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Flashcards in Pharm 4 Exam I Deck (78):
1

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.

2

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

3

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.

4

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

5

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

6

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.

7

Why do bacteriostatic drugs require an intact immune system?

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

8

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

9

What is important pharmacologically about the Porin pores?

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

10

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

11

Three major phases of bacterial cell wall synthesis

- 1. Synthesis of murein monomers from amino acids
- 2. Polymerization of the murein monomers into peptidoglycan polymers
- 3. Crosslinking of the polymers

12

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

13

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

14

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

15

What is another name for transpeptidase?

Penicillin binding proteins (PBP)

16

What do transpeptidases

Form an intermediate that can attach and form a crosslink.

17

What do autolysins do?

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

18

If murein synthesis is blocked then what else is blocked

Mediated autolysis and cell wall synthesis

19

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

20

Which two enzymes are required for bacterial gene expression?

- RNA polymerase
- DNA topoisomerase

21

What is the function of DNA topoisomerase?

- To regulate the coiling of DNA. Thus bacterial ribosomes can be targets for selective abx.

22

What are the stages of bacterial transcription?

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

23

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.

24

Define bacterial resistance

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

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