- Published with
permission from Mimi Porter 3-01 (1997
Article)
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A product that is certain to change the way
medications are delivered to animals was introduced
at the recent American Association of Equine
Practitioners meeting. Iontophoresis, also called
ion transfer, makes use of direct current to drive
water soluble medications into subcutaneous tissue.
Iontophoresis is an attractive mode of drug
delivery for the equine practitioner because of the
minimal ionic concentrations required for its
effectiveness, and because of its non-invasive
nature.
Historical
Background of Iontophoresis.
- Athough it is new
to the equine industry marketplace, iontophoresis
is not a new modality . Drugs have been
successfully introduced into the tissues below the
skin surface by means of electric current since
Fabre-Palaprat recovered iodide in the urine
following its electrical transfer in 1833. The
safety and comfort of this method of drug transfer
is pointed out in the use of zinc ion transfer for
corneal ulcers in 1929, and in calcium ion transfer
through the eye for the treatment of diseases of
the eye in 1932. Bee venom was used in therapeutic
iontophoresis in 1938. In 1940, epinephrine was
administered to asthmatic patients by electricity.
It was observed that when the drug was deposited in
the skin in this manner, it was absorbed gradually
and the supply was available for a period of time.
Histamine ion transfer was advocated in 1944, for
the treatment of subacromial bursitis. The
versatility of this procedure is indicated in the
broad spectrum of ions used in the early days.
Because current levels are low, indications and
contraindications of iontophoresis pertain to the
ion selected and its physiological action in the
tissues, rather than to the use of electricity. The
electrical current merely repels the drug ion
through the skin pores and the hair follicles.
]
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Iontophoresis was approved by the FDA in the
1970's. The use of this modality is increasing in
human physical therapy and orthopedic medicine for
the treatment of injury, arthritis, and over-use
syndromes. Each year over 4 million people
successfully receive drugs delivered by
iontophoresis.
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- Theoretical
Basis of Iontophoresis:
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The Greek ion or iontos refers to an atom having a
negative or a positive charge as a result of the
loss or gain of one or more electrons. Phoresis
refers to being carried. A direct electric current
provides the electromotive force to move the
ionized particle of the drug past the barrier of
the skin and into the deeper tissues. The route of
entry is through the pores, the sweat glands, and
the hair follicles. Additionally, the overall
resistance of the skin will decrease somewhat under
the influence of electricity, allowing further
passive passage of the drug into the dermal layers.
The skin acts as a reservoir of the drug, extending
its release into the deeper layers after the
iontophoresis device is removed.
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- An
iontophoresis device consists of:
- 1. A low voltage
direct current generator, the power source. Modern
units are the size of the palm of the hand and are
powered by a 9-volt alkaline battery.
- 2. Lead wires
consisting of a positive lead and a negative lead.
One unit has dual channel capability, enabling
treatment of two different sites at once.
- 3. Electrodes,
consisting of a buffered drug containment electrode
for delivery of the drug, and the grounding
electrode, also called the dispersive or return
electrode.
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The central process of iontophoresis is the
movement of ions.The basis of ion transfer lies in
the principle that like poles repel and unlike
poles attract. Ions, being particles with a
positive or a negative charge are repelled in to
the skin by an identical charge the electrode
places over it. When a direct electric current
activates the electrodes, anions in the solution,
ions with a negative charge, move toward the
positive electrode. Positively charged ions
(cations) move toward the negative electrode. The
electrical current will drive ions through the skin
that would not be absorbed passively . The quantity
of ions that are made to cross the skin barrier is
directly proportional to the current density and to
the amount of time the current flows through the
solution. Current density is determined by the
strength of electric field and electrode size. Most
units use a current strength of 0.4mA, or 1mA per
square inch of electrode surface. This current
strength is just below sensory perception. Smaller
electrodes concentrate the current, making it more
readily felt by the patient.
