SULFONAMIDES, TRIMETHOPRIM, NITROFURANTOIN, AND FOSFOMYCIN Flashcards
Why has the use of sulfonamides decreased?
Use of sulfonamides has decreased due to resistance and the incidence of allergic reactions to sulfa drugs.
MOA of Sulfonamides
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.
Activity of Sulfonamides
inhibit both gram-positive and gram-negative bacteria.
Protazoa - Toxoplasma gondii
Resistance to sulfonamides is mediated by?
Mutations that result in excessive production of PABA cause organisms to develop resistance.
MOA of Trimethoprim
inhibits bacterial dihydrofolic acid reductase. Essentially, inhibits the synthesis of purines and ultimately to DNA
What happens when a Sulfonamide and Trimethoprim are giving together?
results in synergistic activity of both drugs
Activity of Trimethoprim
active against both gram-positive and gram-negative organisms
Resistance of Trimethoprim
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
Nitrofurantoin use is limited to? Is it a sulfonamide?
UTIs, Not a sulfonamide
MOA of Nitrofurantoin
Ultimately, protein synthesis, aerobic energy metabolism, DNA and RNA synthesis, and cell wall synthesis are inhibited
Resisitance of Nitrofurantoin
Resistant mutants are rare
What is Fosfomycin and is it a sulfonamide?
a bactericidal antibiotic available in the United States only as an oral formulation for the treatment of UTIs
Not a sulfanamide
MOA of Fosfomycin
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.
Activity of Fosfomycin
activity against most urinary pathogens
Resistance of Fosfomycin
uncommon but has been reported. The bacterial mechanisms of resistance most commonly described are enzymatic modification of fosfomycin.
Absorption of Sulfonamides
Oral sulfonamides are absorbed readily from the GI tract.
Distribution of Sulfonamides
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.
Absorption of Trimethoprim
well-absorbed following oral administration. .
Distribution of Trimethoprim
It is widely distributed in body tissues, including prostatic tissues, and crosses the placenta. Distribution into breast milk occurs with high concentrations.
Absorption of Nitrofurantoin
readily absorbed via oral administration.
Absorption of Fosfomycin
oral bioavailability of 34% to 58%
Distribution of Fosfomycin
Very little drug is protein-bound. Fosfomycin distributes into the kidneys, bladder wall, prostate, and CSF fluid if the meninges are inflamed.
Metabolism of Sulfinamide
Metabolism in the liver by conjugation and acetylation to inactive metabolites
Excretion of Sulfinamide
Renal excretion is mainly by glomerular filtration
Metabolism of Nitrofurantoin
Approximately 50% to 70% is rapidly metabolized by body tissues to inactive metabolites.
Excretion of Nitrofurantoin
Renal excretion is via glomerular filtration and tubular secretion. Needs renal dosing for CrCl <30
Excretion of Fosfomycin
eliminated as unchanged drug primarily through renal excretion (up to 60% of an oral dose) and in feces (18%)
What abx should be used with caution for patients with folate deficiency.
Trimethoprim
What electrolyte should be monitored when using Trimethoprim
Potassium. risk for hyperkalemia
Metabolism and Excretion of Trimethoprim
Liver metabolism < 20%
80% excreted in urine as unchanged drug
