FLUOROQUINOLONES
ASSOCIATED

TENDINOPATHY

Dr. P.Naina Mohamed
Pharmacologist
INTRODUCTION
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Fluoroquinolones cause tendinopathies such as tendinitis and tendon
rupture of Achilles t...
RISK FACTORS
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Risk factors for the development of fluoroquinolone-induced
tendinopathy are…
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PROPOSED PATHOPHYSIOLOGY


The exact pathophysiology of FQ-induced tendinopathy
remains elusive; however, some concepts h...
PROPOSED PATHOPHYSIOLOGY
Fluoroquinolones
Chelating properties

Interact with regulating proteins of tenocytes
Damage at t...
PROPOSED PATHOPHYSIOLOGY
Fluoroquinolones

Chelation of magnesium in joint cartilage
Radical formation

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Irreversi...
PROPOSED PATHOPHYSIOLOGY
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FQs have a direct cytotoxic effect on enzymes found in
mammalian musculoskeletal tissu...
CLINICAL MANIFESTATIONS
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The Achilles tendon is most commonly affected in FQ-induced
tendinopathy, occ...
MANAGEMENT
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Treatment should include rest and decreasing the physical load on
the tendon.
Treatment with ...
FDA’S INFORMATION TO HEALTHCARE
PROFESSIONALS
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Pain, swelling, inflammation, and tears of tendons including ...
CONCLUSION
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Pefloxacin, fleroxacin, levofloxacin, and ofloxacin were found to
induce the greatest numbe...
REFERENCES
http://www.fda.gov/drugs/drugsafety/postmarketd
rugsafetyinformationforpatientsandproviders/uc
m126085.htm
 ht...
http://web.ebscohost.com/ehost/pdfviewer/pdfview
er?sid=8bbc7a7b-8d30-45e4-97ea4283c8f34935%40sessionmgr4&vid=2&hid=12
 h...
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Fluoroquinolones associated tendinopathy

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Fluoroquinolones may induce tendinopathy characterised by tendinitis or tendon rupture.

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Fluoroquinolones associated tendinopathy

