Pharm 4 Exam I Flashcards
Define MIC
Minimum Inhibitory Concentration- Minimum concentration of a drug that will inhibit the growth of a pathogen after 18-24 hours of incubation in vitro.
When is a pathogen considered sensitive to a drug?
If the concentration of the drug that will inhibit the growth of a pathogen is low
When is a pathogen considered resistant to a drug?
If the minimum concentration of drug needed to inhibit the growth of the pathogen is high.
Define time dependent bactericidal agents
Drugs that exhibit a constant rate of killing independent of its concentration as long the drug concentration is greater than the MBC. Ex Beta lactam
Define concentration dependent bactericidal agents
Drugs that exhibit rate of killing that increases with the concentration of the drug as long as the drug concentration is greater than the MBC. Ex. Vancomycin and Aminoglycosides
Define MBC
Minimum Bactericidal Concentration - The lowest drug level at which 99.9% of a culture of bacteria or other microorganisms is killed after 18-24 hours incubation in vitro.
Why do bacteriostatic drugs require an intact immune system?
Because they do not kill the existing microorganism only prevent multiplication.
Characteristics of the GN cell wall
- Second lipid bilayer called the outer membrane which hinders hydrophilic molecules
- Has Porin pores that transverse the outer membrane
- The murein layer is porous enough to allow hydrophilic molecules to pass through
What is important pharmacologically about the Porin pores?
Through them hydrophilic abx can gain access to the murein layer of GN bacteria
Characteristics of GP cell wall
- Cell wall is a thick coat of murein which is porous.
- Murein layer is thicker than GN
- No outer membrane
Three major phases of bacterial cell wall synthesis
- Synthesis of murein monomers from amino acids
- Polymerization of the murein monomers into peptidoglycan polymers
- Crosslinking of the polymers
Describe the first step in bacterial cell wall synthesis. Synthesis of murein monomers.
- Synthesis of murein monomers from amino acids
- Takes place in the cytoplasm
- Begins with the modification of glucose into NAG and NAM
- Next the peptide component is added by a series of peptide transferases
Describe the second step in bacterial cell wall synthesis. Polymerization.
- Polymerization of the murein monomers into peptidoglycan polymers
- Occurs in the cytoplasmic membrane
- murein monomers are ferried across the lipid bilayer, assisted by phosphorylated bactoprenol
- In the periplasmic space the monomer is attached to the chain via bonds between NAM and NAG
- This is catalyzed by transglycosydase
Describe the third step in bacterial was synthesis. Crosslinking of the polymers.
- Crosslinking of the polymers occurs in the paraplasmic space (between the cytoplasmic membrane and the murein layer)
- Murein chains are crosslinked to one another by transpeptidease enzymes
What is another name for transpeptidase?
Penicillin binding proteins (PBP)
What do transpeptidases
Form an intermediate that can attach and form a crosslink.
What do autolysins do?
They punch small holes in the peptidoglycan wall which allow for remodeling to occur
If murein synthesis is blocked then what else is blocked
Mediated autolysis and cell wall synthesis
Compare the bacterial RNA polymerase to that of human cells
- Bacteria only 1 RNA polymerase is present which has 5 subunits
- Humans have 3 RNA polymerases which are much more complex
Which two enzymes are required for bacterial gene expression?
- RNA polymerase
- DNA topoisomerase
What is the function of DNA topoisomerase?
- To regulate the coiling of DNA. Thus bacterial ribosomes can be targets for selective abx.
What are the stages of bacterial transcription?
- Initiation - RNA polymerase separates a section of DNA
- Elongation - RNA polymerase synthesizes complementary DNA strand
- Termination - A termination sequence is reached on the mRNA
What are the subunits of 70S ribosomes and their functions?
- 30S subunit is responsible for decoding the mRNA
- 50S subunit catalyzes the peptide bond formation.
Define bacterial resistance
Bacterial growth is not halted by the maximum abx that can be tolerated
Methods of bacteria developing resistance
- Spontaneous mutations of DNA
- DNA transfers from one bacterium to another
- Resistance encoded R factors (resistance plasmids)
- Efflux pumps
- Enzyme inactivation
Which drugs are inhibitors of topoisomerase
Floroquinolones
MOA of flouroquinolones
GN - Eliminate DNA gyrase
GP - Eliminate topoisomerase IV
Contraindications of flouroquinolones
- Pregnancy
- Children - causes joint pain
Side effects of flouroquinolones
- Well tolerated
- Tendon rupture
How do flouroquinolones enter the cell?
By passive diffusion through the pores of the outer membrane
What is the function of the topoisomerases
They change the configuration of DNA by cutting, passing through and the resealing DNA