Nucleic Acid Inhibitors

Question 1

there are 2 nucleic acid inhibitors

Answer 1

1. Inhibitors of Folic Acid Synthesis
2. Direct Inhibitors of Nucleic Acid Synthesis

Question 2

what are the Folic Acid Synthesis inhibitors?

how does each work?

Answer 2

1. Sulfonamides: analogues of PABA; inhibits dihydropteroate synthase and the synthesis of folic acid in microbe
2. Trimethoprim: analogue of folic acid; inhibits the dihydrofolate reductase

Question 3

systemic sulfonamides are divided into long, intermediate and short acting…name these.

Answer 3

• Sulfisoxazole (short acting)
• sulfamethoxazole (intermediate acting)
• Sulfadoxine (long acting)

Question 4

what is the topical sulfonamide?

how do bacteria create resistance against sulfonamides?

Answer 4

silver sulfadiazine

1. Increased PABA synthesis: overcomes the inhibition of dihydropteroate synthetase
2. Decreased uptake
3. Altered enzyme: dihydropteroate synthetase mutates

Question 5

how do bacteria become resistant to trimethoprim?

what is the trimethoprim drug?

Answer 5

alter dihydrofolate reductase

TMP-SMK

(trimethoprim alone= bacteriostatic)

(TMP-SMX = bacteriocidal)

Question 6

for what do you use:

• Sulfasalazine?
• sulfacetamide?
• silver sulfadiazine?
• sulfadiazine + Pyrimethamine?

Answer 6

• ulcerative colitis, rheumatoid arthritis
• conjunctivitis
• Burns
• Toxoplasmosis

Question 7

using sulfonamides can cause these toxicities

Answer 7

• Nausea, Vomiting - common
• Stevens-Johnson syndrome: severe rash
• Crystalluria = Nephrotoxic due to crystal formation (white urine)
• Hemolysis in G-6-PD deficiency
• Phototoxicity

Question 8

when do you use trimethoprim? (DOC only)

what toxicity can occur by using trimethoprim?

Answer 8

• Nocardiosis
• Urinary Tract Infectio
• prevention and treatment of Pneumocystis jirocecii in AIDS (CD4 count less than 200)

Megaloblastic anemia, granulocytopenia

Question 9

what is the only direct inhibitor of nucleic acid synthesis?

how does it work?

there are 2 groups or fluoroquinolones…say them…

Answer 9

Fluoroquinolones

Inhibiting bacterial Topoisomerase II (DNA gyrase)

1. first group: norfloxacin
2. second group: cipro, lomeflaxin, ofloxacin, levofloxacin, pefloxacin
3. third group: Sparfloxacin, Moxifloxacin, Travofloxacin, Gatifloxacin

Question 10

how do bacteria develop resistance to fluoroquinolones?

Answer 10

efflux pump

Changed sensitivity of the target enzymes topoisomerase IV (Gr + ve bacteria ) and topoisomerase II (Gr – ve bacteria)

Question 11

what is the least active fluoroquinolone?

when is that same fluoroquinolone used?

when do you use second group of fluoroquinolone?

Answer 11

Norfloxacin

Urinary tract infection

Cipro: Typhoid, Gonorrhea,

Ofloxacin: Gonorrhoea/Chlamydia

Levofloxacin: Drug resistant pneumococci (DOC)

Question 12

what is the only 3rd group fluoroquinolone you have to remember and what does it do?

Answer 12

Sparfloxacin: drug resistant pneumococci