Pharm 4 Exam I Flashcards

(78 cards)

1
Q

Define MIC

A

Minimum Inhibitory Concentration- Minimum concentration of a drug that will inhibit the growth of a pathogen after 18-24 hours of incubation in vitro.

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2
Q

When is a pathogen considered sensitive to a drug?

A

If the concentration of the drug that will inhibit the growth of a pathogen is low

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3
Q

When is a pathogen considered resistant to a drug?

A

If the minimum concentration of drug needed to inhibit the growth of the pathogen is high.

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4
Q

Define time dependent bactericidal agents

A

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

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5
Q

Define concentration dependent bactericidal agents

A

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

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6
Q

Define MBC

A

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.

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7
Q

Why do bacteriostatic drugs require an intact immune system?

A

Because they do not kill the existing microorganism only prevent multiplication.

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8
Q

Characteristics of the GN cell wall

A
  • 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
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9
Q

What is important pharmacologically about the Porin pores?

A

Through them hydrophilic abx can gain access to the murein layer of GN bacteria

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10
Q

Characteristics of GP cell wall

A
  • Cell wall is a thick coat of murein which is porous.
  • Murein layer is thicker than GN
  • No outer membrane
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11
Q

Three major phases of bacterial cell wall synthesis

A
    1. Synthesis of murein monomers from amino acids
    1. Polymerization of the murein monomers into peptidoglycan polymers
    1. Crosslinking of the polymers
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12
Q

Describe the first step in bacterial cell wall synthesis. Synthesis of murein monomers.

A
  • 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
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13
Q

Describe the second step in bacterial cell wall synthesis. Polymerization.

A
  • 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
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14
Q

Describe the third step in bacterial was synthesis. Crosslinking of the polymers.

A
  • 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
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15
Q

What is another name for transpeptidase?

A

Penicillin binding proteins (PBP)

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16
Q

What do transpeptidases

A

Form an intermediate that can attach and form a crosslink.

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17
Q

What do autolysins do?

A

They punch small holes in the peptidoglycan wall which allow for remodeling to occur

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18
Q

If murein synthesis is blocked then what else is blocked

A

Mediated autolysis and cell wall synthesis

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19
Q

Compare the bacterial RNA polymerase to that of human cells

A
  • Bacteria only 1 RNA polymerase is present which has 5 subunits
  • Humans have 3 RNA polymerases which are much more complex
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20
Q

Which two enzymes are required for bacterial gene expression?

A
  • RNA polymerase

- DNA topoisomerase

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21
Q

What is the function of DNA topoisomerase?

A
  • To regulate the coiling of DNA. Thus bacterial ribosomes can be targets for selective abx.
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22
Q

What are the stages of bacterial transcription?

A
    1. Initiation - RNA polymerase separates a section of DNA
    1. Elongation - RNA polymerase synthesizes complementary DNA strand
    1. Termination - A termination sequence is reached on the mRNA
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23
Q

What are the subunits of 70S ribosomes and their functions?

A
  • 30S subunit is responsible for decoding the mRNA

- 50S subunit catalyzes the peptide bond formation.

