B lactum antibiotics by JITENDRA BHANGALE

8/5/2012

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© 2010 Delmar, Cengage Learning1

By- Jitendra Bhangale

Assistant Professor & Head,

Department of Pharmacology,

Smt N. M. Padalia Pharmacy College,

Ahmedabad


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 BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad

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

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In gram-positive microorganisms, the cell wall is 50 to 100 moleculesthick, but it is only 1 or 2 molecules thick in gram-negative bacteria.

The peptidoglycan is composed of glycan chains, which are linear strandsof 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, TazobactamBy Jitendra Bhangale

Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad


Cocci:

Streptococci

Pneumococci,

Staphylococcus aureus

Gram negative cocci-

Nelsseria gonorrhoeae

N. meningitidis


Bacilli: Gram-positive bacilli-

B. anthracis,

Corynebacterium diphtheriae

Clostridia

Listeria

spirochetes

But Bacteroides fragilis is largely

resistant.

Antibacterial spectrum

PnG is a narrow spectrum antibiotic primarily to gram-positive

bacteria

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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



Adverse reaction

ThrombophlebitisMental confusionMuscular twitchingsConvulsionsComaHypersensitivity rashItchingUrticariaFeverWheezingAngioneuroticEdemaSerum sicknessExfoliative dermatitis


Immediate type of

hypersensitivity-

Angioedema

Bronchospasm

serum sickness

Contact dermatitis

Jarisch-Herxheimer reaction

(shivering, fever, myalgia,

exacerbation of lesions, even

vascular collapse)

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Therapeutic uses

Streptococcal infections

Pneumococcal infections

Meningococcal infections


Gonorrhoea

Syphilis

Diphtheria

Tetanus and gas gangrene


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



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.



Examples:

Aminopenicillins:

Ampicillin

Bacampicillin

Amoxicillin

Carboxypenicillins:

Carbenicillin

Ticarcillin


Ureidopenicillins:

Piperacillin

Mezlocillin

Azlocillin

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Ampicillin is not degraded by

gastric acid.

Oral absorption is incomplete.

Food interferes with

absorption.


Uses

Urinary tract infections:

Respiratory tract infections:

Meningitis:

Gonorrhoea

Typhoid fever:

Cholecystitis

Antibacterial spectrumIt is active against all organisrn sensitive to PnG; in addition many

gram-negative bacilli, e.g. H. Influenzae, E-Coli, Proteus andShigella


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.



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.



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.By Jitendra Bhangale

Asst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad



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It was originally obtained from the fungus Cephalosporium acremonium.


First Generation CephalosporinsParenteral

CephalothinCefazolin

OralCefadroxilCephalexinCephradine

Second generation cephalosporinsParenteral

CefuroximeCefoxitin

OralCefuroxime axetilCefaclor


Third Generation CephalosporinsParenteral

CefotaximeCeftizoximeCeftriaxoneCeftazidimeCefoperazone

OralCefpodoxime proxetilCefdinirCeftibutenCeftamet pivoxilCefixime

Forth generation cephalosporinsParenteral

CefepimeCefpirome

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Parenteral

Cephalothin

Cefazolin

Oral

Cefadroxil

Cephalexin

Cephradine


Streptococci

Gonococci

Meningococci

C. diphtheriae

H. influenzae

Clostridia

Actinomyces

Klebsiella

E. coli


Antibacterial spectrum for Ist generation cephalosporins

It is a narrow spectrum antibiotic primarily to gram-positive bacteria

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Parenteral

Cefuroxime

Cefoxitin

Oral

Cefuroxime axetil

Cefaclor


E coli

H. influenzae

Pr. mirabills

C. diphtheriae

H. Influenzae

None inhibits P. aeruginosa


Antibacterial spectrum for II generation cephalosporins

It is a narrow spectrum antibiotic primarily to gram-negative

bacteria

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ParenteralCefotaximeCeftizoximeCeftriaxoneCeftazidimeCefoperazone

OralCefpodoxime proxetilCefdinirCeftibutenCeftamet pivoxilCefixime


E coli

Pseudomonas

H. Influenzae

Not active on anaerobes

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


Antibacterial spectrum for III generation cephalosporins

It is primarily active against gram-negative bacteria.

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Parenteral

Cefepime

Cefpirome

Oral

Not invented yet


Highly resistance to B lactamase


Antibacterial spectrum for IV generation cephalosporins

Similar to III generation cephalosporins.

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Pain

Diarrhoea

Hypersensitivity reactions

Nephrotoxicity

Bleeding

Neutropenia and thrombocytopenia



Respiratory, urinary and soft tissue infections

Penicillinase producing staphylococcal infections

Septicaemias

Surgical prophylaxis

Meningitis

Gonorrhoea

Typhoid


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B lactum antibiotics by JITENDRA BHANGALE

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