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**Host and Defense > Antibiotics IV > Flashcards

Antibiotics IV Flashcards

1
Q

What is a key intermediate in the synthesis of dihydrofolic acid in bacteria?

A

Para-aminobenzoic Acid (PABA)

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2
Q

Dihydrofolic acid is converted into what in bacterial metabolism?

A

Tetrahydrofolic Acid (Folic Acid)

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3
Q

What is Tetrahydrofolic acid used for in bacteria?

A

It is essential for DNA and RNA synthesis

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4
Q

What are two key drugs in preventing the conversion of PABA to Dihydrofolic acid and then to Tetrahydrofolic acid?

A
  1. Sulfamethoxazole (SMX)

2. Trimethoprim (TMP)

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5
Q

What does Sulfamethoxazole do?

A

They are structurally similar enough to PABA that they compete for and inhibit Dihydropteroate Synthetase (Which makes Dihydrofolic acid)

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6
Q

What does Trimethoprim do?

A

Inhibits Dihydrofolate reductdase (which converts Dihydrofolic acid to Tetra hydrofolic acid)

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7
Q

Why are folate synthesis inhibitors so effective?

A

Humans lack the enzymes needed to convert PABA to tetrahydrofolic acid. So the only enzymes available to inhibit are bacterial, thus bacterial growth is selectively inhibited via folate deficiency

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8
Q

How do humans get folate?

A

Through Dietary resources, such as green leafy vegetables

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9
Q

What happens with increasing levels of sulfa drug?

A

The more likely it is to outcompete and bind to enzyme

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10
Q

Name the two important Sulfonamide Antibiotics.

A
  1. Sulfamethoxazole

2. Silver sulfadiazine

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11
Q

How is Sulfamethoxazole administered?

A

-Orally (systemic use)

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12
Q

How is Silver Sulfadiaxine administered?

A

Topically (For skin burns)

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13
Q

Is Sulfamethoxazole bacteriostatic or bactericidal?

A

Bacteriostatic

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14
Q

T/F Sulfamethoxazole is most effectively used as a monotherapy

A

FALSE

No longer used clinically as a monotherapy

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15
Q

What is the mechanism of Sulfamethoxazole?

A

Competitive inhibitor of dihydropteroate synthetase

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16
Q

What does Sulfadiazine do?

A

Inhibits dihydropteroate synthetase, which prevents folate synthesis in Gram + and - bacteria

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17
Q

Is the spectrum for Sulfadiazine and Silver sulfadiazine broad or narrow?

A

Broad

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18
Q

Is sulfadiazine and Silver Sulfadiazine bacteriostatic or bactericidal?

A

Bacterostatic

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19
Q

What are the clinical uses for Sulfadiazine and Silver sulfadiazine?

A

Oral monotherapy for UTIs and burns

20
Q

What is Silver Sulfadiazine?

A

Topical sulfonamide/silver antibacterial cream

21
Q

What is Topical Silver Sulfadiazine used for?

A

Prevention and treatment of infections related to skin burns or superficial wounds

22
Q

What are the adverse side effects of Sulfadiazines and Silver Sulfadiazine?

A
  1. Sulfa-Hypersensitivity*
  2. Photosensitivity*
  3. Allergic patients have cross-sensitivity to all sulfa-containing drugs

*Main adverse effects

23
Q

What can accumulation of sulfadiazine and silver sulfadiazine in at risk patients lead to?

A
  1. Hemolytic anemia (glucose-6-phosphate patients)
  2. Nephrotoxicity (renally impaired patients
  3. Kernicterus in infants (Brain damage due to excessive bilirubin in blood and brain)
24
Q

What are the two key enzymes that are inhibited to stop folic acid synthesis?

A
  1. Dihydropteroate Synthetase

2. Dihydrofolate reductase

25
Q

Is trimethoprim (TMP) bacteriostatic or bactericidal?

A

Bacterostatic

26
Q

T/F Trimethoprim is 20-50x more potent than sulfonamides alone

A

TRUE

27
Q

T/F Because trimethoprims are so potent, they are usually used as a monotherapy

A

FALSE,

  • Rarely used alone
  • Usually used with sulfonamides
28
Q

What is the mechanism of Trimethohprim?

A

Binds to and inhibits Dihydrofolate reductase and prevents conversion of Dihydrofolic acid to tetrahydrofolic acid

29
Q

Where does Trimethoprim’s selectivity come from?

A

The fact that it has greater affinity for bacterial dihydrofolate reductase than the hosts (over 1000x)

30
Q

What are some adverse effects of Trimethoprim?

A
  1. Pseudomembranous colitis (C. diff overgrowth)

2. Hematological disorders including boon marrow suppression

31
Q

How effective is TMP against recurrent UTIs?

A

It’s ok, Flouroquinolones are better

32
Q

What is Cotrimoxazole?

A

A mixture of TMP and Sulfamethoxazole

33
Q

What is the spectrum of Cotrimoxazole?

A

This combination is more effective than either of its individual components agains gram + and - bacteria, Chlamydias, nocardias, and protozoa

34
Q

How effective is cotrimoxazole against anaerobes?

A

No anaerobic coverage

35
Q

Is Cotrimoxazole bactericidal or bacterostatic?

A

It is time-dependent Bactericidal

36
Q

What is the synergistic combination of cotrimoxazole?

A

1 part trimethoprim and 5 parts sulfamethoxazole

**can be administered IV or orally

37
Q

What are the medical uses of Cotrimoxazole?

A
  1. Drug of choice for treatment of Pneumocystis Jirovecii pneumonia
  2. Gram + aerobes (recurrent UTIs)
  3. H. Flu (respiratory tract infections and otitis)
38
Q

What does the combination in Cotrimoxazole do to make the drug more effective?

A

Provides 2 step blockade of folate synthesis (blocks both enzymes), inhibiting bacterial DNA synthesis

39
Q

Why wouldn’t Prontosil work in vitro?

A

It was a prodrug that required bioactivation by the body to be converted to its active metabolite.

40
Q

What is the active metabolite of Prontosil?

A

Sulfanilamide

41
Q

What happened in the Elixir Sulfanilimide Tragedy?

A

Sulfanilimide didn’t taste good so a company solubilized it in diethylene glycol and made into sometehing tht tasted good. Turns out is was poisonous and was teh most consequential mass poisoning of the United States in the 20th century.

42
Q

What was congresses reaction to the Elixir Sulfanilimide tragedy?

A

Passed the Federal Food, Drug and Cosmetic Act

43
Q

What was the world’s first sulfonamide?

A

Prontosil

44
Q

What is the active form of Prontosil called?

A

Sulfanilimide

45
Q

What was the only active drug on the market before Prontosil?

A

Salvarsan (used to treat syphilis)

**Host and Defense (31 decks)

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