Lecture 5 Sulfa/Quinalones

Question 1

Sulfanilamide, the first sulfonamide (Sulfon) discovered, is derived from _____, which is inactive ______

Answer 1

protonosil; in vitro

Question 2

The incorporation of ____ into the folic acid nucleus is inhibited competitively by the sulfonamides.

Answer 2

PABA (p-aminobenzoic acid)

Question 3

What enzyme do sulfon drugs inhibit?

Answer 3

dihydropterate synthase

Question 4

The activity of sulfons can be reversed by adding large quantities of _____ to the diet

Answer 4

PABA

Question 5

Sulfanilamide is ____ acidic than PABA

Answer 5

less

Question 6

The attachment of electron-withdrawing heteroaromatic rings ____ the sulfanilimide nitrogen and enhanced the ____

Answer 6

acidified;

potency

Question 7

Increased acidity in sulfon drugs decreases the incidence of ______. Large amounts of ____ should still be drank to decrease kidney damage

Answer 7

crystalluria;

water

Question 8

bactrim =

Answer 8

sulfamethoxazole (SMX) and trimethoprim (TMP)

Question 9

Trimethroprim works by inhibiting _____

Answer 9

bacterial dihydrofolate reductase

Question 10

When used together, SMX + TMP is bacterio_____

Answer 10

cidal

Question 11

2 AIDS associated illnesses that Bactrim treats:

Answer 11

pneumocystis jirovecii

toxoplasmosis

Question 12

What sulfon drug is used to treat ulcerative colitis and chron’s?

Answer 12

sulfasalazine

Question 13

sulfasalazine is a prodrug that is not absorbed well in the ___ tract. One of its metabolites is 5-aminosalicylic acid, which has _______ activity.

Answer 13

GI;

anti-inflammatory

Question 14

Examples of sulfonamide derivatives that are cross allergenic:
Diuretetics: _____ _____ inhibitors, ______, and _____

Answer 14

carbonic anhydrase; thiazide; furosemide

Question 15

Adverse reactions of sulfon drugs include ____uria, and hematopoietic disturbances, such as _____, ______cytopenia, and ______cytopenia

Answer 15

crystall;

anemia; granulo; thrombo

Question 16

Resistance to sulfon drugs: mutations leading to–>

1. Increased production of ____
2. decreased affinity of _______
3. decreased cell _____

Answer 16

PABA;
dihydropterate synthase;
permeability

Question 17

Sulfonamides are generally metabolized by N-4 N-__________ and in some cases N-1 ________

Answer 17

acetylation;

glucuronidation

Question 18

What is the mechanism of quinolones (quinos), according to sketchy and FA?

Answer 18

inhibit bacterial topo-isomerase II (aka DNA gyrase) and topo-iosmerase 4

Question 19

2nd gen quinolones have a _____ substituent at C6 and a ______ at C7 = increased potentcy and activity

Answer 19

Fluorine;

heterocyclic ring

Question 20

3rd and 4th gen quinos have increased gram + activity, especially against _____

Answer 20

strep pneumo

Question 21

____ is quniolone that is considered a drug of last resort due to severe side effects

Answer 21

Moxifloxacin

Question 22

In general, what do topoisomerases do? (according to FA)

Answer 22

create single or double strand breaks in the DNA helix to remove supercoils

Question 23

Topoisomerases have evolved that ____ DNA by cutting one (topoisomerase __) or two (topoisomerase __) DNA strands and allowing strand passage through the break

Answer 23

unwind;

I; II

Question 24

Topisomerases carry out nucelophillic attack that cleaves DNA via a _____ residue binding to the __ end of DNA

Answer 24

tyrosine; 5’

Question 25

Topoisomerases are responsible for reversible reactions: one reaction is DNA _____ and the opposite reaction is DNA _____

Answer 25

cleavage; religation

Question 26

Specifically, Qunilones block _____ after separation by the topoisomerases

Answer 26

religation

Question 27

General topoisomerase mechanism: the _ DNA segment is cleaved, the ___ DNA segment passes through, the ___ DNA segment religates

Answer 27

G (gate segment); T (Transported segment); G

Question 28

Topoisermase cleavage/religation requires ____ and ATP ____ is involved

Answer 28

Mg2+; hydrolysis

Question 29

Quinolones bind to the _____ complex, inhibiting ____. This causes double strand breaks and eventual death of bacteria due to _____

Answer 29

cleavage; religation; apoptosis

Question 30

The most common use of quinolones is for _____; _____ in males

Answer 30

UTI’s; prostatitis

Question 31

What STD’s are quinolones good for?

Answer 31

Chlamdyia, Neisseria, Haemophilus ducreyi

Question 32

Quinolones are effective for treatment of ___ diarrhea caused by ____ E.coli

Answer 32

traveler’s; enterotoxigenic

Question 33

_____ as a sole therapy is effective in 50% of diabetic foot infections

Answer 33

cipro

Question 34

Quinolone resistance:
decreased cellular ____
efflux _____
point mutations in ________

Answer 34

permeability;
pumps;
DNA gyrase

Question 35

Are serum drug levels or interstitial fluid drug levels typically higher with fluoroqunilones?

Answer 35

interstitial

Question 36

What property do quinolones share with tetracyclines?

Answer 36

form chelates with heavy metals

Question 37

_____ converts Cipro into an inactive metabolite that is secreted in the urine

Answer 37

UGT

Question 38

Quinilones may damage _____ _____ and cause reversible _____ and are not normally recommended for treatment of patients under 18

Answer 38

growing cartilage; arthropathy

Question 39

In elderly patients quinolones may cause ____

Answer 39

tendonitis or tendon rupture

Question 40

Photosensitivity has been reported with this quinolone:

Answer 40

lomefloxacin

Question 41

______ has been associated with hypo and hyperglycemia in diabetic patients

Answer 41

gaitfloxacin