Diclofenac chemical structure
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Voltaren

Diclofenac (marketed as Voltaren®, Voltarol® and Cataflam®) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation, such as in arthritis or acute injury. It can also be used to reduce menstrual pain. more...

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Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom Voltarol can be supplied with either the sodium salt or potassium salt, while Cataflam in some other countries is the potassium salt only. Diclofenac is available in stomach acid resistant formulations (25 and 50 mg), fast disintegrating oral formulations (50 mg), slow- and controlled-release forms (75, 100 or 150 mg), suppositories (50 and 100 mg), and injectable forms (50 and 75 mg). Diclofenac is also available over the counter (OTC) in some countries: Voltaren® dolo (12.5 mg diclofenac as potassium salt) in Switzerland and Germany, and preparations with 25 mg diclofenac are OTC in New Zealand. OTC use is approved for minor aches and pains and fever associated with common infections.

Diclofenac is available as a generic drug in a number of formulations.

Mechanism of action

The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its anti-inflammatory/antipyretic/analgesic action is inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX).

Diclofenac, it seems, may also be a unique member of the NSAIDs. There is some evidence that diclofenac inhibits the lipooxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a molar basis.

Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have therefore a somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin.

The action of one single dose is much longer (6 to 8 hours) than the very short half-life of the drug indicates. This could partly be due to a particular high concentration achieved in synovial fluids.

Common uses

Diclofenac is used for musculoskeletal complaints, especially arthritis (rheumatoid arthritis, osteoarthritis, spondylarthritis, ankylosing spondylitis), gout attacks, and pain management in case of kidney stones and gallstones. An additional indication is the treatment of acute migraines. Diclofenac is used commonly to treat mild to moderate post-operative or post-traumatic pain, particular when inflammation is also present, and is effective against menstrual pain.

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Management of corneal abrasions
From American Family Physician, 7/1/04 by Stephen A. Wilson

Most of the human eye lies within a protective bony orbit. The exposed anterior portion has other anatomic and functional protections. The eyebrow and eyelashes partially shield the eye from small particles. Eyelids close rapidly and reflexively when ocular danger is sensed. A tear response attempts to wash away anything that reaches the ocular surface. Tears also lubricate the eye and prevent tissue dehydration.

Despite built-in protections, eye injuries still occur. One such injury is abrasion of the outermost layer of the eye. Although damage to the white part of the eye usually is of little significance, corneal abrasion can be serious. When minor abrasions occur, healthy cells quickly fill the defect to prevent vision-diminishing infection or irregularity in refraction. If the abrasion penetrates the cornea more deeply, the healing process takes longer--24 to 72 hours. (1,2) Deeper scratches can cause corneal scarring that can impair vision to the point where corneal transplant is needed. Specific incidence and prevalence data are not available, but corneal abrasion is the most common eye injury in children presenting to emergency departments. (3)

Function and Structure of the Cornea

The cornea (Figure 1) is a highly organized group of cells and proteins with three functions: barrier protection, filtration of some of the ultraviolet wavelengths in sunlight, and refraction (the cornea is responsible for 65 to 75 percent of the eye's capacity to focus light on the retina). The cornea must be totally transparent to refract light properly. Therefore, it has no blood vessels and instead is nourished by tears, environmental oxygen, and the aqueous humor of the anterior chamber.

Within its thin dimensions--about 11.6 mm vertically, 10.5 mm horizontally, 1 mm thick peripherally, and 0.55 mm thick centrally--the cornea has five distinct, transparent layers; from anterior to posterior they are epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium (Figure 2).

Diagnosing Corneal Abrasion

A history of recent ocular trauma and subsequent acute pain suggests corneal abrasion. Other symptoms include photophobia, pain with extraocular muscle movement, excessive tearing, blepharospasm, foreign body sensation, gritty feeling, blurred vision, and headache. Symptoms can be present without the patient's recollection of trauma and with as little trauma as aggressive eye rubbing.

The diagnosis of corneal abrasion can be confirmed by visualizing the cornea under cobalt-blue filtered light after the application of fluorescein, which will cause the abrasion to appear green (Figures 3 and 4). If examination is limited by pain, instillation of a topical anesthetic (e.g., proparacaine [Ophthetic], tetracaine [Pontocaine]) may be needed. During the examination it is important to assess for and remove any foreign bodies, some of which may leave a rust residue (Figure 5).

