SlideShare uma empresa Scribd logo
1 de 143
Baixar para ler offline
PENICILLINS
CEPHALOSPORINS & OTHER
β-LACTUM ANTIBIOTICS
Dr. Rajendra Nath
Professor
PENICILLINS CEPHALOSPORINS &
OTHER β-LACTUM ANTIBIOTICS
• Useful & frequently prescribed AM
agents .
• Share a common structure & mech.
of action i.e. – inhibition of synth. of
the bact. peptidoglycan cell wall .
PENICILLINS CEPHALOSPORINS &
OTHER β-LACTUM ANTIBIOTICS
• β- lactums - include Cephalosporin
antibiotics which are classified by
generations .
PENICILLINS CEPHALOSPORINS &
OTHER β-LACTUM ANTIBIOTICS
• β- lactamase inhibitors e.g.-
Clavulanate , Sulbactum etc. are
used to extend the spectrum of
Penicil. against β- lactamase prod.
organisms.
PENICILLINS CEPHALOSPORINS &
OTHER β-LACTUM ANTIBIOTICS
• Other β- lactums include –
- Carbapenems including Meropenem
& Imipenem which have broadest AM
spect. of any antibiotics .
• Monobactums – e.g.- Aztreonam has
G-ve spect. resembling that of Amino
-glycosides .
PENICILLINS CEPHALOSPORINS &
OTHER β-LACTUM ANTIBIOTICS
Bact. resist. against the β- lactum
antb.s continues to ↑at high rate.
Mech. -
- by β –lactamase that destroy the antb
- alteration in or acquisition of novel
penicil. binding proteins ( PBPs) .
- Decreased entry & / or efflux of antb.s
.
PENICILLINS
-One of the most important gp of
antibiotics.
- However numerous other AM agents
have been prod. since the first penicil.
become available.
- These are still used widely & many of
these are currently the DOC for a
large no. of infectious diseases .
PENICILLINS
- In 1928 in laboratory of St mary’s
hosp. London , A. Fleming observed
that a mold contaminating one of the
bact. cultures caused the bact. in its
vicinity to undergo lysis. Because the
the mold belonged to the genus
Penicillium , Fleming named the antb.
PENICILLINS
substance as Penicillin .
Chemistry :
Basic struct. consists of
1. Thiazolidine ring (A) connected to
2. β- lactum ring (B) to which attach
3. Side chain (R) .
PENICILLINS
O S CH3
R C NH CH CH C
2 B A CH3
O = C N CH COOH
Amidase 1 Penicillin
Penicillinase site of action
PENICILLINS
A. Thiazolidine ring
B. β- lactam ring
1. Site of action of penicillinase
2. Site of action of amidase
PENICILLINS
- The penicillin nucleus itself is the
chief struct. requirement for biologic.
activity . Metabolic transformation/
chem. alteration of this portion of the
mol. causes loss of all sig. AB activity
- Side chain determine many of the AB
& pharmacol. character of a particular
PENICILLINS
type of Penicillin.
- Penicil. G ( benzyl penicil. ) has the
greatest AM activity of these & is the
only natural penicil. used clinically.
Semi-synthetic Penicillins :
It has been discovered that 6- amino-
penicillanic acid could be obtained from
PENICILLINS
cultures of P. chrysojenum lead to the
dev. of the semi-synth. Penicil.s .by
adding different side chains in this .
-6-aminopenicillanic acid is now prod.
in large quantities with the aid of the
amidase from P. chrysojenum .
PENICILLINS
Unitage of Penicillin :
- one Int. unit ≡ 0.6 μg of the cryst. sod.
salt of Penicil. G.
-1mg of pure Penicil. G ≡ 1667 units.
Mech. of Penicillins :
-The cell walls of bact. are essential for
their normal growth & development.
PENICILLINS
- Peptidoglycan is a heteropolymeric
component of the cell wall that
provides rigid mech. stability .
- Cell wall is 50-100 mols thick in G+ve
& ½ molecule thick in G-ve bacteria .
- Peptidog. is composed of glycan
chains having linear strands of two
PENICILLINS
alternating amino sugar (N-acetyl –
glucosamine & N- acetyl muramic acid)
& they are cross-linked by peptide
chain .
Biosynth. of Peptidoglycan :
involves three stages
PENICILLINS
Final stage involves completion of the
cross link .This accomplished by a
transpeptidation react. that occurs outside
the cell memb.( with the help of
Transpeptidase enz. which is memb.
bound ). These enz.s & related proteins
are now called as Penicillin Binding
Proteins ( PBPs).
PENICILLINS
It is this last step in peptidoglycan
synth. that is inhibited by the β- lactum
antb.s & glycopeptide antb.s
(e.g.Vancomyc.)
PENICILLINS
- Main target for the action of penicil.s
& cephalosporins are these
Penicil. Binding Proteins (PBPs) .All
bact. have such entities e.g.- E .coli
Penicillins and Cephalosporins.ppt
PENICILLINS
PENICILLINS
has 7 & S. aureus has 4 PBPs .
The PBPs vary in their affinity for diff.
β – lactum antb.s , although interact.
become covalent .
- ↓ of transpept.( PBP-I) causes formation of
spheroplast & rapid lysis.
- ↓ of PBP-II & III ( Carboxypeptidase &
endopeptidase enz.s) cause delayed lysis
or production
PENICILLINS
of spherical cells & large filamentous
form of bacterium.
Penicil.↓ synth. of cell wall & thereby
expose the org.s to the lethal external
environment which is not matching
with internal osmotic –pressure &
bact . swells & lysis occurs .
PENICILLINS
Death of the bact. also occurs due to
activation of autolysing enz.s called
autolysins or murein -hydrolase .
-Lethality of penicil. involve both lysis
or nonlytic mech.
PENICILLINS
Mech. of bact . Resist. to penicillin
( & Cephalosporins ) :
1.Micro-org may be intrinsically resist.
because of structural diff. in the PBPs
that are the targets of these drugs
(A sensitive strain may acquire resist.
of this type by the dev. of high mol.
PENICILLINS
wt. PBPs that have ↓ affinity for the
antb. e.g.- Penicil. resistance in
Streptococcus gp. emerged
as a result of replacement of its PBPs
with resist. PBPs from S. pneumoniae.
PENICILLINS
2. Other way of bact. resist. is caused
by the inability of the agent to
penetrate to its site of action e.g.-
G-ve bact.
PENICILLINS
- in G+ve bact . the peptidoglycan
polymer is very near the cell surface ,
some G+ve bact. have polysacch.
capsule that are external to the cell
wall but they are not the barrier to the
diffusion of β- lactums .
PENICILLINS
- In G-ve bact. the inner memb. is
analog. to the cytoplasmic memb.
of G+ve bact. & is covered by outer
memb. of Lipopolysaccharide &
capsule ,it functions as a
impermeab. barrier for some antb.s
PENICILLINS
Some small hydrophilic antb.s diffuse
through aqueous channels in the out.
memb. that are formed by protein
called porins .
-Broad spect. Penicil.s e.g. – Ampicill.
& Amoxycill. & most of the Cephalo-
sporins diff. through the pores in the
PENICILLINS
E.coli outer memb. more rapidly than
can Penicill. G ( the no. & size of the
pores vary e.g.- Pseudomonas aeru.
lack the classical high permeability
porins .)
3. Active efflux pumps serve as another
mech. of resist. removing the antb.s
PENICILLINS
PENICILLINS
from its site of action before it can act
e.g.-β- lactum resist. in P.aerug. ,E.coli
& N. gonorrheae .
4.Bact. can also destroy β- lactum antb.
enzymatically by β- lactamases which
inactivates certain of these antb.s .
PENICILLINS
-diff. micro-orgs elaborate a no. of
distinct β- lactamase which often are
described as Penicillinases or Cepha -
linases . These are grouped into 4
clases ( A-D) .
- Class A β- lactamases include the
extend. spect. β –lactamases which
PENICILLINS
degrade Penicil.s , some Cephalospor.
and in some instances ,Carbapenems.
-Class B: β-lactamases are Zn++ dep.
enz. that destroy all β- lactams except
Aztreonam .
- Class C: β- lactamases are active
against Cephalosporins.
PENICILLINS
-Class D : include Cloxacillin deg. enz.s
- G+ve bact. prod. & secrt. a large
amount of β- lactmases . Most of these
are Penicillinases . The information for
Staphylococcal penicillinase is encoded
In a plasmid & this may be transferred
by bacteriophage to other bact.
PENICILLINS
- In G-ve bact. β-lactamases are
found in relatively small amounts .
they are encoded either in chromos.
or in plasmids & may be constitutive
or inducible .
- The plasmids can be transferred
between bact. by conjugation .
PENICILLINS
- Other factors : micro-org.s adhering
to implanted prosthetic devices
( e.g.- catheters , artific. Joints ,
prosth. heart valves etc.) prod.
biofilms & are much less sens. to
antb.s .
- The presence of proteins & other
PENICILLINS
constituents of pus, low pH or low
oxyg. tension does not appreciably
↓ the ability of β-lactum antb.s to kill
bact. However bact. that survive
inside visible cells of the host gener.
are protected from the action of the
β- lactum antb.s .
PENICILLINS
Classification :
According to their spectrum of AM act.
I Narrow spectrum
A. Penicillinase sensitive
i) Penicillin G ( parenteral ) – highly
active against sensitive strains of
G+ve cocci hydrolyzed by
PENICILLINS
penicillinase , not effective against
most strains of S. aureus e.g.-
-Crystalline or Benzyl Penicil. or
Penicil. G.
- Procaine Penicil.
- Benzathine Penicil.
ii) Phenoxy methyl Penicil. or Penicil. V
PENICILLINS
( orally active )
B. Penicillinase resist. Penicil. -e.g.-
Methicillin , Naficillin , Cloxacillin
Oxacillin , Flucloxacillin etc.
have less potent AM activity against
micro-org. sensitive to Penicil. G .
but agent of first choice for
PENICILLINS
penicillinase prod. S. aureus & S. epid
-ermidis .
C. Penicillinase inhibitors .
e.g.- Clavulanic acid ( comb. with
Amoxycil.)
- Sulbactum ( + Ampicillin )
- Tazobactum ( + Piperacillin)
PENICILLINS
They are given with broad spectrum
antb.s to prevent hydrolysis by broad
spect. β- lactamases ( in G-ve bact.
e.g. E.coli .)
II Broad spect. Penicillins :
A. Carboxypenicil. e.g.- Carbenicillin
Carbenicil. Indanyl ,Ticarcillin .
PENICILLINS
their AM activity is extended to include
Pseudomonas , Enterobacter &
Proteus gp. (inferior to Ampicil.against
G+ve cocci & L.monocytogenes &
less active than Piperacil. against
Pseudomonas.& also known as anti-
Pseudomonal penicillins )
PENICILLINS
B. Aminopenicillins : e.g.- Ampicillin ,
Amoxycillin, etc.. They are also
effective against G- ve org.s e.g. –
H. influenzae , E. coli , Proteus mira -
bilis . etc. . But they are sensitive to
penicillinase enzyme. (They are used
now with β- lactamase inhib.s e.g. Clavulanic acid
which further extends their spectrum )
PENICILLINS
C. Uriedopenicillins ( extended spect.
penicil.) : e.g.- Azlocillin , Mezlocillin
& Piperacillin .
Excellent activity against
Pseudomonas ,Klebsiella & other
G-ve org.s
PENICILLINS
Pharmacological propert. in general:
- Following abs. of orally administered
penicil. these agents are distributed
widely through out the body.
- Therapeutic conc. attain readily in
tissues & in secret. e.g. joint fluid ,
pleural fluid ,pericardial fluid & bile
PENICILLINS
-Low conc. in prostatic fluid ,brain
tissue ,intra-ocular fluid & in CSF (conc
of penicil. is < 1% of those in plasma ,
but in inflammed meninges conc. may
↑ upto 5% of plasma ) .
- Eliminated rapidly by glomerular filtr.
& renal tubular secrt. (t½ -30-90 min.)
PENICILLINS
Penicil.G & Penicil. V :
The AM spect. of penicil. G &V are
very similar for aerobic G+ve micro-
org. (but penicil. G is 5-10 times more
active against Neisseria sp. & against
certain anaerobes). They are narrow
spect. & enz. sens. Penicil.s
PENICILLINS
Spectrum :
effective against Pneumococci.
streptococci, Meningococci , non β-
lactamase prod. gonococci & staphy.
(> 90% strains of staphyl. Isolated
from individuals inside or outside
hospitals are now resist.)
PENICILLINS
- Treponima pallidum , bacil. anthracis
& vast majority of strain of C. diphther.
are senst. but some are resist.
- Actinomyces , Clostridium sp.
(anaer. micro-org.) are highly senst.
PENICILLINS
( Bact. fragilis is exception ) .
- None of the Penicil.s are effective
against Amoeba , Plasmodium ,
Rikettsia , fungi or viruses .
Absorption : Oral -
about ⅓rd of oral dose is absorbed
in favorable cond. not destroyed by