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Another factor that determines ion flow is the
weight of the ion molecules. Examining the delivery
efficiency of three differently weighted drugs,
Phipps et al. found that sodium, the lowest
weighted ion of a group that also included
magnesium, potassium, and calcium, had the highest
delivery efficiency. Elements of low atomic weight,
less than 8,000 daltons, migrate much faster than
those of high atomic weight. Such drugs include:
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- 1. local
anesthetics such as lidocaine
- 2. antibiotics
such as gentamicin and ceftiofur
- 3. corticosteroids
such as dexamethasone
- 4. NSAIDS such as
phenylbutazone and funixin meglumine
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A solution with a high concentration of ions will
not increase the number of ions transferred.
Indeed, a solution with a high concentration of
ions may have a low delivery efficiency. Several
investigators have demonstrated that medication at
concentrations of between 1 and 5 percent are
optimal for ion transfer. An analogy could be made
to a doorway through which a finite number of
people can pass at any given time. Because of
competition for space at the doorway, one way to
allow more people to pass through would be to keep
it open longer. Increasing the number of people at
the door would only create congestion. Optimal
dosages for most drugs are achieved in treatment
times of 10 to 20 minutes.
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Continuous direct current is the current of choice
for iontophoresis, since this mode ensures the
maximum ion transfer per unit of applied current.
It provides a constant, unidirectional
electrostatic field between the electrodes to allow
continuous transmission of drug. Other forms of
current, such as high-voltage galvanic, sine wave,
interferential, and microcurrent are not effective
in iontophoresis.
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- Applications of
Iontophoresis:
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In the past, human patients faced a risk of mild
burning or a prickling sensation under
iontophoresis electrodes. For this reason,
lidocaine hydrochloride was added to the delivery
electrode, along with the desired drug. Recent
advances in electrode technology as well as in
current modulation have eliminated the need for
lidocaine to reduce sensation from the electrodes.
These advances have also made it possible to
deliver more drug in less time. Skin pH at the
electrode can affect ion transfer so buffered
electrodes provide the most efficient delivery. As
with any other approach to drug delivery,
iontophoresis must follow a complete veterinary
evaluation and diagnosis to determine the nature of
the injury, its location and extent.
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In iontophoretic drug delivery, it is critically
important that the drug is applied through the
electrode with the appropriate polarity, that is, a
drug with a negative charge is applied with the
negative electrode. If the polarity is reversed,
there will be no drug delivery.
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Before applying the electrodes, inspect the area of
skin to be treated, looking for abrasions,
lacerations, scar tissue, or inflammation. Damaged
skin is more sensitive to electrical current and
may make the application uncomfortable or cause
irritation at the delivery site. Clean the area
thoroughly to remove oils, dirt, sweat, or other
medications. Treatments should take place in a
clean, well lighted area where the horse can relax.
Iontophoresis is well tolerated by the horse.
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Prepare the delivery electrode by attaching the
appropriate lead wire and filling the drug
reservoir pad with at least 6cc of solution. Place
it over the treatment site and apply a wrap to
secure it in place. To prepare the ground, or
return electrode, attach the wire of the opposite
polarity and apply a dab of transmission gel on the
karyra gum pad or wet it with water to increase its
conductivity. This electrode is placed on the same
side of the body, about four inches away from the
delivery electrode and wrapped in place. The
electrodes have an adhesive backing to hold them in
place, but additional wraps are recommended to
ensure good contact and maintain electrode
placement. Maintaining contact between the skin
surface and the electrode is essential to obtain
optimal current flow and to avoid uneven current
density. Generally, shaving the hair coat is
unnecessary, although a very thick coat may inhibit
good contact between the electrode and the skin.
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One device on the market today has a built in
ramping mode to slowly increase the current to
delivery level. At the end of treatment, the
current is automatically ramped down to 0. This
ramping procedure allows a more gradual increase or
decrease in current resulting in a comfortable
treatment without the sensation of being shocked.
The delivery electrode can be left in place for
additional time to allow for any passive absorption
of the medication that may occur. Treatments are
usually given every other day for one to eight
weeks. Generally, results are seen within the first
few treatments.
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Iontophoresis can be used along with, and in many
cases may enhance, other forms of physical therapy.
