Pharmacology of Quinolones and Fluoroquinolones

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of the following is NOT a characteristic of quinolone and fluoroquinolone drugs?

They are generally well absorbed orally.

They inhibit bacterial DNA gyrase.

They achieve high concentrations in the central nervous system (CNS). (correct)

They are bactericidal in action.

Which bacterial enzyme is primarily targeted by quinolone antibiotics?

DNA gyrase (Topoisomerase II) (correct)

Topoisomerase IV

DNA Polymerase

RNA Polymerase

What describes the mechanism of bacterial resistance to quinolones and fluoroquinolones?

Enzymatic inactivation of the drug

Changes in bacterial cell wall permeability

Modification of the drug target site (DNA gyrase) through gene mutations (correct)

Increased expression of efflux pumps

What is the main function of topoisomerase II (DNA gyrase) in bacterial cells?

To introduce negative supercoils into DNA. (A) Signup and view all the answers

Identify a drug that has been removed from the US market due to the potential for QT prolongation and torsade de pointes.

Sparfloxacin (B) Signup and view all the answers

At what concentration do quinolones typically inhibit eukaryotic topoisomerase II compared to bacterial DNA gyrase?

Much higher concentrations for eukaryotic topoisomerase II (A) Signup and view all the answers

Which of these drugs that is mentioned in the content is used specifically for acute skin and skin structure infections (ASSIs)?

Delafloxacin (B) Signup and view all the answers

What is the main reason for the removal of Trovafloxacin from the US market?

Hepatic damage (A) Signup and view all the answers

Which fluoroquinolone demonstrates primary elimination via the renal route?

Ofloxacin (C) Signup and view all the answers

Which statement accurately describes the impact of food on the oral absorption of fluoroquinolones?

Food does not impair absorption, but delays time to peak serum concentration. (B) Signup and view all the answers

In cases of renal dysfunction, dosage adjustments are necessary for all of the following fluoroquinolones EXCEPT:

Moxifloxacin (B) Signup and view all the answers

Which of the following fluoroquinolones are known to have good in-vitro activity against Strep. pneumoniae?

Levofloxacin (B) Signup and view all the answers

Against which of the following microorganisms is Ciprofloxacin more active than Norfloxacin?

Pseudomonas aeruginosa (B) Signup and view all the answers

What is the primary clinical use for prophylactic fluoroquinolones in transurethral surgeries?

To reduce the risk of post-surgical UTI (A) Signup and view all the answers

Which fluoroquinolone is classified as a 'respiratory' fluoroquinolone designed for both oral and intravenous administration?

Levofloxacin (A) Signup and view all the answers

Which of the following fluoroquinolones does NOT require dosage adjustments in patients with renal dysfunction?

Pefloxacin (B) Signup and view all the answers

What is the typical range for the serum half-lives (in hours) observed with the majority of tested fluoroquinolones?

3-11 hours (A) Signup and view all the answers

Which statement is true regarding the use of fluoroquinolones in the treatment of sexually transmitted infections (STIs)?

They are effective against gonorrhea, but not syphilis. (B) Signup and view all the answers

Which of the following is a primary mechanism of action for nitrofurantoin in treating UTIs?

Inhibiting acetyl CoA, disrupting bacterial carbohydrate metabolism. (D) Signup and view all the answers

Why are fluoroquinolones generally not recommended for use in people under 18 years of age?

They can cause arthropathy and damage to immature cartilage of weight-bearing joints. (A) Signup and view all the answers

Which of the following describes the action of methenamine in treating UTIs?

It releases formaldehyde in acidic urine, which is directly toxic to bacteria. (A) Signup and view all the answers

Why are sulfonamides not recommended to be used concurrently with methenamine?

Sulfonamides form insoluble complexes with methenamine, reducing their efficacy. (D) Signup and view all the answers

Which fluoroquinolone is primarily excreted through nonrenal pathways?

Moxifloxacin (D) Signup and view all the answers

In which patient group is nitrofurantoin contraindicated, due to the risk of hemolytic anemia?

Patients with glucose-6-phosphate dehydrogenase deficiency (A) Signup and view all the answers

In a multi-drug regimen for Mycobacterium avium complex (MAC) in HIV patients, which of the following is NOT typically used alongside ciprofloxacin?

Rifampin (B), Ethambutol (D) Signup and view all the answers

Which fluoroquinolone has the highest oral bioavailability?

Levofloxacin (B) Signup and view all the answers

Which drug has the longest half-life among those listed?

Moxifloxacin (B) Signup and view all the answers

Which of these fluoroquinolones is typically dosed twice daily?

Ofloxacin (D) Signup and view all the answers

What is a primary mechanism of resistance to fluoroquinolones?

