G ( Benzyl penicillin )(i.m,slow i.v or infusion) Highest activity against Gram-positive organisms but susceptible to Beta-lactamase. Effective against : Gram-positive aerobic cocci - Staph. aureus- not producing penicillinase, S.pneumoniae ( group A ),S.pyogenes Gram-negative aerobic cocci -N.meningitidis N. gonorrhea-no longer of choice Gram- positive bacilli : Bacillus anthracis Spirochetes : T. pallidum – drug of choice Anaerobes Clostridium spp but inactive against B.fragilis Actinomycetes israelii ( actinomycosis )

5. Repository penicillins Developed to prolong duration of penicillin G in the blood 1.Penicillin G procaine Duration 12- 24 hr Duration 12- 24 hr It is given i.m and not i.v( risk of procaine toxicity ) It is given i.m and not i.v( risk of procaine toxicity ) Seldom used now ( increased frequency of penicillinase producing N. gonorrhea Seldom used now ( increased frequency of penicillinase producing N. gonorrhea

6. Repository penicillins ( cont.) 2. Penicillin G benzathin ( i.m ) Duration 3- 4 weeks Duration 3- 4 weeks Painful at the injection site ( limits its use ) Painful at the injection site ( limits its use ) Uses Uses 1. Syphilis 1. Syphilis 2. Rheumatic fever prophylaxis( inhibits 2. Rheumatic fever prophylaxis( inhibits group A beta- hemolytic streptococci) group A beta- hemolytic streptococci) 3. Streptococcal pharyngitis 3. Streptococcal pharyngitis

7. Class. Of penicillins ( cont. ) Disadvantages of penicillin G A. Destroyed by gastric HCL B. Inactivated by penicillinase C. Narrow spectrum of activity

8. Class. Of penicillins ( cont. ) 2. Acid resistant penicillins Phenoxy- methyl penicillin ( penicillin v), p.o. ( spectrum of activity is similar to penicillin G ) Uses Group A Streptococcal pharyngitis Prophlaxis against group A streptococci in pts with history of rheumatic heart disease. Disadvantages Readily hydroyzed by beta-lactamase

9. Class. Of penicillins ( cont. ) 3. Penicillinase-resistant penicillins Methicillin Oxacillin Methicillin Oxacillin Cloxacillin Dicloxacillin Cloxacillin Dicloxacillin Floxacillin Nafcillin Floxacillin Nafcillin Lower activity against G+ compared to Penicllin G but but Are the choice for infections caused by penicillinase producing S. aureus. However, MRSA & ORSA has emerged. Not effective against G- aerobes( E.coli, klebsiella,N.gonorrhea or pseudomonas spp.) Less active than penicillin on anaerobes. High protein and food binders

10. Class. Of penicillins ( cont ) 4. Broad- spectrum penicillins a) Ampicillin, Ampicillin- sulbactam, Bacampicillin, Amoxicillin, Amoxicillin- clavulanic acid ( augmentin ). a) Ampicillin, Ampicillin- sulbactam, Bacampicillin, Amoxicillin, Amoxicillin- clavulanic acid ( augmentin ). Less active than penicillin G against G+ cocci. Active against G- organisms.

11. Broad-spectrum penicillins ( cont ) Uses H. Influenza infections ( otitis media, sinusitis, chronic bronchitis, pneumonia, bacterial meningitis ). M.catarrhalis E. Coli infections ( Urinary & biliary infections ). Samonella infections ( typhoid fever ) Shigella infections ( ampicillin ) Gonococcal infections ( alternative for penicillin in the treatment of gonorrhea ) Prophlaxis of infective endocarditis Disadvantages Amoxicillin & ampicillin alone are readily destroyed by Staph. Penicillinase.

12. Broad spectrum penicillins ( cont ) B ) Extended- spectrum : Ticarcillin-clavulanic acid, piperacillin,piperacillin-tazobactam ( Tazocin ) Uses Pseud. aeruginosa. For pseud.septicemia, they should be given together with an aminoglycoside ( eg. Gentamicin ). Disadvantages Ticarcillin and piperacillin alone are readily destroyed by S. penicillinase. High dose may lead to hypernatraemia due to sodium content.

13. Absorption,distribution & metabolism Oral absorption of most penicillins is poor Exception: penicillin v Exception: penicillin v Amoxicillin Amoxicillin Food interfer with absorption To increase GI absorption: give ester form: To increase GI absorption: give ester form: Bacampicillin Bacampicillin Carbenicillin indany Carbenicillin indanyDistribution Widely distributed Widely distributed Relatively insoluble in lipid Relatively insoluble in lipid Hence, have poor penetration into cells and BBB Hence, have poor penetration into cells and BBB Inflammation ( eg. Meningitis ) permits entrance into CSF Inflammation ( eg. Meningitis ) permits entrance into CSF

14. Absorp., metabolism ( cont. ) Protein binding differs : Ampicillin and penicillin G 20% bound Ampicillin and penicillin G 20% bound Nafcillin, oxacillin, 90% bound Nafcillin, oxacillin, 90% bound cloxacillin, dicloxacillin cloxacillin, dicloxacillin Metabolism and excretion Not metabolized in human Not metabolized in human Excreted mostly unchanged in urine( except. Nafcillin,oxacillin, cloxacillin, dicloxacillin ) Excreted mostly unchanged in urine( except. Nafcillin,oxacillin, cloxacillin, dicloxacillin ) Probenecid blocks their secretion Probenecid blocks their secretion Half-life 30-60 min ( increased in renal failure) Half-life 30-60 min ( increased in renal failure)

15. Adverse effects of penicillins 1.Hypersensitivity reactions ( occur in 1-10% of pts; fatality occur in 0.002%) ( immediate, accelerated & late allergic rxns) ** Cross-reactions Urticarial rash Fever Bronchspasm Serum sickness Exfoliative dermatitis Stevens- Johnson syndrome Anaphylaxis 2. Super infections 3. Diarrhoea 4. May cause convulsions after high doses by i.v or in renal failure