[FIGURES 3-5 OMITTED]

Rarely, simple corneal abrasions become complicated. Recurrent corneal erosion (RCE)--repeated, spontaneous disruption of corneal epithelium--can occur in corneal tissue weakened by abrasion months or years earlier. Symptoms of RCE include ocular pain, foreign body sensation, photophobia, blepharospasm, decreased vision, and lacrimation on awakening or after rubbing or opening the eyes. These symptoms are annoying to the patient but typically are not severe enough to interfere with activities. (4) Lesions usually are found near the original abrasion; they may recur only rarely or as often as daily. True idiopathic or bilateral lesions suggest a basement membrane dystrophy, characterized by poor adhesion between the epithelial basement membrane and Bowman's layer.

Treatment Options

Although eye patches, topical antibiotics, and mydriatic agents traditionally have been used in patients with corneal abrasions, treatment recommendations recently have evolved. Current recommendations stress the use of topical or oral analgesics and topical antibiotics (Table 1). Most corneal abrasions heal with this approach.

EYE PATCHING

Eye patching is no longer recommended for corneal abrasions. (2,3,5) A meta-analysis of five randomized controlled trials (RCTs) failed to reveal an increase in healing rate or improvement on a pain scale. (5) Two subsequent RCTs (one in children, one in adults) reported similar results. (2,3) In the past, patching was thought to reduce pain by reducing blinking and decreasing eyelid-induced trauma to the damaged cornea. However, the patch itself was the main cause of pain in 48 percent of patients. (6) Children with patches had greater difficulty walking than those without patches. (3) Furthermore, patching can result in decreased oxygen delivery, increased moisture, and a higher chance of infection. Thus, patching may actually retard the healing process. (7,8)

TOPICAL ANALGESICS

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (Voltaren) and ketorolac (Acular) are modestly useful in reducing pain from corneal abrasions. (9) In a systematic review of five RCTs, topical NSAID use decreased pain by an average of 1.3 cm on a standard 10-cm pain scale. (9) Qualitatively, patients using topical NSAIDs indicated greater relief from pain and other symptoms. (9) Patients using topical NSAIDs may take fewer oral analgesics (two of three studies), return to work earlier (one study), and require fewer narcotics. (9)

Topical anesthetics should be avoided after the initial examination. They can retard healing and cause corneal damage.

MYDRIATICS

Mydriatics are no longer recommended for the treatment of pain in patients with corneal abrasions. (10) Mydriatics formerly were prescribed to relieve ciliary muscle spasm that was thought to occur in patients with corneal abrasions. However, in one RCT with limited follow-up, pain was similar in patients using an eye lubricant or mydriatic (2 percent homatropine [Homapin]), alone or combined with a topical NSAID. (10)

TOPICAL ANTIBIOTICS

Because a concomitant infection can cause slower healing of corneal abrasions, some clinicians use prophylactic antibiotic treatment, although there is no strong evidence for this use. A two-year, non-placebo-controlled, prospective cohort study (11) of topical antibiotic prophylaxis for corneal abrasion showed that the use of 1 percent chloramphenicol ointment was associated with lower risk of subsequent ulcer, especially if prophylaxis began within 18 hours after the injury. A single-blind, non-placebo-controlled randomized trial (12) showed that corneal abrasions in patients treated with fusidic acid eye drops did not heal significantly faster than patients treated with chloramphenicol ointment.

If antibiotics are used, ointment (e.g., bacitracin [AK-Tracin], erythromycin, gentamycin [Garamycin]) is more lubricating than drops and is considered first-line treatment. In patients who wear contact lenses, an anti-pseudomonal antibiotic (e.g., ciprofloxacin [Ciloxan], gentamycin, ofloxacin [Ocuflox]) should be used, and contact lens use should be discontinued. Clinical trial data are lacking, but it is recommended that contact lenses be avoided until the abrasion is healed and the antibiotic course completed. (13)

ORAL ANALGESICS

No direct evidence is available from clinical trials for the efficacy of oral analgesics in the treatment of corneal abrasions. However, because most abrasions heal without significant long-term complications, pain relief is the primary concern and the basis for routine use of oral analgesics. Oral analgesics are less expensive than topical preparations. No studies directly address the role, if any, of opioid analgesia. Individual patient characteristics (e.g., age, concomitant illness, drug allergy, ability to tolerate NSAIDs, potential for opioid abuse, employment conditions such as driving and machine operation) should guide therapy.

