Topical salicylates methyl salicylate

Identification of Salicylic Acid in Horse Urine No statutory limit is prescribed for salicylic acid, but it is normally present in horse urine it is important, therefore, to distinguish between normal concentrations and those arising from medication with aspirin or other salicylates such as topically applied methyl salicylate. Normal urine concentrations rarely exceed 10 LLg/ml, but therapeutic doses of aspirin may give concentrations as much as 500 times greater. Addition of 1 ml of freshly prepared ferric chloride solution to 5 ml of urine will give a detectable violet colour when the concentration of salicylic acid exceeds about 100 ig/ml. A positive result should be followed... 

Topical analgesics sometimes are used for mild pain or as an adjunct to systemic therapy. There are limited data to support the use of salicylate-containing rubefacients (e.g., methyl salicylate and trolamine salicylate) or other counterirritants (e.g., menthol, camphor, and methyl nicotinate) in OA.32 See Chap. 57 for more information on these products when used for musculoskeletal disorders. 

Topical rubefacients containing methyl salicylate, trolamine salicylate,... 

Methyl salicylate is a mildly toxic compound and plants that make it may do so as a means of warding off predators. It finds use in human medicine as a constituent of liniments, topical anesthetics. 

Excessive topical applications of methyl salicylates have interactions with anticoagulants such as warfarin.69... 

T.Y.K. Chan, Potential dangers from topical preparations containing methyl salicylate. Hum. Exp. Toxicol. 15 747-750, 1996. 

Topical mbefacients containing methyl salicylate, trolamine salicylate, and other salicylates may have modest, short-term efficacy for treating acute pain associated with OA. 

Methyl salicylate in topical analgesic preparations can cause irritant or allergic contact dermatitis and anaphylactic reactions (6). 

Trolamine (triethanolamine salicylate, TEAS) is a salicylate derivative, which is also known as topical aspirin . It is an amino alcohol that is used for its topical analgesic and antiinflammatory properties. Like the better-known salicylate derivative, methyl salicylate - which has a rubefacient action used to good effect in sports injuries and rheumatism - TEAS is rapidly absorbed through normal skin after topical application. It is used widely for treating sunburn. 

Alternative drug treatments include topical agents such as capsaicin and methyl salicylate, injections with glucocorticoids. 

This cream and ointment contain menthol in an alcohol base gel, combinations of methyl salicylate, and menthol in cream and ointment bases, as well as a combination of methyl salicylate, menthol, and camphor in a nongreasy cream base all are suitable for topical application. The varieties include the ointment (methyl salicylate, 18.3% ... 

Salicylic acid is irritating to skin and mucosa and destroys epithelial cells. The keratolytic action of the free acid is employed for the local treatment of warts, corns, fiingal infections, and certain types of eczematous dermatitis. After treatment with salicylic acid, tissue cells swell, soften, and desquamate. Methyl salicylate foil of wintergreenj is used topically as a counter-irritant for the relief of mild musculoskeletal pain. 

A second approach involves modification of the chemical structure of ALA itself by turning it into an ester. This is somewhat reminiscent of the topical use of methyl salicylate (the methyl ester of salicylic acid) which releases salicylic acid in vivo following enzymatic cleavage of the ester bond. Certain esters of ALA can penetrate the skin more rapidly than ALA itself (presumably because the esters are more hydrophobic), and then subsequently release ALA in vivo following cleavage by tissue esterases. It certainly would be an advance if the use of such pre-ALA compounds increased the depth at which ALA-PDT was effective [155-159]. While the hexyl ester derivative of ALA seems to show better membrane penetration properties and improved PpIX production than other esters [159], a current drawback is the significantly greater toxicity of the hexyl ester compared with ALA itself. While there are still some problems to be worked out, derivatives of ALA may well prove useful in ALA-PDT. 

