Exam 8: Sulfonamides Flashcards
Name 2 Oral Sulfonamides
Sulfadiazine
Sulfamethoxazole
Name 1 Topical Sulfonamide
Silver sulfadiazine
Name 1 Pyrimidine
Trimethoprim
Name one popular sulfonamide combination product
Trimethoprim-Sulfamethoxazole
Bactrim
What is the mechanism of Sulfonamides?
Inhibition of bacterial Folate synthesis
Via competitive inhibition of Dihydropteroate Synthase
They do this by mimicking PABA
Are Sulfonamides -cidal or -static?
Bacteriostatic
What is an advantage of combining a sulfonamide with trimethoprim?
The combo is bactericidal, rather -static
What is the mechanism of Trimethoprim?
Inhibition of bacterial folate synthesis
Via inhibition of Dihydrofolate Reductase
What is Folate?
Vitamin B9
Required for DNA synthesis
Bacteria produce it, humans have to consume it.
What is folate deficiency most associated with?
Birth defects
Neural tube defects
Also megaloblastic anemia
What is an important consideration with any drug that his antifolate properties?
They all have teratogenic potential, at least in principle.
What types of organisms are susceptible to Sulfonamides? Resistant?
Organisms that produce their own folate
Those that obtain pre-formed folate
What are 4 resistance mechanisms to Sulfonamides?
- Mutated dihydropteroate synthase (lowered affinity)
- Increased efflux (Pseudomonas)
- Plasmids with drug-resistant enzymes (enteric gram negatives) Leads to MDR
- Auxotrophy for folate (E. faecalis)
What is the mechanism of resistance to sulfonamides for E. faecalis?
Auxotrophy for Folate
What is a common mechanism of sulfonamide resistance for Pseudomonas?
Increased drug efflux
What is a mechanism of resistance to Sulfonamides that leads to MDR?
Plasmids with drug-resistant enzymes
What happens to Sulfasalazine in the gut? What happens to each metabolite?
Metabolism to sulfapyridine and 5-ASA
5-ASA has topical anti-inflammatory effects
Sulfapyridine has a systemic anti-inflammatory effect
What Sulfonamide is used in burn therapy?
Silver Sulfadiazine
Topical (applied as cream)
What happens to the silver and the sulfa that is topically applied to burns?
They are both anti microbial
Sulfa gets absorbed
Silver does not get absorbed
How long is the half-life of Sulfadoxine? Why?
7-9 days (Really long)
Probably because of protein binding
What sulfonamide could be used in malaria? Why is its use limited?
Sulfadoxine combined with pyrimethamine
Limited by severe side effects and resistance
How do sulfonamides circulate in the plasma?
Bound to albumin to varying degrees
How do Sulfonamides distribute in the body?
Pretty much everywhere
Cross BBB
Cross placenta, enter breast milk
Pregnancy Category C
Why doesn’t Trimethoprim affect human cells, since we do have DHFR?
100,000x more affinity for bacterial DHFR
What is a mechanism of resistance to Trimethoprim?
Altered DHFR enzyme
How does Trimethoprim’s volume of distribution compare to Sulfonamides?
9x higher
How is Trimethoprim removed from the body?
Excreted unchanged in the urine
What ratio is dosing for TMP:SMX?
1:5 (more sulfa)
Results in 1:20 ratio in plasma concentration
What is a scary bug that is usually susceptible to TMP-SMX?
Community acquired MRSA
What are some bugs that are resistant to TMP-SMX?
Ineffective against Bacteroides fragilis, most anaerobes, P. aeruginosa, M. tuberculosis, T. pallidum, Campylobacter, penicillin- resistant pneumococci, and rickettsiae
What is a super common use for TMP-SMX?
UTIs (E. coli)
What is a weird organ that sulfonamides are able to penetrate?
Prostate
Useful in prostatitis
What bug causes most uncomplicated UTI? Complicated?
Uncomplicated: E. coli
Complicated: Probably still E. coli, but some E. faecalis too
Treatments for complicated vs uncomplicated UTIs?
Both use TMP-SMX
Days for uncomplicated
2 weeks for complicated
Definition of complicated UTI?
Any UTI in a male
Or associated with a predisposing lesion
What could you use for a UTI with resistance to TMP-SMX?
Fluoroquinolones
What are 3 GI bugs that can be treated with TMP-SMX?
Salmonella
E. coli (traveler’s diarrhea)
Listeria monocytogenes
What are 4 atypical/rare infections treatable with TMP-SMX?
Nocardia (esp with immunocompromise)
Toxoplasmosis
Pneumocystis j.
Yersenia (Plague)
Cats are a buzzword for…
Toxoplasmosis
Pregnant women should be careful
Two big reasons sulfonamides aren’t used more often?
Side effects can be bad
Resistance is common
Sulfonamide adverse effects?
Skin rashes/hypersensitivites
Crystalluria
Hyperkalemia (TMP reduce renal K secretion)
Acute Hemolytic anemia related to G6PD deficiency
Agranulocytosis, aplastic anemia
What is a big predisposing factor to Sulfa hypersensitivity reactions?
HIV
What condition can predispose patients to non-immune hemolysis?
G6PD deficiency (oxidative stress)
Most common enzyme deficiency worldwide
X linked
Sulfa drugs are more likely to cause anemia in these patients
Sulfonamide drug interactions?
Interfere with other drugs that bind albumin
Warfarin, phenytoin, sulfonureas
Who should avoid Sulfonamides when possible?
Pregnant women
Pregnancy Category C
Especially avoid them in the first trimester ***
Less of a concern late in pregnancy
Other than teratogenesis, what else can sulfonamides cause in the fetus?
Kernicterus (hyperbilirubinemia causing neurologic problems)
Related to albumin binding/bilirubin binding to albumin
