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 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
 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