PENICILLINSPENICILLINS

Beta- lactam antibioticsBeta- lactam antibioticsDerivatives of 6- aminopenicillanic acidDerivatives of 6- aminopenicillanic acidAlteration of the side group resulted in cpds with :Alteration of the side group resulted in cpds with : Broader spectrum of activityBroader spectrum of activity Resistance to penicillinaseResistance to penicillinase Stability in acid PHStability in acid PHMost widely effective antibioticsMost widely effective antibioticsLeast toxic drugs knownLeast toxic drugs known

MECHANISM OF ACTIONMECHANISM OF ACTION

They act by inhibition of bacterial cell wall synthesisThey act by inhibition of bacterial cell wall synthesis

Thus exposing the osmotically less stable membraneThus exposing the osmotically less stable membrane

This cause lysis of bacterial cell wallThis cause lysis of bacterial cell wall

These agents are bactericidalThese agents are bactericidal

Active against multiplying and not resting bacteriaActive against multiplying and not resting bacteria

Inactive against mycobacteria, protozoa, fungi and Inactive against mycobacteria, protozoa, fungi and virusesviruses

Classifications of penicillinsClassifications of penicillins

11..Penicillin G ( Benzyl penicillin )(i.m ,slow i.v or infusion)Penicillin G ( Benzyl penicillin )(i.m ,slow i.v or infusion) Highest activity against Gram-positive organisms but susceptible to Beta-lactamaseHighest activity against Gram-positive organisms but susceptible to Beta-lactamase..

Effective againstEffective against: : Gram-positive aerobic cocci - Staph. aureus- not producing penicillinase, Gram-positive aerobic cocci - Staph. aureus- not producing penicillinase,

S.pneumoniae ( group A ) ,S.pyogenes S.pneumoniae ( group A ) ,S.pyogenes Gram-negative aerobic cocci -N.meningitidisGram-negative aerobic cocci -N.meningitidis

N. gonorrhea-no longer of choiceN. gonorrhea-no longer of choice Gram- positive bacilli : Bacillus anthracisGram- positive bacilli : Bacillus anthracis

Spirochetes : T. pallidum – drug of choiceSpirochetes : T. pallidum – drug of choice

AnaerobesAnaerobes Clostridium spp but inactive against B.fragilisClostridium spp but inactive against B.fragilis

Actinomycetes israelii ( actinomycosis )Actinomycetes israelii ( actinomycosis )

Repository penicillinsRepository penicillinsDeveloped to prolong duration of penicillin G in the Developed to prolong duration of penicillin G in the

bloodblood

1.1. Penicillin G procainePenicillin G procaine

Duration 12- 24 hrDuration 12- 24 hr

It is given i.m and not i.v( It is given i.m and not i.v( risk of procaine toxicityrisk of procaine toxicity))

Seldom used now ( increased frequency of Seldom used now ( increased frequency of penicillinase producing N. gonorrheapenicillinase producing N. gonorrhea

Repository penicillins ( cont.)Repository penicillins ( cont.)2. Penicillin G benzathin ( i.m )2. Penicillin G benzathin ( i.m ) Duration 3- 4 weeksDuration 3- 4 weeks Painful at the injection site ( limits its use )Painful at the injection site ( limits its use ) UsesUses 1. Syphilis1. Syphilis 2. Rheumatic fever prophylaxis( inhibits2. Rheumatic fever prophylaxis( inhibits group A beta- hemolytic streptococci)group A beta- hemolytic streptococci) 3. Streptococcal pharyngitis3. Streptococcal pharyngitis

Class. Of penicillins ( cont. )Class. Of penicillins ( cont. )

Disadvantages of penicillin GDisadvantages of penicillin G

A. Destroyed by gastric HCLA. Destroyed by gastric HCL

B. Inactivated by penicillinaseB. Inactivated by penicillinase

C. Narrow spectrum of activityC. Narrow spectrum of activity

Class. Of penicillins ( cont. )Class. Of penicillins ( cont. )

22 . .Acid resistant penicillinsAcid resistant penicillins Phenoxy- methyl penicillin ( penicillin v), p.oPhenoxy- methyl penicillin ( penicillin v), p.o.. ) ) spectrum of activity is similar to penicillin Gspectrum of activity is similar to penicillin G( (

UsesUsesGroup A Streptococcal pharyngitisGroup A Streptococcal pharyngitisProphlaxis against group A streptococci in pts with Prophlaxis against group A streptococci in pts with history of rheumatic heart diseasehistory of rheumatic heart disease..

DisadvantagesDisadvantagesReadily hydroyzed by beta-lactamaseReadily hydroyzed by beta-lactamase

Class. Of penicillins ( cont. )Class. Of penicillins ( cont. )

33 . .Penicillinase-resistant penicillinsPenicillinase-resistant penicillins Methicillin OxacillinMethicillin Oxacillin

Cloxacillin DicloxacillinCloxacillin Dicloxacillin Floxacillin NafcillinFloxacillin Nafcillin

Lower activity against G+ compared to Penicllin GLower activity against G+ compared to Penicllin G butbut

Are the choice for infections caused by penicillinase producing S. aureusAre the choice for infections caused by penicillinase producing S. aureus..However, MRSA & ORSA has emergedHowever, MRSA & ORSA has emerged..Not effective against G- aerobes( E.coli, klebsiella,N.gonorrhea or Not effective against G- aerobes( E.coli, klebsiella,N.gonorrhea or pseudomonas spp.)pseudomonas spp.)Less active than penicillin on anaerobesLess active than penicillin on anaerobes..High protein and food bindersHigh protein and food binders

Class. Of penicillins ( cont )Class. Of penicillins ( cont )

44 . .Broad- spectrum penicillinsBroad- spectrum penicillins

a) Ampicillin, Ampicillin- sulbactam, a) Ampicillin, Ampicillin- sulbactam, Bacampicillin, Amoxicillin, Amoxicillin- Bacampicillin, Amoxicillin, Amoxicillin- clavulanic acid ( augmentin )clavulanic acid ( augmentin )..

