Sulfonamides,trimethoprim and quinolones 12/17

Question 1

sulfonamides

Answer 1

structural analogs of PABA (para-aminobenzoic acid)

Question 2

MOA of sulf.

Answer 2

competitively inhibit conversion of PABA to folic acid mediated by the enzyme dihydropteroate synthase

bacteriostatic

Question 3

antimicrobial spectrum of sulf.

Answer 3

G+,G-,chlamydia and nocardia

Question 4

mechanisms of resistance for sulf.

Answer 4

microbial overproduction of PABA

structural changes that occur in bacterial dihydropteroate synthase

decreased permeability

Question 5

pharmacokinetics of sulf.

Answer 5

high oral bioavailability

distributed in most tissues (CSF)

acetylation in liver. product has no AB activity but retains toxic potential of parent drug

excreted in urine by glomerular filtration

Question 6

Topical

Answer 6

silver sulfadiazine:burns

sulfacetamide:conjunctivitis,corneal ulcer,other ocular infx

triple sulfa:vaginitis caused by hemophilus vaginalis

Question 7

Oral sulf. (few indications for use of oral agents alone)

Answer 7

sulfasoxazole: uncomplicated UTI
sulfamethoxazole: combined with trimethoprim for uncomplicated UTI

sulfadoxine/pyramethamine:malaria.sulfadoxine is very long acting

sulfadiazine/pyramethamine:toxoplasmosis

dapsone: leprosy (with others)
sulfasalazine: not absorbed,active ingredient is 5-aminosalicylic acid.inflammatory bowel disorder

Question 8

AE of sulf

Answer 8

topical: irritation,burning
oral: hypersens.,n/v/d,crystaluria,hemolytic anemia in pts wit G-6-P dehydrogenase deficiency,kernicterus in newborn (due to significant plasma protein binding and displacement of biliruben)

Also displacement of warfarin increasing its levels

Question 9

trimethoprim

Answer 9

inhibits dihydrofolate reductase of bacteria>mammalian cells. Methotrexate is not selective

bacteriostatic

Question 10

pharmacokinetics of trimethoprim

Answer 10

high oral bioavailability

well distributed in tissues (CSF)

most excreted unchanged in urine

Question 11

Uses of trimethoprim alone

Answer 11

uncomplicated UTI

Question 12

uses of trimethoprim/sulfamethoxazole

Answer 12

PO: pneumonia due to pneumocystis carinii

GI infx:shigella,enteritis

systemic infx:nocardia,salmonella

UTI and resp infx by H.influenzae or S.pneumonae

Listeria meningitis

IV:pneumocystis carinii pneumonia

Question 13

AE of TMP-SMX

Answer 13

rare hematopoietic disturbances

use folinic acid to prevent

Question 14

MOA of quinolones

Answer 14

inhibit topoisomerase II (DNA gyrase) and topoisomerase IV

prevents unwinding of supercoiled DNA required for transcription and duplication

inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA

minimal effect on mammalian enzyme

Question 15

resistence against quinolones

Answer 15

modification of DNA gyrase or topoisomerase IV structure

alteration of membrane permeability into bacterial cell

Question 16

pharmacokinteics of quino.

Answer 16

well absorbed orally (norfloxacin is lowest)

food+antacids decrease bioavailability

widely distributed

plasma protein binding is low

most is eliminated through urine by filtration and proximal tubular secretion (which is inhibited by probenecid)

Question 17

Uses of quinol. topical

Answer 17

eye

ciprofloxacin for conjuctivitis,corneal ulcer

Question 18

most fluroquinolones are used orally

Answer 18

resistant UTI (cipro and levo)

osteomyelitis and cellulitis(levo,moxi,gemi)

infectious diarrhea and typhoid fever

single dose Tx for gonorrhea(cipro and levo)

pseudomonas(cipro and levo)

Anthrax(cipro and levo)

Question 19

levofloxacin,gemifloxacin,moxifloxacin

Answer 19

resp tract infx and community acquired pneumonia

reserved for pts with comorbid/risk factors

Question 20

Cipro

Answer 20

available IV

Question 21

Local AE of quinol.

Answer 21

irritation,stinging,burning

Question 22

systemic AE of quinolones

Answer 22

n/v/d

may damage growing cartilage–> not recommended for pregnant women or kids.can cause tendonitis

some can prolong QT.avoid with other antiarrythmic

Question 23

CRANK to remember AE of sulfonamides

Answer 23

Crystalluria

Rashes

Anemia

Nausea

Kernicterus

Question 24

Pts who are at risk of getting pneumocystis pneumonia and have allergy to sulfa drugs–>

give ATOVAQUONE

Answer 24

collapses mitochondrial membrane potential

use with caution in pts with renal impairment

caution in pregnancy

abd pain,n/v,headache

Question 25

First group of quinolones

Answer 25

against G- and some activity against G+

Cipro

Question 26

second group of quinolones

Answer 26

improved activity against G+;especially S.pneumoniae

levo,moxi,gemi