Tag: Fluoroquinolones

Fluoroquinolones

FLUOROQUINOLONES

Q. 1

Which drug does not need dose adjustment in a patient with creatinine clearance of

 A

Ciprofloxacin

 B

Sparfloxacin

 C

Lomefloxacin

 D

Trovafloxacin

Q. 1

Which drug does not need dose adjustment in a patient with creatinine clearance of

 A

Ciprofloxacin

 B

Sparfloxacin

 C

Lomefloxacin

 D

Trovafloxacin

Ans. D

Explanation:

Dose adjustment is not required for Trovafloxacin, Moxifloxacin, Pefloxacin and Nalidixic acid for patient with decreased creatinine clearence. Trovafloxacin will cause liver damage and increase in liver enzymes. So it is contraindicated in patients with active liver disease.

 
Ref: Sherwood L. Gorbach, John G. Bartlett, Neil R. Blacklo (2004), Chapter 26, “Quinolones”, “Infectious Diesases”, 3rd Edition, Lippincott Publications, USA, Page 253 ; Kalzung, 9th Edition, Page 779.

Q. 2

Fluoroquinolones act on –

 A

DNA histone proteins

 B

DNA gyrase

 C

Camp

 D

mRNA polymerise

Q. 2

Fluoroquinolones act on –

 A

DNA histone proteins

 B

DNA gyrase

 C

Camp

 D

mRNA polymerise

Ans. B

Explanation:

Ans. is ‘b’ i.e., DNA gyrase

o Fluoroquinolones (including ciprofloxacin) inhibit DNA gyrase and topoisomerase IV. For gram negative bacteria, the primary target is DNA gyrase, while topoisomerase IV is inhibited in gram positive bacteria.


Q. 3

Highest photosensitivity is seen with –

 A

Pefloxacin

 B

Gatifloxacin

 C

Levofloxacin

 D

Sparfloxacin

Q. 3

Highest photosensitivity is seen with –

 A

Pefloxacin

 B

Gatifloxacin

 C

Levofloxacin

 D

Sparfloxacin

Ans. D

Explanation:

Ans. is ‘d’ i.e., Sparfloxacin

o Highest incidence of phototoxicity is seen with lomefloxacin (most common) and sparfloxacin, followed by pefloxacin.

Quiz In Between


Q. 4

Drug withdrawn in Inida is ?

 A

Levofloxacin

 B

Gatifloxacin

 C

Moxifloxacin

 D

Ofloxacin

Q. 4

Drug withdrawn in Inida is ?

 A

Levofloxacin

 B

Gatifloxacin

 C

Moxifloxacin

 D

Ofloxacin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Gatifloxacin

o Gatifloxacin has recently been banned in India, due to risk of severe hyperglycemia in elderly.

Note: Following FQs have been withdrawn from the market because of their rare but potentially fatal side effects (Goodman & Gilman 1 Pie 1119)

o Temafloxacin                             Immune hemolytic anemia                         o Grepafloxacin           Cardiotoxicity

o Trovafloxacin                         Hepatotoxicity                                            o Clinafloxacin             Phototoxicity


Q. 5

Which of the following fluoroquinolones does not require dose adjustment in a patient with creatinine clearance of < 50mg/min -

 A

Ciprofloxacin

 B

Trovafloxacin

 C

Lomefloxacin

 D

Sparfloxacin

Q. 5

Which of the following fluoroquinolones does not require dose adjustment in a patient with creatinine clearance of < 50mg/min -

 A

Ciprofloxacin

 B

Trovafloxacin

 C

Lomefloxacin

 D

Sparfloxacin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Trovofloxacin

  • Fluoroquinolones that are excreted primarily by non renal mechanism and for which adjustment is not needed in renal pathology include :
  1. Nalidixic acid                      3. Trovafloxacin                  5. Moxifloxacin
  2. Grepofloxacin                     4. Pefloxacin
  • Fluroquinolones that are primarily excreted by renal mechanisms and for which dose adjustment is needed include:

1. Ciprofloxacin                      3. Gatifloxacin                              5. Lomefloxacilin                7. Ofloxacin

2. Cinafloxacin                       4. Levofloxacilin                            6. Norfloxacin

  • Sparfloxacin has 50% renal and 50% faecal route of excretion and hence dose adjustment may be required in renal pathology.

Q. 6

All are true about ciprofloxacin except

 A

C/I in pregnancy

 B

DNA inhibition

 C

Most potent 1st generation fluoroquinolone

 D

More active at acidic pH

Q. 6

All are true about ciprofloxacin except

 A

C/I in pregnancy

 B

DNA inhibition

 C

Most potent 1st generation fluoroquinolone

 D

More active at acidic pH

Ans. D

Explanation:

Ans. is ‘d’ i.e., More active at acidic pH

Ciprofloxacin is the most potent first generation FQ.

o Ciprofloxacin inhibit DNA gyrase and is contraindicated in pregnancy.

