Flouroquinolones associated permanent nerve damage

P.Naina MohamedPharmacologist

Introduction FDA has required the manufacturers on 15th Aug 13, to add the

serious side effect of Peripheral neuropathy associated with fluoroquinolone antibacterial drugs, in to their drug labels and Medication Guides.

Approved fluoroquinolone drugs include Nevofloxacin, Ciprofloxacin, Moxifloxacin, Norfloxacin, Ofloxacin and Gemifloxacin.

Fluoroquinolones induced peripheral neuropathy may include symptoms in arms and legs such as dysesthesia (pain), burning, paresthesia (tingling), hypoesthesia (numbness), weakness and other sensorimotor problems. 

This fluoroquinolones induced serious nerve damage, may occur soon after these drugs are taken and may be permanent.

Fluoroquinolones Structurally Quinolones contain a quinoline ring

system and hence given the name quinolones. Fluoroquinolones also contain a fluorine atom at the

6-position of the quinoline ring to increase the potency.

Fluoroquinolones and quinolones are not used for regular treatment of bacterial infections due to their severe side effects in rare cases.

They are generally used for more resistant strains of bacteria and are especially useful in genitourinary infections.

Mechanism of ActionFluoroquinolones

Bind to the A-subunit of DNA gyrase (topoisomerase II type) enzyme

Prevents the binding of substrate to the active site of DNA gyrase

Absence of formation of enzyme – substrate complex

Blockade of unwinding of double-stranded DNA into a single stranded structure

Prevention of synthesis of mRNA

Inhibition of bacterial protein synthesis

Antibacterial activity

Gram-positive and Gram-negative bacterias

Gram-positive bacterias: Fluoroquinolones inhibit DNA gyrase

(topoisomerase II), which is responsible for supercoiling of gram-positive bacterial DNA during DNA replication.

Gram-negative bacterias: But, in case of gram-negative bacteria,

Fluoroquinolones inhibit topoisomerase IV, an enzyme responsible for relaxation of supercoiled circular DNA and separation of the inter-linked daughter chromosomes.

Possible mechanism of toxicity

Fluoroquinolones

May induce axonal degeneration with secondary breakdown of the myelin sheath,

or more rarely primary segmental demyelinisation

Peripheral neuropathy

Conclusion Inform the patients to contact the healthcare

professional, if they develop symptoms of peripheral neuropathy.

Ask the patients to read the Medication Guide with every prescription.

If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped, and the patient should be switched to another, non-fluoroquinolone antibacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk.

References http://www.fda.gov/Safety/MedWatch/SafetyInformat

ion/SafetyAlertsforHumanMedicalProducts/ucm365302.htm?source=govdelivery

http://www.ncbi.nlm.nih.gov/pubmed/11793615 http://jac.oxfordjournals.org/content/37/4/831.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/8722551 http://www.medscape.com/viewarticle/411159 http://www.ncbi.nlm.nih.gov/pubmed/10945507