Micro Final - Chapter 9

Front 1

chemotherapeutic agents

Back 1

- chemical agents used to treat disease

- destroy pathogenic microbes or inhibit their growth within a host

- most are antibiotics

> microbial products or their derivitives that kill suceptible microbes or inhibit their growth

Front 2

sources of antimicrobial drugs

Back 2

1. natural products from bacteria and fungi

2. synthetic products

3. semi-synthetic products

- natural antibiotics modified to improve stability in the body

Front 3

selective toxicity (definition)

Back 3

the ability of a drug to kill or inhibit a pathogen while damaging the host as little as possible

Front 4

therapeutic dose (definition)

Back 4

the drug level required for clinical treatment

Front 5

toxic dose (definition)

Back 5

the drug level at which the drug becomes too toxic for the patient (ie. produces side effects)

Front 6

therapeutic index (definition)

Back 6

ratio of toxic dose to therapeutic dose

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side effects (definition)

Back 7

undesirable effects of a drug on host cells

Front 8

narrow-spectrum drugs (definition)

Back 8

attack only a few different pathogens

Front 9

broad-spectrum drugs (definition)

Back 9

attack many different pathogens

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cidal agent

Back 10

kills microbes

Front 11

static agent

Back 11

inhibits the growth of microbes

Front 12

measuring the effectiveness of antimicrobial drugs

Back 12

effectiveness is expressed in 2 ways:

1. minimal inhibitory concentration (MIC)

2. minimal lethal concentration (MLC)

Front 13

minimal inhibitory concentration (definition)

Back 13

the lowest concentration of a drug that inhibits a pathogen

Front 14

minimal lethal concentration (definition)

Back 14

the lowest concentration of a drug that kills a pathogen

Front 15

dilution susceptability tests

Back 15

- involves inoculating media containing different concentrations of a drug

- the broth or agar with the lowest concentration showing no growth in the MIC

- if broth is used, tubes showing no growth can be subcultured into drug-free medium

> the broth from which a microbe can't be recovered is the MLC

Front 16

disk diffusion tests

Back 16

1. disks impregnated with specific drugs are placed on agar plates inoculated with a test microbe (bacterial lawn)

2. drug diffuses from disk into agar, establishing a concentration gradient

3. observe the clear zones (no growth) around the disks (zone of inhibition)

Front 17

the Kirby-Bauer method

Back 17

a standardized method for the disk diffusion test

- the sensitivity/resistance is determined using tables relating zone diameter with microbial resistance

Front 18

the E-test

Back 18

- convenient for use with anaerobic pathogens

- similar to disk diffusion method, but uses strips rather than disks

- intersection of elliptical zone of inhibition with strip indicates MIC

Front 19

mechanisms of action of antimicrobial drugs: inhibitors of cell wall synthesis

Back 19

- most sensitive; high therapeutic index

- penicillin's

> most are 6-aminopenicillianic acid derivatives and differ in the side chain attached to the amino group

> most crucial feature of the molecule is the B-lactam ring

> essential for bioactivity

> many penicillin resistant organisms produce B-lactamase (penicillinase) which hydrolyzes a bond in this ring

Front 20

penicillins: mode of action

Back 20

1. blocks the enzyme that catalyzes transpeptidation (the formation of cross-links in peptidoglycan)

2. prevents the synthesis of complete cell walls leading to lysis of cells

3. acts only on growing bacteria that are synthesizing new peptidoglycan

4. binds to periplasmic proteins (penicillin-binding proteins aka PBP's)

5. may activate bacterial autolysins and murein hydrolases

6. stimulate bacterial holins to form holes or lesions in the plasma membrane

Front 21

penicillin V

Back 21

- naturally occurring

- narrow-spectrum

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penicillin G

Back 22

- naturally occurring

- narrow-spectrum

Front 23

semi-synthetic penicillins

Back 23

have a broader spectrum than naturally occurring ones

Front 24

issues with penicillin

Back 24

- resistance to penicillins, including semi synthetic analogs, continues to be a problem

- roughly 1-5% of adults in the US are allergic to penicillin

> the allergy can lead to a violent allergic response and death

Front 25

cephalosporins

Back 25

- orginally isolated from the fungus Cephalosporium

- structually and functionally similar to penicillins

- broad-spectrum antibiotics that can be used by most patients that are allergic to penicillins

Front 26

the 4 categories of cephalosporins (based on their spectrum of activity)

