Medchem Lecture 19

Front 1

microbial metabolites or synthetic analogues inspired by them that inhibit the growth and survival of microorganisms without serious toxicity to the host

Back 1

antibiotics

Front 2

_______ _______ is the key concept of antibiotics

Back 2

selective toxicity

Front 3

Initially extracts of _________ were screened simply for their ability to kill pathogenic microorganism in vitro... those that did were pushed through complex tests in attempts to discover clinically useful agents

Back 3

fermentations

Front 4

______ ________ _______ coupled with high throughput screening make it possible to screen hundreds of thousands of compounds for antimicrobial activity in a short time

Back 4

combinatorial chemical synthesis

Front 5

Some bacteria are immune to treatment from the outset because of what two reason?

Back 5

1. they do not take up the antibiotic
2. they lack the susceptible target

Front 6

Almost all antibiotics have the capacity to be ________ in vitro

Back 6

bactericidal

Front 7

To kill bacteria if the concentration or dose is sufficiently high

Back 7

bactericidal

Front 8

At lower concentrations bacterial multiplication is prevented even though the microorganism remains viable... what type of action?

Back 8

bacteriostatic action

Front 9

The smallest concentration that will kill a bacterial colony is the ________ bactericidal concentration

Back 9

minimum

Front 10

What is the difference between a minimum bactericidal dose and a bacteriostatic dose?

Back 10

characteristic of given families of antibiotics

Front 11

What happens if a bacteriostatic antibiotic is withdrawn prematurely from a patient?

Back 11

microorganism can resume growth and infection can reestablish itself because the culture is still alive

Front 12

This type of agent will interrupt the fulminating state (rapid growth) and give the immune system a chance to deal with the disease, with cure usually following

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bacteriostatic agent

Front 13

The first concentration which produces no visible growth is known as

Back 13

minimum inhibitory concentration (MIC)

Front 14

The last concentration that produces no visible growth is known as

Back 14

minimum bactericidal concentration (MBC)

Front 15

What two factors helps determine which antibiotics are the best choice for certain diseases?

Back 15

1. determining the specific disease
2. what susceptibility patterns are exhibited by the causative microorganism

Front 16

Individual species of bacteria are associated with particular infective diseases and the specific antibiotics are more likely to be useful than others for killing them... this is known as

Back 16

empiric-based theory

Front 17

These antibiotics are derived from fungi and have names ending in the suffix -cillin

Back 17

penicillins

Front 18

These antibiotics are also fungal products and have names beginning with the prefix -cef

Back 18

cephalosporins

Front 19

These synthetic antibiotics have names that mostly end in the suffix -floxacin

Back 19

fluoroquinolones

Front 20

Some antibiotics are produced by fermentation of soil microorganisms belonging to various streptomyces species with names ending in suffix

Back 20

-mycin
*streptomycin

Front 21

Other antibiotics are produced by fermentation of various soil microbes known as micromonospora species and have names ending in suffix

Back 21

-micin
*gentamicin

Front 22

Some antimicrobial families have the potential of inhibiting a wide range of bacterial genera belonging to both gram+ and gram- cultures and are called what

Back 22

broad spectrum antibiotics

Front 23

Some antimicrobial families only inhibit a few bacterial genera and are called what

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narrow spectrum antibiotic

Front 24

The failure of microbes to be killed or inhibited by treatment. Can be INTRINSIC or ACQUIRED

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resistance

Front 25

When bacteria may not all be killed and survivors are thought to have been resting during the drug treatment time and therefore remain viable when tested subsequently

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persistence

Front 26

Some antibiotics exert a significant toxicity to certain microorganisms that persists for a time after the drug is withdrawn and the concentration of drug in the blood falls below the MIC

Back 26

postantibiotic effect

Front 27

Associated primarily with β-lactam antibiotics. It is a phenomenon in which low doses in vitro against certain bacteria (staphylococci and streptococci) produce lysis, whereas higher doses do not.

Back 27

biphasic ("eagle") effect

Front 28

Microbial resistance is mediated by the production of bacterial enzymes that attack the antibiotic molecule, changing its structure to an inactive form.
* A susceptible antibiotic is apparently less potent when larger numbers of bacteria are present in the medium than when fewer cells are employed. The more bacteria that are present, the more antibiotic-destroying enzyme that is present, and the more antibiotic that is required to overcome this to achieve the desired response. An antibiotic that is not enzyme modified is comparatively free of inoculum effects.

