This article outlines the common antimicrobials and their mechanisms of action. You should have a familiarity with the mechanisms as in the exam, you may be asked something like which of the following drugs target the 30S subunit.

This image summarises the key drugs

Kendrick Johnson, CC BY-SA 3.0, via Wikimedia Commons

Penicillins are bactericidal agents derived from Penicillium fungi. They disrupt bacterial cell wall synthesis by inhibiting the enzyme responsible for cross-linking peptidoglycan layers. Penicillins are molecularly modified through the addition of different side chains to the beta-lactam ring, enhancing their spectrum of activity or making them resistant to beta-lactamases. They are primarily effective against Gram-positive bacteria like Staphylococci, Streptococci, and Clostridia, and some Gram-negative bacteria such as E. coli. Flucloxacillin, a molecular variant, is resistant to beta-lactamase, making it effective against beta-lactamase-producing Staphylococci.

Cephalosporins inhibit cell wall synthesis but have a broader spectrum than penicillins due to their resistance to beta-lactamase enzymes. Their structure allows modifications that extend their activity against Gram-negative bacteria, including Pseudomonas and Bacteroides. The efficacy of later generations against more diverse bacteria highlights the importance of molecular modifications in extending antimicrobial action.

Aminoglycosides, like gentamicin, bind irreversibly to the 30S subunit of bacterial ribosomes, preventing protein synthesis. Their action is primarily against Staphylococci and aerobic Gram-negative bacteria. However, their use is limited by nephrotoxic and ototoxic side effects. Amikacin, a derivative, offers better activity against certain resistant Gram-negative bacteria with less retinal toxicity.

Tetracyclines bind to the 30S ribosomal subunit, inhibiting protein synthesis. They are effective against a broad range of bacteria, including Chlamydia and Rickettsia. Molecular modifications have improved their efficacy and reduced resistance. Their use is contraindicated in pregnancy and children under ten due to risks of tooth discoloration and bone growth inhibition.

Chloramphenicol targets the 50S ribosomal subunit, blocking peptide bond formation and thus protein synthesis. It is effective against various bacteria, including Staphylococci and Haemophilus influenzae. Due to risks of aplastic anaemia and grey baby syndrome, its use is restricted to severe infections where other antibiotics are not suitable.

Metronidazole interferes with DNA synthesis in anaerobic bacteria and protozoa by causing strand breakage. This action is crucial for treating infections like trichomoniasis and giardiasis. Its ability to cross the blood-brain barrier makes it effective against central nervous system infections.

Fluoroquinolones, such as ofloxacin, inhibit DNA gyrase and topoisomerase IV, enzymes critical for bacterial DNA replication. They cover a wide range of bacteria, including Gram-negative and atypical pathogens. Resistance concerns have led to modifications to target additional bacterial enzymes and reduce side effects.

Vancomycin, a glycopeptide, prevents cell wall synthesis by binding to the D-Ala-D-Ala terminus of peptidoglycan precursors. It is effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Molecular alterations have been explored to overcome resistance mechanisms and improve pharmacokinetics.

Amphotericin B binds to ergosterol in fungal cell membranes, forming pores that lead to cell death. Its broad-spectrum antifungal activity is essential for treating systemic fungal infections, although its use is limited by significant nephrotoxicity.

Fluconazole inhibits ergosterol synthesis, disrupting fungal cell membrane integrity. It is effective against Candida and Cryptococcus species but not Aspergillus. Its good penetration into the central nervous system makes it valuable for treating meningitis.

Acyclovir is activated by viral thymidine kinase and then inhibits viral DNA polymerase. It is highly effective against herpes simplex virus (HSV) and varicella-zoster virus (VZV). Ganciclovir, similar in structure but more effective against cytomegalovirus (CMV), is modified by the addition of a hydroxymethyl group, increasing its phosphorylation and activity against viral targets.

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