Summary Pharmacology essential notes!

CELL
WALL
INHIBITORS



PENICILLINS

ACTION:
Interferes
with
the
last
step
of
cell
wall
synthesis,
the
transpeptidation
(cross-­‐linkage).

Binding
of
penicillin-­‐binding-­‐proteins
(PBP)
as
well
as
production
of
autolysins



RESISTANCE:
By
beta-­‐lactamase/penicillinase
activity,
decreased
permeability
by
the
drug
or
efflux

pump,
and
altered
PBP
(MRSA
uses
this
mechanism)



ADVERSE
REACTIONS:
Hypersensitivity
to
penicilloic
acid
as
the
antigenic
Macrolides
=
gram+

metabolite.
Diarrhea
(ampicillin
poorly
absorbed).
As
with
most
Aztreonam
=
gram-­‐

antibiotics
may
result
in
pseudomembranous
colitis
aka
exudative

inflammation
caused
by
C.
difficile.
Treat
with
metronidazole.
Nephritis
especially
with
methicillin.

Neurotoxic.
Hematologic.
Cation
toxicity
due
to
combination
with
sodium
or
potassium.




1’st
generation

Narrow
spectrum,
beta-­‐lactamase
sensitive.
Used
against
gram-­‐pos
and
gram-­‐neg
cocci,
gram-­‐
pos
bacilli
and
spirochetes.

Act
synergistically
with
aminoglycosides
(protein
synthesis
inhibitors).

Least
toxic
drug,
but
increasing
resistance.

Excretion
through
organic
acid
tubular
secretory
system
which
is
inhibited
competitively
by

Probenecid
(uric
acid
drug).
Penicillin
G
is
also
secreted
into
breast
milk.
Penicillin
V
is
less

active
than
Penicillin
G
against
gram-­‐neg.



• Penicillin
G
(Benzylpenicillin)
i.v.

• Penicillin
V
(Apocillin)
oral



2nd
generation

Beta-­‐lactamase-­‐resistant
penicillins.
Anti-­‐staph
penicillins.
Decreased
absorption
in
stomach
by

food.
Methicillin
only
used
to
identify
strains
of
staph
aureus.

• Methicillin


• Nafcillin

Eliminated
by

• Oxacillin
i.v.
bile,
not
kidneys

• Dicloxacillin
(Diclin,
Diclocil,
Dicloxacillin)
oral



3rd
generation

Extended-­‐spectrum
penicillins.
Used
with
beta-­‐lactamase
inhibitors.
• Clavulanic
acid

• Ampicillin
(Ampicillin,
Pentrexyl)
i.v.
• Sulbactam

• Amoxicillin
oral
• Tazobactam



4th
generation

Anti-­‐pseudomonal
penicillins.
Piperacillin
is
the
most
potent
one.

• Carbenicillin

• Ticarcillin

• Piperacillin
(Tazocin,
Piptazira,
Piperacillin/Tazobactam)






















, CELL
WALL
INHIBITORS



CEPHALOSPORINS

ACTION:
Same
mechanism
of
action
as
penicillin,
but
tend
to
be
more
resistant
to
beta-­‐
lactamases.

They
are
divided
into
generations
based
on
their
bacterial
susceptibility
and
resistance
to
beta-­‐
lactamases.
May
be
susceptible
to
ESBL
(extended-­‐spectrum
beta-­‐lactamases).
Generally
poor
oral

absorption.
IV
and
IM
preferable.
All
cross
placenta.
Highest
rate
of
cross-­‐sensitivity
between
penicillin

and
1st
generation
cephalosporins.



ADVERSE
REACTION:
Disulfiram-­‐like
side-­‐effect
(Cefoperazone)



1st
generation

These
are
penicillin
G
substitutes
and
kills
gram-­‐pos
and
few
gram-­‐neg.
PEcK
=
Proteus

mirabilis,
E.
Coli,
Klebsiella
pneumonie.
Cefazolin
penetrates
bone.

• Cefazolin


• Cephalexin
(Keflex)

• Cephalothin
(Keflin)



2nd
generation

Kills
HENPEcK
=
Haemophilus
influenza,
Enterobacter
aerogenes,
Neisseria,
Proteus
mirabilis,
E.

Coli,
Klebsiella
pneumonie.
Cefuroxime
crosses
BBB.

• Cefotetan

• Cefoxitin

• Cefuroxime
(Zinacef,
Cefuroxim)



3rd
generation

Management
in
sepsis
and
meningitis.
But
inferior
to
treatment
against

MSSA
compared
to
1st
generation
cephalosporins.
Enhanced
activity

3rd
and
4th

against
HENPEcK
+
Pseudomonas
aeroginosa.

generation
has
to

Not
effective
against
LAME
=
Listeria
(Ampicillin),
Atyipcals/mycoplasma

some
extent

(macrolides),
MRSA
(Vancomycin),
Enterococci
(Amoxicillin
or

replaced
the

Ampicillin).

aminoglycosides

• Ceftriaxone

• Cefotaxime

• Ceftazidime
(Fortum)

• Cefoperazone



4th
generation

Kills
E.
coli,
Klebsiella
pneumoniae,
Proteus
mirabilis,
Pseudomonas


• Cefepime