Penicillin

Penicillins, also penicillins (from Latin "penicillium" brush mould), refers to a group of antibiotically active substances that are structurally derived from 6-aminopenicillanic acid. Penicillins belong to the group of beta-lactam antibiotics. The molecular formula is R-C9H11N2O4S, where "R" stands for a variable side chain.

In addition to naturally occurring penicillins formed as secondary metabolites of various Penicillium, Aspergillus, Trichophyton, and Streptomyces species, the group of penicillins includes biosynthetically of semi-synthetically produced penicillins.

Naturally occurring penicillins

The starting substance of penicillins, 6-aminopenicillanic acid, is formed biologically from L-alpha-aminoadipic acid and the amino acids L-cysteine and L-valine, with isopenicillin N being formed first. The replacement of the L-α-aminoadipyl residue by other organic acid residues, catalyzed by acyltransferase, gives rise to various penicillins. Of the natural penicillins, only penicillin G (benzylpenicillin) is therapeutically significant, which is obtained fermentatively from Penicillium chrysogenum. In addition to Penicillium species as biological producers, penicillins are also produced by other molds such as Acremonium chrysogenum (formerly Cephalosporium acremonium) and Aspergillus nidulans, and by certain bacteria belonging to the order Actinomycetales.

Bio- and semi-synthetic penicillins

The orally active penicillin V (phenoxymethylpenicillin) is produced fermentatively by the addition of a synthetic precursor, phenoxyacetic acid ("biosynthesis"). Semi-synthetic further developments of the natural penicillins are formed by the reaction of 6-aminopenicillic acid with carboxylic acid halides. Their advantage over penicillin G is acidity and/or stability towards the enzyme penicillinase, or an extended spectrum of activity.

The basic structure of penicillins consists of 6-aminopenicillanic acid, a bicyclic dipeptide of L-cysteine and L-valine (betalactam ring). The 6-aminopenicillanic acid is bound by the D-alanine transpeptidase of the bacteria. Thus, the enzyme is blocked. The enzyme is responsible for the cross-linking of peptidoglycans in the cell walls of gram-positive bacteria. The enzyme becomes active especially in dividing bacteria. By preventing cross-linking, penicillins irreversibly weaken the stability of the cell wall. Furthermore, the constant build-up and degradation of the defective cell wall leads to toxic degradation products.

The effect of penicillins only affects dividing bacteria. Dormant bacteria are not affected by penicillins, since no cell wall synthesis takes place.

Penicillin G and V are effective against gram-positive bacteria but not against gram-negative bacteria (with the exception of gram-negative cocci such as neisseria), as these have an additional outer membrane above their cell membrane. This prevents the pharmacological approach of penicillin.

Notice!

The development of resistance to penicillin G is a major clinical and therapeutic problem. There is also the problem of cross-resistance. Cross-resistance leads to penicillin-resistant bacteria becoming resistant to other betalactam antibiotics (e.g. cephalosporins). Multi-resistance is particularly feared in the case of Staphylococcus aureus (MRSA). The exchange of resistance genes between different bacterial species means that antibiotic resistance is also passed on to other species.

Hoigné Syndrome (rarely with intramuscular application).

Bronchospasm, BB changes, vasculitis, purpura, dry mouth, gastrointestinal disorders, allergic reactions, cross-allergy with cephalosporins, RR decrease, CK increase, myocarditis, central nervous excitation with epileptic seizures, hyperuricemia, arthralgias, myalgias, hyperhidrosis.

Notice! Allergic reactions in 0,5-2% (6-aminopenicillanic acid, cross-allergy to all penicillins; see below penicillin allergy). Herxheimer's reaction at the beginning of treatment of syphilis.

See Table 2.

Classification of penicillins

Essential interactions of penicillins