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21 Cards in this Set

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Single sulfona/mides
Once single sulfas were the mainstay of chemotherapy but now less used in US because resistance is  common.
Trimethoprimsulfamethoxazole is
a synergistic combo that is very often used
Pathogens are only susceptible
if they require PABA to synthesize folic acid.
All Sulfas are chemical congeners of
PABA
MECHANISM OF ACTION OF THE SULFONAMIDES
Most are
-Some inhibit indirectly by
-Single sulfas are bacteriostatic as they -Selective since
competitive inhibitors of DHPS
-serving as an alternative substrate & exhausting the pteridine cofactor.
prevent new DNA synthesis.
-people use dietary folate & don’t require this path.
The individual sulfonamides are rarely drugs of first choice with the exceptions cited below
-Has the shortest t½
SULFISOXAZOLE
-Very soluble in water so unlikely to cause crystalluria
(5-6 hr)
SULFISOXAZOLE
Ineffective for
Sometimes used for Rx of uncomplicated UTIs because 10-20x concentrated in urine
Other drugs preferred for UTIs now (TMP-SMX, a quinolone, fosfomycin, ampicillin)
SMX acetyl + erythromycin for otitis media & upper resp. tract infections in children
CNS infections (low lipid sol)
SULFADIAZINE (ORAL)
-Achieves highest concentration in
-limits its use
-Urine flow must be
-shoud use
-CSF (30-80% of plasma)
Relatively rapidly absorbed & excreted T 1/2= 10hrs
Crystalluria
- brisk, alkaline
-Bicarbonate to reduces reabsorption
SILVER SULFADIAZINE (SILVADENE): TOPICAL
-not useful
Agent of choice for prevention of infections in 2nd & 3rd degree burn
Silver released is broad--
-spectrum agent x bacteria and fungi
Reduces colonization, encourages healing but
-against established deep infections
Used topically on burns with little toxicity but systemic absorption is poss.
SULFASALAZINE (AZULFIDINE):
-Used for
-an active antiinflammatory inhibits cyclooxygenase)
-toxic
POORLY ABSORBED

-Held in GI tract/bowel & excreted in feces
-inflammatory bowel disease (IBD), ulcerative colitis, regional enteritis
Sulfasalazine ▬▬▬► Sulfapyridine + 5-aminosalacylate
5AS (mesalamine) A comparable conc. of mesalamine in the colon cannot otherwise be obtained
-Can cause systemic toxic effects because of absorption of sulfapyridine
SULFACETAMIDE
Used for Rx of many sulfonamide-sensitive ophthalmic infections
An alternate for Rx of Chlamydia trachomatis
High concentrations (30%) aren’t irritating or allergenic & are of neutral pH
Readily penetrates ocular fluids, tissues
DEVELOPMENT OF RESISTANCE TO SULFONAMIDES
-Reduced sulfonamide uptake
-Alteration of drug binding site on dihydropteroate synthase can occur even during therapy
-Overproduction of PABA (competitive with drug at active site)
PHARMACOKINETICS OF SULFONAMIDES
Most are well absorbed orally (70-95%)
Most are widely distributed including into the CSF, fetus ( but sulfadiazine best for penetration of BBB)
Acetylation occurs in liver
inactivates &
decreases solubility
may be more readily excreted in the kidney
Elimination is by glomerular filtration with 10-20x concentration in urine
URINARY TRACT TOXICITY
-Crystals of sulfonamide & acetylated sulfonamide can cause renal damage
-Biggest problem is with sulfadiazine (Remember fluids, bicarbonate!)
-Must use reduced dosage (or cease use) if kidney function is impaired.
hypersensitivity rxns
Skin Rashes (2-3%) during 1st wk
Stevens-Johnson Syndrome
most serious rash (exfoliative)
most common with sulfadoxine (long-acting) but can occur with other sulfa drugs
Drug Fever (3%)
Photosensitivity
MECHANISM OF TMP-SMX
TMP [trimethoprim) competitively inhibits DHFR (dihydrofolate reductase)
SMX potentiates TMP by reducing [dihydroptoric ace that is availabe to compete with trimeth].
These combos are both bacteriocidal rather than bacteriostatic.
MECHANISM OF TRIMETHOPRIM & PYRIMETHAMINE
-Both competitively inhibit dihydrofolate reductase
-Both are superadditive with sulfas
-Both are bactericidal with sulfameth-oxazole
-Their selectivity is due to highly specific binding to bacterial/protozoal DHFR relative to the human DHFR (100,000/1).
RX USES OF TMP-SMX - I
-Treatment of choice or important alternate for 32 bacterial infections
-Gram-negative bacilli
-Actinomycetes
-Parasites
-Often used for oral Rx of uncomplicated UTIs
-Often used for Rx of otitis media in kids due to H. influenzae or Strep. pneumoniae
-Chronic bronchitis
-Shigellosis & Traveler's diarrhea, esp. in kids
DRUG RESISTANCE TO TMP-SMX
Much less common than against a single sulfonamide: only occurs via plasmid transfer.
TOXICITY OF TMP-SMX
AIDS patients: more frequent SEs including fever, rashes, leukopenia, & diarrhea.
-can produce anti-folate side effects lke anemia etc. can be prevented with folinic acid
-can cause cns effects like headache, depression, and hallucinations
-contra indicated in pt with renal malfunction
pharmokinetics
well absorbed orally with peak conc in 2 hr and t 1/2 = 11 hr; IV for serious infections.
-very lipid soluble and enters all body compartments.
-as with most sulfonamides, TMP crosses the placenta and achieves high urinary conc.