  1. 1. FLUOROQUINOLONES ASSOCIATED TENDINOPATHY Dr. P.Naina Mohamed Pharmacologist
  2. 2. INTRODUCTION        Fluoroquinolones cause tendinopathies such as tendinitis and tendon rupture of Achilles tendon and also other tendons like rotator cuff (the shoulder), the hand, the biceps, and the thumb. Rupture of the Achilles tendon may require surgical repair. Tendon rupture can occur during or after completion of fluoroquinolone use. There are reports of symptoms and tendon disruptions occurring months after discontinuation of the medication. FDA’s recent evaluation of the medical literature and the post-marketing adverse event reports submitted to the Adverse Events Reporting System (AERS) confirmed that serious reports of tendinitis and tendon rupture with the fluoroquinolones continue to be reported in similar or increased numbers. The FDA recommends that at the first sign of tendon pain, swelling, or inflammation, patients should stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician for tendon evaluation and transition to a non-fluoroquinolone antibiotic. Tendon rupture is a serious adverse event that could potentially be prevented or reduced in frequency or severity by appropriate use of a fluoroquinolone, patient selection, and careful monitoring.
  3. 3. RISK FACTORS  Risk factors for the development of fluoroquinolone-induced tendinopathy are…               Age (over 60 years) Renal failure Long-term dialysis Kidney, heart, and lung transplantation Corticosteroid use Hypercholesterolemia, Gout Rheumatoid arthritis Diabetes mellitus Hyperparathyroidism Participation in sports Previous tendinopathy from fluoroquinolones Fluoroquinolones dose should be adjusted based on renal function to avoid possible drug accumulation. The median duration of fluoroquinolone use before the onset of tendon injury is eight days.
  4. 4. PROPOSED PATHOPHYSIOLOGY  The exact pathophysiology of FQ-induced tendinopathy remains elusive; however, some concepts have been suggested. Fluoroquinolones Chelating properties Form complex with several metal ions (e.g., calcium, magnesium, aluminum) Direct toxicity to type 1 collagen synthesis Promote collagen degradation
  5. 5. PROPOSED PATHOPHYSIOLOGY Fluoroquinolones Chelating properties Interact with regulating proteins of tenocytes Damage at the tendon structure  In addition, recent study suggests that apoptosis as the final event in the pathogenetic mechanism.
  6. 6. PROPOSED PATHOPHYSIOLOGY Fluoroquinolones Chelation of magnesium in joint cartilage Radical formation    Irreversible cartilage lesions This hypothesis is further substantiated by the fact that quinolone-induced cartilage lesion can be diminished by supplementing with magnesium and/or tocopherol. Narrowed vasculature of the tendon and paratendon suggest that changes in blood flow may play a role. The low supply of blood to the tendons, particularly the Achilles, which is further decreased with age, likely predisposes to injury.
  7. 7. PROPOSED PATHOPHYSIOLOGY     FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue. Because animal studies have shown that FQs may damage juvenile weight-bearing joints, most FQs are contraindicated in children and during pregnancy and lactation. Experiments on immature laboratory animals (dogs, rabbits, and rats) have shown that FQs cause cartilage damage by inducing necrosis of chondrocytes (36 hours after treatment), disruption of the extracellular matrix, and formation of vesicles and fissures at the articular surface. In-vitro studies in cultured tendon cells have confirmed the clinical observation that FQs can increase the risk of tendon rupture.
  8. 8. CLINICAL MANIFESTATIONS         The Achilles tendon is most commonly affected in FQ-induced tendinopathy, occurring in 89.8 percent of cases. Other tendons, such as biceps brachii, supraspinatus, and extensor pollicis longus, can also be affected. Other sites included the triceps epicondyle, flexor tendon sheath, patellar tendon, quadriceps muscle, rotator cuff, and subscapularis terrea. Up to 50 percent of cases may present with bilateral involvement. Depending on the degree of involvement of the joint, patients may experience pain, swelling, or inflammation in the tendon area for up to two weeks before rupture occurs. Signs of tendon rupture can include a “snap” or “pop“ in the area, bruising, or immobility of the joint. Tendon rupture is almost always preceded by spontaneous pain at the bony insertion 2 to 3cm above the insertion point, believed to be correlated with diminished vascularization at this anatomic site. FQ-induced tendinitis is distinguished from other forms of tendinopathy by both the abrupt onset and sharp pain that occur spontaneously upon walking or palpation.
  9. 9. MANAGEMENT        Treatment should include rest and decreasing the physical load on the tendon. Treatment with a FQ should be discontinued and physical therapy initiated. During the first month of rehabilitation of an Achilles tendinopathy, the affected tendon should be protected with a heel lift, counterforce bracing, and crutches to decrease the tensile load transmitted to the Achilles tendon during walking for six weeks to six months. Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months. Patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop. Tendinosis usually recovers over a time course of weeks, usually within two months, after cessation of FQ therapy. In cases of FQ-induced tendon rupture, orthopedic treatment should proceed, as in other cases of tendon disruption, with consideration given to operative therapy after assessing the potential risks versus anticipated benefits of surgical intervention
  10. 10. FDA’S INFORMATION TO HEALTHCARE PROFESSIONALS      Pain, swelling, inflammation, and tears of tendons including the Achilles, shoulder, hand, or other tendons can happen in patients taking fluoroquinolone antibiotics. Patients receiving a FQ should be counseled to call healthcare provider right away at the first signs or symptoms of pain, swelling or inflammation in a tendon area. These could be symptoms of tendinitis or tendon rupture. Some medicines may interact with a fluoroquinolone and cause serious side effects. Also, some medical conditions may aggravate side effects of fluoroquinolones. Fluoroquinolones, like any drug, have possible side effects include seizures, hallucinations, depression, heart rhythm changes (QTc prolongation and torsade de points), and intestine infection with diarrhea. Rarely, damage to the liver, kidneys or bone marrow, and changes to blood sugar may occur. Fluoroquinolones are antimicrobials that are effective in treating infections caused by certain bacteria but not viruses (common cold or the flu).
  11. 11. CONCLUSION         Pefloxacin, fleroxacin, levofloxacin, and ofloxacin were found to induce the greatest number of lesions. Administration of enoxacin, norfloxacin, and ciprofloxacin had little or no effect. A research suggested that the substituent at the seventh position of the fluoroquinolone molecule may increase toxicity. Pefloxacin, fleroxacin, levofloxacin, and ofloxacin have a methylpiperadinyl moiety at 7th position, whereas enoxacin, norfloxacin, and ciprofloxacin have a piperadinyl substituent. The fluoroquinolone should be discontinued if the patient experiences pain or inflammation in a tendon (symptoms that may precede rupture of the tendon), or tendon rupture. Avoid exercise and use of the affected area. Healthcare professionals should consider the potential benefit and risks to each individual patient before prescribing a fluoroquinolone antimicrobial. Fluoroquinolones should only be used for the treatment or prevention of bacterial infections but not viral infections such as the common cold or influenza.
  12. 12. REFERENCES http://www.fda.gov/drugs/drugsafety/postmarketd rugsafetyinformationforpatientsandproviders/uc m126085.htm  http://web.ebscohost.com/ehost/pdfviewer/pdfview er?sid=3be7af79-1ff0-4873-aaa7d4cc4253d1d7%40sessionmgr10&vid=2&hid=12  http://cid.oxfordjournals.org/content/36/11/1404.f ull  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC29 21747/  http://www.ncbi.nlm.nih.gov/pubmed/10832946  http://www.jwatch.org/id201212120000004/2012/ 12/12/achilles-tendinitis-tendon-rupture-and 
  13. 13. http://web.ebscohost.com/ehost/pdfviewer/pdfview er?sid=8bbc7a7b-8d30-45e4-97ea4283c8f34935%40sessionmgr4&vid=2&hid=12  http://www.ncbi.nlm.nih.gov/pubmed/10372859  http://web.ebscohost.com/ehost/pdfviewer/pdfview er?sid=3be7af79-1ff0-4873-aaa7d4cc4253d1d7%40sessionmgr10&vid=2&hid=12  http://aac.asm.org/content/41/11/2389.long  http://www.ncbi.nlm.nih.gov/pubmed/18236349  http://web.ebscohost.com/ehost/pdfviewer/pdfview er?sid=76bd06f2-5ce7-4319-ab5c0b84093ea69a%40sessionmgr12&vid=2&hid=12 
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