Microbiology - Controlling Microbial Growth in the Body: Antimicrobial Drugs (Ch. 10)
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What is a structural analog?
A structural analog is a chemical that competes with a structurally similar molecule.
What are the six characteristics of an ideal antimicrobial agent?
- 1) Readily available
- 2) Inexpensive
- 3) Chemically stable (transportation and storage)
- 4) Easily administered
- 5) Nontoxic and nonallergenic
- 6) Selectively toxic against a wide range of pathogens
What is spectrum of action?
What two categories are there?
- Spectrum of action is the amount of different kinds of pathogens a drug acts against.
- The two main categories are:
- 1) Broad-spectrum drugs
- 2) Narrow-spectrum drugs
Why are broad-spectrum antimicrobials not always good to use?
Broad-spectrum antimicrobials can kill an excessive amount of pathogens, leading to very little competition for nutrients and space for the remaining pathogens (a reduction in microbial antagonism). Thus, the remaining microbes can colonize in large amounts, possibly leading to secondary- or even super-infections.
What does topical or local administration mean?
These refer to drugs that are applied directly to external infections.
What are the three possible routes drugs can be administered for internal infections?
- 1) Orally
- 2) Intravenously (IV)
- 3) Intramuscularly (IM)
What are R-plasmids?
What else are they known as?
They are extrachromosomal pieces of DNA containing genes for resistance to antimicrobial drugs that can be acquired via horizontal gene transfer.
*They are also known as R-factors.
What is cross resistance?
Cross resistance is a phenomenon in which resistance to one antimicrobial drug confers resistance to similar drugs.
What is synergism?
Synergism is the interplay between drugs that results in an efficacy that exceeds the efficacy of either drug one their own.
What class of drugs is used to inhibit the synthesis of fungal cell walls?
What sugar molecule is unique to fungal cell walls that this drug effects?
The sugar molecule is 1, 3-D-glucan, and it is not found in mammalian cells.
What type of cells can polyenes destroy?
How do they work?
- They can destroy fungal cells.
- They attach to ergosterol, a lipid constituent of fungal membranes, in the process disrupting the membrane and causing lysis of the cell.
What is a nucleotide analog?
A nucleotide analog is a compound that is structurally similar to a normal nucleotide and can be incorporated into DNA. This can lead to mismatched base pairing and thus destroy pathogens, particularly viruses.
What are the three main categories of adverse side effects?
- 1) Toxicity
- 2) Allergies
- 3) Disruption of normal microbiota
What are beta-lactams and how do they work?
(Give 2 examples)
Beta-lactams are one of the most prominent antimicrobial agents. They contain functional portions called beta-lactam (β-lactam) rings, which inhibit peptidoglycan formation by irreversibly binding to the enzymes that cross-link NAM subunits (these subunits are cross-linked by short peptide chains). Improperly formed peptidoglycan makes the cell more susceptible to the effects of osmotic pressure and cell eventually lyses.
*Penicillins and cephalosporins are two examples of beta-lactams.
What are three commons tests used to ascertain the efficacy of antimicrobials?
- 1) Diffusion-susceptibility test (Kirby-Bauer test)
- 2) Minimum Inhibitory Concentration Test (MIC)
- 3) Minimum Bacteriacidal Concentration Test (MBC)
What are the three horizontal gene transfer processes?
- 1) Transformation
- 2) Transduction
- 3) Conjunction
Describe the makeup of prokaryotic vs. eukaryotic ribosomes.
- Prokaryotic ribosomes - 70s with 30s and 50s subunits.
- Eukaryotic ribosomes - 80s with 60s and 40s subunits.
Why do drugs that act agains mycobacteria have to be administered for months or even years to be effective?
- Because drugs that work on inhibiting synthesis of cell walls only prevent bacteria from increasing the amount of cell wall material, and not on existing cell walls, they are only effective on the bacterial cells that are reproducing.
- Mycobacteria typically only reproduce every 12-24 hours (which is significantly slower than other types of bacteria), so drugs must be administered for a longer time to be effective.
How do azoles and allyamines work?
They inhibit the synthesis of ergosterol, which is needed to keep a fungal cell's membrane intact, so the fungal cell dies.
What class of drugs is commonly used to inhibit metabolic pathways in pathogens?
How does it work?
- They are structural analogs of para-aminobenzoic acid (PABA). PABA is needed for the synthesis of nucleotides required for DNA and RNA synthesis. Sulfonamides compete with PABA molecules for the active sites used in the production of dihydrofolic acid. (Dihydrofolic acid is later converted into tetrahydrofolic acid (THF) and used as a coenzyme in the synthesis of purine and pyrimidine nucleotides). Thus, DNA and RNA production is decreased and eventually cell metabolism ceases, leading to the death of the cell.
What is selective toxicity?
Selective toxicity is the principle by which an effective antimicrobial agent must be more toxic to a pathogen than to the pathogen's host.
Who was Paul Ehrlich?
He was a visionary German scientist who proposed the term chemotherapy to describe the use of chemicals that could selectively kill pathogens while having little or no effect on the patient.
*Popularized the concept of a "magic bullet"
What are synthetics?
Synthetics are antimicrobials that are completely synthesized in a laboratory.
About what fraction of children born in the early 1900's died from infectious disease before the age of 5?
What are drugs?
Drugs are chemicals that affect physiology in any manner.
What are chemotherapeutic agents?
Chemotherapeutic agents are drugs that act against diseases.
What are antimicrobial agents?
What is another term for them?
Antimicrobial agents are chemotherapeutic agents used to treat microbial infection.
*They are also known as antimicrobials.
What drugs work by inhibiting protein synthesis in prokaryotic pathogens?
- 1) Aminoglyosides
- 2) Tetracyclines
- 3) Lincosamides
- 4) Streptogramins
- 5) Macrolides
- 6) Oxazolidinones
- 7) Antisense Nucleic Acids
What are vancomycins and cycloserines?
They are two different antimicrobial drugs that disrupt the formation of gram-positive cell walls by interfering with particular alanine-alanine bridges that link NAM subunits.
The drugs isoniazed (INH) and ethambutol only work on which genus of bacteria? Why?
They only work on mycobacterium, most notably the agents of leprosy and tuberculosis. This is because their complex walls have a layer of arabinogalactan-mycolic acid (in addition to the usual peptidoglycan layer). These drugs disrupt that layer.
What are the six mechanisms of action of antimicrobial drugs?
- 1) Inhibition of cell wall synthesis
- 2) Inhibition of protein synthesis
- 3) Inhibition of a general metabolic pathway
- 4) Inhibition of DNA or RNA synthesis
- 5) Inhibition of a pathogen's attachment to, or recognition of, a host
- 6) Disruption of cytoplasmic membrane
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