Nucleic Acid Synthesis Inhibitors

Question 1

What are the classes of nucleic acid synth inhibitors?

Answer 1

Fluoroquinolones

• 1st: nalidixic acid
• 2nd: ciprofloxacin
• 3rd: levofloxacin
• 4th: gemifloxacin, moxifloxacin

Sulfonamides

• sulfmethoxazole
• sulfadiazine
• sulfasalazine

Trimethoprim

Co-trim-oxazole
-combination of trimethoprim and sulfmethoxazole

Question 2

Sulfonamides? What are they? MOA?

Answer 2

PABA analogs

in bacteria PABA –> folic acid –> DHF –> THF

enzymes:
dihyrdrofolate synth –> dihydrofolate reductase –> dihydrofolate reductase

Sulfonamides replace PABA –> decrease purine synthesis
*competitive inhibitors

Question 3

Sulfonamides are bacteriostatic or cidal? Spectrum?

Answer 3

gram positive and gram negative

all nucleic acid synthesis kill gram pos and neg

bacteriocidal

Question 4

sulfonamides Resistance mech? 4

Answer 4

plasmid transfer or random mutation

1. in dihydropteroate synthase
2. inc PABA
3. dec cell perm
4. dec drug accumulation

Question 5

Sulfonamides admin? Used to treat

Answer 5

topical, oral

Topical: ocular or burn infections

Oral: UTIs

Sulfasalazine: oral: ULCERATIVE COLITIS, ENTERITIS IBD

Question 6

Sulfonamides adverse effects?

Answer 6

• Hypersensitivity
• hematopoietic disturbances (in pts with G6PDH def)

-crystalluria
sulfonamides are acetylated in the liver –> precipitate at neutral or acidic pH –> kidney damage

-kernicterus
sulfa drugs displace other drugs from albumin

Question 7

Sulfonamides contraindications?

Answer 7

Newborns and babies under 2 months

kernicterus

Question 8

Trimethoprim bacteriocidal or static? spectrum?

Answer 8

affects both gram positive and negative

• bacterioSTATIC
• doesnt kill just stops growth

Question 9

Trimethoprim MOA?

Answer 9

inhibits dihydrofolate reductase

inhibits (not 100% stops)
purine
pyrimidine
AA (methionine) synthesis

Question 10

Trimethoprim contraindications

Answer 10

DO NOT GIVE IN PREGNANCY

-antifolate effects in mammals

Question 11

Trimethorprim used to treat?

Answer 11

UTIs, bacterial prostatitis and vaginitis

high concentrations get to prostatic and vaginal fluids

Question 12

What cephalosporin is known to cause kernicterus?

Answer 12

Ceftriaxone

Question 13

Cotrimoxazole is a combination of what? MOA?

Answer 13

trimethoprim (dihhyrdofolate reducatse inhib) and sulfamethoxazole (sulfonamide - PABA analog)

Bacteriocidal
-synergism: ibhibits sequential steps in THF synth

Question 14

Cotrimoxazole used to treat?

Answer 14

Uncomplicated UTIs
(DOC)

Opportunistic infections in the immunocompromised (ie. cancer –> chemo)

Question 15

Cotrimoxazole admin?

Answer 15

oral or IV

Question 16

Cotrimoxazole AE?

Answer 16

dermatologic
hematologic (like sulfa drugs )

higher AE in AIDS patients

Question 17

Contrimoxazole contraindications?

Answer 17

Contraindicated in pregnancy
esp 1st trimester ***

remember cotrimoxazole contains trimethoprim (red folate therefore also contraindicated in pregnancy)

Question 18

Name of miscellaneous drug? What does it treat?

Answer 18

Polymyxcin B: cationic detergent

MOA: binds to bacterial cell membranes
binds to endotoxins (LPS) –> inactivates it

bacteriocidal

treats infected superficial skin lesions

Question 19

Polymyxin B admin?

Answer 19

topical only
infected superficial skin lesions

systemically –> severe nephrotoxicity

Question 20

Polymyxcin B spectrum?

Answer 20

gram positive only

remember MOA : bind to endotoxins

Question 21

What is the name of the urinary antiseptic? spectrum?treats? admin?

Answer 21

Nitrofurantoin

gram positive and negative
(cover all the bases)

tx: lower UTIs
admin: oral

Question 22

Nitrofurantoin AE?

Answer 22

hemolytic anemia in people that are G6PDH deficient

recall MOA:
in urine, nitrofurantoin gets reduced –> forms reactive intermediate which damages bacterial DNA

Question 23

Nitrofurantoin bacteriocidal or static?

Answer 23

can be both

Question 24

Nitrofurantoin contraindications>

Answer 24

Mom at full term
infants under a month

babies have immature G6P DH

-and people with renal insufficiency
remember the drug basically stays in the urine and has no systemic effects