Vol. 22, No.
7 July 2000 V
CE Refereed Peer Review
FOCAL POINT
★Although topical drugs may be
absorbed in sufficient quantities
to exert systemic pharmacologic
and toxic effects, following a few
simple protocols will significantly
reduce the incidence of adverse
effects.
KEY FACTS
■ The stratum corneum is the layer
of the epidermis that provides
the most important barrier for
transdermal drug absorption.
■ Unless the topical bioavailability
of a drug is low, the dose
administered topically should
not exceed the systemic dose.
■ Only a fraction of drug delivered
to the eye by a commercial
ophthalmic dropper actually
remains in contact with the
cornea and conjunctiva long
enough to provide therapeutic
effects.
■ Although blinking of the eyes
actually increases the risk of
systemic drug absorption after
application of an ophthalmic
drop, keeping the eyes closed
decreases systemic drug
absorption and increases the
duration of drug contact with
the cornea and conjunctiva.
Systemic Absorption of
Topically Administered
Drugs
Washington State University
Katrina Mealey, DVM, PhD
ABSTRACT: A growing number of pharmaceutical agents are being designed for topical appli-
cation to the skin and eyes. Drug absorption, defined as movement of a drug from the site of
administration to the systemic circulation, is not desired. Instead, the intent of these agents is
to maximize the concentration of the drug at the disease site while minimizing potential sys-
temic adverse effects. Although this goal is achieved in most situations, systemic toxicity—in
both humans and animals—has been reported after topical administration of a number of
drugs. As the number and variety of topical pharmaceutical agents on the market increase, the
risk of systemic adverse effects will also rise. This article describes potential systemic adverse
effects resulting from topical application of drugs in animals and examines drugs that may
cause systemic toxicity, the clinical signs of toxicity associated with these agents, and meth-
ods that may be used to reduce systemic absorption of topical drugs.
P
harmacologic therapy of the eyes and skin offers several unique oppor-
tunities. The topical route of application is especially appropriate for
many diseases affecting these organs. In this article, topical therapy refers
to drugs applied to the skin (including the external ear canal) and eyes
(cornea and conjunctiva) with the intent of treating disease localized to these
areas. No other organ systems are as readily accessible for treatment and/or
for monitoring therapeutic efficacy. Additionally, this route of application
generally allows for maximizing drug concentration at the desired site of ac-
tion while minimizing the concentration of drug at other sites that may result
in adverse effects. Therefore, the concentration of active drug supplied in
many of these topical preparations is quite high relative to systemic doses of
the same drug. A poor understanding of factors affecting the systemic
bioavailability of these agents and the perceived safety level of topical drug
preparations may engender inappropriate prescribing practices and result in
excessive dosing. Consequently, sufficient amounts of a drug may be absorbed
into the systemic circulation to cause clinical signs of toxicity. Although the
general pharmacokinetic principles governing the use of drugs applied to the
skin and eyes are the same as for oral and injectable preparations, special
properties of these organs present unique opportunities and challenges for
drug delivery.
Small Animal/Exotics
TRANSDERMAL DRUG
ABSORPTION
The physiologic function of
the skin is to provide a two-
way barrier between the body’s
internal and external environ-
ments. The skin prevents the
loss of water, electrolytes, and
proteins from the body and
protects the body’s internal
milieu from physical, chemi-
cal, and infectious environ-
mental insults. Transdermal
drug absorption, therefore,
necessarily involves transgres- Figure 1—Schematic drawing of the structure of the stra- animals; therefore, an equiva-
sion of this barrier. tum corneum. Keratinocytes function as a barrier to lipid- lent amount of drug applied
soluble agents at the same time as the intercellular lipid
The major variables influ-
matrix functions as a barrier to water-soluble agents.
encing the degree of transder-
mal drug absorption that may
occur include the chemical characteristics of the drug,
variables affecting the skin itself, and the nature of the
vehicle containing the drug.1 Lipid-soluble drugs with
low molecular weight formulated at high concentra-
tions will be absorbed to a greater extent than will larg-
er water-soluble drugs formulated at low concentra-
tions. Many factors involving the skin itself affect
transdermal drug absorption. Healthy, intact skin gen-
erally serves as an effective barrier to drug absorption,
and diseased or denuded skin provides a minimal ob-
stacle. The stratum corneum, the outermost layer of
the epidermis, is the most important component of this
barrier.2,3 In fact, the rate of drug absorption through
isolated stratum corneum is approximately equal to the
rate of absorption through whole skin.1 Interestingly,
this layer provides a functional barrier for both lipid-
and water-soluble agents. Cells of the stratum corneum
(keratinocytes) do not contain nuclei or cytoplasmic or-
ganelles. Instead, they are filled with several hydrophilic
proteins (such as keratin) that function as a barrier to
lipid-soluble agents. The intercellular spaces of the stra-
tum corneum contain an abundance of high-molecular-
weight lipid molecules, which serve as a barrier to wa-
ter-soluble agents (Figure 1). Thus, the stratum corne-
um consists of multiple layers of keratinocyte “bricks”
(capable of repelling lipid-soluble agents) that are ce-
mented together with a lipid matrix (capable of re-
pelling water-soluble agents).
Transdermal drug absorption also varies from one
