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Nucleic Acid Synthesis inhibitors (Casey)
Kaplan + lecture+ First Aid (Casey)
23
Pharmacology
Graduate
11/04/2012

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Cards

Term
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Definition
Folic acid synthesis
Term
What are the nucleic acid synthesis inhibitors?
Definition
  • Sulfonamides
  • Trimethoprim
  • Pyrimethamine
Term
What are some examples of sulfonamides?
Definition
  • Sulfamethoxazole (SMX)
  • Sulfisoxazole
  • Sulfadiazine
Term
What is the mechanism of action for sulfonamides?
Definition

PABA antimetabolites inhibit dihydropteroate synthetase

 

Term
What are sulfonamides used against?
Definition

Gram +

Gram -

Nocardia

Chlamydia

Term
What is sulfasalazine and how does it work?
Definition
  • Prodrug
  • Bacteria breaks it to 5-aminosalicylic acid (NSAID) and sulfapyridine (RA)
Term
What are the toxicities of sulfonamides?
Definition
  • Hypersensitivity rxn
  • Hemolysis if G6PD deficient
  • Nephrotoxicity (tubulointerstitial nephritis)
  • Phtosensitivity
  • Kernicterus in infants
  • Displace other drugs from albumin (warfarin)
Term
What resistance issues do sulfonamides have?
Definition
  • Altered enzyme (bacterial dihydropteroate synthetase
  • Decreased uptake
  • Increased PABA synthesis
Term
What is the MOA of trimethorpim?
Definition
Inhibits bacterial dihydrofolate reductase
Term
Are nucleic acid synthesis inhibitors bacteriostatic or bacteriocidal?
Definition
Bacteriostatic
Term
What can trimethoprim be used for?
Definition
  • Used in combo w/ sulfonamides 
  • Ex: trimethoprim-sulfamethoxazole (TMP-SMX)
  • Combo against UTIs
  • Shigella
  • Salmonella
  • Pneumocystis jiroveci pneumoni
Term
What are the toxicities of trimethorpim?
Definition
  • Bone marrow suppression (TMP)
  • Megaloblastic anemia
  • Leukopenia
  • granulocytopenia
  • (Treat w/ supplemental folinic acid, leucovorin rescue)
Term
What is the MOA of fluoroquinolones?
Definition
  • Directly inhibits DNA
  • Blocks DNA gyrase (topoisomerase II and IV) 
  • TOP II: Prevents relaxation of supercoils 
  • TOP IV: prevents sister chromatids from combining
Term
Are fluoroquinolones bacterostatic or bactericidal?
Definition
Bactericidal
Term
What are examples of quinolones?
Definition

Ciprofloxacin
Norfloxacin
Ofloxacin
sparfloxacin
moxifloxacin
gatifloxacin
enoxacin

Term
What are quinolones used for?
Definition
  • G- rods of urinary and GI tracts 
  • Pseudomonas
  • Neisseria
  • Some G+ organisms
Term
What are the toxicities of quinolones?
Definition
  • Don't use with antacids
  • Phototoxicity (skin rashes)
  • Tendonitis/ tendon rupture in adults
  • Leg cramps/myalgias in children
  • NOT IN PREGNANT WOMEN AND CHILDREN (damages cartilage)
  • "Lones hurt attachment to Bones"
Term
How do bacteria get resistance to quinolones?
Definition

Chromosome-encoded mutation in DNA gyrase

Term
What class of drug does metronidazole fall under?
Definition
None, because its mechanism of action is not certain
Term
Is metronidazole bacteriostatic or bactericidal?
Definition
Bactericidal
Term
What is the possible MOA of metronidazole?
Definition
Forms free radical toxic metabolites in bacterial cell that damage DNA
Term
What is metronidazole used for?
Definition
  • Drug of choice for: Giardia, Trichomonas, Entamoeba
  • Most anaerobe G- (bacteroides) & C. dif
  • Use w/ bismuth/amoxicillin for "triple therapy" against H. Pylori
  • "GET GAP on the Metro!"
Term
What are the side effects for metronidazole?
Definition
  • Metallic taste
  • Disulfram like effect w/ alcohol
  • headache 
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