Antimetabolites

Question 1

antimetabolites are divided into 2 based on their MOA

Answer 1

1. Anti-folate drugs (sulfonamide, trimethoprim)
2. Bacterial DNA replication inhibitors (fluoroquinolone)

Question 2

sulfonamides inhibit _________________

Answer 2

dihydropteroate synthase, thereby inhibiting folate synthesis

Question 3

trimethoprim is classified under

Answer 3

pyrimidine

Question 4

sulfonamides: weak acid :: trimethoprim: ________________

Answer 4

weak base

Question 5

what are the organisms that sulfonamide inhibits

Answer 5

gram positive, gram negative, Nocardia sp., Chlamydia trachomatis, some protozoa

Question 6

what other organisms does sulfonamide acts against?

Answer 6

E. coli, K. pneumoniae, Salmonella, Shigella, Enterobacter

Question 7

sulfonamide resistance

Answer 7

1. overproduction of PABA (p-aminobenzoic acid)
2. production of folic acid-synthesizing enzyme that has low affinity for sulfonamides
3. impaired permeability to sulfonamides

Question 8

types of sulfonamides

Answer 8

1. oral absorbable (sulfisoxazole, sulfamethoxazole, sulfadiazine, sulfadoxine)
2. oral non-absorbable
3. topical (sodium sulfacetamide, mafenide acetate)

Question 9

absorption site of sulfonamides

Answer 9

stomach and small intestines

Question 10

sulfonamides are widely distributed in?

Answer 10

tissues and body fluids

Question 11

sulfonamide protein binding

Answer 11

20% to 90%

Question 12

a portion of sulfonamides undergo ________________ or _______________ in the liver

Answer 12

acetylation or glucuronidation

Question 13

how are sulfonamides excreted

Answer 13

through glomerular filtration

Question 14

oral absorbable sulfonamides

Answer 14

1. sulfisoxazole, sulfamethoxazole
2. sulfadiazine
3. sulfadoxine

Question 15

used primarily for UTI

Answer 15

sulfisoxazole, sulfamethoxazole

Question 16

used in combination with pyrimethamine for 1st line treatment of acute toxoplasmosis

Answer 16

sulfadiazine

Question 17

long-acting, coformulated with pyrimethamine, and is used as 2nd line treatment for malaria

Answer 17

sulfadoxine

Question 18

oral nonabsorbable sulfonamide

Answer 18

used for ulcerative colitis, enteritis, and other IBD (inflammatory bowel disease)

Question 19

topical sulfonamides

Answer 19

1. sodium sulfacetamide
2. mafenide acetate

Question 20

ophthalmic solution or ointment for treatment of bacterial conjunctivitis

Answer 20

sodium sulfacetamide

Question 21

for burns

Answer 21

mafenide acetate

Question 22

pyrimidines

Answer 22

1. trimethoprim
2. pyrimethamine

Question 23

trimethoxybenzylpyrimidine

Answer 23

trimethoprim

Question 24

benzylpyrimidine

Answer 24

pyrimethamine

Question 25

inhibits bacterial form and prevents formation of tetrahydrofolate

Answer 25

trimethoprim

Question 26

pyrimidine (trimethoprim & pyrimethamine) resistance can result from

Answer 26

1. reduced cell permeability 2. overproduction of dihydrofolate reductase 3. production of an altered reductase with reduced drug binding

Question 27

usually given orally

Answer 27

trimethoprim

Question 28

pyrimidines are well absorbed in the _______ and widely distributed in _______________

Answer 28

gut; body fluids

Question 29

T/F: trimethoprim/pyrimethamine are more lipid soluble than sulfamethoxazole

Answer 29

T

Question 30

pyrimidines are weak base concentrates in __________________ and _________________

Answer 30

prostatic fluid and vaginal fluid

Question 31

given alone in acute UTI and used for CAP

Answer 31

trimethoprim

Question 32

TMP-SMX targets what organisms

Answer 32

gram positive, gram negative, opportunistic pathogens (Pneumocystis jirovecii, T. gondii, Nocardia)

Question 33

TMP-SMX are also used for?

Answer 33

UTI, prostatitis, COPD exacerbation, acute otitis media, traveller’s diarrhea

Question 34

toxicity associated with TMP-SMX

Answer 34

hypersensitivity reactions, cross-allergy, NVD, rare granulocytopenia and thrombocytopenia, hemolysis

Question 35

group of broad spectrum antibiotic; bactericidal and inhibits bacterial DNA replication

Answer 35

fluoroquinolone

Question 36

fluoroquinolones cover what organisms

Answer 36

anaerobic and atypical organisms and some gram positive and multi-drug resistant organism

Question 37

how many fluoroquinolone generations are there?

Answer 37

4

Question 38

1st gen fluoroquinolone

Answer 38

norfloxacin

Question 39

2nd gen fluoroquinolone

Answer 39

ciprofloxacin, ofloxacin

Question 40

3rd gen fluoroquinolone

Answer 40

levofloxacin, moxifloxacin, gemifloxacin

Question 41

4th gen fluoroquinolone

Answer 41

delafloxacin

Question 42

what generation of fluoroquinolone have more gram negative activity

Answer 42

2nd generation (ciprofloxacin, ofloxacin)

Question 43

gonococcus, active against atypical bacteria (M. pneumoniae, C. pneumoniae)

Answer 43

2nd gen (ciprofloxacin, ofloxacin)

Question 44

fluoroquinoline generation that is less active against gram negative bacteria with greater activity against gram positive cocci and MRSA, anaerobes

Answer 44

3th generation (levofloxacin, moxifloxacin, gemifloxacin)

Question 45

T/F: fluoroquinolones does not have good oral bioavailability

Answer 45

F - good oral bioavailability

Question 46

fluoroquinolones have ________________ of distribution; accumulates in the ___________

Answer 46

large volume; tissues

Question 47

how are fluoroquinolones eliminated?

Answer 47

tru kidney via secretion

Question 48

fluoroquinolone that has hepatic clearance and may be used in renal failure

Answer 48

moxifloxacin

Question 49

T1/2 of fluoroquinolones

Answer 49

3-9 hrs

Question 50

primary method of fluoroquinolone elimination

Answer 50

via renal tubular secretion

Question 51

bactericidal, interferes with DNA topoisomerase with a post antibiotic effect

Answer 51

fluoroquinolone

Question 52

fluoroquinolone resistance

Answer 52

1. decrease intracellular accumulation due to changes in porins 2. efflux mechanisms 3. change in sensitivity of target enzymes via point mutation

Question 53

fluoroquinolone toxicity

Answer 53

GI distress, skin rashes, headache insomnia phototoxicity, tendinitis, tendon rupture not for pregnant women or growing children newer agent: QT interval prolongation