Point mutations on the enzyme binding sites (D) Signup and view all the answers

Which combination of antibiotics is used in treating multi-drug resistant tuberculosis (MDR-TB)?

Ciprofloxacin and Amikacin (A) Signup and view all the answers

Which fluoroquinolone has the highest peak serum concentration?

Delafloxacin (D) Signup and view all the answers

What is a clinical application of fluoroquinolones in neutropenic patients?

Decreasing gram-negative bacteremias (D) Signup and view all the answers

Which of these fluoroquinolones has the lowest oral bioavailability?

Delafloxacin (A) Signup and view all the answers

Which of the following best describes the use of ciprofloxacin in treating infections?

It is used in combination with vancomycin for empiric therapy of both MRSA and Pseudomonas aeruginosa infections. (B) Signup and view all the answers

Which statement accurately reflects the role of fluoroquinolones in treating respiratory infections?

They exhibit good in-vitro activity against a wide range of respiratory pathogens, including H.influenzae, Moraxella catarrhalis, and Legionella pneumophila. (C) Signup and view all the answers

Which statement best describes the use of moxifloxacin in treating urinary tract infections (UTIs)?

It is not indicated for the treatment of UTIs due to inadequate therapeutic levels in the urinary tract. (D) Signup and view all the answers

What is the role of fluoroquinolones in treating prostatitis?

They, including norfloxacin, ciprofloxacin, levofloxacin, and ofloxacin, are equally efficacious in treating prostatitis. (D) Signup and view all the answers

What is the role of fluoroquinolones in the treatment of sexually transmitted diseases (STDs)?

They can be given for Chlamydia urethritis but have limited use in the treatment of Gonorrhea due to emerging resistance. (A) Signup and view all the answers

Which of the following statements accurately describes a limitation of fluoroquinolones in the treatment of STDs?

They have no activity against Treponema pallidum, the causative agent of syphilis. (D) Signup and view all the answers

For which group of infections are Norfloxacin, ciprofloxacin or ofloxacin indicated?

Traveler’s diarrhea and shigellosis. (B) Signup and view all the answers

For which infection is Delafloxacin indicated and available in oral and parenteral formulation?

Acute skin and skin structure infections (ASSIs) and community acquired pneumonia (CAP). (A) Signup and view all the answers

What is a key factor that makes fluoroquinolones suitable for treating chronic osteomyelitis?

Their oral availability and broad spectra of activity. (A) Signup and view all the answers

Which statement is most accurate regarding the use of fluoroquinolones in the treatment of gonorrhea?

Ofloxacin and ciprofloxacin are effective as an alternative to IM ceftriaxone or oral cefixime, but resistant strains are emerging. (A) Signup and view all the answers

Study Notes

DNA Synthesis Inhibitors: Quinolones & Fluoroquinolones

Quinolones in the market include Ciprofloxacin (Cipro, Proquin P#), Ofloxacin (Floxin, P#), Norfloxacin (Noroxin), Levofloxacin (Levaquin, Quixin P#), Gemifloxacin (Factive), Moxifloxacin (Avelox, Vigamox), Lomefloxacin (Maxaquin), Delafloxacin (Baxdela), Besifloxacin (ophthalmic, conjunctivitis), and Nalidixic acid (original quinolone, seldom used).
Some drugs are used to treat acute skin and skin structure infections (ASSSI), and some are used in MRSA infections - denoted by an asterisk (*).

Drugs Removed from the Market

Sparfloxacin (Zagam) was removed due to QT prolongation and torsades de pointes.
Grepafloxacin (Raxar) was removed due to torsades de pointes.
Trovafloxacin-Alatrofloxacin (Trovan) was removed due to hepatic damage.
Gatifloxacin (Tequin) was removed due to commercial reasons (ophthalmic formulation still available).

Mechanism of Action

DNA strands must separate for replication and transcription.
Topoisomerase II (DNA gyrase in prokaryotes) introduces negative supercoils in DNA to prevent positive supercoiling during unwinding; this is an ATP-dependent process involving cutting and resealing DNA.
DNA gyrase in E. coli is a large enzyme with one A subunit (105kD) and two B subunits (95kD each).
Quinolones inhibit gyrase-mediated DNA supercoiling at concentrations of 0.1 to 10 ug/mL.
Quinolones also inhibit topoisomerase IV in bacteria.
Eukaryotes use a different topoisomerase II, which is inhibited by quinolones at higher concentrations (100 to 1000 ug/mL).
Fluoroquinolones are bactericidal.

Mechanism of Resistance

Point mutations in the GyrA gene, encoding a subunit of DNA gyrase, are a mechanism of quinolone resistance.