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24
Q

Define bacterial resistance

A

Bacterial growth is not halted by the maximum abx that can be tolerated

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25
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
26
Which drugs are inhibitors of topoisomerase
Floroquinolones
27
MOA of flouroquinolones
GN - Eliminate DNA gyrase | GP - Eliminate topoisomerase IV
28
Contraindications of flouroquinolones
- Pregnancy | - Children - causes joint pain
29
Side effects of flouroquinolones
- Well tolerated | - Tendon rupture
30
How do flouroquinolones enter the cell?
By passive diffusion through the pores of the outer membrane
31
What is the function of the topoisomerases
They change the configuration of DNA by cutting, passing through and the resealing DNA
32
Which drugs are inhibitors of bacterial RNA synthesis?
Rifamycins
33
MOA of Rifamycins
- They form a complex with bacterial DNA independent of RNA polymerase - This prevents initiation of RNA synthesis (not elongation)
34
Contraindications of Rifamycins
None
35
Side effects of rifamycins
- Discoloration of secretions | - Cholestatic jaundice and hepatitis
36
Which antibiotics are inhibitors of translocation?
Lincosamides
37
MOA of Lincosomides
- Bind to 23S rRNA molecule of the 50S subunit - Inhibit peptidyl transferase - Blocks elongation, meaning it blocks the transfer of amino acids to the peptide chain
38
Contraindications of Liconsamides
None
39
Side effects of lincosamides
- Pseudomembranous colitis | - They can wipe out normal flora allowing pathogenic flora to grow
40
Which drugs target the 30S RSU?
- Aminoglycosides | - Tetracyclines
41
MOA of Aminoglycosides
- Create pores in the outer membrane - Bind irreversibly to the 30S RSU - Interferes with the function of the ribosome causing the 30S RSU to misread mRNA
42
Contraindications for Aminoglycosides
Renal dysfunction
43
Side effects of aminoglycosides
- Ototoxicity | - Nephrotoxicity
44
MOA of tetracyclines
- Bind reversibly to 16S subunit of the 30S RSU - Inhibits translation by blocking tRNA to the A site of mRNA - Weakens ribosome tRNA interaction
45
Contraindications of tetracyclines
- Pregnancy, lactation | - Children under 8 because of tooth discoloration
46
Side effects
- GI nausea and vomiting | - Mottling of teeth because of calcium binding
47
Which drugs target the 50S RSU?
- Macrolides | - Oxazolidinodes
48
MOA of Oxazolidinones
- Inhibits the formation of the 70S RSU - Bind to the 23 rRNA site on the 50S RSU near the interface with the 30S - Inhibits translocation/ protein synthesis
49
Contraindications of oxazolidinones
None
50
Side effects of Oxazolidinones
- Serotonin syndrome | - Hyperlactemia and metabolic acidosis
51
MOA of macrolides
- Bind reversibly to the 23S subunit on the 50S RSU - Inhibit peptidyl transferase which blocks the binding of amino acids onto the peptide chain - Inhibits translocation
52
Contraindications of macrolides
Hepatic dysfunction
53
Side effects of macrolides
- Significant increase in gut motility | - Acute cholestatic hepatitis
54
Which genetic inhibitors are bacteriostatic?
- Tetracycline - Lincosamides - Macrolides - Oxazolidinones
55
Which genetic inhibitors are bactericidal?
- Fluroquinolones - Rifamycins - Aminoglycosides
56
What are the subclasses of Beta Lactams
- Penicillins - Cephalosporins - Monobactam - Carbapenem
57
Beta lactams are effective only against organisms which are doing what?
Actively proliferating
58
MOA of beta lactams
- Interfere with the last step in bacterial wall synthesis (crosslinking) - Bind to PBP's (transpeptidases) - Expose the membrane to autolysins
59
Beta lactams are effective on GN or GP?
GP because they have a thick peptidoglycan layer. GN are protected by the liposaccharide layer
60
Contraindications of penicillins
Hypersensitivity allergy
61
Side effects of penicillins
Hypersensitivity rash
62
What are beta lactamases?
Antibiotic inactivating enzymes
63
MOA of beta lactamases?
Hydolytically inactivate beta lactam rings of penicillins and cephalosporins
64
How are cephalosporins different chemically from penicillins?
They have a 6 member core instead of a 5 member core
65
How are cephalosporins classified?
1st - 4th generation based on susceptibility to beta lactamases. 1st is narrow spectrum 4th is broad spectrum (IV only)
66
Contraindications for cephalosporins
Anaphylaxis to penicillin
67
Side effects of cephalosporins
- Bone marrow suppression - Nephrotoxicity - Pseudomembranous toxicity
68
Contraindications of carbapenems
``` Seizure activity (Imipenum) ```
69
Side effects of Carbapenems
- N/V - Neurotoxicity - Fever
70
Which drugs are inhibitors of murein polymer synthesis?
Glycopeptides
71
MOA of glycopeptides
- Bind to the D-ALA-D-ALA terminus of the murein monomer - Inhibit transglycosidase - Block the action of murein units
72
Contraindications of Glycopeptides
None
73
Side Effects of glycopeptides
- Flushing | - Ototoxicity
74
Which type of bacteria are glycopeptides effective against, GN or GP?
GP because GN have a liposaccaride layer that covers and protects the peptidoglycan layer
75
MOA of Sulfonamides
- Compete with the substrate for the bacterial enzyme dihydropteroate synthase - Inhibits the synthesis of tetrhydrofolte (THF)
76
Contraindications of Sulfonamides
Allergy to sulfa antibiotics
77
Side effects of Folate Sulfonamides
- Precipitate urine - N/V/D - Photosensitivity
78
Which drugs are Folate Synthesis Inhibitors?
Sulfonamides