species to another2,4 and from one area of the body to
another.5 One probable reason for species differences in
drug absorption is simply that the thickness of the stra-
tum corneum differs among species. Another reason
may be differences in the metabolic capacity of the
LIPID-SOLUBLE DRUGS ■ STRATUM CORNEUM ■ PHARMACEUTICAL VEHICLES
Compendium July 2000
skin.6 Regional variations in
drug penetration occur simply
because the thickness of the
stratum corneum varies with
anatomic location. Greater
drug absorption would occur
with an equivalent topical dose
of a drug applied to the scro-
tum or axillary region than
to the footpads or dorsal tho-
racic region.2 It is also impor-
tant to remember that smaller
animals have a greater surface
area:mass ratio than do larger
topically results in a greater
systemic dose in smaller pa-
tients.
The vehicle within which a drug is contained greatly
affects the rate and extent of transdermal drug absorp-
tion. Examples of pharmaceutical vehicles include wa-
ter, alcohol, dimethyl sulfoxide (DMSO), or more
complex formulations such as ointments, lotions, gels,
pastes, aerosols, or creams.2 Vehicles have traditionally
been considered pharmacologically inert, but many
may provide therapeutic benefits in and of themselves
(via moistening or drying effects). The nature of a vehi-
cle may increase or decrease drug absorption by a num-
ber of mechanisms (Table I). Many of these factors
have unpredictable effects on the pharmaceutical and
pharmacokinetic properties of a particular drug, mak-
ing it extremely difficult to predict the efficacy and po-
tential toxicity of individual agents contained within an
untested, compounded formulation. Practitioners
should be aware that the responsibility of ensuring the
safety and efficacy of compounded products not ap-
proved by the FDA resides solely with the veterinarian
prescribing the drug. A simple example of a com-
pounded product includes the formulation resulting
from the addition of an injectable antimicrobial agent
such as gentamicin or enrofloxacin solution to a com-
mercial otic preparation. Unpredictable interactions of
the vehicle within the commercial preparation may en-
hance systemic absorption of the added drug, resulting
in an increased risk of systemic toxicity.
Pharmaceutical companies have exploited the con-
cept of systemic absorption of topically applied drugs
for decades. The application of nitroglycerin ointment
to the skin results in rapid systemic venodilation,
demonstrating both the rate and extent of systemic
drug absorption that can be achieved after topical ad-
ministration. Fentanyl and several antiparasitic agents
Compendium July 2000
TABLE I
Effect of Vehicle Characteristics on Transdermal Drug Absorption
Characteristic Effect on Absorption
High solubility of drug in vehicle Decreased
Ability of vehicle to hydrate stratum Increased
corneum
Stability of active ingredient Increased
in vehicle
High concentration of soluble drug Increased
in vehicle
Physical and chemical interactions Increased or
of vehicle with skin decreased
are formulated to be applied to the skin, undergo ab-
sorption, and exert systemic effects. A number of other
drugs have the potential to produce systemic effects in
veterinary patients when applied topically. In these cas-
es, however, this is not the desired effect.
Systemic Effects
Gentamicin-induced nephrotoxicity was diagnosed
in a cat that was treated topically with injectable gen-
tamicin solution.7 This patient had an infected, open
wound that was lavaged with 10 ml of gentamicin solu-
tion (50 mg/ml). Serum concentrations of gentamicin
measured after renal failure was detected were six times
the maximum recommended therapeutic concentra-
tions. The cat was euthanized owing to progressive
azotemia. A similar incident involving a 40-kg rottweil-
er occurred when a veterinarian lavaged a draining tract
with gentamicin solution. Plasma concentrations of
gentamicin in this dog greatly exceeded therapeutic
concentrations. This patient also developed acute renal
failure and required intensive medical management for
many days but eventually recovered. Adverse effects re-
sulting from topical administration of over-the-counter
medications has also been documented.8 A 30-kg dog
treated for fleas with pennyroyal oil, obtained by the
owner at a health food store, developed severe neuro-
logic and hepatic toxicity. The dog began vomiting
within 2 hours after application of the drug and died
within 48 hours.8
In a study involving dogs, ointments containing ei-
ther triamcinolone, fluocinonide, or betamethasone
were applied to the skin once daily for 5 consecutive
days.9 Cortisol and corticotropin (ACTH) concentra-
GENTAMICIN ■ AZOTEMIA ■ CORTICOSTEROIDS ■ SYSTEMIC TOXICITIES
Small Animal/Exotics
Mechanism
If a drug has a higher affinity for the vehicle than for
the stratum corneum, diffusion will be decreased
Hydration of stratum corneum increases permeability
(i.e., ointments)
Self-explanatory; stability of many compounded
veterinary drugs is unknown
A high concentration of drug dissolved in vehicle
provides a “steep” concentration gradient down which
the drug can diffuse
The best example is the ability of dimethyl sulfoxide to
increase transdermal absorption of many drugs by
increasing permeability
tions were determined in each dog before, during, and
after administration of the corticosteroid products. All
three corticosteroids caused prompt and sustained pitu-
itary–adrenocortical suppression within 2 days of treat-
ment. One week after the last application of cortico-
steroids, pre- and post-ACTH cortisol concentrations
remained suppressed in all corticosteroid-treated dogs.
Two weeks after the last treatment, the pre-ACTH plas-
ma cortisol concentrations of corticosteroid-treated
dogs returned to normal ranges but the post-ACTH
plasma cortisol concentrations remained suppressed. By
3 weeks after the last treatment, post-ACTH plasma
