Flashcards in Sulfonamide Deck (36):
What was the first effective chemotherapeutic agent employed systemically for the prevention and cure of bacterial infections in man?
What are the important structural features of the sulfonamides?
A sulfamide (SO2) attached to a benzene ring and an amino group(NH2).
What causes inactivation of the sulfonamide?
Hepatic metabolism of amino group
Are sulfonamides broad spectrum or narrow spectrum?
broad spectrum (both Gram pos, Gram neg)
Are sulfonamides bacteriostatic or bacteriocidal?
Bacteriostatic, so immune system is key for resolution.
Instance when a sulfonamide can be bacteriocidal?
High concentration achieved in urine to treat UTI.
On what part of the bacteria will sulfonamide work in treating the UTI?
Affect cell’s ability to replicate by starving it of thymine
Sulfonamides are structural analogues to what compound?
para aminobenzoic acid
Why is PABA important to bacteria and why is its antagonism not toxic to humans?
Bacteria use PABA to make folic acid. We get our folic acid from our diet.
What is folic acid used for?
Synthesis of purines, pyrimidines, and proteins.
Is there a delay in the effect of sulfonamides and why?
Yes, bacteria can use up folate pools before using the sulfonamide
How can sulfonamide be bacteriocidal instead of its normal bacteristatic?
When it achieves high enough concentration to cause a thymine-less death by stopping DNA synthesis
Sulfonamides are synergistic with what drug?
Where does Trimethoprim work on the bacteria?
Still at folic acid, except it inhibits dihydrofolate reductase from transformind dihydrofolate to tetrahydrofolate, the carbon donor to proteins, DNA, & RNA
What does Sulfamethoxazole and Trimethoprim do (SMZ/TMP)?
Sequential blockade of folic acid in bacteria
How can bacteria gain resistance to sulfonamides?
1. Alter enzyme using PABA so it only uses PABA and not the sulfonamide
2. Increase capacity to inactivate or destroy sulfonamide
3. Alternative metabolic pathway for synthesis
4. Increase PABA synthesis to outcompete the sulfonamide
Are sulfonamides soluble or insoluble?
Insoluble. Transformed to soluble salts.
What is the character of gut absorption for sulfonamides?
Rapid 70%-100% absorbed from oral
Can Sulfonamides be given subcutaneously or intramuscular and why?
No, sulfonamide salts are highly alkaline.
What are 2 uses of sulfonamides?
Opthalmic solutions/ointments due to good aqueous humor penetration.
How do sulfonamides travel in the blood and what does this mean for their activity?
They are bound to plasma protein, only unbound drugs can act.
What is a toxicity that can occur with sulfonamide binding to plasma proteins?
They displace bilirubin that can then cross blood brain barrier and deposit in basal ganglion causing brain damage.
What is the distribution of sulfonamides?
Uniform throughout body, crosses blood brain barrier and get into aqueous humor of eye
How is sulfonamide metabolized?
Hepatic at the amino group which eliminates the antibacterial, but keeps the toxicity
How is sulfonamide eliminated?
In urine by filtration through the kidneys.
Sulfonamide for a kidney infection is a drug of choice. Why?
Because its excretion provides for levels 10-25 higher than that in serum
What are some toxic effects from sulfonamides?
GI intolerance, anorexia, nausea, vomiting
What are two MAJOR toxic effects of sulfonamides?
Hypersensitivity rash, Stevens-Johnson syndrome (loss of mucosal lining) in children could be fatal
How can you prevent sulfonamide crystallization in kidneys?
mx high urine ph (alkaline w/ NaHCO3), high urine flow via high fluid intake
With what genetic deficiency will sulfonamides cause hemolytic anemia?
Glucose-6-phosphate dehydrogenase deficiency
What is a toxic effect sulfonamides will have on newborns?
Sulfonamides displace bilirubin causing its deposit in brain leading to brain damage
Is sulfonamide prescribed for oral dental lesions?
No. Used in UTI, topical infections (burns, eyes)
What is the character of sulfonamides that even if put with other sulfonamides they act as if they are alone in solution?
The principle of Independent solubility.
What does principle of independent solubility help with in sulfonamide treatment?
It decreases the risk of urine crystallization.
What does treating with a 3 sulfonamide cocktail allow?
You can get higher therapeutic dose, while avoiding precipitating out in urine.