Penicillins

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

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

Classifications of penicillins )Penicillin G ) Benzyl penicillin ))i.m ,slow i.v or infusion.1 .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

Repository penicillins Developed to prolong duration of penicillin G in the blood 3. Penicillin G procaine Duration 12- 24 hr It is given i.m and not i.v( risk of procaine toxicity) Seldom used now ( increased frequency of penicillinase producing N. gonorrhea

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

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

( .Class. Of penicillins ( cont Acid resistant penicillins .2 .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

( .Class. Of penicillins ( cont Penicillinase-resistant penicillins .3 Methicillin Oxacillin Cloxacillin Dicloxacillin Floxacillin Nafcillin Lower activity against G+ compared to Penicllin G 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

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

( 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

( 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

Absorption,distribution & metabolism Oral absorption of most penicillins is poor Exception: penicillin v Amoxicillin Food interfer with absorption :To increase GI absorption: give ester form Bacampicillin Carbenicillin indany

Distribution Widely distributed Relatively insoluble in lipid Hence, have poor penetration into cells and BBB Inflammation ( eg. Meningitis ) permits entrance into CSF

( .Absorp., metabolism ( cont : Protein binding differs Ampicillin and penicillin G Nafcillin, oxacillin, cloxacillin , dicloxacillin

20% bound 90% bound

Metabolism and excretion Not metabolized in human Excreted mostly unchanged in urine( except. ( Nafcillin,oxacillin, cloxacillin, dicloxacillin Probenecid blocks their secretion (Half-life 30-60 min ( increased in renal failure

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