Antimicrobials; antibacterials, antifungals, antiprotozoans, antivirals,

and antihelminthics 2

Inhibitors of Cell Wall Synthesis

Penicillin Natural penicillins Semisynthetic penicillins Extended-spectrum penicillins

The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G, the original penicillin found in 1928), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V).

Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Penicillin In 1928, Alexander Fleming discovered penicillin produced

by Penicillium, a fungus and in 1940, Howard Florey and Ernst Chain performed first clinical trials of penicillin. Still widely used today, though many types of bacteria have developed resistance following extensive use.

Refers to a group of over 50 chemically related antibiotics All penicillins are β-lactam antibiotics: common core

containing a β-lactam ring called as the nucleus. Differentiated by the side groups

Prevents the cross link of the peptidoglycans interfering with the final stage of the construction of the cell wall

Natural penicillins vs semisynthetic penicillins

The Structure of Penicillins

Figure 20.6

Benzylpenicillin, weak to acid

phenoxymethylpenicillin , resistance to acid

The term "penam" is used to describe the common core skeleton of a member of the penicillins.

Weak points of Natural penicillins

Limitation in oral administration

Short retention time

Susceptibility to penicillinases of resistant bacteria

Narrow spectrum : effective for Gram (+)

Side effect (toxicity) : allergy to penicillins About 10% of people report that they are allergic to penicillin;

however, up to 90% of this group may not actually be allergic. Serious

allergies only occur in about 0.03%.

Development of penicillins To improve the efficacy of penicillins Penicilinase-resistant penicillins Extended-spectrum penicillins Acid resistance for oral administration Longer retention time Reduction of allergic effects

Combination with other chemicals or drugs Modification of the molecular structure Pharmaceutic processing

Procaine penicillin and Benzathine penicillin Longer retention time, but lower concentration in blood The pathogen must be very sensitive to benzathine

penicillin.

The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V).

Retention of Penicillin G

"Microbiology-An introduction" 11th edition, p568, G. J. Tortora, B. R. Funke, and C. L. Case, Pearson

The Effect of Penicillinase on Penicillins

Figure 20.8

Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis

Chemically modified Penicillins

Penicilinase-resistant : Methicillin, oxacillin, nafcillin.

Eventually many bacteria developed resistance to these

antibiotics (eg, MRSA; methicillin-resistant S. aureus)

Extended-spectrum : greater activity to Gram (-).

aminopenicillins (ampicillin, amoxicillin), carboxypenicillins

(carbenicillin, ticarcillin), ureidopenicillins (mezlocillin,

azlocillin; modification of ampicillin)

Semisynthetic Penicillins

First, interrupt the synthesis of the molecule by Penicillium and obtain only the common penicillin nucleus for use

Next, remove the side chains from the molecules and then chemically add other side chains.

Various structures of penicillin derivatives

- active against Pseudomonas aeruginosa.

Combination with other drugs Procaine, benzathine, cilastin : improve the retention time β-lactamase inhibitors : potassium clavulanate (combined with

amoxicillin; Augmentin)

β−Lactam Antibiotics Penicillin Carbapenems Substitute a C for a S,

add a double bond Monobactam Single ring

Cabapenem ring

Monobactam ring