Iontophoresis- specificity towards drugs

Lidocaine has been extensively studied for treatment and prophylaxis of local pain. Using iontophoresis as the method of delivery reduces systemic exposure to this antiarrythmic agent, thus lowering the possibility for cardiac side effects. One common problem is a short duration of action, which is explained by the vasodilation that lidocaine causes, increasing its own clearance. In order to alleviate this problem, combination with epinephrine is indicated to cause local vasoconstriction and thus hold the lidocaine in the tissues in close proximity to the electrode. The efficacy of lidocaine in providing dermal anesthesia has been proven by several randomized controlled clinical trials.(Greenbaum, 2001; Wanke, 1991; Wallace et. al., 2001; Ashburn et. al. 1997; Galinkin et. al., 2002; Miller et. al., 2001; Squire et. al., 2000; Kim et. al., 1999; Sadler et. al., 1999; Meyer et. al., 1990; Russo et. al. 1980). Studies comparing the efficacy of eutectic mixture of local anesthetics (EMLA) to iontophoresis with lidocaine for pre venipuncture analgesia have found mixed results.  These findings support the use of iontophoresis as a viable alternative to EMLA (Greenbaum, 2001; Wanke, 1991; Wallace et. al., 2001; Ashburn et. al., 1997). Several studies have evaluated the cost effectiveness of delivering medications (mostly lidocaine) via iontophoresis. One study comparing the use of iontophoresed lidocaine versus general or spinal anesthesia found that the cost of iontophoresis was half that of other anesthesia for performing bladder surgeries (Jewett et. al., 1999). Other studies have compared the costs of using EMLA versus iontophoresis and all have found iontophoresis to be a more cost effective method of drug delivery.

Dexamethasone is an extremely effective corticosteroid with strong anti-inflammatory effects and a long half-life. Using this medication via iontophoresis enables steroids to be delivered to joints and tissues, while bypassing the various unwanted side effects that accompany systemic treatment with corticosteroids. Its use for treating joint, fascia and tendon inflammation has been well studied (Gudeman et. al., 1997; Crawford et. al., 2002; Schiffman et. al., 1996; Li et. al., 1996). One double-blind, randomized controlled trial involving 39 patients suffering from plantar fasciitis found significant benefit from the addition of dexamethasone 0.4% iontophoresis to the standard treatment regimen during the 2-3 week treatment. However, the duration of increased effect was lost at the four-week follow-up. Therefore, although iontophoresis may not provide a long-term benefit, it does provide for accelerated improvement crucial to performance athletes and highly active patients (Gudeman et. al., 1997). Another interesting application involves combination therapy with dexamethasone and lidocaine combination solution applied at the positive electrode. When the electrical current is turned on, lidocaine is driven into the tissues, toward the negatively charged electrode. Although the dexamethasone in solution is not repelled by the positive electrode, the solution flow into the tissues, driven by the lidocaine is sufficient to draw a substantial amount of dexamethasone into the tissues as well.

The efficacy of NSAIDs has been documented for a long period of time. However, many patients experience routine gastro-intestinal side effects after taking them systemically. Topical preparations are available in compounded form. Deeper penetration may be facilitated by preparation of an iontophoresis solution (Tashiro et. al., 2001). One randomized controlled trial involving 40 patients compared the pain relief produced by iontophoretically delivered sodium salicylate compared to diclofenac for lateral epicondylitis and found that pain in both resisting wrist extension and pressure were more significantly decreased in the diclofenac group (Demirtas et. al., 1998). Ketoprofen and Ketorolac solutions have also been successfully used with iontophoresis (Tashiro et. al., 2000a, 2000b).

The use of antibiotics has been historically documented for various dermatologic infections, ear chondritis and burn infections. Reports of the use penicillin and gentamicin as well as the antiseptic effects of zinc and iodine are available. The available data on the use of this gentamicin via iontophoresis are conflicting. Historical data presents this use as a productive application of iontophoresis. The theory of attempting to deliver antibiotics to a tissue with limited vascularity appears strong. However, in a randomized trial comparing patients who received gentamicin with those who only received standard ear care, there were no differences other than the gentamicin group developing gentamicin resistant organisms (Desai et. al., 1991).

The enzymatic action of hyaluronidase has been used for a variety of indications. Its ionic nature andability to promote fluid resorption makes it an ideal molecule for iontophoresis. Historically this drug was available as the product, Wydase? . However, this product has been discontinued by the manufacturer and thus is only available through compounding pharmacies. The mechanism should decrease the damage involved with hematomas and edema. It is important to remember that hyaluronidase requires a special buffer solution and also has limited shelf life. Also, this product requires refrigeration when it is in solution.

Acetic Acid
The acetate ion in this chemical is believed to reduce calcium deposits. The published studies and case reports on this application are unfortunately conflicting with regard to both acetate penetration and clinical efficacy. One study found reductions in both the size and density of calcium deposits as confirmed by x-ray. Another case report found complete absorption of deposits at 3 months (Psaki et. al., 1955). And a study involving 35 patients with heel pain found “significant” decreases in pain with 27 months of follow-up (Japour et. al., 1999). However, a small (n=21) randomized controlled trial found no significant differences in calcium density or range of motion (Bose et. al., 2001).  Therefore, the success of this treatment may be questionable but is not out of the realm of possibility and should be kept in the armamentarium.



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