Inhibitors of cell wall synthesis
1. Penicillin's
2. Cephalosporins
3. Cycloserine
4. Vancomycin
5. Monobactam
6. Bacitracin
7. Fosfomycin
8. Imipenem & Carbapenems
CHEMISTRY
CLASSIFICATION
MECHANISM OF ACTION
MECHANISM OF RESISTANCE
PHARMACOKINETICS
CLINICAL USES
ADVERSE REACTIONS
DRG INTERACTIONS
CHEMISTRY
All the Penicillin's have basic
structure of
THIAZOLIDINE ring attached to a
β-LACTAM ring &
SECONDARY AMINO group (R,R1)
Both these groups are essential
for Structural integrity of the 6-
aminopenicillanic acid nucleus &
CLASSIFICATION
PENICIL ANTISTAPH EXTENDED
LINS YLOCOCCAL SPECTRUM
PENICILLIN PENICILLINS
S
Penicilli Ampicillin &
nG Cloxacillin Amoxicillin
Dicloxacillin
Penicilli ANTIPSEUDO
nV Nafcillin MONAL
Oxacillin PENCILLINS
Methicillin Piperacillin &
Ticarcillin
Natural occurring (narrow spectrum)
Benzyl penicillin
Penicillin G
Penicillin V
Procaine Penicillin
Penicillinase resistant penicillines
Methicillin
Nafcillin Oxacillin
Cloxacillin Dicloxacillin
Broad spectrum Penicillines
Ampicillin
Amoxycillin
Effective against
pseudomonas
Carbencillin
Ticarcillin
Piperacillin
Corboxy penicillin
Azlocillin
MECHANISM OF
ACTION
β-lactam antibiotics are
structural analogues of D-Ala-D-
Ala substrate covalently binds to
the active site of Penicillin
binding proteins (PBPs).
They stop bacterial growth by
inhibiting Penicillin binding
proteins (PBPs) forms cross links
between peptides responsible
for structural rigidity of cell wall
Thus interfering with the
transpeptidation reaction of bacterial
wall synthesis & peptoglycan
synthesis.
The cell dies probably by autolysins and
disruption of cell wall morphogenesis.
They kill cells only when they are actively
growing and synthesizing cell wall.
RESISTANCE
INACTIVATION OF
ANTIBIOTIC BY
β-LACTAMASES(penicillases)
produced by Staphylococcus
aureus, H. influenzae,
Gonococci which opens up
beta lactum ring and
hydrolyses it to pencilloic
acid which is harmless form.
MODIFICATION OF TARGET
Pencillin
IMPAIRED PENETRATION OF
DRUG TO TARGET PBPs especially
in G-ve species and absent in
G+ve species.
EFFLUX
Certain organism lack cell wall
e.g. mycoplasma.
PHARMACOKINETICS
Pencillins are bacteriocidal drugs
Given by Oral, I/M or I/V routes
ABSORPTION of most PENICILLINS
except AMOXACILLIN is impaired
by food and the drugs should be
administered at least 1 hour
before or 1-2 hours after a meal
Plasma half life 30 minutes to one
hors.
Penetration into the EYE, PROSTATE
and CNS is poor but enhanced at the
time of inflammation.
Dosage
For amoxicillin
Adults > 40 kg 250-500mg every 8
hourly.
Neonates & infants 15mg/kg/12
EXCRETION
Excreted rapidly by the kidneys
10% by glomerular filtration and
90% unchanged by tubular
secretion.
Also excreted in SPUTUM and
MILK to levels (3-15%) of that in
serum
EXCRETION
NAFCILLIN is primarily cleared
by biliary excretion
OXACILLIN, DICLOXACILLIN AND
CLOXACILLIN are eliminated both
by the kidney and biliary
excretion
Blood levels of all penicillin's can
be raised by simultaneous
administration of PROBENECID
0.5g
which impairs renal tubular
secretion of weak acids as β-
lactam antibiotics
Ampicillin, Amoxacillin, Ticarcillin AND
Piperacillin
are also available in combination with
one of the several β-lactamase
inhibitors: Clavulinic Acid, Sulbactum
OR Tazobactam
CLINICAL USES
PENICILLINS ANTISTAPHYLO EXTENDED
COCCAL PEN. SPECTRUM
P.
Greatest Activity Activity
activity against against against
G+ve Staphylococci G+ve &
organisms, and improved
G-ve cocci & Streptococci activity
against G-
non-β-
ve
lactamase
producing organism
Resistant to
anaerobes
hydrolysis by Relatively
Susceptible to
staphylococcal
hydrolysis by β- β-lactamases susceptible
lactamases to
PENICILLIN G:
Bacterial meningitis by
N. Meningitidtis, streptococcus
pneumonia. High doses I/V is
required.
Skin & soft tissue infections
by strep. Pyogenes or
staph aureus.
Endocarditis
by strep. Viridans or
entercoccus faecalis.
Syphilis: (2.4 million units) once
PROCAINE PENICILLIN G
Pneumococcal or
Gonorrheal infection
For rheumatic fever
prophylaxis
AMOXACILLIN
Dose___25-50mg/kg body weight
Acute Tonsillitis, pharyngitis,
sinusitis, Bronchitis of mixed
infection & URTI
Otitismedia (strep. Pyogenes,H.
influenza)
Pneumonia & lower respiratory
tract infections(LRTI)
Urinary tract infections (E. coli),
AMPICILLIN is effective for shigellosis
AMPICILLIN also used in bacteremia,
meningitis, endocarditis, urethritis,
conjunctivitis
FLUCLOXACILLIN is used to treat
Bone & jiont infection by staph. Aureus
Skin & soft tissue infections by strep. Pyogenes or
staph aureus.
Ticarcillins & Piperacillin are used in
Serious infectoins caused by
Pseudomonas aeruginosa.
PIPERACILLIN, MEZLOCILLIN
Are also active against selected
gram negative bacilli as Klebsiella
pneumonias.
Animal bite treated with co-
amoxiclav.
ADVERSE REACTIONS
Diarrhea
Nausea
Vomiting
HYPERSENSITIVITY
In 10% patients Observed within 02
minutes upto 03 days
Serum sickness type reactions
urticaria, fever,
joint swelling, angioneurotic
edema, intense pruritis
occurring 7-12 days after exposure.
Anaphylactic shock (0.05%)
ADVERSE REACTIONS (Specific
drugs)
NAFCILLIN causes neutropenia
OXACILLIN can cause hepatitis
METHICILLIN causes interstitial
nephritis
AMPICILLIN in large doses can
cause pseudomebraneous colitis
AMPICILLIN AND AMOXICILLIN in
large doses can cause skin rashes
that are not allergic in nature
Co-amoxiclave (Augmentin)
Is a combination of
125mg clavulanic acid + 500 mg
amoxicillin
It is effective against plasmid – encoded
beta lactamases e.g. produced by
staphlococci, H.influenzae, N.gonorrhea,
salmonela, shegilla and E.coli.
Side effects:
Diarrhea, rashes, cholestatic jaundice
(clavulanic acid is the cause).