One of the earlier studies demonstrating the role of blood flow on percutaneous absorption in humans used comparison dermal concentrations after topical application in vitro and in vivo (Schaefer and Stuttgen, 1978). Perfusion caused by cutaneous microcirculation also affected responses after the topical penetration of the vasodilator methyl nicotinate in humans (Guy et al., 1983). Altered transdermal drug absorption of the vasoactive nonsteroidal antiinflammatory drug (NSAID) methyl salicylate (MeSA) has also been attributed to changes in in vivo cutaneous perfusion. Exercise, heat exposure, or both increased MeSA absorption more than three times the control levels in six volunteers (Danon etal., 1986). A later case study reported that skin necrosis and other toxic symptoms occurred when a heating pad was used with a topical MeSA and menthol formulation meant to treat arthritic pain (Heng, 1987). 

Heng, M.C., Local necrosis and interstitial nephritis due to topical methyl salicylate and menthol. Cutis, 1987, 39, 442-444. 

Salicylates are widely used for their analgesic and anti-inflammatory properties. They are found in a variety of prescription and over-the-counter analgesics, cold preparations, and topical keratolytic products (methyl salicylate), and even Pepto-Bismol (bismuth subsalicylate). Eiefore the introduction of child-resistant containers, aspirin overdose was one of the leading causes of accidental death in children. Two distinct syndromes of intoxication may occur, depending on whether the exposure is acute or chronic. 

Methyl salicylate, in the form of gels, oil, or ointment applied to the skin, has been found to increase the effects of warfarin. Bleeding and bruising and/or raised INRs have been seen with both high " and low doses of methyl salicylate. One report described the possible additive effects of methyl salicylate oil (Kwan Loong Medicated Oil) and a decoction of Danshen (the root of Salvia miltiorrhiza) on the response to warfarin (see also Coumarins and related drugs + Herbal medicines Danshen (Salvia miltiorrhizay, p.415). A raised prothrombin time has also been reported with topical trolamine salicylate. ... 

Although the evidence is limited, it appears that topical methyl salicylate and trolamine salicylate can increase the effect of warfarin. 

Topical application of products containing the compound methyl salicylate has led to poisonings in some individuals (Chyka et al. 2007). 

Chan, T. Y. 1996a. Potential dangers from topical preparations containing methyl salicylate. Hum. Exp. Toxicol. 15(9) 747-750. Chan, T.Y. 1996b. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Br. Med. J. 72(844) 109-112. 

Case one was a 66-year-old man also taking digoxin and propanolol (Tam et al. 1995). Five days prior to admission due to melena (dark-colored feces) and chest pain, and 2 days prior to treatment, the man had self-treated with a topically applied medicated oil that contained 15% methyl salicylate. Methyl salicylate has been shown to augment the anticoagulant effect of warfarin (Chan 1995, 1998 Chow et al. 1989 Joss and LeBlond 2000 Yip et al. 1990). 

Joss, J.D., and R.F. LeBlond. 2000. Potentiation of warfarin anti-coagulaHon associated with topical methyl salicylate. Ann. Pharmacother. 34(6) 729-733. 

Methyl salicylate is derived from oil of wintergreen—Gaultheria procumbens (Ericaceae). It is an aromatic ester derived from salicylic acid and methanol, though it can now be produced synthetically. Methyl salicylate is mainly used in topical applications and liniments as a counter-irritant and antirheumatic. Internal administration is not recommended since it is quite toxic in large doses. 

Higashi, Y., Kiuchi, T, Furuta, K. 2010. Ef cacy and safety pro le of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain A randomized, double-blind, parallel group, placebo-controlled, multicenter study, 32(l) 34-43. 

Salicylate can be applied to the skin as un-ionized salicylic acid (normally for its keratolytic activity), as a salicylate salt (most commonly trolamine salicylate), as esters such as methyl salicylate and, rarely, as aspirin. In the form most often used in topical products, salicylates work primarily as rubefacients. Rubefacients are compoimds that work by counter-irritation. 

The salicylate compounds used topically share with aspirin the common metabolic breakdown product, free salicylate (see section on aspirin earlier in this text), which is primarily responsible for the toxicity observed. On average, 12-20% of the dose of methyl salicylate is absorbed through the skin. Methyl salicylate is readily hydrolyzed to salicylate, although some methyl salicylate is found in blood. Some unchanged methyl salicylate is excreted in urine as hydrolysis is relatively slow in humans. 

---