PENICILLINS
gastric juice ( 2/3rd destroyed by GJ) .
Penicil. V is more stable in acid hence
better absorbed .
-Food may interfere with abs. of all Penicil.s
-Parenteral – after I.M. inj. peak conc.
of Penicil.G reached with in 15-30
mins .
PENICILLINS
( vol. declines as half life of Penicil. G
is 30 mins ) . Different measures are
there to prolong its existence in body
e.g.
1. Repository prep. -Procain Penicil.
& Benzathine Penicil. they release
PENICILLINS
penicil. G. slowly from the area in
which they are injected & prod. relativ.
low but persistent conc. of antb. in
blood .
Penicil.G. Procaine susp. is an aquous
prep. of the crystalline salt ( H/S test
is done by I.D. test of 0.1 ml of proc.)
PENICILLINS
It is a painless inj.
- Benzath. Penicil. susp. of the salt
obtained by the comb. of 1 mol. of
an ammonium base & 2 mol. of
penicil. G. . The long persistence of
penicil. conc. in blood after I.M. inj.
reduces cost , need for repeated inj.
PENICILLINS
and local trauma.
benz. penicil. has got longest duration
of detectable antb. A dose of 1.2 mill.
unit I.M. → conc. of 0.09 μg/ml on the
1st , 0.02 μg/ml on 14th & 0.002 μg/ml
on 32nd day (avg. duration is 26 days)
2. Use of Probenecid that blocks renal
PENICILLINS
tubular secr. of penicil. & thus exct. ,is
also used to increase the dur. of action
- It also ↑ the conc. of penicil. in CSF
as it does not readily enter the CSF
normally (increase abs. in meningitis)
- Penicil. is secrt. rapidly from the CSF
into blood stream by an active
PENICILLINS
transport process & probenecid compe
-titively ↓ this transport & thus↑ the
conc. of penicil. in CSF.
Excretion :
Penicil. G. is eliminated rapidly from
the body mainly by the kidney ,but
small part in the bile & other routes .
PENICILLINS
Therapeutic Uses :
1.Pneumococcal inf.-Penicil. G (DOC)
-Pneumococcal Pneumonia –
(Penicil. G- 24 million U daily
Penicil. V – 500 mg orally 6 hrly).
-Pneumococ. mening. – until it is
established that penicil.G .is sens.
PENICILLINS
it is treated with Vancomycin + III gen
Cephalosporin ( if sensitive - penicil. G is
given -20-24 mill. U/day x 14 days)
2. Streptococ. Inf. – in scarlet fever
( Streptococ. pharyngitis ) –
penicil. V. -500 mg 6 hrly x 10 days
penicil. G. – 6 lacks U OD x 10 days
PENICILLINS
or single inj. of Benz. Penicil. 1.2 mill U stat.) ,
also effective in –Streptococcal
pneumonia , arthritis , meningitis &
endocarditis .
3. Inf. with Anaerobes :
mixt . of org.s most are sens. to
penicil. G. exception is B. fragilis gp.
PENICILLINS
-Penicil.G. + Metronidazole or Chlora
- mphenicol .
4. Staphylococ inf. – penicil. resist
penicil. e.g.-
Naficillin or Oxacillin
5. Meningococ. Inf. – Penicil G. ( DOC)
given I.V. high dose
PENICILLINS
6. Gonococ. Inf. – resist. to penicil. G
& they are no longer the therapy of
choice ( IIIgen. Cephalosporins -
Ceftriaxone is given ) .
7. Syphilis –
penicil.G. is highly effective in primary,
second. & latent syphilis of < 1 y dur.
PENICILLINS
(Proc. Penicil. -2.4 mill. U /day I.M. + Probenecid
1 gm/ day orally x 10 days or
Benz. Penicil. G. 2.4 mill. U I.M. 1 -3 weekly ).
Pts with late latent syph., neurosyph ,
cardiovas. syph. – 20 mill. U of penicil G.
daily x10 days (child.-50,000 U/kg of Penicil. G
. in two div. doses.)
PENICILLINS
most pts dev. Jerisch Herxheimer reac.
(several hrs after the 1st inj of penicil. G) -
Chills with fever, headach, myalgia &
arthralgia may dev. & syph. lesion
may become more prominent . It fades
with in 48 hrs & does not recur with 2nd
PENICILLINS
inj. ( due to Spirochaetal antigens ).
8. Actinomycosis – Penicil. G. – DOC
( 12 -20 mill. U I.V. /day x 6 wks)
9. Diphtheria-
specific antitoxin (antidiphtheritic serum)
is the only effective tt. however penicil. G
eliminate the carrier state -
PENICILLINS
( Proc. Penicil. 2-3 mill. U / day x 10-12 days.)
10. Anthrax -now resist. in most of the cases
11. Clostridial inf. – penicil. G. is DOC in
(i) Gas gangrene (by C.perfringens,12-20
mill. U/day), debridement of inf. area is
necessary apart from the drug .
(ii) No effect on ultimate outcome of
PENICILLINS
Tetanus ( C. tetani ) ,hence tetanus immunoglob.
(ATS ) is indicated along with debridement of
dead tissue + Penicil G (10-20 mill. U /day I.M.) to
eradicate the bact.
- Fusospiroch. Inf. - Gingivo-stomatitis
e.g.-Trench mouth (Penicil. V.-500 mg 6 hrly x7 d)
12. Rat bite fever : by Spirillium minor senst. to
penicil.( G -12-15 mill. U/d x 3-4 wks)
PENICILLINS
13. Listeria inf. – Ampicillin 1-2 gm 4
hrly. ( +Gentamycin in immuno -comp. host &
pt with meningitis.) & penicil.G(15-20 mill.
U/d) are DOC.
14. Erysepilas –Pasteurella multocida -
wound inf. after dog / cat bite .
senst. to penicil. & Ampicil.s
PENICILLINS
Prophylactic use – was effective in
previous inf.s but still used in
1. Streptococcal inf. & cases of deep
burn.
Single inj. of Benz. Penicil.-1.2 mill.U
2.Recurence of Rheumatic fever –
oral –penicil. V or
PENICILLINS
Benz. Penicil. G – (1.2 mill. U once a
month.)
3. Syphilis – prophyl. for contacts .
4. Surg. procedure in pts with valvular
heart dis.( Dental extractions ).
PENICILLINS
2. Penicillinase resist penicil.:
This type of penicil. is resist. to
hydrolysis by Staphy. penicillinase
(their use should be restricted to the
tt of inf. which are caused by staphy.
that secrete this enz.)
-these are less sens. than is penicil. G
PENICILLINS
against other penicil. senst. micro-org
-Methicil. resist. micro-org.s are
resist. to all the penicil. resist.Penicil.s
& Cephalosp.s .
-Hospital acquired inf. are also resist to
these penicil.
PENICILLINS
e.g.-
Isoxazolyl Penicil.:
Oxacillin , Cloxacillin & Dicloxacillin –
-These are congeneric semi –synth.
Penicil.s .
- These are similar pharmacologically,
abs. adequately after oral administ.
PENICILLINS
( abs. is more effective on empty
stomach) .
Naficillin :
This semisynth. Penicil. is highly resist.
to penicillinase & effective against inf.
caused by penicillinase prod. strains
PENICILLINS
of S. aureus .
- abs. in GIT is irregular ( inactivated
in acid medium ) therefore given
parenteraly ( 1 gm I.M. ) .
- conc. of drug is adequate in CSF for
the tt of S. meningitis .
PENICILLINS
Aminopenicillins :
Ampicillin , Cloxacillin & their cong.s
- these are known as broad spect. antb
have similar AM activity .
-they all are destroyed by β- lactamase
- they are bactericidal for both G+ve &
G-ve bact.
PENICILLINS
- N. gonorrhoeae , E. coli , P. mirabilis,
Salmonella & Shigella were highly
senst. to these when they are first
used but now resist. is increasing.
(Pseudomonas & Klebsiella are
resist.)
PENICILLINS
( however concurrent administ. of a β-
lactamase inhib. e.g.- Clavulanate or
Sulbactum markedly expands the
Spect. of activity of these drugs )
dose – 500mg QID or 0.5 – 1 gm sod.
Ampicil. Inj. I.M. ( adjustment
is req . in cases of renal dysf.)
PENICILLINS
Amoxycillin :
- abs. is more complete & rapid than
Ampicil. & stable in acid & given
orally.
- spect. similar ( except less senst. in
Shigellosis )
- food does not interfere with abs.
PENICILLINS
- Incidence of diarrhea is less
- Effective conc. of orally administ.
Amoxy. are detectable in plasma
twice as long as with Ampicil.
- Probenecid delays exct. of drug .
Uses -1. URTI against S. pyog. & S.
pneumonia & H. influenzae .
PENICILLINS
-effective for sinusitis , otitis media &
acute exacer. of chr. Bronchitis &
epiglottitis
- Addition of β –lactamase inhib.
( Amoxy + Clavulanate & Ampicil +
Sulbactum ) extends the spect. to
H. influenzae & enterobacteriaceae.
PENICILLINS
2. UTI
3. Meningitis – not alone but in comb.
with Vancomycin + 3rd gen. cephalo.
4. Salmonella inf. – bacteremia &
enteric fever ( Typhoid) synd.
respond well to these . Fluoroq. ,
/ Ceftriaxone are DOC but Trimeth.
PENICILLINS
+ Sulfamethoxazole or high doses of
Ampicil. also are effective ( 12 gm/d for
adults) .
Antipseudomonal Penicil.s :
Carboxypenicillins – e.g.-
Carbenicillin ,Carbenicillin indanyl
( indanyl ester of carbenicilin which
PENICILLINS
is acid stable & used orally) &
Ticarcillin .
- They are active against some
strains of Pseudomonas aeruginosa
& certain sp. of Proteus ( that are
resist. to Ampicil.& congener ).
- Hypokalemia may occur.
PENICILLINS
Ureidopenicillins :
e.g.- Mezlocillin & Piperacillin have
superior activity against P.aerug.
- they are also used against Klebsiella
- they are senst. to destruction by β –
lactamases .
PENICILLINS
(In comb. with a β – lactamase
inhib. Piperacil. &Tazobactum has
the broadest AM spect. of the
penicil.s )
Uses – serious inf. caused by G-ve
bacteria.
PENICILLINS
( esp. in pts of impaired immuno -
logical defenses & inf.s acquired in
hospitals)
so greater use in bacteremias ,Pneum.
inf. following burns & UTI .
( in neutropenic pts )
PENICILLINS
Side effects :
1. Hypersenst. React. – they are the
most common ADRs noted in
penicil.s & most comm. cause of
drug allergy – include
maculopap. rash ,urticarial rash
fever , bronchospasm ,vasculitis
PENICILLINS
serum sickness ,exfol. dermatitis,
St. Johnson’s synd. & anaphylaxis.
- It may occur with any dosage form
of penicil.
- Cross allergy occur between diff. gps. of
penicil.s
(occurrence of untoward effects does not
necessarily imply repetitions on
PENICILLINS
subsequent exposure .)
- H/S react. may appear in the
absence of a previous known
exposure to drugs
(may be due to prev. unrecognized exposure to
penicil. in the environment e.g.- foods of animal
origin or from the fungus prod. penicil.)
PENICILLINS
- Although H/S clears after stopping
antb. but may persist for 1-2 wks or
longer after therapy has been
stopped .
- In few instances , it is necessary to
stop the future use of penicil.
PENICILLINS
because of risk of death ( pts should
be warned for this).
Mech.-
penicil. & their breakdown prod.s act
as haptens after covalent react. with
proteins . major breakdown moiety is
penicilloyl moiety which is the major
PENICILLINS
determinant moiety ( MDM) .
- IgE med. react. occur due to MDM
( in 25% other breakdown prod.s are
responsible)
- The most serious H/S react.s are
angioedema ( marked swelling of
lips , tongue ,face, peri-orbital tissue
PENICILLINS
frequently accomp. by asthamatic
breathing.)
- H/S react. can occur with small testing
dose ( intradermal inj. )
2. Serum sickness :
mild fever , rash , leukopenia ,
arthralgia ,purpura, lymphadenopathy
PENICILLINS
spleenomegaly, mental changes ,ECG
abnormalities , albuminuria ,hematuria.
It is mediated by IgG antibodies.
( it occurs when penicil. is continued for a wk or
more but is rare ).
- fever may be the only symptom
- eosinophilia & rarely int. nephritis
PENICILLINS
Management :
- pts history is most practical.
- Intradermal test
-Desensitization is recomm.. Low dose
penicil. in ICU ( 1, 5, 10, 100 & 1000
Unit / day )
- Adrenaline ( S.C. inj.)
PENICILLINS
- Antihistaminic ( injectable)
- Glucocorticoids ( inj.)
3. Other reactions –
-Bone marrow depression leads to
granulocytopenia
-Hepatitis (Oxacil. & Naficillin.)
- inj. can cause local pain & inflammation
(Intrathecal inj. can cause arachinoiditis & severe
encephalopathy .)
CEPHALOSPORINS
History & Source –
First source – Cephalosporium –
acremonium isolated in 1948 by
Brotzu . Crude filtrates from cultures
of this fungus were found to inhibit
the growth of S. aureus to cure
staphylococ. inf. & Typhoid fever
CEPHALOSPORINS
caused by Salmonella sp.
- Cultures shows three distinct antb.s
which were named Cephalosp. P, N,
C .
- With isolation of the active nucleus
of Cephalosp. C. i.e. 7 amino
cephalosporanic acid & with addition
CEPHALOSPORINS
of the side chains it become possible
to prod. synthetic comp.s having equiv.
