CH4 | Folate Antagonists

Question 1

What is folic acid essential for?

Answer 1

A coenzyme essential for the synthesis of RNA, DNA, and certain amino acids.

Question 2

What happens in the absence of folate?

Answer 2

Cells cannot grow or divide.

Question 3

What is the critical folate derivative?

Answer 3

Tetrahydrofolic acid.

Question 4

How do humans obtain folate?

Answer 4

Through dietary intake folate.

Question 5

How do bacteria synthesize folate?

Answer 5

Through de novo folate synthesis.

Question 6

What do sulfonamides do?

Answer 6

Inhibit de novo synthesis of folate.

Question 7

What is the function of trimethoprim?

Answer 7

Prevents microorganisms from converting dihydrofolic acid to tetrahydrofolic acid.

Question 8

What is the effect of the combination of sulfonamides and trimethoprim?

Answer 8

They have a synergistic effect.

Question 9

What are examples of sulfonamides?

Answer 9

Sulfamethoxazole, sulfadiazine, sulfasalazine.

Question 10

What is the mechanism of action (MOA) of sulfonamides?

Answer 10

They are synthetic analogs of PABA that compete with PABA and are bacteriostatic.

Question 11

What type of bacteria do sulfonamides have activity against?

Answer 11

Both Gram-positive and Gram-negative bacteria.

Question 12

How do some bacteria exhibit natural resistance to sulfonamides?

Answer 12

By obtaining folate from their environment.

Question 13

What are the acquired mechanisms of resistance to sulfonamides?

Answer 13

Altered dihydropteroate synthetase, enhanced production of PABA, and decreased cellular permeability.

Question 14

How are sulfonamides absorbed?

Answer 14

Well absorbed after oral administration.

Question 15

Is there an intravenous form of sulfonamides available?

Answer 15

Yes, IV forms are available.

Question 16

Why is sulfasalazine used?

Answer 16

It is not absorbed and is used for chronic inflammatory bowel diseases, acting locally.

Question 17

What are silver sulfadiazine and mafenide used for?

Answer 17

They are used topically for burn-associated sepsis to prevent colonization of bacteria.

Question 18

How do sulfonamides distribute in the body?

Answer 18

They bind to serum albumin and are distributed widely in body tissues.

Question 19

Do sulfonamides penetrate the central nervous system?

Answer 19

Yes, they penetrate well into the CSF and placental barrier.

Question 20

How are sulfonamides metabolized in the liver?

Answer 20

Through acetylation and conjugation.

Question 21

What happens to the acetylated metabolite of sulfonamides at neutral or acidic pH?

Answer 21

It precipitates, leading to crystalluria and potential kidney damage.

Question 22

How are unchanged sulfa drugs and their metabolites excreted from the body?

Answer 22

Via glomerular filtration and secretion.

Question 23

Can sulfonamides be eliminated in breast milk?

Answer 23

Yes, they may be eliminated in breast milk.

Question 24

What are the adverse side effects of sulfonamides?

Answer 24

• Crystalluria.
• Hypersensitivity.
• Hematopoietic disturbances.
• Kernicterus.
• Drug potentiation.

Question 25

What is drug potentiation in the context of sulfonamides?

Answer 25

It refers to the increased effect of another drug when taken with sulfonamides.

Question 26

Who should not use sulfonamides?

Answer 26

Newborns, infants less than 2 months of age, pregnant women, and patients receiving methenamine.

Question 27

Why should patients receiving methenamine avoid sulfonamides?

Answer 27

Because they can crystallize in the presence of formaldehyde.

Question 28

What is the mechanism of action of Trimethoprim?

Answer 28

It is a potent inhibitor of bacterial dihydrofolate reductase, preventing the formation of the metabolically active form of folic acid (tetrahydrofolic acid) in bacterial cells.

Question 29

How does Trimethoprim exhibit selective toxicity?

Answer 29

It binds more readily to the bacterial enzyme than the human enzyme.

Question 30

What is the spectrum of activity of Trimethoprim?

Answer 30

Effective against both Gram-positive and Gram-negative bacteria.

Question 31

How much more potent is Trimethoprim compared to sulfonamides?

Answer 31

20-fold to 50-fold more potent.

Question 32

For which conditions can Trimethoprim be used alone?

Answer 32

Urinary tract infections (UTIs) and bacterial prostatitis.

Question 33

What are the resistance mechanisms to Trimethoprim?

Answer 33

Altered dihydrofolate reductase and decreased permeability.

Question 34

How is Trimethoprim absorbed?

Answer 34

Rapidly absorbed after oral administration.

Question 35

Where is Trimethoprim distributed in the body?

Answer 35

Widely distributed into body tissues and fluids, including CSF.

Question 36

What metabolic process does Trimethoprim undergo?

Answer 36

Undergoes some O-demethylation.

Question 37

What percentage of Trimethoprim is renally excreted?

Answer 37

60% to 80%.

Question 38

What electrolyte imbalance can Trimethoprim cause?

Answer 38

Hyperkalemia.

Question 39

What adverse effects are associated with Trimethoprim?

Answer 39

Effects of folic acid deficiency such as megaloblastic anemia, leukopenia, and granulocytopenia, especially in pregnant patients and those with nutrient-poor diets.

Question 40

How can the adverse effects of folic acid deficiency caused by Trimethoprim be reversed?

Answer 40

By using folinic acid (leucovorin).

Question 41

What is Cotrimoxazole a combination of?

Answer 41

Trimethoprim and sulfamethoxazole. It exhibits synergistic activity.

Question 42

How does the spectrum, resistance, PK, and adverse effects of Cotrimoxazole compare to its individual components?

Answer 42

They are similar to the individual drugs.

Question 43

What is Cotrimoxazole used to treat?

Answer 43

* MRSA. * Respiratory infections – H. influenzae. * Septicemia and meningitis caused by Listeria monocytogenes. * Prostate infections and UTIs. * GIT infections (shigellosis and nontyphoid salmonella). * Toxoplasmosis gondii.

Question 44

What is the preferred treatment for Toxoplasmosis gondii?

Answer 44

Sulfadiazine and pyrimethamine.