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[Iontophoresis: an old therapeutic principle in a new light].

Iontophoresis is defined as the transdermal transport of substances with the aid of electrical currents. It has certain advantages over other forms of drug application and receives presently much scientific interest. This review attempts to outline some basic principles and goes on concentrating on the clinical literature of recent years. In addition to local applications in the skin, systemic effects are in the foreground. Many indications have not yet been tested in controlled trials. Therefore further studies are needed to define the role of iontophoresis as an alternative form of transporting drugs into tissues.

Administration, Cutaneous↗

[Iontophoresis in the treatment of pain].

UNLABELLED: The objective has been to verify the effectiveness of iontophoresis in alleviating conditions of pain by means of a computer-assisted search of the pertinent literature. The search was performed with the aid of the Medline database (1984 bis 1993) and reference lists (studies from 1954). SELECTION CRITERIA: all clinical trials performed with at least one control group as well as all experimental studies conducted within the same period. The selection criteria were met by 10 experimental and 15 clinical studies. The studies were categorized by substance group. The following groups of substances were applied (experimentally/clinically): local anaesthetics (0/6), non steroidal anti-inflammatory drugs (2/3), vinca-alkaloids (1/2), corticosteroids (3/1), morphine (0/1), iodide (4/1) and fluoride (0/1). Both short-term effects (lidocaine, procaine, flufenamic acid, morphine) and long-term effects (benzocaine-salicylamide, diclofenac, Mobilat, vinca-alkaloids, dexamethasone-lidocaine, iodide, fluoride) were studied. Comparisons were made against placebo iontophoresis (lidocaine, procaine, flufenamic acid, diclofenac, Mobilat, vinca-alkaloids, dexamethasone-lidocaine, morphine, fluoride), solely topical administration (procaine, benzocaine-salicylamide, flufenamic acid), placebo administration without current (procaine, flufenamic acid), and other methods (lidocaine, iodide). With one single exception (lidocaine), none of the studies included groups without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

[The use of iontophoresis in dental practice].

The effect of hypersensitivity reducing local NaF-gel treatment with or without iontophoresis was evaluated. Air test was used for pain and pain reduction evaluation. Three consecutive treatments (0, 2, 5 weeks) and a 3 month control examination was performed on 20 and 16 patients. Additional iontophoretic treatment with Pikomed-Dention equipment was found more effective than topical NaF alone. Therapeutic use of iontophoresis could be employed in several other areas of dentistry. More attention should be paid to its use in caries prevention.

Dental Caries↗

[Efficacy and tolerability of ketoprofene administered through iontophoresis in rheumatoid arthritis. Results from a multicentric study].

Three-hundred and twelve patients with osteoarthritic diseases were admitted to a multicenter clinical trial. The patients were given 100 mg Ketoprofen twice-a-day by iontophoresis for 10 consecutive days. Pain relief was almost complete in 94.6% of the patients, improvement of active motility in 83.6%, disappearance of swelling in more than half of the patients and functional improvement in about all the cases. Two allergic skin reactions of a mild degree (0.6%) were registered. Therefore, Ketoprofen administered by iontophoresis showed to be efficacious and safe in the treatment of acute osteoarthritic diseases also in high risk patients.

Acute Disease↗

The effect of calcium channel antagonist administered by iontophoresis on the pain threshold.

Three calcium (Ca) channel antagonists were administered to healthy adult volunteers by iontophoresis alone or in combination with lidocaine to study their effects on the pain threshold. Nicardipine, verapamil or diltiazem administered alone elevated the pain threshold to the same degree as lidocaine. When Ca channel antagonists were administered in combination with lidocaine, the pain threshold elevation was not changed, but the duration of the analgesic action was prolonged when compared with lidocaine alone. These results suggest a role of the calcium channel in the pain control mechanism and the possible clinical application of Ca channel antagonists delivered by iontophoresis in pain management.

Adult↗

Lesions and shocks during iontophoresis.

Although a generally safe procedure, iontophoresis has recognized adverse side effects, including first-degree burns-and in fact, any low-voltage direct-current device has the potential to cause such injuries through electrolysis. In addition, as the reported problems indicate, shocks are possible under certain circumstances. Proper device operation and staff understanding of the causes of skin injuries associated with iontophoresis are essential to minimize the occurrence of these problems. It is also important to instruct the patient to inform the operator of any discomfort experienced during the treatment.