Follow-up and Referral Guidelines

Most patients should be reevaluated in 24 hours; if the abrasion has not fully healed, they should be evaluated again three to four days later. Patients who wear contact lenses should be re-evaluated in 24 hours and again three to four days later even if they feel well. Any worsening of symptoms should prompt a thorough re-evaluation for foreign bodies or full-thickness injuries. Immunocompromised or monocular patients also warrant closer attention and may require earlier ophthalmologic referral.

Referral to an ophthalmologist is indicated for patients with deep eye injuries, foreign bodies that cannot be removed, and suspected RCE. Patients with persistent symptoms after three days, worsening symptoms, and symptoms that do not improve daily also should be referred. Patients who wear contact lenses should be referred if there is no improvement in symptoms within a few hours of lens removal.

Primary Prevention and Screening

Most corneal abrasions are preventable. Persons in high-risk occupations (e.g., miners, woodworkers, metal workers, landscapers) and those who participate in certain sports (e.g., hockey, lacrosse, racquetball) should wear eye protection. Levels of protection include plastic safety glasses, polycarbonate lenses of varying thickness, industrial safety goggles with polycarbonate, and helmets with facemasks. All provide barrier protection from airborne debris (e.g., sand, sawdust, metal) and other objects that could cause ocular trauma (e.g., fingernails, tree branches, sports balls). Eye guards without lenses are not sufficient. Other preventive measures include careful fitting and placement of contact lenses, keeping the fingernails of infants and young children clipped short, and removing low-hanging tree branches or objects from the home environment.

Corneal abrasion, the most common perioperative ocular injury, results from lag-ophthalmos during general anesthesia. It can be prevented by taping the patient's eyelids closed or instilling soft contact lenses or aqueous gels; paraffin-based ointments (e.g., Lacrilube, Duratears) appear to be less effective. (14)

Screening is important in three populations: neonates on mask ventilation, sedated or paralyzed patients on a ventilator, and persons who wear contact lenses. Corneal abrasion, with subsequent Pseudomonas panophthalmitis, can occur in patients in neonatal intensive care units who are receiving continuous positive airway pressure ventilation. It is attributed to the pressure of the masks on the orbit. (15) Eye discharge in mask-ventilated neonates should prompt evaluation for corneal abrasion and infection.

A similar problem can occur in adults who are deeply sedated or receiving neuromuscular blocking agents while on a ventilator, because their protective corneal reflex is suppressed. The incidence of corneal abrasion in this population decreased from 18 to 4 percent when prophylactic lubricating ointment was administered every four hours. (16) Persons who wear contact lenses are at higher risk of developing abrasions that become infected and ulcerate (Figure 6). Soft, extended-wear lenses have been associated with a 10-fold to 15-fold increase in ulcerative keratitis. (17) Case reports and a nonsystematic review suggest that screening for corneal abrasions also may be needed after airbag deployment in auto-mobile crashes. (18,19)

[FIGURE 6 OMITTED]

Prognosis

Healing time depends on the size of the corneal abrasion. Most abrasions heal in two to three days, while larger abrasions that involve more than one half of the surface area of the cornea may take four to five days. (1) In patients with traumatic corneal abrasions who are treated in ophthalmology offices, 28 percent had recurrent symptoms up to three months after the injury. (4)

The authors thank Paula Preisach for help with the preparation of the manuscript. Figures 3, 4, 5, and 6 used with permission from Evan Waxman, M.D.

The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported.

References

(1.) Dua HS, Forrester JV. Clinical patterns of corneal epithelial wound healing. Am J Ophthalmol 1987;104:481-9.

(2.) Le Sage N, Verreault R, Rochette L. Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical trial. Ann Emerg Med 2001;38:129-34.

(3.) Michael JG, Hug D, Dowd MD. Management of corneal abrasion in children: a randomized clinical trial. Ann Emerg Med 2002;40:67-72.