AM activity or greater activity than
parent comp.
Chemistry :
Cephalosp. C contains a side chain
derived from D-α aminoadipic acid
CEPHALOSPORINS
condensed with a dihydrothiazide β-
lactam ring syst. ( 7- aminocephalospo
-ranic acid ).
-- comp.s containing 7- aminocephalo.
acid are relatively stable in dilute
acid & are highly resist. to
penicillinases .
CEPHALOSPORINS
CHEMISTRY:
1
S
R1 C NH–7
3
O N R 2
COO ˉ
- Alteration in position 7 of the β- lactum ring changes the
AB activity & alteration at post. 3 of di-hydrothiazine
ring is associated with changes in metabolic &
pharmacokinetic prop.s .
CEPHALOSPORINS
Mech. –
↓ cell wall synthesis ≡ Penicillins
Classification :
Well accepted syst. of classif. by
generation is very useful based on gen.
features of AM activity . ( Cephal. Having
A after Cef or Ceph are Ist Gen.
CEPHALOSPORINS
First Generation :
Name Dose Spectrum
Cephazolin 1-1.5 gm 6 hrly well effective against
( t½ -2 hr ) G+ve but less active
Cephalexin (O) 1 gm 6 hrly against G-ve bacterias
( t½ - 0.9 hr) Streptococ.( except
Cephadroxyl (O) 1gm 12hrly Penicillin resist str.)
( t½ -1.1 hr ) Staphylococ. aureus
Cephalothin ( N) (except. Methicillin.
Cephaloridine (N) resist strains ) + PEK
(Cephal. having A after Cef or Ceph are Ist Gen. )
CEPHALOSPORINS
FIRST GENERATION
Cephalexin , po
Cefazolin
Cephalothin
Cephradine , po
Active against G+ cocci ( except. enterococci & MRSA ):
s. pneumoniae, s. pyogenes, s. aureus, &
s. epidermidis
Indicated for streptococcal pharyngitis ( e.g. cephalexin)
Commonly used (eg. Cefazolin) as prophylactic for surgical procedures.
Modest activity against G- bacteria
( Minimal activity against G-cocci & G +ve bacilli )
These do not cross BBB ( not suitable for treating brain abcess /
meningitis ) & all are sensitive to β- lactamase enz. Degradation .
CEPHALOSPORINS
Second Generation :
Cefoxitin (BF*) inj. -2gm 4 hrly They are in between
(t½ - 0.9 hr ) 1st & 3rd gen. little less
Cefaclor (O) 1gm 8 hrly effect. against G+ve &
(t½ - 0.7 hr ) little more against
Cefamandole G- ve ( HNPEK )
( bl , A ) but not as active
Cefuroxime 3gm 8hrly against G+ve org.
( * ,BB) (t½ - 1.7hr) as 1st gen. cephalosp.
Cefotetan inj. 2-3gm 12hrly
( BF, bl ,A )
Loracarbef (O)
( Cephal. Containing PI are 4th gen. )
CEPHALOSPORINS
SECOND GENERATION
Cefoxitin ( mefoxin )
Cefuroxime ( zinacef ) Cef. axetil ( zinnat )
Cefaclor ( ceclor ) Cefprozil ( cefzil )
Mainly effective against G- bacteria ( cocci & bacilli )
Modest activity against G+ bacteria & anaerobes
Cefoxitin active against bowel anaerobes (B. fragilis )
Cefuroxim active against H. influenzae, M. catarrhalis, S. pneumoniae
crosses BBB .
Cef. Axetil- oral form of cefuroxim
Cefaclor active against H. influenzae, M. catarrhalis &E.coli
Cefprozil- similar to cefaclor, c. axetil and augmentin - Liked by children
Second Generations are used primarily for URTIs ( acute otitis media,
sinusitis ) and Lower RTIs ( acute exacerbation of chronic bronchitis)
(These drugs are more stable to β-lactamase degradation )
LORACARBEF: ≡ Cefaclor, can be given orally , overdose can cause seizures
CEPHALOSPORINS
Third Generation :
Cefotaxime inj. 2gm 4-8hrly They are much more
(t-½ -1.1 hr ) act. against G-ve org.
Cefpodoxime 200-400mg 12hrly include. β -lactamase
proxetil ( O) ( t½ - 2.2 hr ) prod. less act against
Ceftriaxone inj. 2gm 12-24hrly G+ve org.( Enterobac
(b½,ch,T,G) (t½ -8 hr ) P.aerug.exct penicilli-.
Cefoperazone inj.1.5-4 gm 8hrly nase prod. ,Serratia ,
( P,b,D,A,T,bl) ( t½ - 2.1 hr ) N. gonor. are more
Cefexime (O) 200-400mg 12hrly sensitive to 3rd gen.)
CEPHALOSPORINS
Ceftazidime ( P) inj. 2 gm 8 hrly
( t½ -1.8 hr )
Cefibuten ( O ) 400mg 4 hrly
( t½ - 2.4 hr )
Cefdinir ( O) 300mg 12 hrly
( t½ - 1.7 hr )
( Cephal. ending with ME are 3rd gen. except-
CefuroxiME )
CEPHALOSPORINS
THIRD GENERATION
Ceftriaxone ( rocephin )
Cefotaxime ( claforan )
Cetazidime ( fortum )
Cefoperazone ( cefobid )
Cefixime ( suprax )
These are highly active against G-ve cocci, bacilli & anaerobes
They have enhanced G- activity, H. influenzae, N. meningitidis, N.gonorrhea,
P. aeruginosae, M. catarrhalis, E.coli, most Klebsiella are sensitive
Ceftriaxone has long half-life . Not advised in neonates (interferes with bilirubin
metabolism )
Cefotaxime preferred in neonate ( does not interfere with bilirubin metabolism ),
as may ceftriaxone.
Ceftazidime & cefoperazone have excellent activity against p. aeruginosae.
Cefixime has similar activity to amoxicillin & cefaclor for actute otitis media
-These drugs are highly resist. to degradation by β- lactamases by G-ve org.s
-These can penetrate BBB ( Except-Cefoperazone & Cefixime )
CEPHALOSPORINS
Fourth Generation :
Cefepime inj. 2 gm 8 hrly comp. to 3rd gen. but
( t½ -2 hr ) more resist. to some
β – lactmases ( induc.
type I ) & not active
Cefpirome against anaerobes
( Cephal. containing PI are 4th gen. )
o = orally , * = resist . to β- lactamases , BF = act. ag. B.
fragilis , P = act. Ag. P. aeruginosa , T = Typhoid , G =
gonorh. , A = alcohol intolerance , N = nephrotoxic
CEPHALOSPORINS
D = Diarrhea , BB = crosses BBB , b = exc. in bile , b½ =
half exct. in bile , bl = bleeding , ch = synd. mimicking
cholecystitis .
Now 5THGeneration has also came , although they inhibit the cell wall
synthesis but in a different way , they bind to & inhibit PBP-2 produced
by MRSA & Penicillin resist . S. pneumoniae which is not inhibited by
majority of antb.s .
-Also active against Enterococcus .& retain the activity of IV gent.
against G-ve bacilli ( esp. E.coli & Pseudomonas)
e.g.-Ceftaroline app. by FDA & Ceftobiprole ( phase III trial)
-Used for comm. aquired bact. Pneumonia & acute Bact. Skin inf. incl.
MRSA )
CEPHALOSPORINS
Mechanism of Bacterial Resistance :
Resist. to Cephalosp. may be related
to the :
-inability of the antb. to reach site of act.
or
- alteration in the PBPs that are targets of
the cephalosp. such
CEPHALOSPORINS
that the antb. bind to bact. enz.s ( β –
lactamases esp. inducible type I ) that can
hydrolyze the β- lactum ring & inactivates
the Cephalosp.s
CEPHALOSPORINS
General features :
Cephalosp.s are excrt. primarily by the
kidney , therefore dosage should be
altered in case of renal insufficiency.
- Probenecid slows the tubular secrt. of
most cephalosporins .
(Cefoperamide & Cefoperazone are
mainly excrt. in bile .)
CEPHALOSPORINS
- Cefotaxime is deacetylated in vivo &
half excrt. through kidney & half in
bile .
- Several of the Cephalosp.s penetrate
CSF in sufficient conc. to be useful
in meningitis (Cefuroxime ,2nd & 3rd
CEPHALOSPORINS
gen. cephalosp.s ) .
- Cephalosp.s cross the placenta &
also found in high conc. in synovial &
pericardial fluid .
- Penetr. in aq. humor of the eye is
good after syst. administ. of 3rd gen.
Cephalosp.s ( in vit. humor it is poor)
CEPHALOSPORINS
Side effects :
1. hypersenst. react. is most common
immed. react. e.g. anaphylaxis ,
bronchospasm & urticarial rash .
- most commonly maculopapular rash
dev. usually after several days of
CEPHALOSPORINS
therapy .
- Cross reactivity occurs in between
Cephalosp.s & penicil.s due to the
structural similarity to the Penicillins
(about 20 % cases who are allergic to penicil.s
are also allergic to Cephalosp.s) .
CEPHALOSPORINS
- Pts with mild react. to penicil.
appear to be at low risk of rashes
or other allergic react. following
administr. of Cephalosp.s . but pts
having recent severe allerg. react.
or anaphylaxis to penicil. should be
given Cephalosp. with great caution
CEPHALOSPORINS
- Rarely causes bone marrow dep.
→ granulocytopenia .
- Nephrotoxicity occurs esp. with
Cephaloridine & Cephalothin .
- Diarrhea with Cephoperazone due to
biliary exc.
- Alcohol intolerance ( disulfiram like
CEPHALOSPORINS
react. in Cefamandole , Cefotetan &
Cefoperazone ).
- Bleeding related to hypoprothrombin –
emia ( Cefotetan & Cefoperazone )
- Superinfection by 3rd ,4th & 5th gent.
Therapeutic Uses :
Used widely- effective prophylactically
& therapeut.
CEPHALOSPORINS
1st Gen. Cephalosp.s –
- excellent for skin & soft tissue inf.s
- colorectal surgery.
- Prophylaxis for intracel. anaerobes .
2nd Gen. Cephalosp.s -
- they are displaced by 3rd gen.
Cephalosp.
CEPHALOSPORINS
- active for URTI , for Penicil. resist.
S. pneumoniae inf.
- Otitis media
- Diabetic foot inf.
3rd Gen. Cephalosp.s :
- with or without Aminoglycosides are
DOC for serious inf. caused by
CEPHALOSPORINS
Klebsiella , Enterobacter ,Proteus ,
Providencia , Serratia & haemophilus
sp.s
- Ceftriaxone is DOC for gonorrhea &
lyme disease & also for Salmonella
inf. ( Typhoid fever ) .
-Meningitis ( Ceftazidime + aminoglyc.
CEPHALOSPORINS
for Pseudomonas meningitis )
- Ceftriaxone & Cefotaxim are good
for community acquired pneumonia
4th Gen. Cephalosp.s :
The Nosocomial inf.s where antb.
resist. owing to extended spect. β-
lactamases
Other β- Lactum Antibiotics
With β –lactum structure that are
neither penicil. nor cephalosp.
Carbapenems
- It contain fused β- lactum by
unsaturated 5 nucleus ring syst. &
containing Carbon atom instead of
sulfur atom .
- have broader spect. of activity than
Other β- Lactum Antibiotics
do most other β –lactum antb.s
- These are synth. antibact. agents
Imipenems :
- marketed in comb. with Cilastatin a
drug that ↓ degradation of imipenem
by renal tubular dipeptidase .
- indicated against refractory nosocom.
Other β- Lactum Antibiotics
infections leading to -
-UTI , LRTI ,
-Gynecological inf.
-Joint inf. &
-Intra abdominal inf. caused by
Other β- Lactum Antibiotics
Enterobacter ,Pseudomonas ,
Acinetobacter & anaerobic inf.( by B.
fragilis & Clostr. difficil ).
-orally not abs. , rapidly hydrolyzed by
dipeptidase in renal tubules to
nephrotoxic metabolites
Other β- Lactum Antibiotics
Therefore Cilastatin is combined ( it ↓
dipeptidase enz.)
S/E – nausea , vomiting , seizures
& cross allergy .
Meropenem :
It is ≡ Imipenem but is not senst. to
renal dipeptidase & with less risk of
Other β- Lactum Antibiotics
of seizures .
Ertapenem :
-having longer t½ therefore given
once a day .
-effective in enterobacteriaceae &
anaerobes . Hence useful in abdom.
& pelvic inf.s.
Other β- Lactum Antibiotics
Monobactums :
Aztreonam - it is β- lactamase resist.
with spect. similar to Aminoglycoside
( G-ve aerobic bacilli ). G+ve & anaer.
org. are resist.
-no cross allergy to β –lactum antb.
-given I.M. or I.V. dose -2 gm/d 6-8 hrly
Other β- Lactum Antibiotics
β – lactamase inhibitors :
certain molecule can inactivate β-
lactamase & thus prev. the destruction
of β – lactam antb. that are substrates
of this enz. ( ↑ effectiveness of β –
lactum antb.s ).
Other β- Lactum Antibiotics
-most active against Plasmid encoded
β- lactamase e.g.-
Clavulanic acid ,
Sulbactum &
Tazobactum .
- They themselves have not any signif.
AM activity .
Other β- Lactum Antibiotics
- They do not inhibit inducible type I
β- lactamase induced in G-ve bacilli.
Useful comb.s are :
1. Amoxycil. + Clavulanic acid –
effective against β –lactamase prod.
strains of Staphylococ. ,H. influenz.
,Gonococci & E. coli .
Other β- Lactum Antibiotics
- indicated in resist. Otitis media,
sinusitis , animal bite wounds
cellulitis & diabetic foot.
2. Ticarcillin + Clavul. Acid :
≡ Imipenem
indicated in mixed nosocomial inf.
along with Aminoglyc.
Other β- Lactum Antibiotics
3. Ampicil + Sulbactum :
indicated in mixed intra abdominal
& pelvic inf.s .( exc. Pseud. & anaer-
obic inf.) .
4. Tazobactum + Piperacil.:
activity against Pseudomonas is not
enhanced but having broadest AM sp.
Bibliography
1.Goodman & Gilman’s ,The Pharmacological
Basis of Therapeutics (12th Edition).
2. Clinical Pharmacology by Lawrence (Latest
edition )

