Pharmacology Exam 1

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synthesis of thymidine by dividing cells is supported by

folic acid
Thymidine is

a precursor to DNA
Bacteria synthesize folic acid from

p-aminobenzoic acid (PABA)
Do not make folic acid and must injest it

vertebrates
Inhibitors of folic acid synthesis
- sulfonamides
- target bacteria
Synthesis of folic acid
- Pteridine+Paba (Dihydropteroate synthase)
- Dihydropteroic acid + glutamate (dihydrofolic acid synthatase)
- Dihydrofolic acid + NADPH (Dihydrofolate reductase)
Sulfanilamide
- poor solubility and absorption
- first sulfonamide
More polar sulfonamides
- sulfamethoxazole
- sulfisoxazole
Sulfadiazine
- absorbed orally
- low solubility
- metabolized by CYP2C9
- more soluble in alkalinized urine
Sulfisoxazole
- more solube than sulfadiazine in urine
- excreted unchanged
- used for UTIs
Mafenide (Sulfamylon)

topical use only
Sulfasalazine (Axulfidine)
- Prodrug
- poor oral absorption
- active drug is sulfapyridine
- used for intestinal infections
Trimethoprim
- DHFR inhibitor
- 5000x more selective for bacteria
Trimethoprim/sulfamethoxazole
- combo block of folate metabolism
- synergistic effect
- MIC is 1/4 the MIC for each drug alone
Calculate the FIC for Trimethoprim/sulfamethoxazole

FIC = 0.25/1 +0.25/1 = 0.5
Methotrexate
- binds tightly to DHFR from all sources
- drawn to cancer cells because of high demand for nucleic acids
Resistance to methotrexate is due to

elevated levels of DHFR in resistant cells
Methotrexate is used in
- rheumatoid arthritis
- psoriasis
Adverse effects of sulfonamides

crystalization in urine causes renal damage
mechanisms to reduce crystals in urin from sulfonamides
- increase urine volume
- alkalinize urine with NaBicarb
Effects of sulfonamides on blood
- acute hemolytic anemia
- aplastic anemia
- agranulocytosis
GI effects of sulfonamides
- Anorexia
- vomiting
Sulfonamide effects on hair folicles

alopecia
Target of quinolones

DNA Gyrase (topoisomerase II)
Mechanism of action of quinolones

block DNA gyrase which blocks tension release in replicating DNA
Selectivity of quinolones

gram negative bacteria
Action of topoisomerase II

change topology from a positive supercoil to a negative supercoil
Naldixic acid
- early quinolone
- used only for lower UTIs
Fluoroquinolones
- Cipro, ofloxacin
- much more effective than naldixic acid
- better absorption and solubility
Half life of quinolones
- 3-10 hours
- once a day dosing
quinolones inhibit
- CYP1A2
- CYP2C9
- CYP3A4
Quinolones inhibit metabolism of
- warfarin
- theophylline
- NSAIDS
- Herbal & food supplements
Quercetin from food and herbal products

inhibits quinolones by biding DNA gyrase
Quinolones are not used in children due to

joint inflammation

Author

Rx2013

61161

Card Set

Pharmacology Exam 1

Description

Sulfonamides and Quinolones

Updated

2011-01-21T23:17:00Z

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