Stretching exercises are used to increase range of
motion and are useful in reducing muscle spasm or
in elongating scars or adhesions. Electrical
stimulation, low level light, or magnetic fields
can be used to maintain pain relief and edema
reduction. Therapeutic ultrasound reduces muscle
spasm, increases membrane permeability, and
increases absorption of the ions.
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Pointing out the compatibility of iontophoresis and
other physical therapy modalities, iodine was used
for its sclerolytic effects in addition to
ultrasound and stretching. The results of this case
study of post-surgical scarring in a tendon were
complete pain relief and normal range of movement
in five treatments.
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- Specific Uses
of Iontophoresis:
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Corticosteroids are the primary drugs used with
iontophoresis in human physical therapy. Formulated
as a water soluble salt, the corticosteroid
molecule has a negative charge. Dexamethasone is
often administered by iontophoresis in the
treatment of joint or musculoskeletal disorders. In
a comparative study of three different approaches
to over-use injury of the shoulder, iontophoresis
provided the most rapid resolution to muscular
pain. Orally administered muscle relaxant and
analgesic medications were given to one subject
group, while another group received treatment with
hot packs and ultrasound. The iontophoresis treated
group received 1cc of 0.4% dexamethasone sodium
phosphate and 2cc of 0.4% lidocaine hydrochloride.
Although all three treatment procedures resulted in
increased pain-free range of motion, the subjects
receiving oral medication had the least increase
and those receiving iontophoresis had the most. The
investigators felt that this was because the
iontophoresis administered the medication directly
to the target tissues.
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In another study, 50 patients with various
musculoskeletal conditions including epicondylitis
and tendonitis, were treated with dexamethasone
sodium phosphate and xylocaine. All showed positive
results within 24 hours after the first treatment.
Cumulative effects of up to three treatments in a
one week period resulted in permanent relief in
some cases.
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A case report of gouty tophi and osseous
degeneration, which would be equivalent to
degenerative joint disease in the horse, showed
positive response to lithium iontophoresis. The
patient reported immediate improvement following
the first treatment. Subsequent treatments resulted
in complete relief of edema and pain.
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Calcific deposits are amenable to treatment with
the acetate ion found in acetic acid. A reduction
in the density of the deposit and in the size of
the deposit was confirmed by x-ray. Two
investigators reported the results of applying
acetic acid solution to bursal calcification,
tendon sites, and myositis ossificans. Radiographs
three months after treatments showed complete
absorption of the heavy calcific deposits seen
before treatment.
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An unpublished study examined the reproducibility
of iontophoretic drug delivery to the hock joint of
the horse. Using three horses, 6 hock joints were
treated with betamethasone at three different
concentrations and three different treatment
durations. The data indicated a 2.4% solution of
betamethasone administered in a 40-80mA/min dose
was optimal. These parameters were found to deliver
betamethasone concentrations considerably above
estimated therapeutic concentrations as proposed by
Lillich.
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Copper sulfate has been used to treat fungal
infections such as tinea pedia (athlete's foot)
with marked improvement in 24 hours. Perhaps this
could lead to investigations of iontophoresis
treatments for white line disease or fungal skin
diseases in horses.
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- Benefits of
Iontophoresis:
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Iontophoresis offers the benefits of being painless
and non-invasive. In addition, there is no danger
of infection or damage due to needle insertion or
to impact from a bolus of fluid. The local
concentration of the drug is high, while the
systemic concentration is minimal. Only minute
amounts of the drug reach the systemic circulation,
greatly reducing side effects. Drug dosage is
accurately controlled by controlling the quantity
of electrical current used to transfer the drug.
For areas such as the distal tarsal joint or around
the hoof, where injection is difficult,
iontophoresis offers an alternative mode of drug
delivery. As the medication passes through the
tissues, the peri-articular tissues, as well as the
articular surface, are bathed in the medication.
Exposure to mild electrical current provides added
therapeutic effects. Contraindications with this
modality pertain to sensitivity to the drug rather
than to the modality itself. The manufacturer
suggests avoiding electrode placement so that the
current pathway crosses the heart or the brain.
