Title: PENICILLINS
1PENICILLINS
- 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
2(No Transcript)
3MECHANISM 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
4Classifications 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 )
5- 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
6- 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
7Class. Of penicillins ( cont. )
- Disadvantages of penicillin G
- A. Destroyed by gastric HCL
- B. Inactivated by penicillinase
- C. Narrow spectrum of activity
8Class. 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
9Class. 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
10Class. 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.
11Broad-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.
12Broad 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.
13Absorption,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
14Absorp., 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)
15Adverse 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