PENICILLINS

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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

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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

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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 )
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• Repository penicillins
• Developed to prolong duration of penicillin G in
  the blood
• 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

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• 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

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Class. Of penicillins ( cont. )

• Disadvantages of penicillin G
• A. Destroyed by gastric HCL
• B. Inactivated by penicillinase
• C. Narrow spectrum of activity

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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

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Class. Of penicillins ( cont. )

• 3. Penicillinase-resistant penicillins
• 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

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Class. Of penicillins ( cont )

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

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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.

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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.

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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

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Absorp., metabolism ( cont. )

• Protein binding differs
• Ampicillin and penicillin G 20 bound
• Nafcillin, oxacillin, 90
  bound
• cloxacillin , dicloxacillin
• 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)

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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