SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN

Question 1

Why has the use of sulfonamides decreased?

Answer 1

Use of sulfonamides has decreased due to resistance and the incidence of allergic reactions to sulfa drugs.

Question 2

MOA of Sulfonamides

Answer 2

Competitive inhibition synthesis enzymes. Inhibition of this pathway prevents folic acid synthesis, which is required by susceptible organisms for the production of purines and nucleic acids.
If a bacteria doesn’t require folic acid, sulfa is ineffective.

Question 3

Activity of Sulfonamides

Answer 3

inhibit both gram-positive and gram-negative bacteria.
Protazoa - Toxoplasma gondii

Question 4

Resistance to sulfonamides is mediated by?

Answer 4

Mutations that result in excessive production of PABA cause organisms to develop resistance.

Question 5

MOA of Trimethoprim

Answer 5

inhibits bacterial dihydrofolic acid reductase. Essentially, inhibits the synthesis of purines and ultimately to DNA

Question 6

What happens when a Sulfonamide and Trimethoprim are giving together?

Answer 6

results in synergistic activity of both drugs

Question 7

Activity of Trimethoprim

Answer 7

active against both gram-positive and gram-negative organisms

Question 8

Resistance of Trimethoprim

Answer 8

results from reduced cell permeability, overproduction of dihydrofolate reductase, or production of an altered reductase with less drug-binding ability
most common cause is plasmid-encoded resistant reductases

Question 9

Nitrofurantoin use is limited to? Is it a sulfonamide?

Answer 9

UTIs, Not a sulfonamide

Question 10

MOA of Nitrofurantoin

Answer 10

Ultimately, protein synthesis, aerobic energy metabolism, DNA and RNA synthesis, and cell wall synthesis are inhibited

Question 11

Resisitance of Nitrofurantoin

Answer 11

Resistant mutants are rare

Question 12

What is Fosfomycin and is it a sulfonamide?

Answer 12

a bactericidal antibiotic available in the United States only as an oral formulation for the treatment of UTIs
Not a sulfanamide

Question 13

MOA of Fosfomycin

Answer 13

ultimately leads to inhibition of cell wall synthesis. beneficial in the treatment of UTIs because it reduces adherence of bacteria to the epithelial cells in the urinary tract.

Question 14

Activity of Fosfomycin

Answer 14

activity against most urinary pathogens

Question 15

Resistance of Fosfomycin

Answer 15

uncommon but has been reported. The bacterial mechanisms of resistance most commonly described are enzymatic modification of fosfomycin.

Question 16

Absorption of Sulfonamides

Answer 16

Oral sulfonamides are absorbed readily from the GI tract.

Question 17

Distribution of Sulfonamides

Answer 17

They are distributed widely throughout the body and found in all body tissues. They readily enter the CSF, pleura, synovial fluids, and the eye. They cross the placenta and enter breast milk.

Question 18

Absorption of Trimethoprim

Answer 18

well-absorbed following oral administration. .

Question 19

Distribution of Trimethoprim

Answer 19

It is widely distributed in body tissues, including prostatic tissues, and crosses the placenta. Distribution into breast milk occurs with high concentrations.

Question 20

Absorption of Nitrofurantoin

Answer 20

readily absorbed via oral administration.

Question 21

Absorption of Fosfomycin

Answer 21

oral bioavailability of 34% to 58%

Question 22

Distribution of Fosfomycin

Answer 22

Very little drug is protein-bound. Fosfomycin distributes into the kidneys, bladder wall, prostate, and CSF fluid if the meninges are inflamed.

Question 23

Metabolism of Sulfinamide

Answer 23

Metabolism in the liver by conjugation and acetylation to inactive metabolites

Question 24

Excretion of Sulfinamide

Answer 24

Renal excretion is mainly by glomerular filtration

Question 25

Metabolism of Nitrofurantoin

Answer 25

Approximately 50% to 70% is rapidly metabolized by body tissues to inactive metabolites.

Question 26

Excretion of Nitrofurantoin

Answer 26

Renal excretion is via glomerular filtration and tubular secretion. Needs renal dosing for CrCl <30

Question 27

Excretion of Fosfomycin

Answer 27

eliminated as unchanged drug primarily through renal excretion (up to 60% of an oral dose) and in feces (18%)

Question 28

What abx should be used with caution for patients with folate deficiency.

Answer 28

Trimethoprim

Question 29

What electrolyte should be monitored when using Trimethoprim

Answer 29

Potassium. risk for hyperkalemia

Question 30

Metabolism and Excretion of Trimethoprim

Answer 30

Liver metabolism < 20%
80% excreted in urine as unchanged drug