Mais conteúdo relacionado

Semelhante a Penicillins and Cephalosporins.ppt

Semelhante a Penicillins and Cephalosporins.ppt (20)

Beta lactam antibiotics
Beta lactam antibioticsBeta lactam antibiotics
Beta lactam antibiotics
 
Beta Lactams.pptx
Beta Lactams.pptxBeta Lactams.pptx
Beta Lactams.pptx
 
Fundamentals antimicrobial agents
Fundamentals antimicrobial agentsFundamentals antimicrobial agents
Fundamentals antimicrobial agents
 
Penicillins by Dr M H Ghante.pdf
Penicillins by Dr M H Ghante.pdfPenicillins by Dr M H Ghante.pdf
Penicillins by Dr M H Ghante.pdf
 
Penicillin
PenicillinPenicillin
Penicillin
 
PBP2a
PBP2aPBP2a
PBP2a
 
Antibiotic Penicillin
Antibiotic PenicillinAntibiotic Penicillin
Antibiotic Penicillin
 
Antibiotics
AntibioticsAntibiotics
Antibiotics
 
Medicinal chemistry-beta lactam antibiotics
Medicinal chemistry-beta lactam antibioticsMedicinal chemistry-beta lactam antibiotics
Medicinal chemistry-beta lactam antibiotics
 
Penicillins
PenicillinsPenicillins
Penicillins
 
Antibacterial drugs
Antibacterial drugsAntibacterial drugs
Antibacterial drugs
 
Penicillins (ANTIBIOTICS)
Penicillins (ANTIBIOTICS)Penicillins (ANTIBIOTICS)
Penicillins (ANTIBIOTICS)
 
02 cell wall inhibitors (1)
02 cell wall inhibitors (1)02 cell wall inhibitors (1)
02 cell wall inhibitors (1)
 
beta lactam antibiotics,aminoglycosides, quinolones and macrolide antibiotics
beta lactam antibiotics,aminoglycosides, quinolones and macrolide antibioticsbeta lactam antibiotics,aminoglycosides, quinolones and macrolide antibiotics
beta lactam antibiotics,aminoglycosides, quinolones and macrolide antibiotics
 
Antibiotics
Antibiotics Antibiotics
Antibiotics
 
ANTIBACTERIAL DRUGS.pptx
ANTIBACTERIAL DRUGS.pptxANTIBACTERIAL DRUGS.pptx
ANTIBACTERIAL DRUGS.pptx
 
Beta lactam antibiotics
Beta lactam antibioticsBeta lactam antibiotics
Beta lactam antibiotics
 
Antibiotic Groups - β-lactams
Antibiotic Groups - β-lactamsAntibiotic Groups - β-lactams
Antibiotic Groups - β-lactams
 
Pharmacology II Chapter 1 ppt -.pptx
Pharmacology II Chapter 1 ppt -.pptxPharmacology II Chapter 1 ppt -.pptx
Pharmacology II Chapter 1 ppt -.pptx
 
Antibiotics acting on cell wall 1 penicillins 03-05-2018
Antibiotics acting on cell wall 1   penicillins 03-05-2018Antibiotics acting on cell wall 1   penicillins 03-05-2018
Antibiotics acting on cell wall 1 penicillins 03-05-2018
 

Mais de ssuser504dda

children. palliative care.pptx
children.     palliative       care.pptxchildren.     palliative       care.pptx
children. palliative care.pptxssuser504dda
 
PALLIATIVE CARE (GROUP2) BME3 2023.pptx
PALLIATIVE CARE (GROUP2)  BME3 2023.pptxPALLIATIVE CARE (GROUP2)  BME3 2023.pptx
PALLIATIVE CARE (GROUP2) BME3 2023.pptxssuser504dda
 
Group pharmacology uuuuu. .pptx
Group pharmacology   uuuuu.        .pptxGroup pharmacology   uuuuu.        .pptx
Group pharmacology uuuuu. .pptxssuser504dda
 
Group 5_ Year 3 Pharmacology 2023.pptx
Group 5_   Year 3 Pharmacology 2023.pptxGroup 5_   Year 3 Pharmacology 2023.pptx
Group 5_ Year 3 Pharmacology 2023.pptxssuser504dda
 
STEP Session 10b. - Networking.ppt
STEP Session 10b.       - Networking.pptSTEP Session 10b.       - Networking.ppt
STEP Session 10b. - Networking.pptssuser504dda
 
Inter-relgious cooperation -Kiyimba.pptx
Inter-relgious cooperation -Kiyimba.pptxInter-relgious cooperation -Kiyimba.pptx
Inter-relgious cooperation -Kiyimba.pptxssuser504dda
 
IMMUNODEFICIENCIES lecture for bach.pptx
IMMUNODEFICIENCIES lecture for bach.pptxIMMUNODEFICIENCIES lecture for bach.pptx
IMMUNODEFICIENCIES lecture for bach.pptxssuser504dda
 
HEAMOLYTIC ANAEMIAS - nutrition. .pptx
HEAMOLYTIC  ANAEMIAS - nutrition.  .pptxHEAMOLYTIC  ANAEMIAS - nutrition.  .pptx
HEAMOLYTIC ANAEMIAS - nutrition. .pptxssuser504dda
 
GENDER Presentation - per group .pptx
GENDER Presentation - per group    .pptxGENDER Presentation - per group    .pptx
GENDER Presentation - per group .pptxssuser504dda
 
Gender and reproductive health behavpptx
Gender and reproductive health behavpptxGender and reproductive health behavpptx
Gender and reproductive health behavpptxssuser504dda
 
Gender and reproductive health behaviour and Intimate partner-1.pptx
Gender and reproductive health behaviour and Intimate partner-1.pptxGender and reproductive health behaviour and Intimate partner-1.pptx
Gender and reproductive health behaviour and Intimate partner-1.pptxssuser504dda
 
GENDER ANALYSIS IN - HEALTH.pptx
GENDER ANALYSIS IN     -     HEALTH.pptxGENDER ANALYSIS IN     -     HEALTH.pptx
GENDER ANALYSIS IN - HEALTH.pptxssuser504dda
 
