Who?

Question 1

Fluroquinolones

Answer 1

Ciprofloxacin
Levofloxacin
Moxifloxacin

Question 2

Fluroquinolones - Mechanism of Action

Answer 2

Inhibits DNA gyrase (topoisomerase II)
That blocks DNA synthesis by preventing DNA unwinding
Acts on Gram -ve

Inhibits Topoisomerase IV
Prevents separation of DNA during division
Acts on Gram +ve

Question 3

Fluroquinolones- NOT effective against which species

Answer 3

MRSA
Anerobic
E Coli
May lead to C Diff

Question 4

Fluroquinolones- MechAnism of Resistance

Answer 4

• mutation of DNA gyrase
• enhanced drug efflux
• decreased influx

Question 5

Fluroquinolones- Properties

Answer 5

• newer drugs are fluoridated
• active against G+ and G-
• used against resp, skin, urinary, bone, kidney, ear
• concentration dependent killing

Question 6

Fluroquinolones- Classification

Answer 6

Strong against Gram - & better against + Ciprofloxacin, Levofloxacin

Strong against both Moxifloxacin

Question 7

Ciprofloxacin - Major Indications

Answer 7

Gram - (esp. Pseudomonas)

Complicated UTI
Traveler’s diarrhea
Drug resistant -ve rods
PPx/Tax - anthrax

Question 8

Levofloxacin and Moxifloxacin - Major Indications

Answer 8

Gram -ve rods and cocci
Some anerobes
Staph and Strep
Legionella TB

Community acquired atypical Pneumonia
Non-TB mycobacterium

Question 9

Fluroquinolones - ADME

Answer 9

• absorption impaired by metals (antacids)
• usually orally admin
• large volume of distribution
• readily excreted in urine (need dose adj for renal)
• exception: moxifloxacin has hepatic tox,

Question 10

Fluroquinolones - AE

Answer 10

-GI
-damage to growing cartilage
-tendonitis rupture
can occur early on or months after treatment
usually achilles rupture (50% bilateral)
discontinue if there are sign of tendon pain/swelling

Question 11

Fluroquinolones - More Tox

Answer 11

• acute psychosis in patients taking theophylline or NSAID
• QT prolongation (maxi and levo)
• should not generally be given to pregnant women or kids (except CF)
• may interact with P450

Question 12

DNA Synthesis Inihibitors

Answer 12

antifolates

fluroquinolones

Question 13

Antifolates (sulfonamides)

Answer 13

sulfamethoxazole (SMX)
trimethoprim
combo - TMP/SMX

Question 14

Folates in Metabolism do what?

Answer 14

involved in aa as well as nucleic acid synthesis , so need in both DNA and RNA replication/transcription

• IN BACTERIA ONLY - PABA goes to dihydrofolic acid (folate) via dihydropteroate synthase (SMX acts on this enzyme)
• IN HUMANS AND BACTERIA - folate converts via dihydrofolate reductase to tetrahydrofolic acid (which converts to purine). TMP acts on DHFR

Question 15

TMP is selective for what?

Answer 15

Prokaryotic DHFR

Question 16

where do we get folate from?

Answer 16

our diet

Question 17

Resistance to Sulfonamides

Answer 17

impaired uptake
increased efflux
mutation in dihydropteroate synthase
mutation leading to increased PABA synthesis
cross-resistance common

Question 18

What do you need to do when taking sulfonamides?

Answer 18

Drink lots of water, because the sodium salts can precipitate.

Question 19

What is cotrimoxazole?

Answer 19

SMX/TMP PO (Bactrim) - combination is bacteriocidal

Question 20

Cotrimoxazole - Indications

Answer 20

uncomplicated UTI/prostatitis
otitis/sinusitis
MRSA skin and soft tissue

Question 21

Sulfonamides - ADME

Answer 21

t1/2 relatively short
gets into CNS/CSF
no no if pregnant
hepatic metabolism 
excreted in urine - conjugated metabolites may precipitate in acidic urine - alkalize

Question 22

Sulfonamides - AE

Answer 22

• hypersensitivity (1-2 weeks) less than 5%
• hematopoietic toxicity (G6PD deficiency)
• newborns can’t excrete - kernicterus (bilirubin in the CNS)