Burns, Electric↗

Transdermal iontophoresis of salmon calcitonin can reproduce the hypocalcemic effect of intravenous administration.

Salmon calcitonin (sCt) was administered by transdermal iontophoresis in rabbits, using a new drug reservoir assembled directly on the skin, based on a dry disc containing sCt to be dissolved at the application site. The hypocalcemic effect was taken as a measure of the pharmacodynamic response. In rabbits, the results obtained show that salmon calcitonin skin penetration by iontophoresis, using pulsatile current of 0.8 mA/cm2 on a reservoir containing 100 IU/Kg of sCt, was governed by the quantity of electric charge applied, mimicking the hypocalcemic response of 10 IU/Kg intravenous administration.

Administration, Cutaneous↗

Iontophoresis. A novel drug administration for extraction of deciduous teeth. A clinical evaluation.

Iontophoresis has a wide range of application in dentistry, one of which is to produce a non invasive technique of analgesia. With the avoidance of needle, in this technique better patient management and good doctor-patient relationship can be built. This study provides an insight into the comparative evaluation of 2%, 4% and 6% lignocaine hydrochloride (plain) in providing analgesia iontophoretically while extraction of deciduous teeth. Patient satisfaction was seen when higher drug concentration and longer duration of iontophoresis was applied.

Adolescent↗

Transient elevation of spontaneous release at the frog neuromuscular junction following acetylcholine iontophoresis.

Miniature end-plate currents (m.e.p.c.s) were recorded from frog neuromuscular junctions using a two-electrode voltage clamp. The m.e.p.c. frequency was temporarily elevated following 10s iontophoretic applications of acetylcholine (ACh) when the junctions were clamped at 100 mV. This post-ACh "burst" of quanta was also observed at unclamped junctions. At-100 mV, the intensity of the burst was proportional to the amount of current flowing across the end-plate during ACh iontophoresis, but usually did not reach its peak until the end-plate receptor channels were almost completely closed. Addition of 0.5 microM TTX to the Ringer's solution, or total replacement of sodium with guanidine, lithium, or methylamine did not inhibit the burst. No burst was observed in Ca2+-free, EGTA solutions, or in Ca2+-free solutions containing 2 mM Mn2+. Sr2+ effectively substituted for Ca2+. Addition of 2 mM Co2+ or Mn2+ to normal Ringer's did not inhibit the burst. Presynaptic muscarinic receptors did not obviously contribute to the burst, since it was not blocked by atropine, nor produced by oxotremorine or pilocarpine. The ACh analogs carbachol and acetyl-beta-methylcholine also produced the burst. The burst was highly dependent on the muscle membrane potential during the period of ACh iontophoresis, becoming more intense at potentials negative to -100 mV and disappearing at -60 mV. The critical importance of the post-synaptic membrane potential suggests that the burst may be due to an action of the muscle end-plate on the motor nerve terminal, possibly by the movement of an anionic substance through open end-plate receptor channels, but this hypothesis does not account for the delay of the burst until near the end of the ACh-induced end-plate current.

Acetylcholine↗

[The effect of iontophoresis on accelerating orthodontic tooth movement]

This paper reported that acceleration of tooth movement can be gained by submucosal injection of some kind of medicine.To avoid the pain caused by the injection,conventional drug administration was ameliorated in this study by adopting the method of ionophoresis rabibits were divided into 2 groups and the standard otthodontic appliances were placed in the lower incisors of all animals.The 2 groups were separately recieved submucosal iontophoresis and injection of 0.9% NaCl which served as control.The result showed that animals with iontophoresis,in whose periodontal pression side more osteoclasts were observed histologically,had gained rapider tooth movement than those with injections.

Journal Article↗

Separation of forearm hemodynamics into skin and muscle components by means of i-epinephrine iontophoresis.