Less active than penicillin G against G+ cocci. Less active than penicillin G against G+ cocci. Active against G- organismsActive against G- organisms..

Broad-spectrum penicillins ( cont )Broad-spectrum penicillins ( cont )

UsesUsesH. Influenza infections ( otitis media, sinusitis, chronic bronchitis, H. Influenza infections ( otitis media, sinusitis, chronic bronchitis, pneumonia, bacterial meningitis )pneumonia, bacterial meningitis )..M.catarrhalisM.catarrhalisE. Coli infections ( Urinary & biliary infections )E. Coli infections ( Urinary & biliary infections )..Samonella infections ( typhoid fever )Samonella infections ( typhoid fever )Shigella infections ( ampicillin )Shigella infections ( ampicillin )Gonococcal infections ( alternative for penicillin in the treatment of Gonococcal infections ( alternative for penicillin in the treatment of gonorrhea )gonorrhea )Prophlaxis of infective endocarditisProphlaxis of infective endocarditis

DisadvantagesDisadvantagesAmoxicillin & ampicillin alone are readily destroyed by Staph. Amoxicillin & ampicillin alone are readily destroyed by Staph. PenicillinasePenicillinase..

Broad spectrum penicillins ( cont )Broad spectrum penicillins ( cont )

B ) Extended- spectrum : Ticarcillin-clavulanic acid, B ) Extended- spectrum : Ticarcillin-clavulanic acid, piperacillin,piperacillin-tazobactam ( Tazocin )piperacillin,piperacillin-tazobactam ( Tazocin )UsesUsesPseud. aeruginosa. For pseud.septicemia, they Pseud. aeruginosa. For pseud.septicemia, they should be given together with an aminoglycosideshould be given together with an aminoglycoside

) )eg. Gentamicineg. Gentamicin.( .( DisadvantagesDisadvantagesTicarcillin and piperacillin alone are readily destroyed Ticarcillin and piperacillin alone are readily destroyed by S. penicillinase. High dose may lead to by S. penicillinase. High dose may lead to hypernatraemia due to sodium contenthypernatraemia due to sodium content..

Absorption,distribution & metabolismAbsorption,distribution & metabolism

Oral absorption of most penicillins is poorOral absorption of most penicillins is poor Exception: penicillin vException: penicillin v

AmoxicillinAmoxicillinFood interfer with absorptionFood interfer with absorption

To increase GI absorption: give ester formTo increase GI absorption: give ester form:: BacampicillinBacampicillin

Carbenicillin indanyCarbenicillin indany

DistributionDistribution Widely distributedWidely distributed

Relatively insoluble in lipidRelatively insoluble in lipid Hence, have poor penetration into cells and BBBHence, have poor penetration into cells and BBB

Inflammation ( eg. Meningitis ) permits entrance into CSFInflammation ( eg. Meningitis ) permits entrance into CSF

Absorp., metabolism ( cont. )Absorp., metabolism ( cont. )

Protein binding differsProtein binding differs: : Ampicillin and penicillin G 20% boundAmpicillin and penicillin G 20% bound Nafcillin, oxacillin, 90% boundNafcillin, oxacillin, 90% bound

cloxacillin , dicloxacillincloxacillin , dicloxacillin

Metabolism and excretionMetabolism and excretion Not metabolized in humanNot metabolized in human

Excreted mostly unchanged in urine( except. Excreted mostly unchanged in urine( except. Nafcillin,oxacillin, cloxacillin, dicloxacillin ) Nafcillin,oxacillin, cloxacillin, dicloxacillin )

Probenecid blocks their secretionProbenecid blocks their secretion Half-life 30-60 min ( increased in renal failure)Half-life 30-60 min ( increased in renal failure)

Adverse effects of penicillinsAdverse effects of penicillins

1.Hypersensitivity reactions1.Hypersensitivity reactions ( occur in 1-10% of pts; ( occur in 1-10% of pts; fatality occur in 0.002%)fatality occur in 0.002%) ( immediate, accelerated & late allergic rxns) ( immediate, accelerated & late allergic rxns) ** Cross-reactions** Cross-reactions Urticarial rashUrticarial rash FeverFever BronchspasmBronchspasm Serum sicknessSerum sickness Exfoliative dermatitisExfoliative dermatitis Stevens- Johnson syndromeStevens- Johnson syndrome AnaphylaxisAnaphylaxis

2. Super infections2. Super infections3. Diarrhoea3. Diarrhoea4. May cause convulsions4. May cause convulsions after high doses by i.v or in after high doses by i.v or in

renal failurerenal failure