Clinical Considerations in Prescribing Antimicrobial Drugs.
- Alexander Fleming reported in 1929 that the antibacterial action of penicillin released from Penicillium. He defined antibiotics as antimicrobial agents that are produced naturally by an organism. Today, antibiotic means "an antibacterial agent", excluding antiviral and antifungal agents.
Penicillin is a natural occurring antibiotic. Additionally, by altering the chemical structure of antibiotics, semisynthetics are produced. These are more effective, last longer, or easier to administer than natural antibiotics. Synthetics are antimicrobials that are completely synthesized in a laboratory.
Mechanisms of Antimicrobial Action
Because there are many differences between the structure and metabolism of pathogenic bacteria and their eukaryotic hosts, antibacterial drugs constitute the greatest number of diversity of antimicrobial agents. Although they can have a variety of effects on pathogens, antimicrobials can be catagorized into 6 different groups according to their mechanisms of action.
1.) Inhibition of cell wall synthesis. (Penicillins) The most common antibacterial agents act by preventing cross-linkage of NAM subunits (a macromolecule of peptinoglycan in bacteria). Thus, cell walls of pathogens are weakened and are less resistant to the effects of osmotic pressure. The underlying cytoplasmic membrane bulges through the weakened portion as water moves into the cell and the cell lyses.
2.) Inhibition of protein synthesis. (Tetracyclines) Understanding this inhibition first requires understanding the process of translation. The tetracyclines can change the shape of certain subunits, making it impossible for the ribosome of the cell to read the codons of RNA properly. Some antimicrobials can prevent movement of the ribosome from one codon to the next altogether. As a result, translation is frozen and protein synthesis is stopped.
3.) Disruption of cytoplasmic membrane.(Polymyxins) Some antimicrobials have the ability to become part of the cytoplasmic membrane and thus, damaging it. The drug amphotericin B binds to molecules of ergosterol, causing them to congregate and form a spore within the membrane.
4.) Inhibition of metabolic pathways. (Sulfonamides) Humans take simple folic acids found in our diets and covert them to into tetrahydrofolic acid (THF). As a result, our human metabolism is unaffected by sulfonomides. Some pathogens desire certain acids to be converted into THF, a reaction required for their DNA and RNA synthesis. Sulfonamides decrease this acid production which slows the production of proteins required for pathogenic synthesis.
5.) Inhibition of nucleic acid synthesis. (analogs) DNA and RNA are built from purine and pyrimidine nucleotides and are critical to cell survival. Because only slight differences exist between nucleic acids of both prokaryotic and eukaryotic cells, drugs that affect replication often acts against both types of cells. Generally these drugs are not used to treat infections, but rather as research in DNA replication and to slow replication of cancer cells. Analogs change the shape of nucleic acid molecules and prevent further replication, trascription, or translation.
Additionally, viral acid synthesis is faster than the synthesis of cells, so viruses are more susceptible to analogs than their hosts.
Here is what we've discussed so far
6.) Prevention of virus attachment.(Arildone) Viruses must attach to their host's cells via chemical interaction. Attachment of viruses can be blocked by peptide and sugar analogs of either attachment or receptor proteins. When these sites are blocked, viruses can neither attach or enter a host cell. Arildone blocks receptor sites of polio viruses and some cold viruses, making them unable to attach to host cells.
The ideal antimicrobial agent to treat infection would probably be one that is:
1.) readily available
3.) chemically stable (for ease of transport and shelf-life considerations)
4.) easily administered
5.) nontoxic and nonallergenic
6.) selective toxicity against a wide range of pathogens
Oral drugs are easy to take and usually low cost, but are not monitored, which holds the capabilitiy of resistance.
Injectable drugs are high cost, quickly effective, the entire dosage is ensured, and are closely monitored.
Topical drops and mists are usually low cost, but are not monitored and can gain resistance without proper use. Underdosage and overdosage is especially dangerous with mists.
The spectrum of action is the number of different kinds of pathogens an antimicrobial agent can act against. Narrow-spectrum drugs act only against a few kinds of pathogens, where broad-spectrum drugs can act against a wide range of organisms. Using a broad-sprecrum antibiotic can also kill normal flora that is necessary to defend against pathogenic organisms in the first place. For example, a woman taking erythromycin for a throat infection, is more susceptible to vaginitis resulting from excessive yeast growth when the agent kills normal bacteria contained in the vagina.
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