cortisol concentrations of dogs treated with triamcin-
olone acetonide had returned to normal ranges but re-
mained suppressed in dogs treated with fluocinonide
and betamethasone. By 4 weeks after the last treatment,
all indices of pituitary–adrenocortical function were
within the control range for all groups.
Many other drugs used in veterinary medicine have
the potential to be absorbed through the skin and cause
systemic effects. The anticancer agent 5-fluorouracil
has been reported to cause systemic effects after topical
application.10 Organophosphate and carbamate insecti-
cides are formulated for topical use on dogs and cats to
control fleas, ticks, and mites. Systemic toxicities have
occurred as a result of accidental exposure (i.e., when
products labeled for use on dogs are used on cats or
when cattle products are used on small animals), mis-
use (inappropriate dilution of dips), or excessive sensi-
tivity.11
Decreasing Systemic Absorption
Factors that increase the risk of systemic adverse ef-
Small Animal/Exotics
fects as a result of topical
drug administration include
the dose and dosing interval,
the transdermal bioavailabili-
ty of the drug (frequently not
known), the size of the pa-
tient, and the condition of
the skin. When administering
a topical drug to an animal, I
recommend calculating the
largest systemic dose that can
safely be administered. For
example, if gentamicin solu-
tion is to be used to lavage an
open wound in a 4.5-kg cat, Figure 2—Potential course of an ophthalmic drug after body, iris, and, most impor-
the systemic dose of genta- topical administration. The most important route for sys- tantly, the nasal mucosa. Sys-
micin should be calculated. temic absorption is through the nasolacrimal system.
The maximum systemic dose
of gentamicin (intravenous) for such an animal is ap-
proximately 18 mg every 12 hours. The quantity of
gentamicin used to lavage the wound should therefore
not exceed 18 mg in a 12-hour period. Furthermore,
when considering concomitant drug therapies, the fact
that the patient is receiving gentamicin, or other drugs
that might interact with gentamicin, should be taken
into account. Aminoglycoside antibiotics should not be
administered to this patient by any other route, nor
should other potentially nephrotoxic drugs such as
furosemide or NSAIDs be administered because they
are additive risk factors for gentamicin-induced
nephrotoxicosis. A similar protocol should be followed
for other topically administered drugs to minimize the
likelihood of adverse effects.
Because of its lipophilic nature, the stratum corneum
2,12
may act as a reservoir for many drugs. Consequently,
the local half-life may be sufficiently long to allow
once-daily application. In humans, for example, once-
daily application of corticosteroid preparations is as ef- µl if the subject is not allowed to blink; however, with
fective as are multiple applications in most circum-
2
stances. Direct access to the skin may predispose the
patient to frequent topical applications, increasing the
risk of systemic adverse effects. Because broken or
abraded skin is an ineffective barrier, drugs applied to
such areas should be expected to achieve higher con-
centrations within the systemic circulation.
OPHTHALMIC DRUG ABSORPTION
Although there are several routes of ocular drug ad-
ministration (e.g., subconjunctival, intraocular), this
discussion focuses only on topical ocular drug delivery.
When a drug is applied topically to the eye, several pos-
sible pathways may be followed (Figure 2). Absorption
of a drug through the corneal and conjunctival epitheli-
NEPHROTOXIC DRUGS ■ LIPOPHILIC NATURE ■ NASAL MUCOSA ■ HEPATIC METABOLISM
Compendium July 2000
um is the desired route for lo-
calized ocular drug effects.
For this to occur, a drug must
remain in the cul-de-sac and
precorneal tear film.13,14
The eyes are relatively se-
cluded from access by drugs
within the systemic circula-
tion, but the opposite is not
true. Drugs can reach the sys-
temic circulation after topical
ocular delivery by several routes
(Figure 2), including through
the aqueous humor, ciliary
temic absorption of a drug
through the nasal mucosa oc-
curs when fluid volume exceeds that which can be re-
tained on the surface of the cornea and drains through
the nasolacrimal ducts. Increased tear production and
blinking enhance nasolacrimal drainage. When the lids
are closed during the blink reflex, muscular contrac-
tions dilate the upper part of the lacrimal sac and com-
press the lower portion. Thus tears are aspirated into
the sac, and fluid that has collected in the lower part of
the lacrimal sac is forced down the nasolacrimal duct.
As the lids open, muscular relaxation causes the col-
lapse of the upper part of the lacrimal sac, squeezing
fluid into the lower portion. In this way, the act of
blinking exerts a suction-force-pump action in remov-
ing excess fluid from the surface of the cornea and con-
junctiva and promotes drainage into the nasolacrimal
system.13
Normal tear volume in humans is approximately 7
µl14 (tear volume in dogs and cats has not been report-
ed). The human eye can hold a maximum volume of 30
blinking only about 10 µl can be retained.14 Commer-
cial eyedrops deliver a volume of 25 to 50 µl per drop.15
Thus when a drop is applied to the eye, a significant
portion is lost through overflow onto the eyelids,
through the nasolacrimal system, and into the nasal mu-
cosa. The nasal mucosa is supplied with a rich capillary
network that is easily penetrated by most drugs. Venous
drainage of the nasal mucosa occurs through the maxil-
lary vein, which empties into the external jugular vein.
Drug absorption by this route avoids first-pass hepatic
metabolism; consequently, drugs that undergo hepatic
metabolism can attain high systemic concentrations.
Systemic Effects
Several ophthalmic drugs used in veterinary medicine
Compendium July 2000 Small Animal/Exotics