Emulating the prophet- Shk. Magambo.pptx
Emulating the prophet- Shk. Magambo.pptxEmulating the prophet- Shk. Magambo.pptx
Emulating the prophet- Shk. Magambo.pptxssuser504dda
 
Concepts in Gender and sex - edited.pptx
Concepts in Gender and sex - edited.pptxConcepts in Gender and sex - edited.pptx
Concepts in Gender and sex - edited.pptxssuser504dda
 
Anti - depressants September - 2023.pdf
Anti  - depressants September - 2023.pdfAnti  - depressants September - 2023.pdf
Anti - depressants September - 2023.pdfssuser504dda
 
Anti-Angina & Anti arryhthias Drugs .ppt
Anti-Angina & Anti arryhthias Drugs .pptAnti-Angina & Anti arryhthias Drugs .ppt
Anti-Angina & Anti arryhthias Drugs .pptssuser504dda
 
Teams and teamworks _ 1706078762594.pdf
Teams and teamworks _  1706078762594.pdfTeams and teamworks _  1706078762594.pdf
Teams and teamworks _ 1706078762594.pdfssuser504dda
 
Presentation. M. ............ 1.pptx
Presentation.  M.    ............ 1.pptxPresentation.  M.    ............ 1.pptx
Presentation. M. ............ 1.pptxssuser504dda
 
anti heart failure assignment final.pptx
anti heart failure assignment final.pptxanti heart failure assignment final.pptx
anti heart failure assignment final.pptxssuser504dda
 
Presentation of gender and diseases.pptx
Presentation of gender and diseases.pptxPresentation of gender and diseases.pptx
Presentation of gender and diseases.pptxssuser504dda
 

Mais de ssuser504dda (20)

children. palliative care.pptx
children.     palliative       care.pptxchildren.     palliative       care.pptx
children. palliative care.pptx
 
PALLIATIVE CARE (GROUP2) BME3 2023.pptx
PALLIATIVE CARE (GROUP2)  BME3 2023.pptxPALLIATIVE CARE (GROUP2)  BME3 2023.pptx
PALLIATIVE CARE (GROUP2) BME3 2023.pptx
 
Group pharmacology uuuuu. .pptx
Group pharmacology   uuuuu.        .pptxGroup pharmacology   uuuuu.        .pptx
Group pharmacology uuuuu. .pptx
 
Group 5_ Year 3 Pharmacology 2023.pptx
Group 5_   Year 3 Pharmacology 2023.pptxGroup 5_   Year 3 Pharmacology 2023.pptx
Group 5_ Year 3 Pharmacology 2023.pptx
 
STEP Session 10b. - Networking.ppt
STEP Session 10b.       - Networking.pptSTEP Session 10b.       - Networking.ppt
STEP Session 10b. - Networking.ppt
 
Inter-relgious cooperation -Kiyimba.pptx
Inter-relgious cooperation -Kiyimba.pptxInter-relgious cooperation -Kiyimba.pptx
Inter-relgious cooperation -Kiyimba.pptx
 
IMMUNODEFICIENCIES lecture for bach.pptx
IMMUNODEFICIENCIES lecture for bach.pptxIMMUNODEFICIENCIES lecture for bach.pptx
IMMUNODEFICIENCIES lecture for bach.pptx
 
HEAMOLYTIC ANAEMIAS - nutrition. .pptx
HEAMOLYTIC  ANAEMIAS - nutrition.  .pptxHEAMOLYTIC  ANAEMIAS - nutrition.  .pptx
HEAMOLYTIC ANAEMIAS - nutrition. .pptx
 
GENDER Presentation - per group .pptx
GENDER Presentation - per group    .pptxGENDER Presentation - per group    .pptx
GENDER Presentation - per group .pptx
 
Gender and reproductive health behavpptx
Gender and reproductive health behavpptxGender and reproductive health behavpptx
Gender and reproductive health behavpptx
 
Gender and reproductive health behaviour and Intimate partner-1.pptx
Gender and reproductive health behaviour and Intimate partner-1.pptxGender and reproductive health behaviour and Intimate partner-1.pptx
Gender and reproductive health behaviour and Intimate partner-1.pptx
 
GENDER ANALYSIS IN - HEALTH.pptx
GENDER ANALYSIS IN     -     HEALTH.pptxGENDER ANALYSIS IN     -     HEALTH.pptx
GENDER ANALYSIS IN - HEALTH.pptx
 
Emulating the prophet- Shk. Magambo.pptx
Emulating the prophet- Shk. Magambo.pptxEmulating the prophet- Shk. Magambo.pptx
Emulating the prophet- Shk. Magambo.pptx
 
Concepts in Gender and sex - edited.pptx
Concepts in Gender and sex - edited.pptxConcepts in Gender and sex - edited.pptx
Concepts in Gender and sex - edited.pptx
 
Anti - depressants September - 2023.pdf
Anti  - depressants September - 2023.pdfAnti  - depressants September - 2023.pdf
Anti - depressants September - 2023.pdf
 
Anti-Angina & Anti arryhthias Drugs .ppt
Anti-Angina & Anti arryhthias Drugs .pptAnti-Angina & Anti arryhthias Drugs .ppt
Anti-Angina & Anti arryhthias Drugs .ppt
 
Teams and teamworks _ 1706078762594.pdf
Teams and teamworks _  1706078762594.pdfTeams and teamworks _  1706078762594.pdf
Teams and teamworks _ 1706078762594.pdf
 
Presentation. M. ............ 1.pptx
Presentation.  M.    ............ 1.pptxPresentation.  M.    ............ 1.pptx
Presentation. M. ............ 1.pptx
 
anti heart failure assignment final.pptx
anti heart failure assignment final.pptxanti heart failure assignment final.pptx
anti heart failure assignment final.pptx
 
Presentation of gender and diseases.pptx
Presentation of gender and diseases.pptxPresentation of gender and diseases.pptx
Presentation of gender and diseases.pptx
 

Último

Forensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationForensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationKavitha Krishnan
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
Transport across cell membrane (passive, active, vesicular)
Transport across cell membrane (passive, active, vesicular)Transport across cell membrane (passive, active, vesicular)
Transport across cell membrane (passive, active, vesicular)MedicoseAcademics
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdfHongBiThi1
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptPradnya Wadekar
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationMedicoseAcademics
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfHongBiThi1
 
Employability skills, work experience presentation
Employability skills, work experience presentationEmployability skills, work experience presentation
Employability skills, work experience presentationmarwaahmad357
 

Último (20)

Forensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationForensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentation
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
Transport across cell membrane (passive, active, vesicular)
Transport across cell membrane (passive, active, vesicular)Transport across cell membrane (passive, active, vesicular)
Transport across cell membrane (passive, active, vesicular)
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologyppt
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
How to master Steroid (glucocorticoids) prescription, different scenarios, ca...
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdfSGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
SGK RỐI LOẠN KALI MÁU CỰC KỲ QUAN TRỌNG.pdf
 
Employability skills, work experience presentation
Employability skills, work experience presentationEmployability skills, work experience presentation
Employability skills, work experience presentation
 