It is less active at acidic pH.

Quiz In Between


Q. 7

Ciprofloxacin should not be used with theophylline because-

 A

it decreases efficiency of theophylline

 B

it increases toxicity of theophylline

 C

it decreases efficiency of ciprofloxacin

 D

it decreases absorption of theophylline

Q. 7

Ciprofloxacin should not be used with theophylline because-

 A

it decreases efficiency of theophylline

 B

it increases toxicity of theophylline

 C

it decreases efficiency of ciprofloxacin

 D

it decreases absorption of theophylline

Ans. B

Explanation:

Ans. is ‘b’ i.e., It increases the toxicity of theophylline

Important interactions of FOs

o Plasma concentration of theophylline, caffine and warfarin are increased by ciprofloxacin, norfloxacin and pefloxacin.

o NSAIDSs enhance CNS toxicity of FQS.

o Antacids, sucralfate and iron salts reduce absorption of FQs.


Q. 8

Fluoroquinolone with minimum bioavailability ‑

 A

Levofloxacin

 B

Moxifloxacin

 C

Norfloxacin

 D

Ciprofloxacin

Q. 8

Fluoroquinolone with minimum bioavailability ‑

 A

Levofloxacin

 B

Moxifloxacin

 C

Norfloxacin

 D

Ciprofloxacin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Nortloxacin

Quiz In Between



Fluoroquinolones

FLUOROQUINOLONES


FLUOROQUINOLONES

  • Oral agents.
  • Have long post-antibiotic effect (PAE).

MOA:

  • Acts by inhibiting DNA gyrase (topoisomerase II) & topoisomerase IV –> DNA replication inhibition.

Classification of fluoroquinolones:

  • Based on spectrum of antibacterial activity:        
  • 1st generation:
    • Narrow spectrum; mainly gram-negative.
    • Norfloxacin, lomefloxacin.
  • 2nd generation:
    • Ciprofloxacin & ofloxacin.
  • 3rd generation:
    • More active against gram-positive.
    • Levofloxacin, gatifloxacin, pefloxacin, sparfloxacin.
  • 4th generation:
    • Broadest spectrum.
    • Moxifloxacin, fleroxacin, garenoxacin, gemifloxacin & trovafloxacin.

Pharmacokinetics:

  • Good oral bioavailability (except norfloxacin).
    • Levofloxacin – 100% bioavailability.
  • Multivalent cations interfere with absorption (like tetracycline).               

Metabolism & excretion:

  • Hepatic metabolism & biliary excretion
    • Moxifloxacin & trovafloxacin.
  • Excreted by both renal & hepatic route – 
    • Sparfloxacin & pefloxacin.
  • Excreted by tubular secretion – 
    • All other drugs (ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin & ofloxacin).
    • Probenecid inhibits tubular secretion.

Half-lives:

  • Sparfloxacin, moxifloxacin & trovafloxacin – Long half-lives.
  • Sparfloxacin – Longest half-life among fluoroquinolones.
  • Hence, administered once daily orally.

Dose adjustment:

  • Required in renal disease for all fluoroquinolones, except pefloxacin, moxifloxacin & trovafloxacin (mnemonic: PMT).

Individual drug description:

  • Levofloxacin:
    • L-isomer of ofloxacin.
  • Sparfloxacin:
    • Greater activity against gram-positive organisms; Ineffective against Pseudomonas.

Clinical Uses:

  • Greatest activity against Pseudomonas (maximum with ciprofloxacin).
  • Uses of 1st generation drugs:
    • Norfloxacin – Useful in UTI.
    • Urinary concentration is bactericidal; Ineffective for systemic use.
  • Uses of 2nd generation drugs:
    • Ciprofloxacin – DOC for prophylaxis & treatment of anthrax & for prophylaxis of meningococcal meningitis.

Combination drugs:

  • Ciprofloxacin & ofloxacin – Effective against gonorrhea & other gram-negative organisms including Pseudomonas.
  • Ciprofloxacin & levofloxacin – Only fluoroquinolones effective against Pseudomonas.
  • Levofloxacin -Effective against atypical microorganism (mycoplasma) infection.
  • “Respiratory fluoroquinolones”: 
    • Levofloxacin, gatifloxacin, gemifloxacin & moxifloxacin.
    • Due to their enhanced activity against gram-positive & atypical organisms (chlamydia, mycoplasma & legionella).
  • Moxifloxacin & trovafloxacin: 
    • Widest spectrum including gram (-ve) & gram (+ve) micro-organisms, including anaerobes.
  • Ciprofloxacin, levofloxacin &moxifloxacin:
    • Effective in tuberculosis.
    • For prophylaxis of neutropenic patients.
  • Finafloxacin – 
    • Recently approved for topical treatment of acute otitis externa caused by Pseudomonas & Staphylococcus.
    • Used for adolescent cystic fibrosis with pulmonary exacerbations.