COMPENDIUM
ON CONTINUING EDUCATION
have been reported to cause systemic toxicity. Phenyle-
phrine is an α−adrenergic sympathomimetic amine. It
F O R T H E P R A C T I C I N G V E T E R I N A R I A N ®

is used ophthalmologically for its ability to vasocon- Veterinary Technician reprints also available
strict conjunctival vasculature and for inducing maxi-
mal pupillary dilation prior to ocular surgeries. System- 2001 PRICE SCHEDULE*
ically, phenylephrine causes peripheral vasoconstriction 2 4 8 12 16
with a resultant increase in diastolic and systolic blood Quantity pages pages pages pages pages
pressures. In one report, three dogs scheduled for cataract Black & White
surgery were treated topically with phenylephrine, flur- 100 $ 108 $ 204 $ 416 $ 604 $ 784
500 152 296 616 896 1,156
biprofen, atropine, and prednisolone.16 Each dog devel- 1000 208 412 868 1,260 1,628
oped arterial hypertension, with systolic, diastolic, and 5000 636 1,264 2,828 4,076 5,160
mean arterial pressures ranging from 170 to 205, 90 to 10,000 1,172 2,332 5,280 7,596 9,572
112, and 123 to 148 mm Hg, respectively (normal val- Color
ues do not exceed 160 systolic, 100 diastolic, and 120 100 $ 972 $1,408 $2,856 $4,180 $5,380
500 1,152 1,612 3,112 4,704 6,040
mm Hg mean). Systemic doses of phenylephrine as a 1000 1,264 1,840 3,428 5,260 6,852
pressor agent range from 0.01 to 0.1 mg/kg. The doses 5000 2,328 3,600 7,140 10,672 12,168
these dogs received for ocular effects were estimated to 10,000 3,280 5,792 10,640 16,704 18,812
be 50 to 367 times greater than the intravenous dose *Price includes UPS Ground Shipping to one location.