Penicillins and Cephalosporins.ppt

  • 1. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS Dr. Rajendra Nath Professor
  • 2. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS • Useful & frequently prescribed AM agents . • Share a common structure & mech. of action i.e. – inhibition of synth. of the bact. peptidoglycan cell wall .
  • 3. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS • β- lactums - include Cephalosporin antibiotics which are classified by generations .
  • 4. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS • β- lactamase inhibitors e.g.- Clavulanate , Sulbactum etc. are used to extend the spectrum of Penicil. against β- lactamase prod. organisms.
  • 5. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS • Other β- lactums include – - Carbapenems including Meropenem & Imipenem which have broadest AM spect. of any antibiotics . • Monobactums – e.g.- Aztreonam has G-ve spect. resembling that of Amino -glycosides .
  • 6. PENICILLINS CEPHALOSPORINS & OTHER β-LACTUM ANTIBIOTICS Bact. resist. against the β- lactum antb.s continues to ↑at high rate. Mech. - - by β –lactamase that destroy the antb - alteration in or acquisition of novel penicil. binding proteins ( PBPs) . - Decreased entry & / or efflux of antb.s .
  • 7. PENICILLINS -One of the most important gp of antibiotics. - However numerous other AM agents have been prod. since the first penicil. become available. - These are still used widely & many of these are currently the DOC for a large no. of infectious diseases .
  • 8. PENICILLINS - In 1928 in laboratory of St mary’s hosp. London , A. Fleming observed that a mold contaminating one of the bact. cultures caused the bact. in its vicinity to undergo lysis. Because the the mold belonged to the genus Penicillium , Fleming named the antb.
  • 9. PENICILLINS substance as Penicillin . Chemistry : Basic struct. consists of 1. Thiazolidine ring (A) connected to 2. β- lactum ring (B) to which attach 3. Side chain (R) .
  • 10. PENICILLINS O S CH3 R C NH CH CH C 2 B A CH3 O = C N CH COOH Amidase 1 Penicillin Penicillinase site of action
  • 11. PENICILLINS A. Thiazolidine ring B. β- lactam ring 1. Site of action of penicillinase 2. Site of action of amidase
  • 12. PENICILLINS - The penicillin nucleus itself is the chief struct. requirement for biologic. activity . Metabolic transformation/ chem. alteration of this portion of the mol. causes loss of all sig. AB activity - Side chain determine many of the AB & pharmacol. character of a particular
  • 13. PENICILLINS type of Penicillin. - Penicil. G ( benzyl penicil. ) has the greatest AM activity of these & is the only natural penicil. used clinically. Semi-synthetic Penicillins : It has been discovered that 6- amino- penicillanic acid could be obtained from
  • 14. PENICILLINS cultures of P. chrysojenum lead to the dev. of the semi-synth. Penicil.s .by adding different side chains in this . -6-aminopenicillanic acid is now prod. in large quantities with the aid of the amidase from P. chrysojenum .
  • 15. PENICILLINS Unitage of Penicillin : - one Int. unit ≡ 0.6 μg of the cryst. sod. salt of Penicil. G. -1mg of pure Penicil. G ≡ 1667 units. Mech. of Penicillins : -The cell walls of bact. are essential for their normal growth & development.
  • 16. PENICILLINS - Peptidoglycan is a heteropolymeric component of the cell wall that provides rigid mech. stability . - Cell wall is 50-100 mols thick in G+ve & ½ molecule thick in G-ve bacteria . - Peptidog. is composed of glycan chains having linear strands of two
  • 17. PENICILLINS alternating amino sugar (N-acetyl – glucosamine & N- acetyl muramic acid) & they are cross-linked by peptide chain . Biosynth. of Peptidoglycan : involves three stages
  • 18. PENICILLINS Final stage involves completion of the cross link .This accomplished by a transpeptidation react. that occurs outside the cell memb.( with the help of Transpeptidase enz. which is memb. bound ). These enz.s & related proteins are now called as Penicillin Binding Proteins ( PBPs).
  • 19. PENICILLINS It is this last step in peptidoglycan synth. that is inhibited by the β- lactum antb.s & glycopeptide antb.s (e.g.Vancomyc.)
  • 20. PENICILLINS - Main target for the action of penicil.s & cephalosporins are these Penicil. Binding Proteins (PBPs) .All bact. have such entities e.g.- E .coli
  • 23. PENICILLINS has 7 & S. aureus has 4 PBPs . The PBPs vary in their affinity for diff. β – lactum antb.s , although interact. become covalent . - ↓ of transpept.( PBP-I) causes formation of spheroplast & rapid lysis. - ↓ of PBP-II & III ( Carboxypeptidase & endopeptidase enz.s) cause delayed lysis or production
  • 24. PENICILLINS of spherical cells & large filamentous form of bacterium. Penicil.↓ synth. of cell wall & thereby expose the org.s to the lethal external environment which is not matching with internal osmotic –pressure & bact . swells & lysis occurs .
  • 25. PENICILLINS Death of the bact. also occurs due to activation of autolysing enz.s called autolysins or murein -hydrolase . -Lethality of penicil. involve both lysis or nonlytic mech.
  • 26. PENICILLINS Mech. of bact . Resist. to penicillin ( & Cephalosporins ) : 1.Micro-org may be intrinsically resist. because of structural diff. in the PBPs that are the targets of these drugs (A sensitive strain may acquire resist. of this type by the dev. of high mol.
  • 27. PENICILLINS wt. PBPs that have ↓ affinity for the antb. e.g.- Penicil. resistance in Streptococcus gp. emerged as a result of replacement of its PBPs with resist. PBPs from S. pneumoniae.
  • 28. PENICILLINS 2. Other way of bact. resist. is caused by the inability of the agent to penetrate to its site of action e.g.- G-ve bact.
  • 29. PENICILLINS - in G+ve bact . the peptidoglycan polymer is very near the cell surface , some G+ve bact. have polysacch. capsule that are external to the cell wall but they are not the barrier to the diffusion of β- lactums .
  • 30. PENICILLINS - In G-ve bact. the inner memb. is analog. to the cytoplasmic memb. of G+ve bact. & is covered by outer memb. of Lipopolysaccharide & capsule ,it functions as a impermeab. barrier for some antb.s
  • 31. PENICILLINS Some small hydrophilic antb.s diffuse through aqueous channels in the out. memb. that are formed by protein called porins . -Broad spect. Penicil.s e.g. – Ampicill. & Amoxycill. & most of the Cephalo- sporins diff. through the pores in the
  • 32. PENICILLINS E.coli outer memb. more rapidly than can Penicill. G ( the no. & size of the pores vary e.g.- Pseudomonas aeru. lack the classical high permeability porins .) 3. Active efflux pumps serve as another mech. of resist. removing the antb.s
  • 34. PENICILLINS from its site of action before it can act e.g.-β- lactum resist. in P.aerug. ,E.coli & N. gonorrheae . 4.Bact. can also destroy β- lactum antb. enzymatically by β- lactamases which inactivates certain of these antb.s .
  • 35. PENICILLINS -diff. micro-orgs elaborate a no. of distinct β- lactamase which often are described as Penicillinases or Cepha - linases . These are grouped into 4 clases ( A-D) . - Class A β- lactamases include the extend. spect. β –lactamases which
  • 36. PENICILLINS degrade Penicil.s , some Cephalospor. and in some instances ,Carbapenems. -Class B: β-lactamases are Zn++ dep. enz. that destroy all β- lactams except Aztreonam . - Class C: β- lactamases are active against Cephalosporins.
  • 37. PENICILLINS -Class D : include Cloxacillin deg. enz.s - G+ve bact. prod. & secrt. a large amount of β- lactmases . Most of these are Penicillinases . The information for Staphylococcal penicillinase is encoded In a plasmid & this may be transferred by bacteriophage to other bact.
  • 38. PENICILLINS - In G-ve bact. β-lactamases are found in relatively small amounts . they are encoded either in chromos. or in plasmids & may be constitutive or inducible . - The plasmids can be transferred between bact. by conjugation .
  • 39. PENICILLINS - Other factors : micro-org.s adhering to implanted prosthetic devices ( e.g.- catheters , artific. Joints , prosth. heart valves etc.) prod. biofilms & are much less sens. to antb.s . - The presence of proteins & other
  • 40. PENICILLINS constituents of pus, low pH or low oxyg. tension does not appreciably ↓ the ability of β-lactum antb.s to kill bact. However bact. that survive inside visible cells of the host gener. are protected from the action of the β- lactum antb.s .
  • 41. PENICILLINS Classification : According to their spectrum of AM act. I Narrow spectrum A. Penicillinase sensitive i) Penicillin G ( parenteral ) – highly active against sensitive strains of G+ve cocci hydrolyzed by
  • 42. PENICILLINS penicillinase , not effective against most strains of S. aureus e.g.- -Crystalline or Benzyl Penicil. or Penicil. G. - Procaine Penicil. - Benzathine Penicil. ii) Phenoxy methyl Penicil. or Penicil. V
  • 43. PENICILLINS ( orally active ) B. Penicillinase resist. Penicil. -e.g.- Methicillin , Naficillin , Cloxacillin Oxacillin , Flucloxacillin etc. have less potent AM activity against micro-org. sensitive to Penicil. G . but agent of first choice for
  • 44. PENICILLINS penicillinase prod. S. aureus & S. epid -ermidis . C. Penicillinase inhibitors . e.g.- Clavulanic acid ( comb. with Amoxycil.) - Sulbactum ( + Ampicillin ) - Tazobactum ( + Piperacillin)
  • 45. PENICILLINS They are given with broad spectrum antb.s to prevent hydrolysis by broad spect. β- lactamases ( in G-ve bact. e.g. E.coli .) II Broad spect. Penicillins : A. Carboxypenicil. e.g.- Carbenicillin Carbenicil. Indanyl ,Ticarcillin .
  • 46. PENICILLINS their AM activity is extended to include Pseudomonas , Enterobacter & Proteus gp. (inferior to Ampicil.against G+ve cocci & L.monocytogenes & less active than Piperacil. against Pseudomonas.& also known as anti- Pseudomonal penicillins )
  • 47. PENICILLINS B. Aminopenicillins : e.g.- Ampicillin , Amoxycillin, etc.. They are also effective against G- ve org.s e.g. – H. influenzae , E. coli , Proteus mira - bilis . etc. . But they are sensitive to penicillinase enzyme. (They are used now with β- lactamase inhib.s e.g. Clavulanic acid which further extends their spectrum )
  • 48. PENICILLINS C. Uriedopenicillins ( extended spect. penicil.) : e.g.- Azlocillin , Mezlocillin & Piperacillin . Excellent activity against Pseudomonas ,Klebsiella & other G-ve org.s
  • 49. PENICILLINS Pharmacological propert. in general: - Following abs. of orally administered penicil. these agents are distributed widely through out the body. - Therapeutic conc. attain readily in tissues & in secret. e.g. joint fluid , pleural fluid ,pericardial fluid & bile
  • 50. PENICILLINS -Low conc. in prostatic fluid ,brain tissue ,intra-ocular fluid & in CSF (conc of penicil. is < 1% of those in plasma , but in inflammed meninges conc. may ↑ upto 5% of plasma ) . - Eliminated rapidly by glomerular filtr. & renal tubular secrt. (t½ -30-90 min.)
  • 51. PENICILLINS Penicil.G & Penicil. V : The AM spect. of penicil. G &V are very similar for aerobic G+ve micro- org. (but penicil. G is 5-10 times more active against Neisseria sp. & against certain anaerobes). They are narrow spect. & enz. sens. Penicil.s
  • 52. PENICILLINS Spectrum : effective against Pneumococci. streptococci, Meningococci , non β- lactamase prod. gonococci & staphy. (> 90% strains of staphyl. Isolated from individuals inside or outside hospitals are now resist.)
  • 53. PENICILLINS - Treponima pallidum , bacil. anthracis & vast majority of strain of C. diphther. are senst. but some are resist. - Actinomyces , Clostridium sp. (anaer. micro-org.) are highly senst.
  • 54. PENICILLINS ( Bact. fragilis is exception ) . - None of the Penicil.s are effective against Amoeba , Plasmodium , Rikettsia , fungi or viruses . Absorption : Oral - about ⅓rd of oral dose is absorbed in favorable cond. not destroyed by