By a combination of iontophoresis of I-epinephrine into the skin of one arm and simultaneous venous occlusion plethysmography in both treated (muscle only) and untreated forearms (muscle plus skin), we examined in 16 normal volunteers forearm blood flow, capillary filtration coefficient and venous capacity at cuff pressure of 40 mm of mercury (VC(40)) at rest, during tonic finger exercise and after interrupted repetitive finger exercise. Blood pressure did not change during the testing procedure. Forearm muscle conductance was about 60% to 70% of total conductance and was positively correlated with total conductance during rest and exercise. With standard exercises muscle conductance rises to 1(1/2) to 2(1/2) times resting level, and skin conductance rises to 2(1/2) to 4(1/2) times resting level. The capillary filtration coefficient is almost entirely in the muscle. It doubles in value with tonic exercise but decreases to half its resting value after interrupted repetitive exercise despite greatly increased conductance. Therefore, repetitive exercise-induced dissociation between conductance and filtration surface occurs in striated muscle. The mechanism is yet unknown. VC(40) in muscle is about 84% of total forearm VC(40). During tonic exercise muscle VC(40) was reduced, and during interrupted repetitive exercise the values for muscle and skin returned to resting values. A high correlation between muscle only and muscle-plus-skin for forearm blood flow and the identify between arms for measuring capillary filtration coefficient makes iontophoresis unnecessary for determining these values in forearm striated muscle under these experimental conditions.

Adult↗

Early diagnosis of leprosy by study of the sweat response to iontophoresis with parasympathomimetics.

The final aim of any leprosy control campaign is the eradication of the disease, or at least its reduction to a point where it no longer constitutes a major public health problem. The only possible ways of achieving this end are, firstly, through intensive case-finding and, secondly, through mass treatment.For obvious reasons diagnosis must be made at the earliest possible moment, which is not always easy by ordinary methods. Thus any technique to improve early diagnosis deserves full study. Observation of the sweat response to iontophoresis using parasympathomimetic drugs seems an easy and objective method of detecting leprosy skin lesions; it may therefore constitute a valuable step forward in the improvement of leprosy control.

Early Diagnosis↗

Androgenic regulation of dendritic trees of motoneurons in the spinal nucleus of the bulbocavernosus: reconstruction after intracellular iontophoresis of horseradish peroxidase.

Androgen-sensitive motoneurons in the spinal nucleus of the bulbocavernosus (SNB) in adult male rats were labeled after intracellular iontophoresis of horseradish peroxidase, after which they were fully reconstructed in three dimensions in order to measure their dendritic trees. Three groups of rats were compared: intact adult male rats and male rats castrated as adults and given Silastic tube implants containing either testosterone or nothing. In the high-androgen groups (intact males and testosterone-treated castrates), soma size and the diameter of the first-order dendrites were larger than in blank-treated castrates. Moreover, the terminal dendrites in all groups possessed growth cones, implying that the dendrites of these motoneurons are capable of growth in adulthood. However, there were no statistically significant group differences in the length, membrane surface area, or volume of the dendritic trees, or in the orientation or branching symmetry of dendrites. In general, there were positive correlations between the size of the motoneuronal soma and various measures of the size of the dendritic tree and between the diameter of individual stem (first-order) dendritic branches and the size of remainder of that dendrite. These data suggest that there may be a modest effect of androgen on the size of the dendritic trees of SNB motoneurons in adulthood, although the effect is much smaller than has previously been reported.

Androgens↗

Glucose monitoring by reverse iontophoresis.

Glucose can be extracted through intact skin by electro-osmotic flow (a process called 'reverse iontophoresis') upon the application of a low-level electrical current. Recently we have combined iontophoretic extraction with an in situ glucose sensor in a device called the GlucoWatch biographer. Clinical results with this device show close tracking of blood glucose over a range of 2.2 to 22.2 mmol/l for up to 12 h using a single blood glucose value as calibration. The biographer readings lag behind blood glucose values by an average of 18 min. An analysis of data from 92 diabetic subjects in a controlled clinical setting shows a linear relationship (r=0.88) between GlucoWatch biographer readings and blood glucose. The mean absolute relative difference between the two measurements was 15.6% and more than 96% of the data fell in the (A+B) regions of the Clarke error grid. Similar results have been obtained from subjects using the GlucoWatch biographer in an uncontrolled home environment. The automatic, frequent, and non-invasive measurements obtained with the GlucoWatch biographer provide substantially more information about glucose levels than do the current fingerstick methods. This information can be used for improved decisions about all aspects of diabetes management.

Biosensing Techniques↗

Characterization of the permselective properties of rabbit skin during transdermal iontophoresis.

