Thursday, March 31, 2016

Rheumatic Fever : Aspirin & Anti Inflamatory


  • Anti-inflammatory agents are used to control the arthritis, fever, and other acute symptoms.
  • Salicylates are the preferred agents, although other nonsteroidal agents are probably equally efficacious.
  • Steroids are also effective but should probably be reserved for patients in whom salicylates fail.
  • None of these anti-inflammatory agents has been shown to reduce the risk of subsequent rheumatic heart disease.
Aspirin
  • Low doses (typically 75 to 81 mg/day)
    • are sufficient to irreversibly acetylate serine 530 of cyclooxygenase (COX)-1.
    • This effect inhibits platelet generation of thromboxane A2, resulting in an antithrombotic effect.
  • Intermediate doses (650 mg to 4 g/day)
    • inhibit COX-1 and COX-2, blocking prostaglandin (PG) production, and have analgesic and antipyretic effects.
  • High doses (between 4 and 8 g/day)
    • are effective as antiinflammatory agents in rheumatic disorders; the mechanism(s) of action at these high doses may include both PG-dependent (particularly COX-2-dependent PGE2) and independent effects  
    • However, the usefulness of aspirin at these high doses is limited by toxicity, including tinnitus, hearing loss, and gastric intolerance.
Other NSAIDS
  • efficacy of agents such as naproxen and tolmetin are comparable with that of aspirin, but side effects are typically less frequent.
  • Nonetheless, the majority of centers continue to use aspirin as first-line therapy for ARF
  • anti-inflammatory therapy should be continued until all symptoms have resolved, as long as the medication is well tolerated
  • The efficacy of other anti-inflammatory drugs in the setting of active rheumatic carditis is uncertain, and their potential side effects are comparatively greater than aspirin. Thus, these alternative agents are rarely used.
Glucocorticoids
  • One exception is the use of low-dose glucocorticoids in patients who do not tolerate or are allergic to aspirin.
  • A meta-analysis of eight randomized trials including 996 patients with ARF found that other agents with more significant potential side effects (eg, glucocorticoids, intravenous immune globulin [IVIG]) were not superior to aspirin with regard to development of heart valve lesions and cardiac disease
Practice and Guides
  • if a diagnosis of rheumatic fever has not been established, salicylate therapy is withheld and simple analgesics such as paracetamol and codeine are recommended.
  • Salicylates are withheld to facilitate diagnosis; they reduce arthritic pain but do not affect the long-term outcome of the disease
  • Dose: 80 to 100 mg/kg per day in children and 4 to 8 g/day in adults. [children: 50-60 mg/kg/day orally given in divided doses every 4 hours, may increase to 80-100 mg/kg/day if required]
  • Most patients will only require treatment for 1 to 2 weeks, although some patients need it for up to 6 to 8 weeks.
  • The arthritis caused by acute rheumatic fever is usually exquisitely sensitive to aspirin. Alternate diagnoses should be considered in unresponsive patients
  • If arthritis is refractory following 2 weeks of therapy, then the dose of aspirin can be increased; however, the risk of salicylate toxicity is very high and salicylate levels should be monitored if facilities are available.
  • As the dose is reduced, joint symptoms may recur (so-called 'rebound phenomenon'). This does not represent a recurrence of rheumatic fever, and can be simply treated with another brief course of high-dose aspirin
  • Stopping aspirin therapy should be considered in the setting of a concurrent viral illness because of the risk of Reye's syndrome. If aspirin is given during the influenza season, then influenza vaccine may be given as a precautionary measure.
  • Toxic effects include tinnitus, headache, and tachypnoea, and may start to occur above levels of 20 mg/100 dL. They will usually resolve within a few days of stopping aspirin
References:
  1. http://www.ncbi.nlm.nih.gov/pubmed/22696333
  2. http://emedicine.medscape.com/article/236582-treatment
  3. www.bmj.com
  4. www.uptodate.com

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