Back 26

1. cephalothin

2. cefoxitin

3. cefoperazone

4. ceftriaxone

Front 27

vancomycin

Back 27

- glycopeptide antibiotic

- inhibit cell wall synthesis

- binds to the D-alanyl-D-alanine terminal sequence of peptidoglycan

Front 28

teicoplanin

Back 28

- glycopeptide antibiotics

- inhibit cell wall synthesis

Front 29

protein synthesis inhibitors

Back 29

- many antibiotics bind specifically to the bacterial ribosome

> binding can be to the 30S (small) or 50S (large) ribosomal subunit

- other antibiotics inhibit a step in protein synthesis

> aminoacyl-tRNA binding, peptide bond formation, mRNA reading, translocation

Front 30

aminoglycoside antibiotics

Back 30

- large group all with a cyclohexane ring and amino sugars

- bactericidal

Front 31

aminoglycoside antibiotic mechanism

Back 31

1. bind to the 30S ribosomal subunit

2. the ribosome incorportates the incorrect amino acids

3. the protein cannot fold correctly

Front 32

tetracyclines: structure

Back 32

all have a 4 ring structure to which a variety of side chains are attached

Front 33

tetracyclines

Back 33

- broad-spectrum

- bacteriostatic

- sometimes used to treat acne

Front 34

tetracyclines: mechanism

Back 34

1. combine with the 30S ribosomal subunit

2. inhibits binding of aminoacyl-tRNA molecules to the A site of the ribosome

Front 35

macrolides

Back 35

contain 12- to 22-carbon lactone rings linked to one or more sugars

Front 36

macrolides (e.g Erythromycin)

Back 36

- broad-spectrum

- usually bacteriostatic

- used for patients allergic to penicillin

Front 37

macrolides (e.g Erythromycin): mechanism

Back 37

1. binds to the 23S rRNA of the 50S ribosomal subunit

2. inhibits peptide chain elongation

Front 38

how is the mechanism by which aminoglycosides block synthesis similar to that of the tetracyclines?

(3 ways)

Back 38

1. both act on the 30S subunit

2. aminoglycosides cause tRNA mismatching

3. tetracyclines block tRNA entry

Front 39

lincosamines: mechanism

Back 39

interferes with protein synthesis in microbes

Front 40

lincosamines are produced by

Back 40

the Streptomyces bacteria

Front 41

lincosamines antibiotic activity

Back 41

- broad-spectrum against anaerobic microbes

- less activity against aerobes

Front 42

why are lincosamines used sparingly

Back 42

they can support (indirectly) the growth of C. diff which can result in other disease states

Front 43

chloramphenicol was originally isolated from

Back 43

Streptomyces venezuelae but is now chemically synthesized

Front 44

chloramphenicol: mechanism

Back 44

1. binds to 23S rRNA on the 50S ribosomal subunit

2. inhibits peptidyl transferase reaction

Front 45

when is chloramphenicol used and why

Back 45

only used in life-threatening situations because it is seriously toxic and has numerous side effects

Front 46

metabolic antagonists act as

Back 46

antimetabolites

- antagonize or block the functioning of metabolic pathways by competitively inhibiting the use of metabolites by key enzymes

Front 47

metabolic antagonists are

Back 47

structural analogs

- molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates

- block normal cellular metabolism

Front 48

sulfonamides or sulfa drugs: structure

Back 48

- structurally related to sulfanilamide, a p-aminobenzoic acid (PABA) analog

> PABA is used for the synthesis of folic acid and is made by many pathogens

Front 49

sulfa drugs are

Back 49

selectively toxic due to the competitive inhibition of folic acid synthesis enzymes

Front 50

trimethoprim is a

Back 50

synthetic antibiotic that interferes with folic acid production

Front 51

antibiotic activity of trimethoprim

Back 51

- broad-spectrum

Front 52

trimethoprim can be combined with

Back 52

sulfa drugs

- to increase the efficacy of the treatment

- the combination blocks 2 steps in the folic acid pathway

Front 53

side effects of trimethoprim

Back 53

1. abdominal pain

2. photo sensitivity reactions

Front 54

nucleic acid synthesis inhibition: mechanisms

Back 54

1. block DNA replication

- inhibition of DNA polymerase

- inhibition of DNA helicase

2. block transcription

- inhibition of RNA polymerase

Front 55

nucleic acid synthesis inhibition

Back 55

drugs not as selectively toxic as other antibiotics because bacteria and eukaryotes do not differ greatly in the way they synthesis nucelic acids

Front 56

quinolones

Back 56

- broad-spectrum, bactericidal, synthetic drugs containing the 4-quinolone ring

Front 57

quinolones: mechanism

Back 57

act by inhibiting bacterial DNA-gyrase and topoisomerase II

Front 58

antifungal drugs

Back 58

- fewer effective agents because of similarity of eukaryotic fungal cells and human cells

