Antimicrobial Drugs: Antimicrobial Drugsare antimicrobics synthesized in a laboratory. These drugs are made by man. Antibiotics are (originally) produced by a microorganism in small quantities that will inhibit growth or even kill another organism. Antibiotics are usually from either Fungi or Bacteria.

Antimicrobial drugs are designed to act within the host (us). They must kill the invading pathogen without damaging the host. This is termed selective toxicity. This is usually based upon biochemical differences between the host and the invading microbe.

There are three major differences between the host and invader that can be exploited.

• Unique Enzymes
• Shared Enzymes Essential to Pathogen but not to the host
• Different Pharmacological Properties within the host and pathogen.

An important early antibiotic was discovered by Alexander Flemming (1927). Flemming was searching for antimicrobic agents. One day, he discovered a plate of S. aureus contaminated with a mold (Penicillium = genus). He noticed that there was a “zone of inhibition” around the mold where no bacteria were growing. The substance around the mold was characterized and later termed Penicillin. Penicillin was first used to cure an Oxford policeman with a Staph infection.

Some common mechanisms of Antibiotic/Drug Action

• Inhibition of cell wall synthesis - Affects the bacterial cell wall, thus, causing weak points in the cell wall Examples: Cycloserine and Penicillin
• Inhibition of Nucleic Acid Synthesis - Blocks synthesis of the raw materials involved in the generation of DNA and RNA Inhibits replication and can stop transcription Example: Para-aminosalicyclic acid (PAS)
• Inhibition of Protein Synthesis - Will react with the ribosome-mRNA complex Examples: Streptomycin, Chloroamphenicol
• Interferes with the function of the cell membrane - Interacts with the phospholipids of the membrane and can lead to metabolic insufficiency or lysis of the cell. Antifungals work in this way. Animal cells have cholesterol in their membranes and fungi have ergosterols in their membranes. Thus, target the ergosterols.
• Inhibition of Metabolite Synthesis - Specific Metabolites can be inhibited from forming via inhibitors (competitive and noncompetitive). Sulfonimides = Sulfa Drugs. This is a very important compound for folic acid synthesis by bacteria, and folic acid is important for purine and amino acid synthesis. The sulfa drugs compete with PABA (competitive inhibition) for the active site on the enzyme.

In laboratory tests, there is a simple interaction between the antimicrobial and the microorganism. In the patient, however, the antimicrobial enters into highly complex interactions with the body and microorganism, a relationship entirely different from that in vitro. Furthermore, the eventual success of antimicrobial therapy in each case will be influenced by such factors as:

• the immune response of the host
• the type and site of pathological lesion
• the extent of inflammation
• the local circulation and capillary permeability
• the number of organisms present
• the bacterial virulence
• the ability of the antimicrobial to penetrate and concentrate in effective levels at the site of infection

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