In my previous posts, I looked at toxicology, taking different types of poisoning from vegetable acid poisoning, organic poisoning, animal poisoning, Inorganic acid and base poisoning, and Inorganic metallic poisoning. We are going into another series, and this time we are going into pharmacology, discussing antibiotics, and antimicrobial life. Before I continue, let me quickly explain to you that antibiotics are compounds that inhibit the growth or kill microbes basically bacteria. Let's start the Beta-Lactam antibiotics.
Beta-Lactam antibiotics possess Beta-Lactam rings, and for clarity, Lactam is a cyclic amide, so Beta-Lactam is a square-shaped structure that possesses the Carbonyl group and an amide group where the nitrogen atom is attached to the beta carbon close to the carbonyl group. In the case of penicillins, they can possess a sulfur group such as Thiazolidinedione. The bonds of the square shape molecule are often undtable and bonds between the Amide and the Carbonyl group break easily. Drugs that are beta-lactam includes Penicillin, Cephalosporine, Carbapenems, and Monobactams. So let's quickly discuss Penicillin.
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Penicillin is a beta-lactam drug that has the beta-lactam ring with Thiazolidinedoine which has a sulfur and a R group. The R groups can be modified to become a synthetic drug, as well as protect against Beta-Lactamases and stomach acid.
Remember that Gram Positive bacteria are associated with thick peptidoglycan cell wall where the porins are attached to the lipids in the cell wall while in the gram negative bacteria, the outer lipopolysaccharide has the porins. Continuing, Beta-Lactam drugs such as penicillin are cell wall synthesis inhibitors, and they are more effective on gram positive bacteria than on gram negative bacteria as a result of a well established peptidoglycan layer. Microorganism with peptidoglycan cell wall give support to the bacteria cell wall, ptotect the shape of the cell and help to withstand low osmotic pressure media thereby preventing the lysis of the cell.
Penicillins are bacterocidal causing death of the bacteria by lysing the cell of bacteria through inhibiting the synthesis of the cell wall. Peptodoglycan is composed of a glycan chain which is made up of alternating amino sugars such as N-Acetyl glucosamine and N-acetyl meramec acid, and a peptide chain. The N-acetylmuramic acid is attached to a pentapeptide that possesses 4 and 5 D alamine amino acid where the third amino acid is attached a pentaglycine chain which bond to the 4th D-Alanine Acid of another N-acetylmuramic acid which occur with the enzyme transpeptidase. Penicillin have a structural analog of D-alamine thereby causing it to inhibit the transpeptidase enzyme, therefore inhibiting the bonding and preventing cell wall synthesis. Penicillin like other beta-lactamase drug works efficiently on rapidly dividing bacteria cells that synthesizes cell walls.
While penicillin is very good at inhibiting cell synthesis, some bacteria have been able to develop resistance to it throgh mechanisms such as; the production of beta-lactamase which are enzymes that cleaves to succeptible bonds in the beta-lactam ring of the antibiotics. Bacteria such as Stahylococci, E.coli, Nesseria, and H.influenza poccesses this resistance. Another mechanism of resistance is altering the penicilin binding protein or transpeptidase thereby evading the penicillin, preventing them from attaching to them. Organisms such as methicilin-resistant staphylococci aureus, and penicillin resistant pneumococci possesses these mechanism. Another mechanism of resistance is changing the porin structure in the cell wall thereby changing the size o shape of the porins thereby preventing penicillin from entering the bacteria cell. Aerobic gram negative rod bacteria such as Pseudomonas poccesses this mechanisms.
This said, Penicillin can be classified baseed on their spectrum of action, and sensitivity to beta-lactamase. These are the Narrow Spectrum Penicillin which are sensitive to beta-lactamases (Penicillin G, Procaine Penicillin G, Penicillin V). The Very Narrow Spectrum penicillin are Beta-Lactam Resistance as a result of a change in the R-group which makes them protective (Nafcillin,Oxacillin, Cloxacillin). The Broad Spectrum Penicillin are another class of penicillin, and these penicillin are Beta-Lactam sensitivem (Amoxicillin, and A). The Extended Spectrum Penicillins are another class of penicillin that are sensitive to beta-lactamase (Carboxypenicillin). When administering the Broad Spectrum and Extended spectrum penicillin, Beta Lactamase inhibitors are administered with it so as to prevent the effect of Betalactamases by binding to the Beta-lactamases and be converted to metabolites that will inhibit the beta-lactamases. Beta Lactamase inhibitors are Sulbactam, Toxobactam and so on, and they exist in broad and extended spectrum antibiotics suxh as Augmentin which is clavulonic acid and amoxicilin.picillin.
Penicillin can be secreted in Urine via the kidney, and some by the liver in the bile (Nafcillin and Oxycilin). Penicillin can also pose with side effects such as hypersensitivity which can lead to shock. The hypersensitivity reaction is common with the naturally existing penicillin such as Penicillin G.
This said, Still on beta lactam drugs, I will be discussing Cephalosporin in my next post. I hope you were able to learn about Beta lactam drugs, and Penicillin in this post. Till next time.
https://journals.lww.com/cjasn/Fulltext
https://pubmed.ncbi.nlm.nih.gov/797501/
https://www.ncbi.nlm.nih.gov/books/NBK545311/