The use of iontophoresis to enhance transdermal transport of drugs necessitates further investigations on the membrane used to simulate human skin because one of the transport mechanisms involved, electroosmosis, strictly depends on the properties of the skin (i.e., its isoelectric point, IP). The aim of this work was to characterize rabbit ear skin permselectivity by measuring the sodium transport number at different pH values. This method allowed us to estimate the skin IP. To confirm the validity of the method, mannitol flux was measured. In addition, the sodium transport number method was applied to the study of human skin and a model drug iontophoretic flux through rabbit and human skin was evaluated. The results indicate that rabbit ear skin behaves as a permselective membrane, with an IP between 2 and 3. The same result was obtained using human skin. The mannitol flux data confirm that the direction of electroosmotic flow at physiological pH is in the anode-to-cathode direction. Finally, permeation experiments performed with a model drug showed that the relative electroosmotic and electrorepulsive contributions to the total flux are the same for human and rabbit skin. It can be concluded that rabbit ear skin is a suitable model for the study of iontophoretic permeation of drugs.

Administration, Cutaneous↗

An extended model based on the modified Nernst-Planck equation for describing transdermal iontophoresis of weak electrolytes.

An extended model for iontophoretic enhancement of transdermal drug permeation under constant voltage is described based on the previously modified Nernst-Planck equation, which included the effect of convective solvent flow. This model resulted in an analytical expression for the enhancement factor as a function of applied voltage, convective flow velocity due to electroosmosis, ratio of lipid to aqueous pathway passive permeability, and weighted average net ionic valence of the permeant in the aqueous epidermis domain. The shift of pH in the epidermis compared to bulk caused by the electrical double layer at the lipid-aqueous domain interface was evaluated using the Poisson-Boltzmann equation. This was solved numerically for representative surface charge densities and yielded pH differences between bulk and epidermal aqueous domain between 0.05 and 0.4 pH units. The developed model was used to analyze the experimental enhancement of an amphoteric weak electrolyte measured in vitro using human cadaver epidermis and a voltage of 250 mV at different pH values. Parameter values characterizing the involved factors were determined that yielded the experimental enhancement factors and passive permeability coefficients at all pH values. The model provided a very good agreement between experimental and calculated enhancement and passive permeability. The deduced parameters showed (i) that the pH shift in the aqueous permeation pathway had a notable effect on the ionic valence and the partitioning of the drug in this domain for a high surface charge density and depending on the pK(a) and pI of the drug in relation to the bulk pH; (ii) the magnitude and the direction of convective transport due to electroosmosis typically reflected the density and sign, respectively, of surface charge of the tissue and its effect on enhancement was substantial for bulk pH values differing from the pI of epidermal tissue; (iii) the aqueous pathway predominantly determined passive permeability of the studied compound despite its measurable lipophilicity and therefore the lipid pathway did not notably affect enhancement. Hence, the proposed model can provide a good quantitative insight into the interplay between different phenomena and permeant properties influencing iontophoresis and can potentially be used as a predictive tool of the process.

Administration, Cutaneous↗

Conductivity of drugs used for iontophoresis.

The electrical conductivities of drugs were measured in vitro using a conductivity MHO-meter. These experiments indicate that local anesthetics, vasoconstrictors, some corticosteroids, several anticancer drugs, and several antiviral agents are suitable for iontophoresis. The contribution to conductivity of buffers and nonspecific ions in the same solution with the drug also was defined.

Adrenal Cortex Hormones↗

Characterization of the pore transport properties and tissue alteration of excised human skin during iontophoresis.

Pores through which charged carriers move during iontophoresis were demonstrated by the use of the cathodic (-) iontophoretic transport of fluorescein from the epidermis to the dermis. Both dermatomed (0.8-mm) human cadaver skin and full-thickness female human breast skin were investigated. The density of pores, as visualized by fluorescein transport, was approximately 2-5 cm-2. A set of microelectrodes rastered across the visualized pore gave a maximal response when directly above the pore, demonstrating that the pore was a locus of charge transport. Fluorescein was also sometimes observed at the diffusion cell-tissue interface. This indicates that edge damage had occurred as the result of clamping the tissue in a diffusion cell. Studies were conducted to determine if tissue damage occurred during iontophoretic transport. The electrical resistance across excised skin was measured at 0.2 Hz and found to decrease initially by approximately an order of magnitude after the application of an iontophoretic current of 0.16 mA/cm2 for 1 h. The electrical resistance then increased, reaching a plateau value which was lower than the original tissue resistance before application of an iontophoretic current. Controls were carried out to demonstrate that the observed electrical resistance changes were not just due to tissue hydration effects. These results imply that the passage of current through excised human skin at clinically acceptable current densities can lead to tissue damage which is not fully reversible.

Adult↗