 Penicillins:-

o History:-

oChemistry:-

 A = Thiazolidine ring
 B = β – lactam ring
 R = Side chain

A+B= 6-aminopenicillanic acid nucleus

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Classification of Penicillins:-
(a). Natural:-

 Benzyl penicillin (Pen – G) ----

Phenoxymethyl penicillin (Pen-V) –

Procaine Penicillin ----

Benzathine Penicillin ----

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(b). Semi synth Penicillins:-

(i). Penicillinase resistant penicillins (resistant to staphylococcal

B-lactamases):- (Anti-staphylococcal penicillins)

 Methicillin -----

 Isoxazolyl Penicillins ----

 Oxacillin

 Cloxacillin

 Dicloxacillin

 Flucloxacillin

 Nafcillin ----
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(ii). Extended spectrum Penicillins:-
 Amino – Penicillins:- ----

 Ampicillin

 Amoxicillin

 Esters of ampicillin
(iii). Antipseudomonal Penicillins:-
 Carboxy Pen:-
 Carbenecillin -----
 Ticarcillin -----
 Carfecillin ------
 Ureido – Penicillins: ------
 Azlocillin
 Mezlocillin
 Piperacillin 4
Mechanism of action of Penicillins:-

Inhibit bacterial cell wall synthesis by inhibiting

trasnpeptidation process through interfering the

penicillin binding protein (PBP an enzyme), Halting

peptidoglycan synthesis and the cell dies.

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Resistance to Penicillins:-

 Production of Beta – lacatamases (Many 100 types)

 Reduced permeability of drug

 Modification of penicillin binding proteins. (PBP)

 Efflux pump

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Anti – bacterial spectrum of Penicillins:-

(i). Pen. G & Pen. V:-

G +ve bacteria (Cocci & Bacilli) except BLP staph

aureus.

G –ve Cocci (Neisseria species)

NBLP G –ve anaerobes (Except B. fragilis).

Spirochetes

Not active against G –ve rods & enteric organisms.

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(ii). BLM resistant penicillins:- (Anti-staphylococcal Pen):-

 Resistant to Staph Beta – Lactamases

 Highly active against BLP staph. aureus

 Much less active against other G +ve bact

 Not active → Enterococci, Anaerobes & G –ve Cocci & rods

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Extended spectrum penicillins:-

(i). Aminopenicillins:-

 G +ve organisms

 More activity against group – D streptococci

 Haemophilus sp.

 Listeria

 G –ve enteric org → E. Coli, proteus, salmonella & shigella

 Amoxicillin + clavulanic acid → BLP enteric org.

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(ii). Anti- pesudomonal penicillins:-

Pseudomonas, Enterobacter & other G –ve m.o

Less active for G +ve org.

(iii). Reserved spectrum penicillins:-

 G –ve organisms

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b- Lactamase inhibitors:-

 Clavulanic acid

 Sulbactam

 Trazobactam

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Amoxycillin Plus Clavulanic Acid:-

 Spectrum:-
 Most active against plasmid encoded Beta - latamases
produced by otherwise sensitive m.o.

 Staph aureus

 H– influenzae

 N. Gonorrhoe

 E – coli

 Salmonella

 Shigella

 Kl. Pneumonae
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Pharmacokinetics of Penicillins:-

(a). Absorption:-

 Oral adm

 Parentral adm:

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(b). Distribution:-

 Plasma protein binding:

 20 % → Ampicillin & Amoxicillin

 More than 90 % → Nafcillin & Isoxazolyl penicillins

 Being polar comp

 Poor penetration into BBB, Eye & Prostate

 More penetration of BBB in inflam

 Well distrib → body fluids & spaces

 t ½ = 15 min – 1.3 hrs → ↑10 -- 20 hrs → in anuric pts.

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Metabolism & Exc:-

 No significant metabolism

 Exc – kidney ---- 90 % tub. Sec & 10 % Gl. Fil

 Renal Clearance less efficient in Newborn

 Primarily Hepatic (Bile) → Nafcillin

 Both Renal & Hepatic → Oxa , Cloxa & Dicloxacillin

 Milk & Sputum 3 – 15 %

 Renal exc → ↓↓ by probenicid

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