Fluoroquinolone Pharmacology: Key Terms & Definitions | Quizlet

MOA of fluoroquinolones

inhibition of DNA replication/translation by preventing the relaxation of supercoiled DNA

MOA of Sulfonamides

Inhibits nucleotide precursor biosynthesis

MOA of Rifampin and Fidaxomicin

inhibits RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase

What was the molecule that lead to the discovery of quinolones?

Nalidixic acid

Are quinolones bactericidal or bacteriostatic?

bactericidal

What is the pharmacophore of quinolones?

4-pyridone ring with a 3-carboxylic acid group

What part of the quinolone structure allows for cell wall penetration?

Flourine at C6

Elimination of what bond in a Quinolone eliminates its activity?

2,3 double bond

What substitution at C7 improves gram negative activity of quinolones?

heterocyclic

What positions on a quinolone affect its gram positive potency?

R1 alkyl group

R2 substitutions

2nd gen fluoroquinolones

Ciprofloxacin

Ofloxacin

3rd gen fluoroquinolones

Levofloxacin

Gatifloxacin

Gemifloxacin

4th gen fluoroquinolones

Moxifloxacin

Besifloxacin

Delafloxacin

new Fluoroquinolone with a 4 membered N-ring at the C7 position (azetidine)

1st gen quinolones spectrum of activity

limited to gram negatives

2nd gen quinolones spectrum of activity

Limited to gram negatives and atypicals

Which quinolones cover Pseudomonas?

Ciprofloxacin

Levofloxacin

3rd gen quinolones spectrum of activity

Gram positive (strep)

Gram negative

Atypicals

4th gen quinolones spectrum of activity

Gram positive

Gram negative

Atypicals

Anaerobes

What are the bacterial resistance mechanisms to quinolones?

Altered target

Decreased accumulation

Quinolones ADRs

Athropathy

QT prolongation

Hypo/hyperglycemia

GI upset

Photosensitivity

What are the contraindications of quinolones?

<18 y/o

pregnancy

Myasthenia gravis

Sulfonamides

Sulfamethoxazole

Silver Sulfadiazine

Sulfisoxazole

The amino and sulfonyl groups of a Sulfonamide antibiotic should be at what two positions?

1,4 - para positions

Monosubstitution at what position on a quinolone increases its activity?

N1

Sulfonamides spectrum of activity

Gram positive (including MRSA)

Gram negative

ADRs of Sulfonamides

GI upset

Photosensitivity

Hypersensitivity

SJS

Crystalluria

DHFR Inhibitors

Trimethoprim

Pyrimethamine

MOA of DHFR Inhibitors

inhibit dihydrofolate reductase (sequential blocking)

Sequential blocking

synergistic activity as a result of sequential step in the synthesis of the folic acid pathway

ADRs of Trimethoprim

Rash

Increased SCr

Hyperkalemia

Rifampin MOA

Inhibits DNA-dependent RNA polymerase (bactericidal)

ADRs of Rifampin

Discoloration of body fluids

Hepatotoxicity

GI disturbances

Rifampin spectrum of activity

Mycobacterial infections

Fidaxomicin spectrum of activity

gram positive anaerobes (primarily clostridioides)