  • 55. PENICILLINS gastric juice ( 2/3rd destroyed by GJ) . Penicil. V is more stable in acid hence better absorbed . -Food may interfere with abs. of all Penicil.s -Parenteral – after I.M. inj. peak conc. of Penicil.G reached with in 15-30 mins .
  • 56. PENICILLINS ( vol. declines as half life of Penicil. G is 30 mins ) . Different measures are there to prolong its existence in body e.g. 1. Repository prep. -Procain Penicil. & Benzathine Penicil. they release
  • 57. PENICILLINS penicil. G. slowly from the area in which they are injected & prod. relativ. low but persistent conc. of antb. in blood . Penicil.G. Procaine susp. is an aquous prep. of the crystalline salt ( H/S test is done by I.D. test of 0.1 ml of proc.)
  • 58. PENICILLINS It is a painless inj. - Benzath. Penicil. susp. of the salt obtained by the comb. of 1 mol. of an ammonium base & 2 mol. of penicil. G. . The long persistence of penicil. conc. in blood after I.M. inj. reduces cost , need for repeated inj.
  • 59. PENICILLINS and local trauma. benz. penicil. has got longest duration of detectable antb. A dose of 1.2 mill. unit I.M. → conc. of 0.09 μg/ml on the 1st , 0.02 μg/ml on 14th & 0.002 μg/ml on 32nd day (avg. duration is 26 days) 2. Use of Probenecid that blocks renal
  • 60. PENICILLINS tubular secr. of penicil. & thus exct. ,is also used to increase the dur. of action - It also ↑ the conc. of penicil. in CSF as it does not readily enter the CSF normally (increase abs. in meningitis) - Penicil. is secrt. rapidly from the CSF into blood stream by an active
  • 61. PENICILLINS transport process & probenecid compe -titively ↓ this transport & thus↑ the conc. of penicil. in CSF. Excretion : Penicil. G. is eliminated rapidly from the body mainly by the kidney ,but small part in the bile & other routes .
  • 62. PENICILLINS Therapeutic Uses : 1.Pneumococcal inf.-Penicil. G (DOC) -Pneumococcal Pneumonia – (Penicil. G- 24 million U daily Penicil. V – 500 mg orally 6 hrly). -Pneumococ. mening. – until it is established that penicil.G .is sens.
  • 63. PENICILLINS it is treated with Vancomycin + III gen Cephalosporin ( if sensitive - penicil. G is given -20-24 mill. U/day x 14 days) 2. Streptococ. Inf. – in scarlet fever ( Streptococ. pharyngitis ) – penicil. V. -500 mg 6 hrly x 10 days penicil. G. – 6 lacks U OD x 10 days
  • 64. PENICILLINS or single inj. of Benz. Penicil. 1.2 mill U stat.) , also effective in –Streptococcal pneumonia , arthritis , meningitis & endocarditis . 3. Inf. with Anaerobes : mixt . of org.s most are sens. to penicil. G. exception is B. fragilis gp.
  • 65. PENICILLINS -Penicil.G. + Metronidazole or Chlora - mphenicol . 4. Staphylococ inf. – penicil. resist penicil. e.g.- Naficillin or Oxacillin 5. Meningococ. Inf. – Penicil G. ( DOC) given I.V. high dose
  • 66. PENICILLINS 6. Gonococ. Inf. – resist. to penicil. G & they are no longer the therapy of choice ( IIIgen. Cephalosporins - Ceftriaxone is given ) . 7. Syphilis – penicil.G. is highly effective in primary, second. & latent syphilis of < 1 y dur.
  • 67. PENICILLINS (Proc. Penicil. -2.4 mill. U /day I.M. + Probenecid 1 gm/ day orally x 10 days or Benz. Penicil. G. 2.4 mill. U I.M. 1 -3 weekly ). Pts with late latent syph., neurosyph , cardiovas. syph. – 20 mill. U of penicil G. daily x10 days (child.-50,000 U/kg of Penicil. G . in two div. doses.)
  • 68. PENICILLINS most pts dev. Jerisch Herxheimer reac. (several hrs after the 1st inj of penicil. G) - Chills with fever, headach, myalgia & arthralgia may dev. & syph. lesion may become more prominent . It fades with in 48 hrs & does not recur with 2nd
  • 69. PENICILLINS inj. ( due to Spirochaetal antigens ). 8. Actinomycosis – Penicil. G. – DOC ( 12 -20 mill. U I.V. /day x 6 wks) 9. Diphtheria- specific antitoxin (antidiphtheritic serum) is the only effective tt. however penicil. G eliminate the carrier state -
  • 70. PENICILLINS ( Proc. Penicil. 2-3 mill. U / day x 10-12 days.) 10. Anthrax -now resist. in most of the cases 11. Clostridial inf. – penicil. G. is DOC in (i) Gas gangrene (by C.perfringens,12-20 mill. U/day), debridement of inf. area is necessary apart from the drug . (ii) No effect on ultimate outcome of
  • 71. PENICILLINS Tetanus ( C. tetani ) ,hence tetanus immunoglob. (ATS ) is indicated along with debridement of dead tissue + Penicil G (10-20 mill. U /day I.M.) to eradicate the bact. - Fusospiroch. Inf. - Gingivo-stomatitis e.g.-Trench mouth (Penicil. V.-500 mg 6 hrly x7 d) 12. Rat bite fever : by Spirillium minor senst. to penicil.( G -12-15 mill. U/d x 3-4 wks)
  • 72. PENICILLINS 13. Listeria inf. – Ampicillin 1-2 gm 4 hrly. ( +Gentamycin in immuno -comp. host & pt with meningitis.) & penicil.G(15-20 mill. U/d) are DOC. 14. Erysepilas –Pasteurella multocida - wound inf. after dog / cat bite . senst. to penicil. & Ampicil.s
  • 73. PENICILLINS Prophylactic use – was effective in previous inf.s but still used in 1. Streptococcal inf. & cases of deep burn. Single inj. of Benz. Penicil.-1.2 mill.U 2.Recurence of Rheumatic fever – oral –penicil. V or
  • 74. PENICILLINS Benz. Penicil. G – (1.2 mill. U once a month.) 3. Syphilis – prophyl. for contacts . 4. Surg. procedure in pts with valvular heart dis.( Dental extractions ).
  • 75. PENICILLINS 2. Penicillinase resist penicil.: This type of penicil. is resist. to hydrolysis by Staphy. penicillinase (their use should be restricted to the tt of inf. which are caused by staphy. that secrete this enz.) -these are less sens. than is penicil. G
  • 76. PENICILLINS against other penicil. senst. micro-org -Methicil. resist. micro-org.s are resist. to all the penicil. resist.Penicil.s & Cephalosp.s . -Hospital acquired inf. are also resist to these penicil.
  • 77. PENICILLINS e.g.- Isoxazolyl Penicil.: Oxacillin , Cloxacillin & Dicloxacillin – -These are congeneric semi –synth. Penicil.s . - These are similar pharmacologically, abs. adequately after oral administ.
  • 78. PENICILLINS ( abs. is more effective on empty stomach) . Naficillin : This semisynth. Penicil. is highly resist. to penicillinase & effective against inf. caused by penicillinase prod. strains
  • 79. PENICILLINS of S. aureus . - abs. in GIT is irregular ( inactivated in acid medium ) therefore given parenteraly ( 1 gm I.M. ) . - conc. of drug is adequate in CSF for the tt of S. meningitis .
  • 80. PENICILLINS Aminopenicillins : Ampicillin , Cloxacillin & their cong.s - these are known as broad spect. antb have similar AM activity . -they all are destroyed by β- lactamase - they are bactericidal for both G+ve & G-ve bact.
  • 81. PENICILLINS - N. gonorrhoeae , E. coli , P. mirabilis, Salmonella & Shigella were highly senst. to these when they are first used but now resist. is increasing. (Pseudomonas & Klebsiella are resist.)
  • 82. PENICILLINS ( however concurrent administ. of a β- lactamase inhib. e.g.- Clavulanate or Sulbactum markedly expands the Spect. of activity of these drugs ) dose – 500mg QID or 0.5 – 1 gm sod. Ampicil. Inj. I.M. ( adjustment is req . in cases of renal dysf.)
  • 83. PENICILLINS Amoxycillin : - abs. is more complete & rapid than Ampicil. & stable in acid & given orally. - spect. similar ( except less senst. in Shigellosis ) - food does not interfere with abs.
  • 84. PENICILLINS - Incidence of diarrhea is less - Effective conc. of orally administ. Amoxy. are detectable in plasma twice as long as with Ampicil. - Probenecid delays exct. of drug . Uses -1. URTI against S. pyog. & S. pneumonia & H. influenzae .
  • 85. PENICILLINS -effective for sinusitis , otitis media & acute exacer. of chr. Bronchitis & epiglottitis - Addition of β –lactamase inhib. ( Amoxy + Clavulanate & Ampicil + Sulbactum ) extends the spect. to H. influenzae & enterobacteriaceae.
  • 86. PENICILLINS 2. UTI 3. Meningitis – not alone but in comb. with Vancomycin + 3rd gen. cephalo. 4. Salmonella inf. – bacteremia & enteric fever ( Typhoid) synd. respond well to these . Fluoroq. , / Ceftriaxone are DOC but Trimeth.
  • 87. PENICILLINS + Sulfamethoxazole or high doses of Ampicil. also are effective ( 12 gm/d for adults) . Antipseudomonal Penicil.s : Carboxypenicillins – e.g.- Carbenicillin ,Carbenicillin indanyl ( indanyl ester of carbenicilin which
  • 88. PENICILLINS is acid stable & used orally) & Ticarcillin . - They are active against some strains of Pseudomonas aeruginosa & certain sp. of Proteus ( that are resist. to Ampicil.& congener ). - Hypokalemia may occur.
  • 89. PENICILLINS Ureidopenicillins : e.g.- Mezlocillin & Piperacillin have superior activity against P.aerug. - they are also used against Klebsiella - they are senst. to destruction by β – lactamases .
  • 90. PENICILLINS (In comb. with a β – lactamase inhib. Piperacil. &Tazobactum has the broadest AM spect. of the penicil.s ) Uses – serious inf. caused by G-ve bacteria.
  • 91. PENICILLINS ( esp. in pts of impaired immuno - logical defenses & inf.s acquired in hospitals) so greater use in bacteremias ,Pneum. inf. following burns & UTI . ( in neutropenic pts )
  • 92. PENICILLINS Side effects : 1. Hypersenst. React. – they are the most common ADRs noted in penicil.s & most comm. cause of drug allergy – include maculopap. rash ,urticarial rash fever , bronchospasm ,vasculitis
  • 93. PENICILLINS serum sickness ,exfol. dermatitis, St. Johnson’s synd. & anaphylaxis. - It may occur with any dosage form of penicil. - Cross allergy occur between diff. gps. of penicil.s (occurrence of untoward effects does not necessarily imply repetitions on
  • 94. PENICILLINS subsequent exposure .) - H/S react. may appear in the absence of a previous known exposure to drugs (may be due to prev. unrecognized exposure to penicil. in the environment e.g.- foods of animal origin or from the fungus prod. penicil.)
  • 95. PENICILLINS - Although H/S clears after stopping antb. but may persist for 1-2 wks or longer after therapy has been stopped . - In few instances , it is necessary to stop the future use of penicil.
  • 96. PENICILLINS because of risk of death ( pts should be warned for this). Mech.- penicil. & their breakdown prod.s act as haptens after covalent react. with proteins . major breakdown moiety is penicilloyl moiety which is the major
  • 97. PENICILLINS determinant moiety ( MDM) . - IgE med. react. occur due to MDM ( in 25% other breakdown prod.s are responsible) - The most serious H/S react.s are angioedema ( marked swelling of lips , tongue ,face, peri-orbital tissue
  • 98. PENICILLINS frequently accomp. by asthamatic breathing.) - H/S react. can occur with small testing dose ( intradermal inj. ) 2. Serum sickness : mild fever , rash , leukopenia , arthralgia ,purpura, lymphadenopathy
  • 99. PENICILLINS spleenomegaly, mental changes ,ECG abnormalities , albuminuria ,hematuria. It is mediated by IgG antibodies. ( it occurs when penicil. is continued for a wk or more but is rare ). - fever may be the only symptom - eosinophilia & rarely int. nephritis
  • 100. PENICILLINS Management : - pts history is most practical. - Intradermal test -Desensitization is recomm.. Low dose penicil. in ICU ( 1, 5, 10, 100 & 1000 Unit / day ) - Adrenaline ( S.C. inj.)
  • 101. PENICILLINS - Antihistaminic ( injectable) - Glucocorticoids ( inj.) 3. Other reactions – -Bone marrow depression leads to granulocytopenia -Hepatitis (Oxacil. & Naficillin.) - inj. can cause local pain & inflammation (Intrathecal inj. can cause arachinoiditis & severe encephalopathy .)
  • 102. CEPHALOSPORINS History & Source – First source – Cephalosporium – acremonium isolated in 1948 by Brotzu . Crude filtrates from cultures of this fungus were found to inhibit the growth of S. aureus to cure staphylococ. inf. & Typhoid fever
  • 103. CEPHALOSPORINS caused by Salmonella sp. - Cultures shows three distinct antb.s which were named Cephalosp. P, N, C . - With isolation of the active nucleus of Cephalosp. C. i.e. 7 amino cephalosporanic acid & with addition
