Shared Flashcard Set

Details

Sulfonamides
development, mechanism of action, sulfa agents, ADRs
31
Pharmacology
Professional
10/23/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
TMP-SMX
Definition
trimethoprim-sulfamethoxazole
Term
What is the mechanism of action for sulfonamides?
Definition
interfere with bacterial synthesis of folic acid
Term
How does the drug interfere with bacterial synthesis of folic acid?
Definition
it competitively inhibits the enzyme dihydropteroate synthetase which eventually causes a decreased amount of tetrahydrofolic acid which inhibits cell growth
Term
What does dihydropteroate synthetase do?
Definition
responsible for incorporating para-aminobenzoic acid (PABA) into dihydrofolic acid
Term
What is tetrahydrofolic acid responsible for?
Definition
it is a cofactor necessary for the synthesis of purines, thymidine, and DNA
Term
How is the absorption of sulfonamides?
Definition
generally good oral bioavailability
Term
What determines how much of the drug gets distributed throughout the body?
Definition
the degree of plasma protein binding. only free drug can pass across membranes so if drug is bound to protein than it mostly stays in the blood stream
Term
How are sulfonamides metabolized?
Definition
hepatically metabolized by acetylation and glucuronidation
Term
Will sulfonamides effect the clearance of another drug?
Definition
No, there is not a lot of liver related drug interactions.
Term
How are sulfonamides excreted?
Definition
both parent drug and metabolites are primarily eliminated by the kidney
Term
What is the problem with some of the older compounds and elimination?
Definition
older compounds may crystallize in acidic urine so you need to tell the patient to drink a lot of water
Term
sulfisoxazole
Definition
rapidly absorbed and excreted
half-life=3.5 hours (dosed 4x daily)
previously used to treat UTIs
otitis media
little difficult on the stomach
Term
sulfadiazine
Definition
low urine solubility (not good for UTIs)
used in combination with other antibacterials to treat nocardial infections and toxoplasmosis
not frequently used
Term
sulfamethoxazole
Definition
slower excretion (can treat UTIs)
half-life=9 hours (dosed 2x daily)
combined (almost exclusively) with trimethoprim for its synergistic bactericidal effect
Term
trimethoprim-sulfamethoxazole mechanism of action
Definition
inhibits bacterial synthesis of folinic acid at two sequential steps
Term
What are the advantages of trimethoprim-sulfamethoxazole?
Definition
bactericidal-synergistic activity
slows development of resistance
Term
What are the four categories or classes of mechanisms of resistance?
Definition
1. bacteria produces enzyme that destroys drug
2. bacteria alters binding site for drug
3. bacteria limits the amount of drug that gets into the cell
4. bacteria has efflux pumps
*exception* bacteria produce more substrate than drug can inhibit
Term
How do bacteria exhibit resistance to sulfonamides?
Definition
bacteria increase the production of PABA
bacteria synthesize an altered dihydropteroate synthetase and/or dihydrofolate reductase
bacteria increase the production of dihydropteroate synthetase
bacteria reduce the drug uptake
Term
What is the optimal synergistic ratio of serum concentration of TMP to SMX?
Definition
1:20
1 (trimethoprim): 20 (sulfamethoxazole)
Term
How do you achieve the optimal synergistic ratio by using a fixed oral or intravenous combination?
Definition
1:5 fixed oral or intravenous combination
Term
What is the spectrum of activity for sulfonamides (good)?
Definition
S. aureus (including MSSA and MRSA)
H. influenzae (upper respiratory infections, meningitis)
Stenotrophanomas maltophilia
Listeria monocytogenes
Pneumocystis jiroveci
T. gondii
Term
What are the organisms that sulfonamides have only modest activity against?
Definition
Enterobacteriaceae (PESKY-MESS)
S. pneumoniae
Term
What organisms do sulfonamides have poor activity against?
Definition
S. pyogenes (strep throat, SSTI)
P. aeruginosa
Enterococci
anaerobes
Term
What is the difference between intrinsic resistance and acquired resistance?
Definition
acquired: mutation occurred to allow resistance
pseudomonas and anaerobes often intrinsically resistant
Term
What are the therapeutic uses of sulfonamides?
Definition
genitourinary tract (uncomplicated UTIs)
GI tract (traveler's diarrhea)
respiratory infections (acute exacerbations of bronchitis, otitis media, sinusitis)
treatment and prevention of Pneumocystis pneumonia
community-acquired MRSA infections
Term
What are the adverse effects of sulfonamides?
Definition
hypersensitivity reaction (skin rashes)
gastrointestinal (mild N/V, D)
hematologic (thrombocytopenia and neutropenia)
photosensitivity
nephrolithiasis
Term
What are the contraindications of sulfonamides?
Definition
pregnant women
glucose-6-phosphate dehydrogenase deficiency
hypersensitivity
folic acid deficiency
increased risk of experiencing hematologic toxicity
Term
sulfacetamide
Definition
ophthalmic preparation used to treat superficial infections of the eye
penetrates well into ocular fluids
antimicrobial resistance limits usefulness
Term
mafenide
Definition
a broad spectrum topical sulfa
used primarily in burn patients
effective against P. aeruginosa
diffuses well through devascularized areas, is absorbed, metabolized, and then eliminated by the kidney
Term
silver sulfadiazine
Definition
topical sulfa with broad spectrum (including Pseudomonas) used to inhibit bacterial growth on burn wounds
silver ion is an active component
advantages: less pain than with mafenide and fewer applications
sulfadiazine is absorbed and high concentrations can be acheived--crystaluria can be a problem
Term
sulfasalazine
Definition
combination of a sulfa and antiinflammatory agent
used in treatment of inflammaotry bowel disease
poorly absorbed from the GI tract
metabolized by intestinal bacteria to sulfapyridine (absorbed and renally excreted) and 5-aminosalicylic acid
Supporting users have an ad free experience!