(4.) Eke T, Morrison DA, Austin DJ. Recurrent symptoms following traumatic corneal abrasion: prevalence, severity, and the effect of a simple regimen of prophylaxis. Eye 1999;13:345-7.

(5.) Flynn CA, D'Amico F, Smith G. Should we patch corneal abrasions? A meta-analysis. J Fam Pract 1998;47:264-70.

(6.) Arbour JD, Brunette I, Boisjoly HM, Shi ZH, Dumas J, Guertin C. Should we patch corneal erosions? Arch Ophthalmol 1997;115:313-7.

(7.) Campanile TM, St Clair DA, Benaim M. The evaluation of eye patching in the treatment of traumatic corneal epithelial defects. J Emerg Med 1997;15:769-74.

(8.) Kaiser PK. A comparison of pressure patching versus no patching for corneal abrasions due to trauma or foreign body removal. Corneal Abrasion Patching Study Group. Ophthalmology 1995;102:1936-42.

(9.) Weaver CS, Terrell KM. Evidence-based emergency medicine. Update: do ophthalmic nonsteroidal anti-inflammatory drugs reduce the pain associated with simple corneal abrasion without delaying healing? Ann Emerg Med 2003;41:134-40.

(10.) Carley F, Carley S. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Mydriatics in corneal abrasion. Emerg Med J 2001;18:273.

(11.) Upadhyay MP, Karmacharya PC, Koirala S, Shah DN, Shakya S, Shrestha JK, et al. The Bhaktapur eye study: ocular trauma and antibiotic prophylaxis for the prevention of corneal ulceration in Nepal. Br J Ophthalmol 2001;85:388-92.

(12.) Boberg-Ans G, Nissen KR. Comparison of Fucithalmic viscous eye drops and Chloramphenicol eye ointment as a single treatment in corneal abrasion. Acta Ophthalmol Scand 1998;76:108-11.

(13.) Weissman BA. Care of the contact lens patient: reference guide for clinicians. St. Louis: American Optometric Association, 2000.

(14.) White E, Crosse MM. The aetiology and prevention of perioperative corneal abrasions. Anesthaesia 1998;53:157-61.

(15.) Cole GF, Chaudhuri PR, Carroll LP. Mask for continuous positive airway pressure: does it cause corneal abrasions? Br Med J [Clin Res Ed] 1982;284:19.

(16.) Lenart SB, Garrity JA. Eye care for patients receiving neuromuscular blocking agents or propofol during mechanical ventilation. Am J Crit Care 2000;9:188-91.

(17.) Schein OD, Glynn RJ, Poggio EC, Seddon JM, Kenyon KR. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med 1989;321:773-8.

(18.) Ball DC, Bouchard CS. Ocular morbidity associated with airbag deployment: a report of seven cases and a review of the literature. Cornea 2001;20:159-63.

(19.) Lee WB, O'Halloran HS, Pearson PA, Sen HA, Reddy SH. Airbags and bilateral eye injury: five case reports and a review of the literature. J Emerg Med 2001;20:129-34.

(20.) Haefner SM, Bratton SL, Annich GM, Bartlett RH, Custer JR. Complications of intermittent prone positioning in pediatric patients receiving extracorporeal membrane oxygenation for respiratory failure. Chest 2003;123:1589-94.

STEPHEN A. WILSON, M.D., is assistant director for predoctoral education and faculty research at the University of Pittsburgh Medical Center (UPMC) St. Margaret Family Practice Residency Program and clinical instructor of family medicine at the University of Pittsburgh School of Medicine, where he received his medical degree. He completed a family practice residency and a fellowship in faculty development at UPMC St. Margaret.

ALLEN LAST, M.D., is a first-year fellow in the UPMC St. Margaret Faculty Development Fellowship Program and is matriculating through the University of Pittsburgh Graduate School of Public Health. He received his medical degree from the University of Wisconsin Medical School, Madison, and completed a family practice residency at UPMC St. Margaret.

Address correspondence to Stephen A. Wilson, M.D., UPMC St. Margaret Family Practice Residency, 815 Freeport Rd., Pittsburgh, PA 15215 (e-mail: wilsons2@upmc.edu). Reprints are not available from the authors.

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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