Back 28

inoculum effect

Front 29

Antibiotics are conveniently classified by their activity against microoraganisms depending on their reaction to this method

Back 29

gram stain method

Front 30

This type of gram stain is colored blue by contact with the methyl violet-iodine process
*due to outer membrane and thick cell wall surrounding

Back 30

gram-positive stain

Front 31

This type of gram stain is colored pink when treated with the red dye safranin
*lipopolysaccarides on outer membrane is responsible for this

Back 31

gram-negative stain

Front 32

Gram stain is dependent on what layer of bacterial cells to determine the infectious bacteria and decide on which therapy is appropriate

Back 32

the outer layers of the bacterial cells

Front 33

What is one common bacteria that is neither gram-positive or gram-negative and has waxy cells
*acid-fast

Back 33

mycobacteria

Front 34

Anitbiotic Use in the Absence of Infection:
This use of antibiotics is used in preoperative bowel sanitization and orally for treatment of viral sore throats

Back 34

prophylactic use

Front 35

Anitbiotic Use in the Absence of Infection:
This use of antibiotics is used to help animals grow more rapidly to marketable size
*may potentially contaminate food we consume or provide reservoirs of drug-resistant enteric microorganisms

Back 35

agricultural use

Front 36

Are antimicrobials modeled after any natural product?

Back 36

NO, only antibiotics

Front 37

Sulfonamdies, Trimethoprim, Quinolones and Methenamine are all examples of antimicrobials or antibiotics?

Back 37

antimicrobials

Front 38

These are inhibitors of bacterial cell wall biosynthesis or inhibitors of protein biosynthesis

Back 38

antibiotics

Front 39

β-lactams: Penicillins, Cephalosporins, Carbapenems, and Monobactams are all examples of what type of antibiotics

Back 39

cell wall biosynthesis inhibitors

Front 40

Aminoglycosides, Macrolides and ketolides, Tetracyclines, and Cyclic peptides are all examples of what type of antibiotics

Back 40

protein biosynthesis inhibitors

Front 41

This red dye has been proved to be active in vivo against streptococcal infections and it is a SULFONAMIDE

Back 41

prontosil rubrum

Front 42

Sulfanilamide is a colorless cleavage product formed by reductive liver metabolism of this prodrug sulfonamide

Back 42

prontosil rubrum

Front 43

MOA of this drug:
microbial biosynthetic pathway leading to TETRAHYDROFOLIC ACID SYNTHESIS results in this drug used as a false metabolite and inhibits the enzyme dihycropteroate synthesis. It competes for the active PABA site.

Back 43

MOA of sulfonamides

Front 44

How can the antimicrobial efficacy of sulfonamides be reversed? By adding....

Back 44

significant quantities of PABA into the diet

Front 45

This sulfonamide stands out because although it is administered orally it isn't absorbed in the gut and the majority of the dose is delivered to the distal bowel

Back 45

sulfasalazine

Front 46

This prodrug sulfonamide undergoes reductive metabolism by gut bacteria and converts into sulfapyridine and 5-aminosalicyclic acid (active)
*used for ulcerative colitis and Crohn's disease

Back 46

sulfasalazine

Front 47

This antimicrobial inhibits dihydrofolate reductase and therefore prevents biosynthesis of folic acid derivative and the thymidine required for DNA

Back 47

trimethoprim

Front 48

This class of antimicrobials are rapidly bactericidal and inhibit DNA gyrase and topoisomerase IV (key bacterial enzymes that dictate conformation of DNA)

Back 48

quinolones

Front 49

These antimicrobials comprise a group of synthetic substances possessing in common an N-1-alkylated 3-carboxypyrid-4-one ring fused to another aromatic ring, which itself carries other substituents.

Back 49

quinolones

Front 50

This class of antimicrobials were of little clinical significance until the discovery of the addition of a fluoro group to the 6-position, which greatly increased the biological activity

Back 50

quinolones
*fluoroquinolones

Front 51

This is the first of the second-generation quinolones and has a broad spectrum and equivalent in potency to many of the fermentation derived antibiotics

Back 51

norfloxacin

Front 52

These two drugs dominate the worldwide flouroquinolone market

Back 52

ciprofloxacin and levofloxacin

Front 53

What ability do quinolones have that other drugs to not that decreases solubility and reduces drug absorption?

