Micro - Antimicrobials (Antimicrobials inhibiting Folate synthesis & DNA)

Question 1

What are 3 examples of sulfonamides?

Answer 1

(1) Sulfamethoxazole (SMX) (2) Sulfisoxale (3) Sulfadiazine

Question 2

What is the mechanism of sulfonamides?

Answer 2

Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase.

Question 3

Are sulfonamides bacteriostatic or bacteridical?

Answer 3

Bacteriostatic

Question 4

What is the clinical use for sulfonamides?

Answer 4

Gram-positive, Gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.

Question 5

What is the medication for simple UTI?

Answer 5

Triple sulfas or SMX for simple UTI

Question 6

What are 6 toxicities of sulfonamides?

Answer 6

(1) Hypersensitivity reactions (2) Hemolysis if G6PD deficient (3) Nephrotoxicity (tubulointerstitial nephritis) (4) Photosensitivity (5) Kernicterus in infants (6) Displace other drugs from albumin (e.g., warfarin)

Question 7

What effect can sulfonamides have on G6PD deficient patients?

Answer 7

Hemolysis if G6PD deficient

Question 8

What effect can sulfonamides have related to albumin? Give a specific example of this.

Answer 8

Displace other drugs from albumin (e.g., warfarin)

Question 9

What are 3 mechanisms of resistance against sulfonamides?

Answer 9

(1) Altered enzyme (bacterial dihydropteroate synthase), (2) decreased uptake, or (3) increased PABA synthesis

Question 10

Draw the folate synthesis pathway from PABA to DNA/RNA/Protein, noting where sulfonamides and trimethoprim/pyrimethamine act.

Answer 10

Pg. 185 in First Aid 2014 for visual at bottom of the page

Question 11

What is the mechanism of trimethoprim?

Answer 11

Inhibits bacterial dihydrofolate reductase.

Question 12

Is trimethoprim bacteriostatic or bactericidal?

Answer 12

Bacteriostatic.

Question 13

With what other drug is trimethoprim used in combination, and why? For what is this combination used clinically?

Answer 13

Used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX], causing sequential block of folate synthesis; Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.

Question 14

What are 3 toxicities associated with trimethoprim? How may this be alleviated?

Answer 14

(1) Megaloblastic anemia (2) Leukopenia (3) Granulocytopenia; May alleviate with supplemental folic acid; Think: “TMP: Treats Marrow Poorly”

Question 15

What is are 8 examples of fluoroquinolones?

Answer 15

(1) Ciprofloxacin (2) Norfloxacin (3) Levofloxacin (4) Ofloxacin (5) Sparfloxacin (6) Moxifloxacin (7) Gemifloxacin (8) Enoxacin

Question 16

What is another drug type that acts similarly to fluoroquinolones? What is a specific example of this type of drug?

Answer 16

Nalidixic acid (a quinolone)

Question 17

What is the mechanism of fluoroquinolones?

Answer 17

Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV.

Question 18

Are fluoroquinolones bacteriostatic or bactericidal?

Answer 18

Bactericidal

Question 19

With what must fluoroquinolones not be taken?

Answer 19

Must not be taken with antacids

Question 20

What is the clinical use for fluoroquinolones?

Answer 20

Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms

Question 21

What are the 5 most common toxicities of fluoroquinolones?

Answer 21

(1) GI upset (2) Superinfections (3) Skin rashed (4) Headache (5) Dizziness

Question 22

Again, what are the 5 most common toxicities of fluoroquinolones? What are 4 less common toxicities of fluoroquinolones?

Answer 22

(1) GI upset (2) Superinfections (3) Skin rashes (4) Headache (5) Dizziness; Less commonly, can cause (1) tendonitis, (2) tendon rupture, (3) leg cramps, and (3) myalgias; Think: “fluoroquinoLONES hurt attachments to your BONES.”

Question 23

What are 3 patient populations in which fluoroquinolones are contraindicated, and why?

Answer 23

Contraindicated in (1) pregnant women, (2) nursing mothers, and (3) children under 18 years old due to possible damage to cartilage.

Question 24

What cardiovascular toxicity may be caused by some fluoroquinolones?

Answer 24

Some may cause prolonged QT interval

Question 25

In what 2 patient populations may fluoroquinolones cause tendon rupture?

Answer 25

May cause tendon rupture in people > 60 years old and in patients taking prednisone

Question 26

What is the mechanism of resistance against fluoroquinolones?

Answer 26

Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.

Question 27

What is the mechanism of metronidazole?

Answer 27

Forms free radical toxic metabolites in the bacterial cell that damage DNA.

Question 28

Is metronidazole bacteriostatic or bactericidal?

Answer 28

Bactericidal

Question 29

What is the clinical use for metronidazole?

Answer 29

Antiprotozoal. Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile). Used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. Pylori.; Think: “GET GAP on the Metro with Metronidazole!”

Question 30

What treats anaerobic infection below the diaphragm versus above the diaphragm?

Answer 30

Metronidazole treats anaerobic infection below the diaphragm versus clindamycin (anaerobic infection above diaphragm)

Question 31

What drugs are used in “triple therapy” against H. pylori?

Answer 31

Metronidazole used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. pylori

Question 32

What can occur when metronidazole is taken with alcohol? What are 2 other toxicities to associate with metronidazole?

Answer 32

Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; Headaches, Metallic taste