B lactum antibiotics by JITENDRA BHANGALE

8/5/2012

By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad
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© 2010 Delmar, Cengage Learning

These are antibiotics having a B-lactam ring.

The two major groups are penicillins and cephalosporins.

Monobactams and carbapenems are relatively newer additions.

By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2
© 2010 Smt N. M. Padalia

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8/5/2012


It was originally obtained from the fungus Penicillium notatum, but the
present source is a high yielding mutant of P. chrysogenum.


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In gram-positive microorganisms, the cell wall is 50 to 100 molecules
thick, but it is only 1 or 2 molecules thick in gram-negative bacteria.
The peptidoglycan is composed of glycan chains, which are linear strands
of two alternating amino sugars (N-acetylglucosamine and N-
acetylmuramic acid) that are cross-linked by peptide chains.

The cell walls of bacteria are
essential for their
normal growth and
development.
Peptidoglycan provides rigid
mechanical stability by
virtue of its highly cross-
linked latticework
structure.


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The final stage involves completion of the cross-link.

This is accomplished by a transpeptidation reaction that occurs

outside the cell membrane.

The transpeptidase itself is membrane-bound.

The terminal glycine residue of the pentaglycine bridge is linked to

the fourth residue of the pentapeptide (D-alanine), releasing

the fifth residue (also D-alanine).

It is this last step in peptidoglycan synthesis that is inhibited by

the b-lactam antibiotics.

There are additional, related targets for the actions of penicillins
and cephalosporins; these are collectively termed penicillin-
binding proteins (PBPs). All bacteria have several such entities

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Penicillin G

Acid resistance to Penicillin G (Semisynthetic)

Penicillin V

Penicillinase-resistant penicillins

Methicillin, Nafcillin, Oxacillin, Cloxacillin & Dicloxacillin

Extended spectrum penicillins

Aminopenicillins: Ampicillin, Bacampicillin, Amoxicillin

Carboxypenicillins: Carbenicillin, Ticarcillin

Ureidopenicillins: Piperacillin, Mezlocillin, Azlocillin

B-lactamase inhibitors: Clavulanic acid, Sulbactam, Tazobactam

Antibacterial spectrum
PnG is a narrow spectrum antibiotic primarily to gram-positive
bacteria

Bacilli: Gram-positive bacilli-
Cocci:
B. anthracis,
Streptococci
Corynebacterium diphtheriae
Pneumococci,
Clostridia
Staphylococcus aureus
Listeria
Gram negative cocci-
spirochetes
Nelsseria gonorrhoeae
But Bacteroides fragilis is largely
N. meningitidis
resistant.

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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad

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Pharmacokinetics
Absorption
Penicillin G is acid labile-destroyed by gastric acid.
Absorption of sod. PnC from i.m. site is rapid and complete.
Distribution
It is distributed mainly extracellularly; reaches most body fluids,
but penetration in serous cavities and CSF is poor.
Excretion
Very rapid renal excretion

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Adverse reaction
Immediate type of
Thrombophlebitis
Mental confusion hypersensitivity-
Muscular twitchings Angioedema
Convulsions
Coma Bronchospasm
Hypersensitivity rash serum sickness
Itching
Urticaria Contact dermatitis
Fever Jarisch-Herxheimer reaction
Wheezing
Angioneurotic (shivering, fever, myalgia,
Edema exacerbation of lesions, even
Serum sickness
Exfoliative dermatitis vascular collapse)

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Therapeutic uses Gonorrhoea

Streptococcal infections Syphilis

Pneumococcal infections Diphtheria

Meningococcal infections Tetanus and gas gangrene

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Acid-resistant alternative to Penicillin-G.

This is nothing but Phenoxymethyl penicillin.

It is acid stable therefore oral absorption is better.

The antibacterial spectrum of penicillin V is identical to PnG,
gram negative bacteria and anaerobes.

It is used only for streptococcal pharyngitis,

sinusitis,

otitis media,

prophylaxis of rheumatic fever

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Side chains of this class of penicillin protect the B-lactam ring from

attack by staphylococcal penicillinase.

Examples:

Methicillin

Nafcillin

Oxacillin

Cloxacillin

Dicloxacillin

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It is highly penicillinase resistant but not acid resistant-must be
injected.
MRSA have emerged in many areas.
The drug of choice for these organisms is vancomycin/linezolid,
but ciprofloxacin can also be used.
Adverse effect:
Haematuria
Albuminuria
Reversible interstitial nephritis
It has been replaced by cloxacillin.

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It has an isoxazolyl side chain and is highly penicillinase as well

as acid resistant.

Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl

penicillins, similar to cloxacillin, but not marketed in India.

Nafcillin is another parenteral penicillinase resistant penicillin.