Also the area of the eye should be avoided. Abraded
skin or new scar tissue should be avoided as these
areas are sensitive to electrical current, making
the treatment uncomfortable.
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The equipment available today is efficient and
miniaturized. The possibility of shock or burns, a
problem with iontophoresis in the past, are now
eliminated by advanced electrode design and
modulated current. Iontophoresis has the potential
to provide substantial benefits when this mode of
therapy is applied in the appropriate manner. There
is little doubt that many substances can be
introduced into the body by this method.
Iontophoresis offers a means of introducing
medications through the surface of the skin in a
safe, easy and painless manner. As with many new
modes of therapy, however, there is need for more
studies that document the use and effects of
iontophoresis in various clinical situations.
-
- References:
- 1. Data compiled
by Empi, Inc., St Paul, MN. 1996.
- 2. Phipps, JB,
Padmanabhn, RV, Lattin, GA. Iontophoretic delivery
of model inorganic and drug ions.
- J Pharm Sci.
78:365-369.1989.
- 3. O'Malley, E,
Oester, Y: Influence of some physical chemical
factors on iontophoresis using radio-isotopes. Arch
Phys Med Rehabil. 36:310. 1955.
- 4. Murray, W,
Levine, LS, and Seifter, E: The iontophoresis of
C2, esterified glucocorticoids: Preliminary report.
Phys Ther. 43:579. 1963.
- 5. Tannenbaum, M.
Iodine iontophoresis in reducing scar tissue. Phys
Ther 60:792. 1980.
- 6. Costello, CT,
Jeske, AH. Iontophoresis: Application in
Transdermal Medication Delivery. Phys Ther.
75:104-112. 1995.
- 7. Delacerda, F. A
Comparative Study of Three Methods of Treatment for
Shoulder Girdle Myofascial Syndrome. J Orthopaed
Sports Phys Ther.4:51-54. 1982.
- 8. Harris, PR.
Iontophoresis: Clinical Research in Musculoskeletal
Inflammatory Conditions. J Orthopaed Sports Phys
Ther. 4:109-112. 1980.
- 9. Kahn, J. A Case
Report: Lithium Iontophoresis for Gouty Arthritis.
J Orthopaed Sports Phys Ther. 4:113-114. 1980.
- 10. Kahn, J.
Acetic Acid Iontophoresis. Phys Ther Forum. Dec 3.
p.9-10. 1990.
- 11. Paski, C,
Carol, J. Acetic acid ionization: A study to
determine the absorptive effects upon calcified
iondinitis of the shoulder. Phys Ther Rev.
35:84.1955.
- 12. Dorian, R.
Clinical Investigation of Iontophoresis of
Betamethasone in the Horse Hock Joint. unpublished
study. Edna Valley Veterinary Clinic/The Equine
Center. San Luis Obispo, CA. 1996.
- 13. Lillich, JD,
et al. Plasma, urine, and synovial fluid
disposition of methylprednisolone acetate and
isoflupredone acetate after Intra-articular
administration in horses. AJVR. 57:187-192. 1996.
- 14. Haggard, HW,
Strauss, MJ, and Greenberg, LA. Fungous infections
of hand and feet treated by copper iontophoresis.
JAMA. 112:1229. 1939.
-
- Additional
Reading & Links:
- http://www.iomed.com
-
- Cummings, J.
Iontophoresis. in Clinical Electrotherapy. Roger
Nelson & Dean Currier, eds. Appleton &
Lang. p231-241. 1987.
-
- Li, LC, Scudds,
RA. Iontophoresis: An Overview of the Mechanisms
and Clinical Application. Arth Care Res. 8:51-61.
1995.
-
- Li, LC, et al. The
Efficacy of Dexamethasone Iontophoresis for the
Treatment of Rheumatoid Arthritic Knees: A Pilot
Study. Arth Care and Res. 9:126-132. 1996.
-
- Wearly, L, Liu,
JC, and Chien, YW. Iontophoresis-Facilitated
Transdermal Delivery of Verapamil.I. in vitro
Evaluation and Mechanistic Studies. J Controlled
Rel. 8:237-250. 1989.
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