> many have a low therapeutic index and are toxic

- fungi are able to degrade many compounds including drugs

- it is easier to treat superficial mycoses than systemic infections

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treating superficial mycoses (ex. Candida, atheletes foot)

Back 59

- topical and oral

- mechanisms:

1. disrupts membrane permeability and inhibit sterol synthesis

2. disrupts mitotic spindle; may inhibit protein and DNA synthesis

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treating systemic mycoses

Back 60

- difficult to control and can be fatal

- 3 common drugs:

1. amphotericin B

> binds sterols in membrane

2. 5-flucytosine

> disrupts RNA functions

3. fluconazole

Front 61

treating mycoses: amphotericin B

Back 61

1. binds to ergosterol and damages membranes

2. administered orally

3. stays in suspension

4. poorly absorbed

5. stable in GI tract

6. for GI tract infections

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treating mycoses: nystatin

Back 62

1. binds to ergosterol and damages membranes

2. administered IV

3. serious side effects

4. for systemic infections

Front 63

antiviral drugs: drug development

Back 63

- drug development has been slow because it is difficult to specifically target viral replication

- drugs currently used inhibit virus-specific enzymes and life cycle processes

Front 64

antiviral drugs: amantidine

Back 64

- used to prevent influenza infections

- blocks penetration and uncoating of influenza virus

Front 65

antiviral drugs: adenine arabinoside (vidarabine)

Back 65

- inhibits herpes virus enzymes involved in DNA and RNA synthesis and function

Front 66

antiviral drugs: tamiflu

Back 66

- anti-influenza agent

- a neuraminidase inhibitor

> essential for release of new particles from infected cell

- not a cure

- leads to resistant viruses

- prescribed prophylactically

Front 67

anti-HIV drugs: azidothymidine (AZT)

Back 67

nucleoside reverse transcriptase inhibitors

Front 68

anti-HIV drugs: ritonavir

Back 68

- viral protease inhibitor

> mimic peptide bond that is normally attacked by the protease

Front 69

anti-HIV drugs: fusion inhibitors

Back 69

prevent HIV entry into the cell

Front 70

most effective HIV drugs

Back 70

drug cocktails to curtail resistance

Front 71

1. infection begins with HIV fusion

Back 71

fusion inhibitors block this step

Front 72

2. once inside a host cell, HIV uncoats and its reverse transcriptase forces the host to make DNA from the viral RNA

Back 72

RT inhibitors block this step

Front 73

3. the viral DNA is transcribed and translated into a linear polypeptide that is cut to release viral proteins

Back 73

protease inhibitors block this step

Front 74

4. viral DNA is added to the host DNA by the action of a viral integrase

Back 74

integrase inhibitors block this step

Front 75

why is malaria, like AIDS, now treated with several drugs simultaneously?

Back 75

many strains of the malaria parasite are resistant to drugs that used to be effective. Now single drugs are no longer effective. Furthermore, the use of multiple drugs require multiple mutations to occur simultaneously which is hoped to reduce the chance of resistance of occurring again

Front 76

antiprotozoan drugs: mechanism

Back 76

the mechanism of antiprotozoan drugs is not known

Front 77

what special considerations must to taken into account when treating infections caused by protozoan parasites?

Back 77

protozoan parasites are geographically endemic, and each variety may need it's own drug

Front 78

ability of a drug to reach the site of infection depends on:

Back 78

mode of administration: oral, topical, or parenteral (non oral)

Front 79

factors influencing the ability of a drug to reach concentrations exceeding the MIC

Back 79

1. amount administered

2. route of administration

3. speed of uptake

4. rate of clearance (elimination) from the body

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drugs resistance is an increasing problem because...

Back 80

1. once resistance originates in a population, it can be transmitted to other bacteria

2. a particular type of resistance mechanism is not confirmed to a single class of drugs

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drug resistance mutants arise...

Back 81

spontaneously and are then selected

Front 82

microbes in ______ or ______ may be growing ______ and not be _______

Back 82

abscesses, biofilms, slowly, susceptible

Front 83

development of a resistant strain of bacteria

Back 83

1. a population of microbial cells that contains both drug-sensitive cells and drug-resistant cells is exposed to the drug

2. drug-sensitive cells are inhibited by the exposure to the drug

3. the remaining drug-resistant cells grow over time

4. resulting in a population of (mostly) drug-resistant cells

Front 84

overcoming drug resistance

Back 84

1. give drug in appropriate concentrations to destroy susceptible

2. give 2 or more drugs at the same time

3. use drugs only when necessary