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Examples:
Ureidopenicillins:
Aminopenicillins: Piperacillin
Ampicillin Mezlocillin
Bacampicillin Azlocillin
Amoxicillin

Carboxypenicillins:

Carbenicillin

Ticarcillin

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Antibacterial spectrum
It is active against all organisrn sensitive to PnG; in addition many
gram-negative bacilli, e.g. H. Influenzae, E-Coli, Proteus and
Shigella

Uses
Ampicillin is not degraded by Urinary tract infections:
gastric acid. Respiratory tract infections:
Oral absorption is incomplete. Meningitis:
Food interferes with Gonorrhoea
absorption. Typhoid fever:
Cholecystitis

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It is an ester prodrug of ampicillin which is nearly completely

absorbed from the g.i.t.

Talampicillin,

Pivampicillin,

Hetacillin are other prodrugs of ampicillin

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Oral absorption is better

Food does not interfere with absorption

Incidence of diarrhoea is lower.

Uses:

Bronchitis, urinary infection and gonorrhoea.

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Carboxypenicillins

The special feature of this penicillin congener is its activity against
pseudomonas aeruginosa and indole positive proteus which
are not inhibited by PnG or aminopenicillins.

It is inactive orally and is excreted rapidly in urine

High doses have also caused bleeding by interferring with platelet
function

Ticarcillin

It is more potent than carbenicillin against Pseudomonas.

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Piperacillin
This antipseudomonal penicillin is about 8 times more active than
carbenicillin.
It has good activity against Klebsiella and is used mainly in
neutropenic/immunocompromised patients having serious
gram-negative infections, and in burns.
Mezlocillin
It has activity similar to ticarcillin aqainst Pseudomonns and
inhibits Klebsiella as well.
It is given parenterally primarily for infections caused bv enteric
bacilli.
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B-lactamases are a family of enzymes produced by many gram-

positive and gram-negative bacteria that inactivate B-lactam

antibiotics by opening the B-lactam ring.

Examples:

Clavulanic acid

Sulbactam and.

Tazobactam

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Clavulanic acid is obtained from Streptomyces clavuligerus, it has
a b-lactam ring but no antibacterial activity of its own.

It inhibits a wide variety (class II to class V) of B-lactamases.

Clavulanic acid is a progressive inhibitor.

It is also called a 'suicide’ inhibitor, it gets inactivated after
binding to the enzyme.

It permeates the outer layers of the cell wall of gram negative
bacteria and inhibits the periplasmically located B-
lactamase.

Sulbactam and Tazobatam are semisynthetic B lactamase
inhibitor.
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It was originally obtained from the fungus Cephalosporium acremonium.

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Third Generation Cephalosporins
First Generation Cephalosporins
Parenteral
Parenteral
Cefotaxime
Cephalothin
Ceftizoxime
Cefazolin
Ceftriaxone
Oral
Ceftazidime
Cefadroxil
Cefoperazone
Cephalexin
Oral
Cephradine
Cefpodoxime proxetil
Second generation
Cefdinir
cephalosporins
Ceftibuten
Parenteral
Ceftamet pivoxil
Cefuroxime
Cefixime
Cefoxitin
Forth generation cephalosporins
Oral
Parenteral
Cefuroxime axetil
Cefepime
Cefaclor
Cefpirome

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Oral
Parenteral
Cefadroxil
Cephalothin
Cephalexin
Cefazolin
Cephradine

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Antibacterial spectrum for Ist generation cephalosporins
It is a narrow spectrum antibiotic primarily to gram-positive bacteria

Streptococci
Gonococci
Meningococci
C. diphtheriae
H. influenzae
Clostridia
Actinomyces
Klebsiella
E. coli

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Parenteral Oral

Cefuroxime Cefuroxime axetil

Cefoxitin Cefaclor

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Antibacterial spectrum for II generation cephalosporins
It is a narrow spectrum antibiotic primarily to gram-negative
bacteria

E coli

H. influenzae

Pr. mirabills

C. diphtheriae

H. Influenzae

None inhibits P. aeruginosa

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Parenteral Oral
Cefotaxime Cefpodoxime proxetil
Ceftizoxime Cefdinir
Ceftriaxone Ceftibuten
Ceftazidime Ceftamet pivoxil
Cefoperazone Cefixime

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Antibacterial spectrum for III generation cephalosporins
It is primarily active against gram-negative bacteria.

E coli

Pseudomonas

H. Influenzae

Not active on anaerobes

(particularly Bact. fragilis), Staph. aureus and Ps. aeruginosa

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Parenteral
Oral
Cefepime
Not invented yet
Cefpirome

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Antibacterial spectrum for IV generation cephalosporins
Similar to III generation cephalosporins.

Highly resistance to B lactamase

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Pain

Diarrhoea

Hypersensitivity reactions

Nephrotoxicity

Bleeding

Neutropenia and thrombocytopenia

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Respiratory, urinary and soft tissue infections

Penicillinase producing staphylococcal infections

Septicaemias

Surgical prophylaxis

Meningitis

Gonorrhoea

Typhoid

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8/5/2012

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B lactum antibiotics by JITENDRA BHANGALE

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