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General Concepts
Dean's Slides - Lecture 7
30
Pharmacology
Professional
01/26/2013

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Term
What is selective toxicity?
Definition
= selectivity - better able to kill bacteria over host cells.
Higher = more selectively toxic against microbe.
Term
What is the MoA of penicillins?
Definition
Cell wall inhibitors - eukaryotes have no cell wall!
Term
What is the MoA of erythromycin and tetracycline?
Definition
Inhibit protein synthesis
Term
What is the MoA of amphotericinB?
Definition
Inhibits cell membrane function. Both eukaryotes and prokaryotes have cell membranes = low selectivity
Term
What is therapeutic ratio?
Definition
AKA therapeutic index - ratio of toxic dose to effective dose: Toxic/Therapeutic.
**Want toxic dose to be high, and therapeutic dose to be low. IF they are close to each other, we get a narrow therapeutic index.
Term
How does TI relate to selectivity?
Definition
- Direct relationship - goes in the same direction (positive or negative)
- Indirect - opposite directions
Term
What antibiotics affect protein synthesis?
Definition
- Chloramphenicol - inhibits 50S
- Erythromycin - Inhibits 50S
- Aminoglycosides - Inhibits 30S
- Tetracycline - inhibits aminoacyl, stopping tRNA from binding to ribosome
Term
What is the difference between a 'static' and a 'cidal' antibiotic?
Definition
- Static - Inhibits replication, relying on host to kill the cells
- Cidal - directly kills microbes. For severe infections and the immunocompromised.
Term
How does the growth curve affect antibiotics?
Definition
The log/exponential phase is when organisms multiply, and when antibiotics should be taken. Since we don't know phase of growth, always take antibiotic for the prescribed time
Term
What is MIC and MBC?
Definition
- MIC - Minimum amount required to stop growth of organism. Target = 10*MIC
- MBC - minimum amount to kill organism
Term
How does protein binding affect antibiotics?
Definition
Inactivates them, but if the 1% that is not reaches 10*MIC, it is effective.
Term
What is a superinfection?
Definition
Overgrowth, usually by yeast, seen with broad spectrum antibiotics - disturbs normal flora.
Term
What is the break point?
Definition
The MIC needed to determine susceptibility. Either susceptible, intermediate, resistant
Term
What is intracellular killing?
Definition
Organisms hide inside macrophages - Mycobacterium tuberculosis and Legionella pneumophila
**FQNs can kill the organisms
Term
What is the post antibiotic effect?
Definition
Suppression of an organism after exposure and removal of an antibiotic. Seen in antibiotics that inhibit DNA or protein synthesis - against gram(-)
Term
What are L-cells?
Definition
Microbes without cell walls - Mycoplasma pneumoniae. Penicillins will not work.
Term
What are the different spectrums of an antibiotic?
Definition
- Narrow - Works on either gram(+) or gram(-)
- Intermediate - gram(+) or gram (-) with some extended activity. 1st gen cephalosporins
- Broad - gram(+) and gram(-)
Term
What is the plate diffusion test?
Definition
Zone of inhibition is directly proportional to log of antibiotic concentration.
**Less contamination, quick, easy
Term
What is the serial dilution test?
Definition
Series of tubes with 2x conc. of antibiotics - determines the MIC and can be cultured to determine MBC
** determine MIC, very sensitive,
Term
How is serial dilution a good test?
Definition
Can test several organisms by streak, rarely contaminated, quick, can determine MIC
Term
What are the 3 mechanisms of drug resistance?
Definition
- Mutation - change in gene sequence. Not from antibiotics.
- Recombination - usually conjugation, takes up long pieces of chromosome.
- Acquisition of plasmids - episomes can attach to chromosomes. Often code for resistance.
Term
What are the components of a plasmid?
Definition
- Transfer unit - contains a gene, RTF, that directs transfer during conjugation
- R-determinant - contains genetic determinants. Can exist without transfer unit
Term
What is the biochemical basis of resistance?
Definition
- Decr permeability - most common mechanism, decreased uptake/incr efflux
- Enzyme inactivation
- Alteration at target site - competing substances (PABA and sulfa) or drug receptor (Reductase instead of synthetase in sulfa)
- Decreased receptor affinity for drug - ribosome modified, PBPs larger, DNA-gyrase (FQNs)
Term
What agents act on DNA?
Definition
Griseofulvin
Metronidazole
FQNs
Term
What agents inhibit protein synthesis?
Definition
- 50s - Chloramphenicol, macrolides
- 30S - Tetracyclines - static
- 30S - Aminoglycosides - Cidal
Term
What agents affect cell wall synthesis?
Definition
Cephalosporins
Penicillins
Vancomycin
Term
What agents affect the cell membrane?
Definition
Polymyxin
AmphotericinB
Nystatin
Ketoconazole
Term
What agents block metabolic steps in microorganisms?
Definition
- Sulfa - inhibits PABA so the bug does not get folic acid
Term
What is an ideal antibiotic?
Definition
- Broad spectrum and cidal
- Low toxic
- Stable, water soluble, acid stable
Term
What are the rules for antibiotic combination?
Definition
- Static + Static = additive
- Cidal + static = Antagonistic
- Cidal + Cidal = synergism
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