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thetized dogs. The use of ocular adrenergic agents is Quantity _____________ ❏ Black & White ❏ Color
contraindicated in humans receiving monoamine oxi- ❏ With Review Questions ❏ Without Review Questions
dase inhibitors or tricyclic antidepressants because of
Author _________________________________________
the potential for severe drug interactions. The risk of
such an interaction in animals may increase as these Title of Article ___________________________________
classes of drugs are used more frequently for their be- ______________________________________________
havior-modifying properties. From Vol. _________________ No. ______________
Glucocorticoids are one of the most frequently used
❏ Compendium ❏ Veterinary Technician
topical ophthalmic medications in veterinary medicine.
These drugs are used to treat conditions such as bleph- ❏ Payment Enclosed (All payments must be in US funds drawn
on a US branch of a US bank.)
aritis, conjunctivitis, episcleritis, keratitis, iritis, and
uveitis. Systemic effects associated with ophthalmic glu- ❏ Purchase Order Attached
cocorticoid use have been reported in dogs.17,18 In one Contact Person ___________________________________
case, polymyopathy was reported to result from chronic Phone __________________________________________
ophthalmic administration of a 0.1% dexamethasone
preparation.17 Topical ophthalmic use of both dexa- SHIP TO:
methasone and prednisolone (1% prednisolone acetate) NAME
in dogs was reported to cause elevations in liver enzymes
(alkaline phosphatase and alanine aminotransferase), al- COMPANY OR PRACTICE