  • 104. CEPHALOSPORINS of the side chains it become possible to prod. synthetic comp.s having equiv. AM activity or greater activity than parent comp. Chemistry : Cephalosp. C contains a side chain derived from D-α aminoadipic acid
  • 105. CEPHALOSPORINS condensed with a dihydrothiazide β- lactam ring syst. ( 7- aminocephalospo -ranic acid ). -- comp.s containing 7- aminocephalo. acid are relatively stable in dilute acid & are highly resist. to penicillinases .
  • 106. CEPHALOSPORINS CHEMISTRY: 1 S R1 C NH–7 3 O N R 2 COO ˉ - Alteration in position 7 of the β- lactum ring changes the AB activity & alteration at post. 3 of di-hydrothiazine ring is associated with changes in metabolic & pharmacokinetic prop.s .
  • 107. CEPHALOSPORINS Mech. – ↓ cell wall synthesis ≡ Penicillins Classification : Well accepted syst. of classif. by generation is very useful based on gen. features of AM activity . ( Cephal. Having A after Cef or Ceph are Ist Gen.
  • 108. CEPHALOSPORINS First Generation : Name Dose Spectrum Cephazolin 1-1.5 gm 6 hrly well effective against ( t½ -2 hr ) G+ve but less active Cephalexin (O) 1 gm 6 hrly against G-ve bacterias ( t½ - 0.9 hr) Streptococ.( except Cephadroxyl (O) 1gm 12hrly Penicillin resist str.) ( t½ -1.1 hr ) Staphylococ. aureus Cephalothin ( N) (except. Methicillin. Cephaloridine (N) resist strains ) + PEK (Cephal. having A after Cef or Ceph are Ist Gen. )
  • 109. CEPHALOSPORINS FIRST GENERATION Cephalexin , po Cefazolin Cephalothin Cephradine , po Active against G+ cocci ( except. enterococci & MRSA ): s. pneumoniae, s. pyogenes, s. aureus, & s. epidermidis Indicated for streptococcal pharyngitis ( e.g. cephalexin) Commonly used (eg. Cefazolin) as prophylactic for surgical procedures. Modest activity against G- bacteria ( Minimal activity against G-cocci & G +ve bacilli ) These do not cross BBB ( not suitable for treating brain abcess / meningitis ) & all are sensitive to β- lactamase enz. Degradation .
  • 110. CEPHALOSPORINS Second Generation : Cefoxitin (BF*) inj. -2gm 4 hrly They are in between (t½ - 0.9 hr ) 1st & 3rd gen. little less Cefaclor (O) 1gm 8 hrly effect. against G+ve & (t½ - 0.7 hr ) little more against Cefamandole G- ve ( HNPEK ) ( bl , A ) but not as active Cefuroxime 3gm 8hrly against G+ve org. ( * ,BB) (t½ - 1.7hr) as 1st gen. cephalosp. Cefotetan inj. 2-3gm 12hrly ( BF, bl ,A ) Loracarbef (O) ( Cephal. Containing PI are 4th gen. )
  • 111. CEPHALOSPORINS SECOND GENERATION Cefoxitin ( mefoxin ) Cefuroxime ( zinacef ) Cef. axetil ( zinnat ) Cefaclor ( ceclor ) Cefprozil ( cefzil ) Mainly effective against G- bacteria ( cocci & bacilli ) Modest activity against G+ bacteria & anaerobes Cefoxitin active against bowel anaerobes (B. fragilis ) Cefuroxim active against H. influenzae, M. catarrhalis, S. pneumoniae crosses BBB . Cef. Axetil- oral form of cefuroxim Cefaclor active against H. influenzae, M. catarrhalis &E.coli Cefprozil- similar to cefaclor, c. axetil and augmentin - Liked by children Second Generations are used primarily for URTIs ( acute otitis media, sinusitis ) and Lower RTIs ( acute exacerbation of chronic bronchitis) (These drugs are more stable to β-lactamase degradation ) LORACARBEF: ≡ Cefaclor, can be given orally , overdose can cause seizures
  • 112. CEPHALOSPORINS Third Generation : Cefotaxime inj. 2gm 4-8hrly They are much more (t-½ -1.1 hr ) act. against G-ve org. Cefpodoxime 200-400mg 12hrly include. β -lactamase proxetil ( O) ( t½ - 2.2 hr ) prod. less act against Ceftriaxone inj. 2gm 12-24hrly G+ve org.( Enterobac (b½,ch,T,G) (t½ -8 hr ) P.aerug.exct penicilli-. Cefoperazone inj.1.5-4 gm 8hrly nase prod. ,Serratia , ( P,b,D,A,T,bl) ( t½ - 2.1 hr ) N. gonor. are more Cefexime (O) 200-400mg 12hrly sensitive to 3rd gen.)
  • 113. CEPHALOSPORINS Ceftazidime ( P) inj. 2 gm 8 hrly ( t½ -1.8 hr ) Cefibuten ( O ) 400mg 4 hrly ( t½ - 2.4 hr ) Cefdinir ( O) 300mg 12 hrly ( t½ - 1.7 hr ) ( Cephal. ending with ME are 3rd gen. except- CefuroxiME )
  • 114. CEPHALOSPORINS THIRD GENERATION Ceftriaxone ( rocephin ) Cefotaxime ( claforan ) Cetazidime ( fortum ) Cefoperazone ( cefobid ) Cefixime ( suprax ) These are highly active against G-ve cocci, bacilli & anaerobes They have enhanced G- activity, H. influenzae, N. meningitidis, N.gonorrhea, P. aeruginosae, M. catarrhalis, E.coli, most Klebsiella are sensitive Ceftriaxone has long half-life . Not advised in neonates (interferes with bilirubin metabolism ) Cefotaxime preferred in neonate ( does not interfere with bilirubin metabolism ), as may ceftriaxone. Ceftazidime & cefoperazone have excellent activity against p. aeruginosae. Cefixime has similar activity to amoxicillin & cefaclor for actute otitis media -These drugs are highly resist. to degradation by β- lactamases by G-ve org.s -These can penetrate BBB ( Except-Cefoperazone & Cefixime )
  • 115. CEPHALOSPORINS Fourth Generation : Cefepime inj. 2 gm 8 hrly comp. to 3rd gen. but ( t½ -2 hr ) more resist. to some β – lactmases ( induc. type I ) & not active Cefpirome against anaerobes ( Cephal. containing PI are 4th gen. ) o = orally , * = resist . to β- lactamases , BF = act. ag. B. fragilis , P = act. Ag. P. aeruginosa , T = Typhoid , G = gonorh. , A = alcohol intolerance , N = nephrotoxic
  • 116. CEPHALOSPORINS D = Diarrhea , BB = crosses BBB , b = exc. in bile , b½ = half exct. in bile , bl = bleeding , ch = synd. mimicking cholecystitis . Now 5THGeneration has also came , although they inhibit the cell wall synthesis but in a different way , they bind to & inhibit PBP-2 produced by MRSA & Penicillin resist . S. pneumoniae which is not inhibited by majority of antb.s . -Also active against Enterococcus .& retain the activity of IV gent. against G-ve bacilli ( esp. E.coli & Pseudomonas) e.g.-Ceftaroline app. by FDA & Ceftobiprole ( phase III trial) -Used for comm. aquired bact. Pneumonia & acute Bact. Skin inf. incl. MRSA )
  • 117. CEPHALOSPORINS Mechanism of Bacterial Resistance : Resist. to Cephalosp. may be related to the : -inability of the antb. to reach site of act. or - alteration in the PBPs that are targets of the cephalosp. such
  • 118. CEPHALOSPORINS that the antb. bind to bact. enz.s ( β – lactamases esp. inducible type I ) that can hydrolyze the β- lactum ring & inactivates the Cephalosp.s
  • 119. CEPHALOSPORINS General features : Cephalosp.s are excrt. primarily by the kidney , therefore dosage should be altered in case of renal insufficiency. - Probenecid slows the tubular secrt. of most cephalosporins . (Cefoperamide & Cefoperazone are mainly excrt. in bile .)
  • 120. CEPHALOSPORINS - Cefotaxime is deacetylated in vivo & half excrt. through kidney & half in bile . - Several of the Cephalosp.s penetrate CSF in sufficient conc. to be useful in meningitis (Cefuroxime ,2nd & 3rd
  • 121. CEPHALOSPORINS gen. cephalosp.s ) . - Cephalosp.s cross the placenta & also found in high conc. in synovial & pericardial fluid . - Penetr. in aq. humor of the eye is good after syst. administ. of 3rd gen. Cephalosp.s ( in vit. humor it is poor)
  • 122. CEPHALOSPORINS Side effects : 1. hypersenst. react. is most common immed. react. e.g. anaphylaxis , bronchospasm & urticarial rash . - most commonly maculopapular rash dev. usually after several days of
  • 123. CEPHALOSPORINS therapy . - Cross reactivity occurs in between Cephalosp.s & penicil.s due to the structural similarity to the Penicillins (about 20 % cases who are allergic to penicil.s are also allergic to Cephalosp.s) .
  • 124. CEPHALOSPORINS - Pts with mild react. to penicil. appear to be at low risk of rashes or other allergic react. following administr. of Cephalosp.s . but pts having recent severe allerg. react. or anaphylaxis to penicil. should be given Cephalosp. with great caution
  • 125. CEPHALOSPORINS - Rarely causes bone marrow dep. → granulocytopenia . - Nephrotoxicity occurs esp. with Cephaloridine & Cephalothin . - Diarrhea with Cephoperazone due to biliary exc. - Alcohol intolerance ( disulfiram like
  • 126. CEPHALOSPORINS react. in Cefamandole , Cefotetan & Cefoperazone ). - Bleeding related to hypoprothrombin – emia ( Cefotetan & Cefoperazone ) - Superinfection by 3rd ,4th & 5th gent. Therapeutic Uses : Used widely- effective prophylactically & therapeut.
  • 127. CEPHALOSPORINS 1st Gen. Cephalosp.s – - excellent for skin & soft tissue inf.s - colorectal surgery. - Prophylaxis for intracel. anaerobes . 2nd Gen. Cephalosp.s - - they are displaced by 3rd gen. Cephalosp.
  • 128. CEPHALOSPORINS - active for URTI , for Penicil. resist. S. pneumoniae inf. - Otitis media - Diabetic foot inf. 3rd Gen. Cephalosp.s : - with or without Aminoglycosides are DOC for serious inf. caused by
  • 129. CEPHALOSPORINS Klebsiella , Enterobacter ,Proteus , Providencia , Serratia & haemophilus sp.s - Ceftriaxone is DOC for gonorrhea & lyme disease & also for Salmonella inf. ( Typhoid fever ) . -Meningitis ( Ceftazidime + aminoglyc.
  • 130. CEPHALOSPORINS for Pseudomonas meningitis ) - Ceftriaxone & Cefotaxim are good for community acquired pneumonia 4th Gen. Cephalosp.s : The Nosocomial inf.s where antb. resist. owing to extended spect. β- lactamases
  • 131. Other β- Lactum Antibiotics With β –lactum structure that are neither penicil. nor cephalosp. Carbapenems - It contain fused β- lactum by unsaturated 5 nucleus ring syst. & containing Carbon atom instead of sulfur atom . - have broader spect. of activity than
  • 132. Other β- Lactum Antibiotics do most other β –lactum antb.s - These are synth. antibact. agents Imipenems : - marketed in comb. with Cilastatin a drug that ↓ degradation of imipenem by renal tubular dipeptidase . - indicated against refractory nosocom.
  • 133. Other β- Lactum Antibiotics infections leading to - -UTI , LRTI , -Gynecological inf. -Joint inf. & -Intra abdominal inf. caused by
  • 134. Other β- Lactum Antibiotics Enterobacter ,Pseudomonas , Acinetobacter & anaerobic inf.( by B. fragilis & Clostr. difficil ). -orally not abs. , rapidly hydrolyzed by dipeptidase in renal tubules to nephrotoxic metabolites
  • 135. Other β- Lactum Antibiotics Therefore Cilastatin is combined ( it ↓ dipeptidase enz.) S/E – nausea , vomiting , seizures & cross allergy . Meropenem : It is ≡ Imipenem but is not senst. to renal dipeptidase & with less risk of
  • 136. Other β- Lactum Antibiotics of seizures . Ertapenem : -having longer t½ therefore given once a day . -effective in enterobacteriaceae & anaerobes . Hence useful in abdom. & pelvic inf.s.
  • 137. Other β- Lactum Antibiotics Monobactums : Aztreonam - it is β- lactamase resist. with spect. similar to Aminoglycoside ( G-ve aerobic bacilli ). G+ve & anaer. org. are resist. -no cross allergy to β –lactum antb. -given I.M. or I.V. dose -2 gm/d 6-8 hrly
  • 138. Other β- Lactum Antibiotics β – lactamase inhibitors : certain molecule can inactivate β- lactamase & thus prev. the destruction of β – lactam antb. that are substrates of this enz. ( ↑ effectiveness of β – lactum antb.s ).
  • 139. Other β- Lactum Antibiotics -most active against Plasmid encoded β- lactamase e.g.- Clavulanic acid , Sulbactum & Tazobactum . - They themselves have not any signif. AM activity .
  • 140. Other β- Lactum Antibiotics - They do not inhibit inducible type I β- lactamase induced in G-ve bacilli. Useful comb.s are : 1. Amoxycil. + Clavulanic acid – effective against β –lactamase prod. strains of Staphylococ. ,H. influenz. ,Gonococci & E. coli .
  • 141. Other β- Lactum Antibiotics - indicated in resist. Otitis media, sinusitis , animal bite wounds cellulitis & diabetic foot. 2. Ticarcillin + Clavul. Acid : ≡ Imipenem indicated in mixed nosocomial inf. along with Aminoglyc.
  • 142. Other β- Lactum Antibiotics 3. Ampicil + Sulbactum : indicated in mixed intra abdominal & pelvic inf.s .( exc. Pseud. & anaer- obic inf.) . 4. Tazobactum + Piperacil.: activity against Pseudomonas is not enhanced but having broadest AM sp.
  • 143. Bibliography 1.Goodman & Gilman’s ,The Pharmacological Basis of Therapeutics (12th Edition). 2. Clinical Pharmacology by Lawrence (Latest edition )