Nucleic Acid Synthesis Antibiotics

Question 1

Drugs that inhibit folic acid synthesis

Answer 1

Sulfonamides, Trimethoprim, and pyrimethamine

Question 2

Difference between sulfonamides and trimethoprim

Answer 2

Sulfonamides inhibit dihydropteroate synthetase (NOT found in humans)

Trimethoprim and pyrimethamine inhibit dihydrofolate reductase (found in humans)

Question 3

Sulfasalazine (5-ASA SP)

Answer 3

Prodrug used in ulcerative colitis (5-ASA) and rheumatoid arthritis (SP)

Remember that Oral Vancomycin can also be used to treat UC

Question 4

Ag sulfadiazine

Answer 4

used in burns

(silver is the more important component b/c sulfonamides are “useless” on their own)

Question 5

Uses of trimethoprim-sulfamethoxazole (cotrimoxazole)

aka TMP-SMX

Answer 5

DOC in Nocardia

Listeria (backup)

Gram (-) and (+) infections

Fungus: pneumocystis jiroveci (CD4<200)

Protozoa: toxoplasma gondii (CD4<100)

-sulfadiazine + pyrimethamine

Question 6

Pharmacokinetics of folate inhibitors

Answer 6

Sulfonamides are hepatically acetylated (conjugation)

Renally excreted metabolites cause crystalluria*

High protein binding (drug interaction and kernicterus in neonates**)

*Conjugate is less soluble than parent drug

**Avoid during 3rd trimester, displaces bilirubin from albumin

Question 7

Side effects of folate inhibitors

Answer 7

Sulfonamides: Hypersensitivity (rashes, Stevens-Johnson syndrome), Hemolysis in G6PD deficiency, Phototoxicity

Trimethoprim/pyrimethamine: BM suppression (leukopenia)

Question 8

What is folate required for?

Answer 8

Conversion of Uracil to Thymine (via methylation)

and the production of Adenine and Guanine

Question 9

Direct inhibitors of Nucleic Acid Sythesis

Answer 9

Quinolones:

Ciprofloxacin, Levofloxacin, and other “-floxacins”

Question 10

MOA of Ciprofloxacin

Answer 10

Quinolones are bactericidal and interfere with DNA synthesis

Inhibit topoisomerase II (DNA gyrase–controls super coiling) and topoisomerase IV (separates replicated DNA during cell division)

Resistance is increasing

Question 11

Activity and clinical uses of quinolones

Answer 11

UTIs, STDs/PIDs

Skin, soft tissue, and bone infections by gram (-) organisms

Diarrhea

Bacillus anthracis

Question 12

Pharmacokinetics of quinolones

Answer 12

Iron and calcium limit their absorption (similar to the chelating effect seen with tetracyclines–do not take with food)

Eliminated by the kidney by filtration and active secretion (blocked by probenecid)

Question 13

Side effects of quinolones

Answer 13

1. Tendonitis, tendon rupture (achilles)
2. Phototoxicity, rashes
3. CNS effects
4. Contraindicated in pregnancy and children (inhibiton of chondrogenesis)
5. Increased QT interval