tered hepatic glycogen metabolism resulting in marked ADDRESS

glycogen accumulation in hepatocytes, and suppression
of the hypothalamic-hypophysis-adrenocortical axis.17,18 CITY STATE ZIP

Systemic absorption has been documented to occur BILL TO:

following topical ophthalmic administration of at- NAME
ropine,19 cyclosporine (in rabbits),20 and timolol21 in an-
imals. In one study, atropine sulfate 1% solution was COMPANY OR PRACTICE

administered topically to the left eyes of 19 dogs for 14 ADDRESS

days and tear production in both eyes was monitored
before, during, and after treatment. Although atropine CITY STATE ZIP

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cantly decreased in both eyes. Three weeks after the last Veterinary Learning Systems
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creased compared with baseline values in both treated Trenton, NJ 08618
No telephone calls accepted.
and untreated eyes.19 In another study,16 cyclosporine

GLUCOCORTICOIDS ■ TEAR PRODUCTION

Small Animal/Exotics
2% eyedrops were administered to rabbits at a dosage
of one drop every 12 hours for 5 days or one drop ev-
ery 6 hours for 10 days. Low cyclosporine concentra-
tions were detected in plasma. Although there are no
reports of systemic absorption or systemic side effects
of cyclosporine in dogs, routine use of topical cy-
closporine for treatment of keratoconjunctivitis sicca in
dogs had been somewhat limited. A commercially for-
mulated veterinary product containing cyclosporine
was recently introduced; therefore, ophthalmic admin-
istration of cyclosporine is likely to increase.
Timolol (β1 and β2 antagonist) is used topically to treat
glaucoma. This drug reduces intraocular pressure by in-
hibiting aqueous humor formation by the ciliary body.15
The recommended dose of ophthalmic timolol in dogs
and cats is one drop of 0.5% solution two to three times
daily.22 The actual quantity of timolol delivered in one
drop (50 µl) is 0.25 mg. The oral dose of timolol for
dogs is 0.5 to 5 mg three times daily.23 Because the oral
bioavailability of timolol is only 50%, owing to first-pass
hepatic metabolism, a single ophthalmic dose of timolol
approaches the systemic dose. Systemic effects resulting
from ophthalmic timolol in dogs reportedly include de-
creased heart rate and blood pressure.21 These effects may
lead to decompensation of congestive heart failure in sus-
ceptible patients. Several deaths in human asthmatic pa-
tients have occurred after topical administration of timo-
lol as a result of severe bronchoconstriction.24
Decreasing Systemic Absorption
Systemic absorption of ophthalmic medications can
be reduced by following a few simple procedures. Over-
flow of drug into the nasolacrimal system can be mini-
mized by instilling only one drop of medication. If
more than one drop is deemed necessary, the second
drop should be administered a minimum of 10 minutes
after the first one in order to avoid overflow into the
nasolacrimal system. Prevention of drug entry into the
nasolacrimal system can be accomplished by occluding
the lacrimal ducts with gentle fingertip pressure over
the medial aspect of the lower eyelid. Keeping the lids
closed allows for greater retention of instilled ocular
medication. Larger volumes are retained and no fluid
enters the lacrimal sac when the lids are closed, result-
ing in greater delivery of drug to the eye with conse-
quent reductions in system drug concentrations. Ad-
herence to these techniques will not only help prevent
systemic absorption of ophthalmic drugs but will also
increase therapeutic efficacy.
PREVENTING UNINTENTIONAL
HUMAN EXPOSURE
Systemic absorption of topically administered drugs
TIMOLOL ■ DIMETHYL SULFOXIDE ■ ORGANOPHOSPHATES
Compendium July 2000
may also pose a threat to individuals who work with
veterinary patients. Because of its venodilating effects,
topical nitroglycerin paste is used to treat cardiogenic
pulmonary edema.25 Because nitroglycerin paste is read-
ily absorbed transdermally, individuals working with
this drug should wear nonpermeable gloves. Al-
trenogest is an orally administered synthetic progesta-
tional agent indicated for estrus synchronization in
mares. The solution can be absorbed transdermally, and
the manufacturer recommends that pregnant women
and individuals with hormone-responsive tumors or
other diseases adversely affected by progesterone-type
hormones do not handle the product. Rarely, topical
exposure to chloramphenicol has resulted in aplastic
anemias in humans.26
Dimethyl sulfoxide is a chemical that, during the
course of its use as an agricultural solvent, was discov-
ered to alleviate arthritic pain.27,28 It soon became wide-
ly and promiscuously used for the topical treatment of
a variety of inflammatory conditions. The discovery of
DMSO-induced lens opacities in animals resulted in
termination of these uses.29–31 DMSO is rapidly ab-
sorbed through intact skin and has a remarkable capaci-
ty to enhance transdermal absorption of many other
chemicals and drugs.32–35 Topical use of DMSO in hu-
mans has been reported to cause photophobia, distur-
bances in color vision, headache, nausea, diarrhea, and
local inflammatory reaction (believed to result from the
drug’s ability to degranulate mast cells).27,36 Rubber
gloves should be worn when handling this drug.
Organophosphates are routinely used in small animal
veterinary hospitals for the topical treatment of fleas,
ticks, and mites. Frequently, the same few individuals
in one veterinary clinic are repeatedly exposed to these
agents (i.e., the same person bathes and dips all ani-
mals). Chronic exposure to organophosphates can re-
sult in headaches, gastrointestinal disturbances, and
central nervous system signs.37 Personnel working with
these chemicals should wear protective clothing (e.g.,
water-impermeable aprons, long gloves).
CONCLUSION
Topically administered medications are generally well
tolerated in veterinary patients. However, they have
been documented to cause adverse effects in dogs and
cats. Because of the perceived high margin of safety of
these drugs, neither the clinician nor the owner may as-
sociate drug administration with an adverse systemic ef-
fect. Veterinarians should be aware of the potential for
systemic adverse effects associated with any topically ap-
plied drug, particularly when the drug is used chronical-
ly or when the patient has concurrent medical condi-
tions (e.g., cardiac, endocrine, or respiratory disease)
Compendium July 2000 Small Animal/Exotics

that may be exacerbated by topical drug administration.

Drug interactions involving topically applied medica-
tions should be considered for patients receiving other
medications, and the patients should be monitored ac-
cordingly. This article discussed adverse effects associat-
CALL
ed with topical administration of several drug classes,
but certainly other drugs and routes of exposure also
have the potential to cause toxicity in veterinary pa-
FOR
tients. Increased awareness of the potential complica-

PAPERS

I
tions resulting from topical drug administration should
allow for improved client education and better monitor-
ing of patients, minimizing the risk of iatrogenic disease.

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About the Author
Dr. Mealey is affiliated with the Department of Clinical Sci-
ences, College of Veterinary Medicine, Washington State
University, Pullman. She is a Diplomate of the American
College of Veterinary Internal Medicine and the American
College of Veterinary Clinical Pharmacology.