PENICILLIN

By : abdelmnaem elgelia
Classification:
 Cell wall synthesis inhibitors
Beta-lactams (penicillins, cephalosporins, aztreonam, imipenem)
Poly-peptides (bacitracin, vancomycin)
 Protein synthesis inhibitors

Aminoglycosides
Tetracyclins
Macrolides
Chloramphenicol
Clindamycin
 Folate antagonists

Sulfonamides
Trimethoprim
 Quinolones
BACTERIAL CELL WALL
 Gram-negative (e.g. E.coli, Salmonella)
Few peptidoglycan layers(Lipopolysaccheride)

Gram-positive (e.g. Staphylococci, Listeria)

Many peptidoglycan layers(Lipoteichoic acid)
 Mechanism of action
Penicillin binds to cell wall of bacteria, Prevention from
developing a cross link in peptidoglycans, and lyses it.
Penicillins inactivate the transpeptidase, in order to destroy
the cell wall
 Activation of autolysins enzymes
Affect more on growing bacteria
Penicillin resistance started to show in the 1940’s, in 1960
50% of bacteria were resistant.
RESISTANCE TO PENICILLINS
1) Production of β-lactamases

2) The occurrence of modified penicillin-binding sites

3) Decreased permeability to the drug

 Penicillins classification

– Narrow spectrum – penicillinase sensitive

– Narrow spectrum – penicillinase resistant

– Broad spectrum penicillins

– Extended-spectrum penicillins
Narrow spectrum – penicillinase (= β-lactamase)
sensitive
• Benzylpenicillin
– Naturally occuring
– Poor oral availability (sensitive to stomach acid)
– given by injection
– Active against gram-positive bacteria
• Phenoxymethylpenicillin
– Better oral availability (acid resistant)
Narrow spectrum – penicillinase (= β-
lactamase) resistant

• Methicillin
– Semisynthetic
– Poor oral availability (only parenteral)
– Active against gram-pos bacteria
– Mostly used for Staphylococcus aureus
• Oxacillin
– Good oral availability
• Cloxacillin
• Dicloxacillin
Broad spectrum – penicillinase (= β-lactamase)
sensitive(= Aminopenicillins)

• Ampicillin
– Semisynthetic
– Good oral availability
– Active against gram-pos and gram-neg bacteria
– Active against enterobacteria
• Amoxicillin
– Excellent oral availability
Extended spectrum – penicillinase (= β-lactamase)
sensitive (= Carboxypenicillins)

• Carbenicillin
– Semisynthetic
– Poor oral availability
– Active against gram-pos and gram-neg bacteria
– Active against Pseudomonas aeruginosa, Klebsiella
• Ticarcillin
• Mezlocillin
• Pipercillin
PHARMACOKINETIC:

Absorbtion orally
Distrubution
BBB
Placenta
Renal execretion
Metabolizetion
Therapeutic use
Treatment of:
Gram+ cocci___________________Staph ,strepto >>>>abcess
Gram _ cocci__________________nisseria >>>>meningitis
Gram + bacilli_________________anthrax ,tetanus ,gas gangrene
spirochetes >>>> syphilis
actinomycese >>>>actinomycosis
Gram – bacilli__________________UTI , H.Pylori , typhoid fever
Pseudomonas infection ( + gentamicin)
Prophlaxis uses:
Bacterial endocarditis
Rheumatic fever
impairment of platelet aggregation.
irritative responses to penicillin at site of
injection
phlebitis or thrombophlebitis
nausea, with or without vomiting
Intrathecal injection of penicillin G may
produce arachnoiditis
PROBENECID
 Probenecid is an oral drug used for reducing blood uric
acid levels in patients with hyperuricemia (high uric
acid)
 Probenecid prevents attacks of gout by reducing uric
acid levels in the blood.
 It does this by preventing the reabsorption of uric acid
by the kidney and increasing its excretion from the
body in the urine.
 Probenecid also blocks excretion by the kidney of
penicillin and related antibiotics and is used for
increasing the levels of the antibiotics in the blood and
increasing their effectiveness when treating infections.
PRESCRIBED FOR:
Probenecid is used for the treatment of
hyperuricemia associated with gout. It also is
used for increasing blood levels of penicillin-
type antibiotics (for example, ampicillin and
amoxicillin).
SIDE EFFECTS:
Common side effects of probenecid include headache,
dizziness, nausea, vomiting, skin rash, sore gums, and
fever.
Probenecid may cause a flare of gout and kidney
stones, and it is not started during an acute attack of
gout.
Serious but rare side effects include reduced red
blood cell counts (anemia), liver damage and severe
allergic reactions.