Pharmacokinetics and Classification

Quinolones have good oral bioavailability and penetrate most tissues except the CNS.
Peak serum levels are reached within 3 hours of administration.
Food does not significantly affect absorption but may delay the time to peak serum levels.
Serum half-lives range from 3-11 hours.
Some quinolones are eliminated renally (Ofloxacin, Lomefloxacin, Cinoxacin), while others are not (Pefloxacin, Nalidixic acid).
Gemifloxacin is eliminated via renal and biliary routes.
Levofloxacin is primarily eliminated renally.
Dosage adjustments are necessary in cases of renal dysfunction for certain quinolones.

Antimicrobial Spectrum

Fluoroquinolones are generally bactericidal and effective against various bacteria, including E. coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria (and others associated with periodontal disease, diarrhea, and dysentery).
MIC for 90% of these strains is typically less than 0.2 ug/mL.
Ciprofloxacin is more effective than norfloxacin against Pseudomonas aeruginosa, enterococci and pneumococci.
Fluoroquinolones show activity against Staphylococcus including some MRSA strains.
Resistance to quinolones can develop during therapy.
The drugs are effective against various gram-negative organisms, as well as certain species of Brucella, Mycoplasma, Chlamydia and Mycobacteria.
Ciprofloxacin and Ofloxacin have MIC90 of 0.5 to 3ug/ml for mycobacteria.
They are used in the treatment of gonorrhea but not syphilis.
Prophylactically used in certain transurethral surgeries to reduce post-surgical UTIs.

Indications

Respiratory Tract Infections: Poor activity against Streptococcus pneumoniae, anaerobic bacteria, thus beta-lactams are often preferred. Levofloxacin and moxifloxacin are effective against Streptococcus pneumoniae and anaerobic bacteria and other specific respiratory pathogens. Levofloxacin may be administered intravenously or orally for infections such as community-acquired, nosocomial and ventilator-associated pneumonias.
UTIs: Quinolones such as Norfloxacin, Ciprofloxacin, Levofloxacin and Ofloxacin, along with TMP-SMX are equally efficacious. Moxifloxacin does not reach therapeutic levels in the urinary tract and is not indicated for UTIs.
Prostatitis: Norfloxacin, Ciprofloxacin, Levofloxacin, and Ofloxacin are equally efficacious.
STDs: Quinolones show no activity against Treponema pallidum. Contraindicated during pregnancy.
GI Infections: Effective against traveller's diarrhea, shigellosis - Norfloxacin, Ciprofloxacin, and Ofloxacin are effective. Norfloxacin is superior to TMP-SMX for cholera. Ciprofloxacin and Ofloxacin cure Salmonella typhi enteric fever. Delafloxacin is used in acute skin and skin structure infections (ASSIS) and Community-acquired pneumonia (CAP).
Bone Joint and Soft Tissue Infections: Effective against Staphylococcus aureus in chronic osteomyelitis; use in combination with anaerobic drugs for diabetic foot infections.
Multi-drug resistant Tuberculosis (MDR-TB) and atypical mycobacterial infections: Quinolones such as Ciprofloxacin are included in multi-drug regimens for M. avium complex infections in AIDS patients.

Other Indications

Used in neutropenic cancer patients with fever to reduce the incidence of gram-negative bacteremias.
Can be used in the treatment of tuberculosis and atypical mycobacteria.
Treat meningococci in carriers.
Resistance is mostly due to point mutations in the enzymes where fluoroquinolones bind.
Elimination varies based on the drug:
- Renal: Ofloxacin, lomefloxacin, cinoxacin, norfloxacin, ciprofloxacin, enoxacin
- Non-renal: Nalidixic acid, Pefloxacin

Toxicity

Common side effects include gastrointestinal disturbances (diarrhea, nausea, vomiting), skin rashes, headache, dizziness, insomnia, and abnormal liver function.
Not recommended for young patients and during pregnancy due to cartilage erosion concerns.
Tendonitis and tendon rupture have been reported.
Not recommended for use in people under 18 due to possible arthropathy and cartilage damage in weight-bearing joints.

Urinary Antibiotics

Nitrofurantoin (1953): Active at acidic pH; inhibits acetyl-CoA, used for UTIs; similar to nalidixic acid. Adverse effects include acute pneumonitis, neuropathies, and hemolysis (in glucose-6-phosphate dehydrogenase deficient patients). Contraindicated in neonates and pregnant women due to hemolytic anemia potential.
Methenamine (1939): Decomposes into formaldehyde in acidic urine; increases urinary pH and effectiveness against certain bacterial strains; not effective against Proteus, which increase pH. Bacterial resistance does not develop. Contraindicated in hepatic insufficiency.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on quinolone and fluoroquinolone antibiotics with this quiz. Covering their mechanisms, resistance, and specific drug profiles, this quiz is essential for pharmacology students. Dive deep into the characteristics, uses, and impacts of these important medications.