Contraindications:

  • Epilepsy.
  • In children less than 18 yrs old & in pregnancy – Due to cartilage problems.

Adverse effects:

  • GI distress (most common).
  • CNS side effects (headache & dizziness; rarely seizures).
  • Tendinitis resulting in tendon rupture (rarely in adults).
  • Phototoxicity (maximum incidence with lomefloxacin & sparfloxacin).
  • Sparfloxacin & gatifloxacin prolong QTc interval.

Withdrawn fluoroquinolones: 

  • Temafloxacin – Immune hemolytic anemia.
  • Gatifloxacin – Dysglycemic effects.
  • Trovafloxacin – Hepatotoxicity.
  • Grepafloxacin – Cardiotoxicity, arrhythmias due to increasing QT interval.
  • Clinafloxacin – Phototoxicity.
  • Recent FDA warning on peripheral neuropathy by fluoroquinolones.

Drug interactions:

  • With methylxanthines (theophylline):
    • Fluoroquinolones (particularly ciprofloxacin or pefloxacin) increase plasma methylxanthines concentration (Theophylline).
    • Enhances theophylline toxicity.
  • With NSAID’s:
    • NSAIDs increase CNS toxicity (seizures) of these drugs.
    • Hence, contra-indicated in epilepsy.

Exam Important

  • Fluoroquinolones have long post-antibiotic effect (PAE).
  • Fluoroquinolones act by inhibiting DNA gyrase (topoisomerase II) & topoisomerase IV –> DNA replication inhibition.
  • 1st generation fluoroquinolones (Norfloxacin lomefloxacin) are narrow spectrum, mainly gram-negative.
  • Ciprofloxacin & ofloxacin are 2nd generation fluoroquinolones.
  • 3rd generation fluoroquinolones are more active against gram-positive.
  • Levofloxacin, gatifloxacin, pefloxacin, sparfloxacin belong with 3rd generation fluoroquinolones.
  • Broadest spectrum fluoroquinolones are 4th generation flouroquinolones.
  • Moxifloxacin & trovafloxacin is hepatic metabolism & biliary excretion.
  • Sparfloxacin & pefloxacin is excreted by both renal & hepatic route.
  • All other drugs (ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin & ofloxacin) excreted by tubular secretion.
  • Sparfloxacin, moxifloxacin & trovafloxacin exhibit long half-lives, administered once daily orally.
  • Sparfloxacin is longest half-life among fluoroquinolones.
  • Dose adjustment required in renal disease for all fluoroquinolones, except pefloxacin, moxifloxacin & trovafloxacin (mnemonic: PMT).
  • Norfloxacin is useful in UTI, urinary concentration is bactericidal.
  • Ciprofloxacin is DOC for prophylaxis & treatment of anthrax & meningococcal meningitis prophylaxis.
  • Ciprofloxacin & ofloxacin is effective against gonorrhea.
  • Ciprofloxacin & levofloxacin is only fluoroquinolones effective against Pseudomonas.
  • “Respiratory fluoroquinolones” include Levofloxacin, gatifloxacin, gemifloxacin & moxifloxacin, due to their enhanced activity against gram-positive & atypical organisms (chlamydia, mycoplasma & legionella).
  • Moxifloxacin & trovafloxacin is widest spectrum including gram (-ve) & gram (+ve) micro-organisms, including anaerobes.
  • Ciprofloxacin, levofloxacin & moxifloxacin are effective in tuberculosis.
  • Finafloxacin is approved for topical treatment of acute otitis externa, caused by Pseudomonas & Staphylococcus.
  • Fluoroquinolones are contraindicated in epilepsy.
  • Maximum incidence of phototoxicity is with lomefloxacin & sparfloxacin.
  • Sparfloxacin & gatifloxacin prolong QTc interval.
  • Grepafloxacin is cardiotoxicity, arrhythmias increasing QT interval.
  • Recent FDA warning on peripheral neuropathy by fluoroquinolones.
  • Fluoroquinolones (particularly ciprofloxacin or pefloxacin) increase plasma methylxanthines concentration (Theophylline), enhances theophylline toxicity.
  • NSAID’s with fluoroquinolones, NSAIDs increase CNS toxicity (seizures) of these drugs, hence contra-indicated in epilepsy.

 

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