Sulfonamides & Trimethoprim Flashcards
T/F
All sulfonamides are similar in structure to para-aminobenzoic acid (PABA).
T/F
PABA is a precursor required by bacteria for folic acid synthesis.
T/F
Sulfonamides may have an increased affinity for the enzyme than the natural substrate, PABA.
TRUE
TRUE
TRUE
What is the mechanism of action for Sulfonamides?
- Bacteria require tetrahydrofolic acid (derivative of folic acid), as a cofactor in the synthesis of thymidine, purines, and, ultimately DNA.
- Bacterial cell walls are impermeable to folic acid. Bacteria must synthesize it from PABA.
- Because of the sulfonamides structural similarity to PABA, they compete with PABA for the enzyme dihydropteroate synthetase; thus, depriving the cell of tetrahydrofolic acid.
Why aren’t host cells affected by Sulfonamides?
Require preformed folic acid; they cannot synthesize folic acid. Therefore they don’t use PABA.
Sulfonamides are Bacteriocidal or Bacteriostatic?
BACTERIOSTATIC
How are sulfonamides primarily excreted?
What application does that have on their use?
glomerular filtration
Good for UTIs
What adverse reactions are associated with sulfonamides?
Nephrotoxicity
Kernicterus (if given in 3rd trimester)
Anaphylaxis (sulfa allergy)
Why don’t you want to give Sulfonamides to a pregnant (3rd trimester) patient with UTI?
Kernicterus (brain damage) occurs in neonate who has increased unconjugated bilirubin in blood
What bugs are covered by Sulfonamides?
Staph.
Strep.
Bacillus anthracis
Haemophilus spp. Providencia Salmonella Shigella PEK CE
Atypicals: Nocardia asteroides Chlamydia trachomatis Toxoplasma gondii Plasmodium falciparum
What G+ bugs are covered by Sulfonamides?
Staph.
Strep.
Bacillus anthracis
What G– bugs are covered by Sulfonamides?
Haemophilus spp.
Providencia
Salmonella
Shigella
PEK
CE
What Atypical bugs are covered by Sulfonamides?
Nocardia asteroides
Chlamydia trachomatis
Toxoplasma gondii
Plasmodium falciparum
What ABX might you use for the following indications:
- Uncomplicated UTI
- Pneumocystis carinii (treatment and prophylaxis)
- Nocardosis
- Toxoplasmosis
- Malaria (chloroquine-resistant)
- Rheumatic fever prophylaxis (pcn allergic)
Sulfonamides
What 3 mechanisms do microorganisms use for sulfonamide resistance?
- Overproduction of PABA
- Decreased permeability of the bacteria to the drug.
- Structural change in dihydropteroate synthetase resulting in decreased affinity for the sulfonamide
Is Trimethoprim Bacteriocidal or Bacteriostatic?
BACTERIOSTATIC
bactericidal with high concentrations
What is the Trimethoprim mechanism of action?
- Inhibits dihydrofolate reductase thus preventing the formation of tetra hydrofolic acid.
- 50,000x more active against bacterial dihydrofolate reductase than human enzyme
T/F
Trimethoprim targets the same enzyme (dihydrofolate reductase) as methotrexate, the cancer drug.
TRUE
How are sulfonamides primarily excreted?
What application does that have on their use?
glomerular filtration
Good for UTIs
Why must you be careful providing Trimethoprim to: • Alcoholics • Pregnant women • Debilitated ptns • Malabsorptive syndromes
Folate Deficiency
What bugs are covered by Trimethoprim?
Staph.
Strep.
Bacillus anthracis
EK
SPCE
Pneumocystis carinii**
What G+ bugs are covered by Trimethoprim?
Staph.
Strep.
Bacillus anthracis
What G– bugs are covered by Trimethoprim?
EK
SPCE
What Atypical bugs are covered by Trimethoprim?
Pneumocystis carinii**
What ABX might you use for the following indications:
- Acute Uncomplicated UTI
- Recurrent UTI prophylaxis
- Traveler’s diarrhea (treatment and prophylaxis)
Trimethoprim
What is Bactrim made up of?
Trimethoprim + Sulfamethoxazole
Is Trimethoprim+Sulfamethoxazole (Bactrim) Bacteriocidal or Bacteriostatic?
BACTERIOCIDAL
T/F
Mechanism Of Action of Trimethoprim+Sulfamethoxazole (Bactrim) is Combined mechanisms of both agents (synergistic); bactericidal and thought to reduce the rate of emergence of resistance.
TRUE
T/F
Bugs covered by Trimethoprim+Sulfamethoxazole (Bactrim) is a combination of those from the two separately.
TRUE
What is the drug of choice for Strenotrophamonas maltophilia?
Trimethoprim+Sulfamethoxazole (Bactrim)
Why won’t you prescribe Trimethoprim+Sulfamethoxazole (Bactrim) to a patient on Warfarin?
Why won’t you prescribe Trimethoprim+Sulfamethoxazole (Bactrim) to a patient on Methotrexate?
Likely to Potentiate anticoagulant effects
Displace methotrexate from protein binding sites, resulting in an increase in free methotrexate concentrations
