Lecture 5 Sulfa/Quinalones Flashcards
Sulfanilamide, the first sulfonamide (Sulfon) discovered, is derived from _____, which is inactive ______
protonosil; in vitro
The incorporation of ____ into the folic acid nucleus is inhibited competitively by the sulfonamides.
PABA (p-aminobenzoic acid)
What enzyme do sulfon drugs inhibit?
dihydropterate synthase
The activity of sulfons can be reversed by adding large quantities of _____ to the diet
PABA
Sulfanilamide is ____ acidic than PABA
less
The attachment of electron-withdrawing heteroaromatic rings ____ the sulfanilimide nitrogen and enhanced the ____
acidified;
potency
Increased acidity in sulfon drugs decreases the incidence of ______. Large amounts of ____ should still be drank to decrease kidney damage
crystalluria;
water
bactrim =
sulfamethoxazole (SMX) and trimethoprim (TMP)
Trimethroprim works by inhibiting _____
bacterial dihydrofolate reductase
When used together, SMX + TMP is bacterio_____
cidal
2 AIDS associated illnesses that Bactrim treats:
pneumocystis jirovecii
toxoplasmosis
What sulfon drug is used to treat ulcerative colitis and chron’s?
sulfasalazine
sulfasalazine is a prodrug that is not absorbed well in the ___ tract. One of its metabolites is 5-aminosalicylic acid, which has _______ activity.
GI;
anti-inflammatory
Examples of sulfonamide derivatives that are cross allergenic:
Diuretetics: _____ _____ inhibitors, ______, and _____
carbonic anhydrase; thiazide; furosemide
Adverse reactions of sulfon drugs include ____uria, and hematopoietic disturbances, such as _____, ______cytopenia, and ______cytopenia
crystall;
anemia; granulo; thrombo
Resistance to sulfon drugs: mutations leading to–>
- Increased production of ____
- decreased affinity of _______
- decreased cell _____
PABA;
dihydropterate synthase;
permeability
Sulfonamides are generally metabolized by N-4 N-__________ and in some cases N-1 ________
acetylation;
glucuronidation
What is the mechanism of quinolones (quinos), according to sketchy and FA?
inhibit bacterial topo-isomerase II (aka DNA gyrase) and topo-iosmerase 4
2nd gen quinolones have a _____ substituent at C6 and a ______ at C7 = increased potentcy and activity
Fluorine;
heterocyclic ring
3rd and 4th gen quinos have increased gram + activity, especially against _____
strep pneumo
____ is quniolone that is considered a drug of last resort due to severe side effects
Moxifloxacin
In general, what do topoisomerases do? (according to FA)
create single or double strand breaks in the DNA helix to remove supercoils
Topoisomerases have evolved that ____ DNA by cutting one (topoisomerase __) or two (topoisomerase __) DNA strands and allowing strand passage through the break
unwind;
I; II
Topisomerases carry out nucelophillic attack that cleaves DNA via a _____ residue binding to the __ end of DNA
tyrosine; 5’
Topoisomerases are responsible for reversible reactions: one reaction is DNA _____ and the opposite reaction is DNA _____
cleavage; religation
Specifically, Qunilones block _____ after separation by the topoisomerases
religation
General topoisomerase mechanism: the _ DNA segment is cleaved, the ___ DNA segment passes through, the ___ DNA segment religates
G (gate segment); T (Transported segment); G
Topoisermase cleavage/religation requires ____ and ATP ____ is involved
Mg2+; hydrolysis
Quinolones bind to the _____ complex, inhibiting ____. This causes double strand breaks and eventual death of bacteria due to _____
cleavage; religation; apoptosis
The most common use of quinolones is for _____; _____ in males
UTI’s; prostatitis
What STD’s are quinolones good for?
Chlamdyia, Neisseria, Haemophilus ducreyi
Quinolones are effective for treatment of ___ diarrhea caused by ____ E.coli
traveler’s; enterotoxigenic
_____ as a sole therapy is effective in 50% of diabetic foot infections
cipro
Quinolone resistance:
decreased cellular ____
efflux _____
point mutations in ________
permeability;
pumps;
DNA gyrase
Are serum drug levels or interstitial fluid drug levels typically higher with fluoroqunilones?
interstitial
What property do quinolones share with tetracyclines?
form chelates with heavy metals
_____ converts Cipro into an inactive metabolite that is secreted in the urine
UGT
Quinilones may damage _____ _____ and cause reversible _____ and are not normally recommended for treatment of patients under 18
growing cartilage; arthropathy
In elderly patients quinolones may cause ____
tendonitis or tendon rupture
Photosensitivity has been reported with this quinolone:
lomefloxacin
______ has been associated with hypo and hyperglycemia in diabetic patients
gaitfloxacin
