EXAM 2 Antimicrobials IV

Question 1

Para-aminobenzoic acid (PABA) is an intermediate in the synthesis of ___, which undergoes a 2 step enzymatic conversion to ___, a co-enzyme substrate essential for DNA and RNA synthesis in bacteria, plants, and fungi.

Answer 1

• dihydrofolic acid
• tetrahydrofolic acid

Question 2

___ are structurally similar enough to PABA to compete for its binding sites on the first enzyme, ___

Answer 2

• sulfamethoxazole
• dihydropteroate synthetase

Question 3

Bacterial growth is selectively inhibited through ___.

Answer 3

folate deficiency

Question 4

what drug is described by the following:

became the the first sulfa antimicrobial drug

changed the world by saving millions of lives between 1934-1942.

A bold orange-red drug, it started as an industrial dye, not an antibiotic

Answer 4

prontosil

Question 5

who invented prontosil?

Answer 5

Dr. Gerhard Domagk at Bayer

Question 6

In 1937, ___, a liquid formulation made in ___, was marketed by the S.E. Massengill Company (Bristol, Tenn.)

Answer 6

• elixir sulfanilamide
• diethylene glycol

Question 7

___ had a sweet taste, so mass production began without testing for toxicity or safety.

Answer 7

elixir sulfanilamide

Question 8

what drug is responsible for the most consequential mass poisoning the United States in the 20th century?

Answer 8

elixir sulfanilamide

Question 9

In reaction to the elixir sulfanilamide disaster, U.S. Congress passed the 1938 Federal ___, which required proof of safety before the release of a new drug to humans.

Answer 9

food, drug, and cosmetic act

Question 10

___ is an oral synthetic sulfonamide antimicrobial agent

Answer 10

Sulfamethoxazole

Question 11

is Sulfamethoxazole bacteriostatic or bactericidal?

Answer 11

bacteriostatic

Question 12

what is the mechanism of sulfamethoxazole?

Answer 12

competitive inhibitor of dihydropteroate synthetase

Question 13

sulfamethoxazole is no longer used as ___

Answer 13

monotherapy

Question 14

sulfadiazine inhibits ___

Answer 14

dihydropteroate synthetase

Question 15

is sulfadiazine broad or narrow spectrum? bactericidal or bacteriostatic?

Answer 15

broad spectrum, bacterostatic

Question 16

what is the clinical use for sulfadiazine?

Answer 16

oral monotherapy for UTIs and burns

Question 17

what drug is described as a topical sulfonamide/silver antibacterial cream used for prevention and treatment of infections related to skin burns or superficial wounds

Answer 17

silver sulfadiazine

Question 18

what are the adverse effects of sulfadiazine and silver sulfadiazine?

Answer 18

• sulfa-hypersensitivity
• photosensitivity
• allergic patients usually have cross sensitivity to all sulfa-containing drugs

Question 19

___ inhibits dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid

Answer 19

trimethoprim

Question 20

what are the two key para-aminobenzoic acid drugs?

Answer 20

sulfamethoxazole and trimethoprim

Question 21

why are folate synthesis inhibitors selective?

Answer 21

• humans lack the enzymes needed to convert PABA to tetrahydrofolic acid
• humans get folate through dietary resources, such as green leafy vegetables

Question 22

what happens when you have PABA with increasing levels of sulfa drug?

Answer 22

the higher levels of sulfa drug, the more likely to outcompete and bind to enzyme

Question 23

accumulation of sulfadiazine and silver sulfadiazine in at risk patients can result in what 3 things?

Answer 23

• hemolytic anemia
• nephrotoxicity
• kernicterus in infants (brain damage due to excessive bilirubin in the blood and brain)

Question 24

is trimethoprim bactericidal or bacteriostatic?

Answer 24

bacteriostatic

it is 20-50x more potent than sulfonamides alone

Question 25

trimethoprim is usually used with ___, but can be used on its own for the treatment of recurrent ___

Answer 25

• sulfonamides
• UTIs

Question 26

what is the mechanism of trimethroprim?

Answer 26

it inhibits dihydrofolate reductase

Question 27

trimethoprim’s selectivity comes from what?

Answer 27

its greater affinity for bacterial dihydrofolate reductase than the host’s

Question 28

what are the adverse effects of trimethoprim?

Answer 28

• pseudomembranous colitis
• hematological disorders including bone marrow suppression (TMP treats marrow poorly)

Question 29

___ is a combination of TMP and SMX

Answer 29

contrimoxazole

Question 30

describe the spectrum of cotrimoxazole

Answer 30

• broad spectrum
• combination is more effective than either of its individual components
• no anaerobic coverage

Question 31

is cotrimoxazole bactericidal or bacteriostatic?

Answer 31

time-dependent bactericidal

combination provides 2-step blockade of folate synthesis, inhibiting bacterial DNA synthesis

Question 32

what drug is described as having the following medical uses:

drug of choice for treatment of pneumocystis jiroveci (carini) pneumonia

gram + aerobes (recurrent UTIs)

h. influenzae (respiratory tract infections and otitis)

Answer 32

cotrimoxazole

Question 33

what is TMP?

Answer 33

trimethoprim

Question 34

what is SMX?

Answer 34

sulfamethoxazole

Question 35

when was salvarsan developed?

Answer 35

1911

Question 36

when was prontosil developed?

Answer 36

1935

Question 37

when was sulfanilimide developed?

Answer 37

1936

Question 38

in 1936, scientists at the pasteur institute discovered that prontosil is a ___ that required ___ by the body to be converted to its active metabolite, sulfanilimide, which is why it didn’t work in vitro

Answer 38

• prodrug
• bioactivation