In class we discussed the many side effects of NSAIDs, where it seems a compromise must be made between your GI tract and cardiovascular system. In hopes of overcoming some of these side effects, there has been much effort towards the development of topical NSAIDs for the treatment of musculoskeletal pains. The goal of these products is to maintain low systemic dosages of the drugs, while being able to reach appropriate levels in the inflamed areas. The review article cited below discusses the benefits of using topical rather than oral NSAIDs when dealing with pain from ailments such as a sprained ankle or osteoarthritis. It also delves into the mechanisms behind these new developments and addresses their safety and effectiveness.
The main challenge in the development of topical NSAIDs comes from crossing the skin’s barrier. The lipophilic outer layer, the stratum corneum, surrounds the aqueous epidermal layer, forcing the drug to posses both hydrophobic and hydrophilic properties. This (combined with finding the best molecular size for absorption) had scientists developing different salts of the same molecule. Differences in the carrier molecules also impacted delivery, where using nanoparticles seem to produce the best effects, while also increasing the time the drug resides in the tissues.
The efficacy of topical NSAIDs might not always be clear as their effectiveness is only seen in some types of musculoskeletal pain. For example clinical trials suggest that the drugs do not have an effect on lower back pain, while positive results were seen in patients with acute sports injuries or chronic arthritis. Topical NSAIDs were also shown to be safer than their oral counterparts, where negative systemic effects were uncommon. This being said, a higher frequency of application could increase these risks, negating the advantage in this delivery system. Although these drugs are still being perfected, I feel that this is a good alternative for those suffering from musculoskeletal pain.
Sources:
Topical NSAID Therapy for Musculoskeletal Pain
Haroutiunian, Simon, Drennan D., Lipman A.
Pain Medicine. 2010; 11: 535-549
It would be great to have topical NSAIDS that could help people suffering from chronic inflammation such as arthritis. However, I think it would be beneficial to research how these topical NSAIDS are lowering the pain contributed by the inflammation vs their effect on reducing the actual problem of chronic inflammation.
ReplyDeleteI enjoyed your post and another approach of NSAIDs application. The big idea here is local accumulation of drug. With oral NSAIDs, you get a high plasma concentration that leads large amount of the active drug in the circulatory system, which leads to active drug acting at non-target sites producing adverse effects. With a topical application, the drug is absorbed near the targeted area and allows for the accumulation of active drug at target site while reducing circulating active drug in plasma levels. However, you pointed out a good point about with chronic application of a topical NSAID you could see a loss of the benefit of reduced adverse effects; I would suspect that by the repeated application and high concentrations of drug will increase the plasma levels leading to the adverse effects as do oral NSAIDs.
ReplyDeleteOne thing I am curious about and not finding promising results is oral vs. topical applications. I am particularly interested in the results that osteoarthritis patients taking topical NSAIDs reported benefits. I started to think about the synovial fluid concentrations of drug between oral and topical and how that contributes to pain relief. I would believe that oral administration in comparison would deliver greater levels of concentration in the synovial fluid than topical application. However, if that were true and we still witness at lower synovial fluid levels with topical application, it would me a much favorable approach to employ and further studying needs to be accomplished.
That's interesting that you bring this up Gena! I was reading an article the other day on a drug called flurbiprofen which is shown to have anti-inflammatory effects and i believe is an anti-fungal as well.
ReplyDeleteWhat the researchers did is compare the effects of oral administration of flurbiprofen to arthritic mice vs topical application. What they found was that topical application significantly suppressed hind limb edema comparable to oral administered groups and even the plasma levels of flurbiprofen between the two groups was comparable, suggesting that the topical application does in fact cause some effect on the system.
The researchers suggest that flurbiprofen may not need to permeate inflamed tissue below the site but may enter the systemic circulation to cause anti-inflammatory effects. I believe that researching topical applications of anti-inflammatories may be a great thing to look into if it causes less side effects (i.e. they also found that the topical flurbiprofen did not cause damage to the gut lining like the oral administration did).
If you are interested in the article:
http://www.ncbi.nlm.nih.gov/pubmed/8847830
I'm all for topical NSAIDs since they do not cross into the system of GI mucous and cause ulcers.
ReplyDeleteMichele makes a good point with the concentrations in the synovial fluids. If less concentration is needed to deliver the same effect as oral NSAIDs, topical will be the way to go.