Term
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Definition
| trimethoprim-sulfamethoxazole |
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Term
| What is the mechanism of action for sulfonamides? |
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Definition
| interfere with bacterial synthesis of folic acid |
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Term
| How does the drug interfere with bacterial synthesis of folic acid? |
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Definition
| it competitively inhibits the enzyme dihydropteroate synthetase which eventually causes a decreased amount of tetrahydrofolic acid which inhibits cell growth |
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Term
| What does dihydropteroate synthetase do? |
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Definition
| responsible for incorporating para-aminobenzoic acid (PABA) into dihydrofolic acid |
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Term
| What is tetrahydrofolic acid responsible for? |
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Definition
| it is a cofactor necessary for the synthesis of purines, thymidine, and DNA |
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Term
| How is the absorption of sulfonamides? |
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Definition
| generally good oral bioavailability |
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Term
| What determines how much of the drug gets distributed throughout the body? |
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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 |
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Term
| How are sulfonamides metabolized? |
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Definition
| hepatically metabolized by acetylation and glucuronidation |
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Term
| Will sulfonamides effect the clearance of another drug? |
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Definition
| No, there is not a lot of liver related drug interactions. |
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Term
| How are sulfonamides excreted? |
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Definition
| both parent drug and metabolites are primarily eliminated by the kidney |
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Term
| What is the problem with some of the older compounds and elimination? |
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Definition
| older compounds may crystallize in acidic urine so you need to tell the patient to drink a lot of water |
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Term
|
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 |
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Term
|
Definition
low urine solubility (not good for UTIs)
used in combination with other antibacterials to treat nocardial infections and toxoplasmosis
not frequently used |
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Term
|
Definition
slower excretion (can treat UTIs)
half-life=9 hours (dosed 2x daily)
combined (almost exclusively) with trimethoprim for its synergistic bactericidal effect |
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Term
| trimethoprim-sulfamethoxazole mechanism of action |
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Definition
| inhibits bacterial synthesis of folinic acid at two sequential steps |
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Term
| What are the advantages of trimethoprim-sulfamethoxazole? |
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Definition
bactericidal-synergistic activity
slows development of resistance |
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Term
| What are the four categories or classes of mechanisms of resistance? |
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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 |
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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 |
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Term
| What is the optimal synergistic ratio of serum concentration of TMP to SMX? |
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Definition
1:20
1 (trimethoprim): 20 (sulfamethoxazole) |
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Term
| How do you achieve the optimal synergistic ratio by using a fixed oral or intravenous combination? |
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Definition
| 1:5 fixed oral or intravenous combination |
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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 |
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Term
| What are the organisms that sulfonamides have only modest activity against? |
|
Definition
Enterobacteriaceae (PESKY-MESS)
S. pneumoniae |
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Term
| What organisms do sulfonamides have poor activity against? |
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Definition
S. pyogenes (strep throat, SSTI)
P. aeruginosa
Enterococci
anaerobes |
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Term
| What is the difference between intrinsic resistance and acquired resistance? |
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Definition
acquired: mutation occurred to allow resistance
pseudomonas and anaerobes often intrinsically resistant |
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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 |
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Term
| What are the adverse effects of sulfonamides? |
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Definition
hypersensitivity reaction (skin rashes)
gastrointestinal (mild N/V, D)
hematologic (thrombocytopenia and neutropenia)
photosensitivity
nephrolithiasis |
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Term
| What are the contraindications of sulfonamides? |
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Definition
pregnant women
glucose-6-phosphate dehydrogenase deficiency
hypersensitivity
folic acid deficiency
increased risk of experiencing hematologic toxicity |
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Term
|
Definition
ophthalmic preparation used to treat superficial infections of the eye
penetrates well into ocular fluids
antimicrobial resistance limits usefulness |
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Term
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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 |
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Term
|
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 |
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Term
|
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 |
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