Back 53

they can CHELATE polyvalent metal ions

Front 54

This antimicrobial is used for disinfection of acidic urine and and recurrent UTIs and is made of ammonia and formaldehyde (-->active component)

Back 54

methenamine

Front 55

This name is given to cyclic amides

Back 55

lactam

Front 56

This (inhibitor of cell walls) is a cyclic amide with four atoms in its ring with the contemporary name of azetidinone
*rare structural feature of penicillins

Back 56

β-lactam

Front 57

What type of shape do penicillins have with the β-lactam ring fused to the 5-membered thiazoldine ring?

Back 57

a "V-shape"

Front 58

What is the most UNSTABLE bond in the penicillin molecule? It breaks down quickly in basic solutions to produce penicilloic acid-->penilloic acid

Back 58

β-lactam amide bond

Front 59

Is the conversion of penicilloic acid-->penilloic acid reversible or irreversible under physiologic conditions?

Back 59

Irreversible

Front 60

What bacterial enzyme catalyzes the hydrolysis reaction of β-lactams (penicillins)?

Back 60

β-lactamase

Front 61

In what type of solutions is the hydrolysis of penicillins complex?

Back 61

acidic solutions

Front 62

Do the three products (penicillamine, penilloic acid and penilloaldehyde) of acidic degradation of penicillins have antibacterial activity?

Back 62

NO antibacterial activity

Front 63

What subunits to antibiotics bind to on the bacterial cell?

Back 63

30S and 50S subunits

Front 64

Interference with bacterial protein biosynthesis prevents repair, cellular growth and reproduction... the action of what?

Back 64

antibiotics

Front 65

This class of antibiotics contains a pharmacophore consisting of either streptamine, 2-deoxystreptamine, or spectinamine

Back 65

aminoglycoside

Front 66

These antibiotics are freely water soluble, basic and not absorbed much in the GI tract and are excreted in active form in urine

Back 66

aminoglycosides

Front 67

These antibiotics are administered either by IM or perfusion

Back 67

aminoglycosides

Front 68

MOA of this class of antibiotics:
Bind to external lipopolysaccaride and diffuse into the cell to destroy the membrane

Back 68

aminoglycosides

Front 69

This class of antibiotics kills mainly gram-negative bacteria
*high toxicity potential so limits their clinical use to severe gram-negative infections

Back 69

aminoglycosides

Front 70

This is the most important aminoglycoside antibiotic, it is water loving and opportunistic

Back 70

gentamicin

Front 71

This aminoglycoside antibiotic is incompatible with β-lactam antibiotics and causes inactivation of both if used together

Back 71

gentamicin

Front 72

This antibiotic is a mixture of several antibiotic components produced by permentation of micromonospora purpurea and other soil microorganisms

Back 72

gentamicin

Front 73

This antibiotic (aminoglycoside) is frequently used for burns, pneumonias and UTIs and is highly virulent

Back 73

gentamicin

Front 74

These antibiotics are large lactone rings that are 14-membered

Back 74

macrolides
*macro=big

Front 75

These antibiotics have four fused 6-membered rings

Back 75

tetracyclines

Front 76

These antibiotics have many adverse affects and a high incidence of resistance which decreases their use

Back 76

tetracyclines

Front 77

What is the main important feature of tetracyclines that can form salts?

Back 77

chelation

Front 78

This class of antibiotic drugs can cause yellowing of the teeth because it is yellow and it is incompatible with antacids

Back 78

tetracyclines

Front 79

What two classes of drugs have the ability of chelation?

Back 79

tetracyclines and quinolones

Front 80

Tetracyclines bind to the ____ subunit of bacterial cells while chloramphenicol binds to the _____ subunit
*both are broad spectrum protein synthesis inhibitors

Back 80

30S and 50S

Front 81

This type of antibiotics is very toxic to humans and are used with common and uncommon amino acids with D absolute stereochemistry and a pendant fatty acid chain

Back 81

cyclic peptides

Front 82

One of the consequences of the unusual architecture of these antibiotics is that these glycopeptide agents are not readily metabolized

Back 82

cyclic peptides

Front 83

MOA for this class of antibiotics:
Attach to bacterial membranes and interfere with their semipermeability so that essential metabolites leak out and undesirable substances pass in

Back 83

cyclic peptides

Front 84

This type of cyclic peptide is highly associated with adverse infusion related events
*too rapid of a rate will cause red mans rash, other bad rxns

Back 84

vancomycin

Front 85

High doses of vancomycin can cause what two major adverse effects

Back 85

nephrotoxicity and ototoxicity (auditory damage-my be permanent)