RX of LUT infections and STIs (Waller DSA) - SRS

Question 1

What are the penicillin drugs highlighted for tx of LUT and STI?

Answer 1

1. Penicillin G (IV, IM)
2. Ampicillin (PO, IV, IM)

Question 2

Which cephalosporin was highlighted for tx of LUT and STI?

Answer 2

Ceftriaxone

Question 3

What beta-lactamase inhibitors were highlighted for LUT and STI?

Answer 3

1. Ampicillin-sulbactam [Unasyn] (IV)

Question 4

Which fluoroquinolone was highlighted for the treatment of LUT and STI?

Answer 4

Cipro

Question 5

What macrolide/ketolide was highlighted for tx of LUT/STI?

Answer 5

1. Azithromycin [Zithromax, Z-pak] (PO, IV, topical)

Question 6

Flagyl was in red on our drug list, what do we also know this drug as?

Answer 6

Metronidazole

Question 7

What sulfonamides/trimethoprim was in red on the drug list?

Answer 7

1. Sulfamethoxazole/trimethoprim [Bactrim] (PO, IV)

Question 8

What are the two urinary tract antiseptics?

Answer 8

1. Methenamine (PO)
2. Nitrofurantoin (PO)

Question 9

Fosfomycin is on our drug list, what is the only route of administration listed for it?

Answer 9

PO (just not sure what else to ask at this point)

Question 10

What azole antifungal is in red on our drug list?

Answer 10

Fluconazole (PO, IV)

Question 11

What is the MOA of Trimethoprim/sulfamethoxazole (TMP/SMX)?

Answer 11

sulfonamides are bacteriostatic, competitive inhibitors of dihydropteroate synthase; while synergistic trimethoprim inhibits dihydrofolate reductase.

Question 12

What are the ADRs of TMP/SMX?

Answer 12

1. Allegic skin rashes
2. nausea
3. vomiting
4. CNS- headache and depression
5. photosensitivity
6. renal dysfunction
7. Stevens-Johnson Syndrome

Question 13

What is a key DDI for TMP/SMX?

Answer 13

CYP inhibitor, so it potentiates the effects of warfarin.

Question 14

If paired with ACEi, ARBs and spironolactone, what is a possible negative consequence you may see from TMP/SMX?

Answer 14

Enhanced hyperkalemic effects

Question 15

1. Nitrofurantoin MOA?
2. Explain the selectivity of this drug

Answer 15

1. MOA: drug reduced forming highly reactive intermediates which damage DNA, bacteria reduce drug more rapidly than mammalian cells, thought to account for selective activity.

Question 16

ADRs of nitrofuranatoin

Answer 16

N/V

Diarrhea

Question 17

In what patients is nitrofurantoin CI?

Answer 17

Pregnant women

Children under 1 month

those with impaired renal function

Question 18

While not a primary ITI drug Methenamine has value as a chronic suppressive therapy. What is the MOA Methenamine?

Answer 18

1. MOA: decomposes in water to formaldehyde, acidification of urine promotes formaldehyde formation, slow process (requires 3 hours to complete).

Question 19

What are the ADRs of methenamine?

Answer 19

1. GI distress,
2. painful/frequent micturition,
3. hematuria,
4. rash,
5. low systemic toxicity at usual doses.

Question 20

What is the MOA of fosfomycin?

Answer 20

1. MOA: bactericidal, inhibits very early stage of bacterial cell wall synthesis. Inactivates pyruvyl transferase which leads to reduced formation of N-acetylmuramic acid, which is only found in bacterial cell walls.

Question 21

What ADRs for fosfomycin?

Answer 21

Diarrhea

Nausea

ab pain

headache

Question 22

MOA ciprofloxacin?

Answer 22

1. MOA: concentration-dependent killing, targets bacterial DNA gyrase and topoisomerase IV.

Question 23

MOA Beta lactam drugs?

Answer 23

1. MOA: inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis. Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid). Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine. Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link. B-lactams are structural analogs of D-Ala-D-Ala. B-lactams covalently bind PBPs preventing cross-linking ultimately leading to cell autolysis.

Question 24

ADRs of fluoroquinolones?

Answer 24

1. GI 3-17% most common (mild nausea, vomiting, abdominal discomfort),
2. CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)
3. , rash,
4. photosensitivity
5. , Achilles tendon rupture.

Question 25

What is the DOC for susceptible enterococci?

Answer 25

Ampicillin (IV)

Question 26

What are some ADRs of Penicillin G?

Answer 26

1. allergic reactions (0.7-10%), 2. anaphylaxis (0.004-0.04%) 3. interstitial nephritis (rare), 4. pseudomembranous colitis, 5. Jarisch-Herxheimer reaction.

Question 27

MOA azithromycin?

Answer 27

1. **MOA:** bacteriostatic, binds reversibly to 50S ribosomal subunit, inhibits translocation of newly synthesized peptidyl tRNA molecule from acceptor site on ribosome to peptidyl donor site.

Question 28

ADRs azithromycin?

Answer 28

1. **ADRs:** GI (epigastric distress), hepatotoxicity, arrhythmia, QT prolongation.

Question 29

What does azithromycin do to CYP?

Answer 29

Inhibits CYP3A4

Question 30

What is the MOA of metronidazole?

Answer 30

1. **MOA:** prodrug, requires reductive activation of nitro groups. Single electron transfer in anaerobic bacteria forms highly reactive nitro radical anions, kills organisms by radically mediated mechanisms that target DNA. Increasing 0₂ inhibits metronidazole as 0₂ competes for electrons.

Question 31

What are some ADRs of metronidazole?

Answer 31

headache, nausea, dry mouth, metallic taste. Vomiting, diarrhea, abdominal distress occasionally. Neurotoxic: dizziness, vertigo, very rarely encephalopathy. Well-reported disulfiram effect à abdominal distress, vomiting, flushing, headache, if alcohol consumed during/within 3 days of drug.

Question 32

What are some DDIs of metronidazole?

Answer 32

induced metabolism of phenobarbital, prednisone, and rifampin. Prolongs prothrombin time in those receiving warfarin.

Question 33

MOA of azole antifungals? Explain the selectivity

Answer 33

1. **MOA:** inhibits fungal cytochrome P450, reducing production of ergosterol. 1. Selective toxicity due to greater affinity for fungal rather than human cytochrome P450 enzymes.

Question 34

What are some ADRs from azoles?

Answer 34

minor GI upset, abnormalities in liver enzymes.

Question 35

Describe the impact of the azoles on the CYPs

Answer 35

1. **DDIs: MANY!!** Inhibits CYP1A2 (weak), CYP2C19 (strong), CYP2C9 (moderate), CYP3A4 (moderate).