NSAIDs topical

Topical NSAID preparations are used infrequently in North America. Theoretically, administration via a topical vehicle targets the joints involved and decreases systemic exposure. Randomized, controlled trials, typically of less than 4 weeks duration, have suggested that topical NSAIDs are superior to placebo in relieving OA pain in the first 2 weeks of treatment, but the effect may decline over time.33 Moreover, data are lacking to quantify the theoretical safety advantage of administering NSAIDs topically. 

The first part of the book examines the fundamental principles of chirality and TLC. It describes the necessary materials, laboratory equipment, procedures, and strategies for the separation, quantification, isolation, and analysis of chiral compounds. The second part evaluates the reaUworld enantioseparations and densitometric analyses. Emphasizing pharmaceutical applications, the book examines the chiral separation mechanisms and methods for analyzing the chiral purity of diastereoisomers, amino acids, beta-blockers, and NSAIDS. Topics also include commercial stationary phases and chiral modifiers of mobile phases. 

Once diagnosed, patients with AlA should avoid aspirin and any other NSAIDs strongly inhibiting COX-1 their education is of utmost importance. They should receive a list of contraindicated and well-tolerated analgesics (table 2). Even topical administration (intravascular or by iontophoresis) of a NSAID may cause an asthma attack and should be avoided. 

Direct irritation of the mucosal lining by NSAIDs occurs because NSAIDs are weak acids. Topical irritation is therefore most pronounced with more acidic NSAIDs such as aspirin. While the direct irritant effects of NSAIDs play a contributory role in the development of NSAID-induced gastritis, this mechanism generally plays a minor role in the evolution of NSAID-induced PUD. 

Topical NSAIDs are available commercially in Canada and Europe. In the United States, these agents may be compounded in specialty pharmacies.35 These agents exert a local anti-inflammatory and analgesic effect.36-38 In soft-tissue injury such as strains and sprains, topical NSAIDs are superior in efficacy to placebo and similar to oral NSAIDs.36,37 Tissue concentrations of topical NSAIDs are high enough to produce anti-inflammatory effects, but systemic concentrations after application remain low.36-38... 

Theoretically, the risk of serious GI adverse events should be less than with oral NSAIDs, but long-term studies evaluating these events are lacking.38 Studies comparing topical NSAIDs with other topical products, including counterirritants, are also needed.35 Local cutaneous adverse reactions (e.g., erythema, pruritus, and irritation) occur in 1% to 2% of patients and may be due in part to the vehicle used.38... 

Evaluate for adverse effects and drug interactions. For patients on topical therapy, evaluate for local adverse effects. For patients on acetaminophen or NSAIDs, inquire about alcohol use. 

Topical non-steroidal anti-inflammatory drugs (NSAIDs) decrease pain from corneal abrasion. Available ocular NSAIDs are diclofenac 0.1%, ketorolac 0.5%, nepafenac... 

If mast cell stabilizers or multiple-action agents are not successful, a trial of a topical NSAID is appropriate. Ketorolac is the only approved topical agent for ocular itching. NSAIDs do not mask ocular infections, affect wound healing, increase intraocular pressure, or contribute to cataract formation like the topical corticosteroids. However, for allergic conjunctivitis, topical ketorolac is not as effective as olopatadine or emedas-tine in trials.15 Full efficacy of ketorolac takes up to 2 weeks.17... 

An individualized approach to treatment is necessary (Fig. 2-1). For mild or moderate pain, topical analgesics or acetaminophen can be used. If these measures fail or if there is inflammation, nonsteroidal antiinflammatory drugs (NSAIDs) may be useful. Appropriate nondrug therapies should be continued when drug therapy is initiated. 

Capsaicin, an extract of red peppers that causes release and ultimately depletion of substance P from nerve fibers, has been beneficial in providing pain relief in OA when applied topically over affected joints. It may be used alone or in combination with oral analgesics or NSAIDs. 

Low-dose opioid analgesics (e.g., oxycodone) may be useful for patients who experience no relief with acetaminophen, NSAIDs, intraarticular injections, or topical therapy. 

Nonselective NSAIDs (including aspirin) cause gastric mucosal damage by two mechanisms (1) a direct or topical irritation of the gastric epithelium, and (2) systemic inhibition of the cyclooxygenase-1 (COX-1) enzyme, which results in decreased synthesis of protective prostaglandins. 

Uses Chronic asthma Actions Topical steroid Dose Two inhalations tid-qid or 4 inhal bid Caution [C, ] Contra Component aU gy Disp Met-dose inhaler SE Cough, oral candidiasis Interactions T Risk of GI bleed W/ ASA, NSAIDs T effects W/ sakneterol, troleandomycin -1- effects W/barbiturates, hydantoins, pheny-toin, rifampin T effects OF diuretics, insulin, oral hypoglycemics, K supl, salicylates, somatrem, live virus vaccines EMS May affect glucose(hyperglycemia) monitor ECG for hypokalemia (flattened T waves) concurrent ASA/NSAID use may t risk of GI bleeding OD Acute OD unlikely to cause life-threatening Sxs, chronic OD may lead to S/Sxs of muscle weakness, and osteoporosis symptomatic and supportive... 

The arylpropionic acid derivatives are useful for the treatment of rheumatoid arthritis and osteoarthritis, for reduction of mild to moderate pain and fever, and for pain associated with dysmenorrhea. Side effects of the drugs are similar to but less severe than those described for the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions when taking ibuprofen and related drugs. Acute hypersensitivity to ibuprofen has been reported in patients with lupus. The hypersensitivity reaction to sulindac can be fatal. The use of sulindac has also been linked to cases of acute pancreatitis. The use of dimethylsulfoxide (DMSO) topically in combination with sulindac has been reported to induce severe neuropathies. The concurrent use of ibuprofen with aspirin reduces the antiinflammatory effects of both drugs. Ibuprofen is contraindicated in patients with aspirin sensitivity leading to bronchiolar constriction and in patients with an-gioedema. As with all NSAIDs, renal and liver function should be normal for adequate clearance of the drugs. 

Ketorolac (Toradol), an NSAID chemically related to indomethacin and tolmetin, is mainly used as an analgesic, not for the treatment of inflammatory disease. It is available in oral, parenteral, and topical formulations. 

Naproxen is a naphthylpropionic acid derivative. It is the only NSAID presently marketed as a single enantiomer. Naproxen s free fraction is significantly higher in women than in men, but half-life is similar in both sexes (Table 36-1). Naproxen is effective for the usual rheumatologic indications and is available in a slow-release formulation, as an oral suspension, and over the counter. A topical preparation and an ophthalmic solution are also available. 

A topical 3% gel formulation of the nonsteroidal anti-inflammatory drug diclofenac (Solaraze) has shown moderate effectiveness in the treatment of actinic keratoses. The mechanism of action is unknown. As with other NSAIDs, anaphylactoid reactions may occur with diclofenac, and it should be given with caution to patients with known aspirin hypersensitivity (see Chapter 36). 

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