DNA Function Inhibitors

Question 1

Fluoroquinolones: examples

Answer 1

• ciprofloxacin
• levofloxacin
• gemifloxacin
• moxifloxacin

Question 2

Fluoroquinolones: mechanism of action

Answer 2

• DNA transcription inhibitor
• targets bacterial DNA gyrase and topoisomerase IV
• rapidly bactericidal

Question 3

Fluoroquinolones: pharmacokinetics

Answer 3

• good oral, parenteral also available
• good penetration into most tissues
• primarily kidney excretion

Question 4

Fluoroquinolones: spectrum/clinical uses

Answer 4

• gram+ cocci (strep. pneumoniae, MSSA)
• gram- cocci (moraxella catarrhalis)
• gram+ bacilli (bacillus anthracis)<–cipro
• gram- bacilli (pseudomonas aeruginosa, E. coli)
• anaerobes
• atypical organisms (chlamydia, mycoplasma pneuemoniae, richettsia)

Question 5

Fluoroquinolones: adverse reactions

Answer 5

• well tolerated
• increased risk of tendon rupture
• GI disturbances
• drug-drug: reduced absorption w/anacids

Question 6

Fluoroquinolones: “1st generation” + spectrum

Answer 6

Naldixic acid: gram- anaerobes (++)

Question 7

Fluoroquinolones: “2nd generation” + spectrum

Answer 7

Cipro & Levo: gram- anaerobes (++), pseudomonas (+), gram+ (+/++)

Question 8

Fluoroquinolones: “3rd generation” + spectrum

Answer 8

Gemi & Moxi: gram- anaerobes (+), pseudomonas (+/-), gram+ (++), atypical (+), anaerobes (++)

Question 9

Nitrofurantoin: mechanism of action

Answer 9

• DNA damage-inducer

- concentration-dependent bacteriostatic/bactericidal effect

Question 10

Nitrofurantoin: pharmacokinetics

Answer 10

• good oral

- short half-life –> urine (renal excretion)

Question 11

Nitrofurantoin: spectrum/clinical uses

Answer 11

• 2nd line urinary tract antiseptic (cannot safely reach plasma levels, but concentrated in renal tubules)
• E. coli & enterocci

Question 12

Nitrofurantoin: adverse reactions

Answer 12

• GI disturbances

- possible link to birth defects

Question 13

Metronidazole: mechanism of action

Answer 13

• DNA damage inducer
• prodrug–>reactive nitro radical anion
• radical anion damages DNA
• bactericidal

Question 14

Metronidazole: pharmacokinetics

Answer 14

• good oral
• good distribution (including bone/CSF)
• liver metabolism
• excreted in breast milk

Question 15

Metronidazole: spectrum/clinical uses

Answer 15

• anaerobes (C. difficile, Bacteriodes fragilis)

- protozoa

Question 16

Metronidazole: adverse reactions

Answer 16

• some GI disturbance
• headaches, dry mouth
• candidal superinfection

Question 17

Sulfonamides: mechanism of action

Answer 17

• DNA synthesis inhibitor
• inhibits folic acid synthesis (PABA analog) which is required for DNA synthesis
• bacteriostatic

Question 18

Sulfonamides: pharmacokinetics

Answer 18

• good oral (best on empty stomach)
• widely distributed
• some protein binding
• n-acetylation metabolism (can be toxic)
• excreted by kidney

Question 19

Sulfonamides: spectrum/clinical uses

Answer 19

• broad spectrum; most common use in TMP/SMX form
• gram+ cocci (MRSA)
• gram- cocci (Moraxella catarrhalis)
• gram- bacilli (enetrobacter, shigella, pseudomonas aeruginosa)
• atypical (chlamydia)

Question 20

Sulfonamides: adverse reactions

Answer 20

• generally safe
• sensitization reactions
• drug-drug: displace from proteins –> bilirubin, anticoagulants

Question 21

Sulfonamides: bacterial resistance

Answer 21

• widespread in vivo
• acquired: increase PABA production or DHPS altered to decrease binding to sulfonamides
• escape: obtain end products of metabolic pathway from pus (why we must drain some purulent infections)
• natural: organisms w/no folic acid requirement

Question 22

Sulfonamides: common drug combination

Answer 22

• synergy w/trimethoprim (TMP)

- sulfamethoxazole + TMP (aka TMP/SMX or “Bactrim”= bactericidal