pharmacology

An Independent Study Course Designed

for Individual Continuing Education

Sport and Exercise

Pharmacology

Independent
Study Course 16.1.6

Ross E. Biederman, DPM

Azusa Pacific University
Azusa, California
 Pharmacology
Mary Ann Wilmarth, PT, DPT, MS, OCS, MTC, Cert MDT—Editor

June 2006

Dear Colleague,

I am pleased to welcome you to Sport and Exercise Pharmacology by Ross E. Biederman,

DPM. This is the sixth and final monograph in the Orthopaedic Section Independent Study
Course series 16.1 entitled Pharmacology.

Dr Biederman is a professor in the Department of Physical Therapy at Azusa Pacific Univer-

sity. In addition, he teaches in the transitional DPT program at Northeastern University. Dr
Biederman attended California Polytechnic University and received his bachelor of science
degree in medical technology from Loma Linda University before completing his doctor of
podiatric medicine degree with the California Podiatric Medical Center and the University
of California Medical Center in San Francisco. He is a diplomate with the American Board
of Surgery and a fellow of the American College of Sports Medicine. Dr Biederman is very
knowledgeable in the areas of pharmacology and diagnostic imaging and has frequently lec-
tured and published on these topics.

This monograph covers pharmacotherapeutics and general considerations in sports includ-

ing pharmacokinetics and the athlete. Dr Biederman discusses the groups of drugs most
commonly encountered in sports rehabilitation along with classification, mechanisms of
action, adverse effects, therapy implications, and specific rehabilitation considerations. The
drugs covered in this monograph include nonsteroidal anti-inflammatory agents, steroid
agents, analgesic agents with opiate analgesics, skeletal muscle relaxants, and peripherally
acting agents, and topical agents in sports medicine. The case studies provide excellent
examples of the above-mentioned topics and issues with pharmacology associated with
rehabilitation, sport, and exercise.

I believe that you will find this monograph to be informative and useful for working with any
patients and athletes who are involved in sport and exercise.

Best regards,

Mary Ann Wilmarth, PT, DPT, MS, OCS, MTC, Cert MDT
Editor

2920 East Avenue South, Suite 200 | La Crosse, WI 54601

Office 608-788-3982 | Toll Free 877-766-3452 | Fax 608-788-3965
 TABLE OF CONTENTS
LEARNING OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PHARMACOTHERAPEUTICS: GENERAL CONSIDERATIONS IN SPORTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PHARMACOKINETICS AND THE ATHLETE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
COMMON DRUG GROUPS IN SPORTS REHABILITATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Nonsteroidal Anti-inflammatory Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Mechanisms of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Algorithms of selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Nonsteroidal anti-inflammatory drugs versus acetaminophen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Nonsteroidal anti-inflammatory drugs and wound healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Summary of rehabilitation considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Steroid Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Classification of steroid agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Glucocorticoid mechanism of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Preparations available . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Summary of rehabilitation considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Analgesic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Opiate analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Opioid receptor groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Classification of opiate medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Summary of rehabilitation considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Skeletal Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Mechanisms of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Peripherally acting agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Therapy implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Summary of rehabilitation considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Topical Agents in Sports Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Summary of rehabilitation considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
CASE STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Case Study 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Case Study 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Case Study 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
REVIEW QUESTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Opinions expressed by the authors are their own and do not necessarily reflect the views of the Orthopaedic Section.

The publishers have made every effort to trace the copyright holders for borrowed material.
If we have inadvertently overlooked any, we would be willing to correct the situation at the first opportunity.
© 2006, Orthopaedic Section, APTA, Inc.

Course content is not intended for use by participants outside the scope of their license or regulations. Subsequent use
of management is physical therapy only when performed by a PT or a PTA in accordance with Association policies,
positions, guidelines, standards, and ethical principals and standards.
Sport and Exercise Pharmacology
Ross E. Biederman, DPM
Azusa Pacific University
Azusa, Calif
LEARNING OBJECTIVES
Upon completion of this monograph, the course par-
ticipant will:
1. Be able to describe the pharmacological classifica-
tion and medical indications for medications com-
monly employed in the treatment of athlete patients.
2. Recognize medications that may present significant
risk to athletes.
3. Recognize exercise-induced changes in drug phar-
macokinetics.
4. Understand the effects and potential adverse effects
of commonly encountered medications in sports
rehabilitation.
5. Understand the nomenclature of pharmacology to
enhance communication and professional coopera-
tion between referring physicians and physical ther-
apists.
6. Be able to integrate pharmacological data into treat-
ment design and delivery of sports injury rehabilita-
tion.
INTRODUCTION
And is not bodily habit spoiled by rest and idleness
but preserved for a long time by motion and exercise?
(Plato, Theaetetus)
Sport and athletic participation require intense effort
and place the body under extreme physical stress. As a
result, medications may affect athletes differently than
they affect nonathletes. The athletic patient requires vig-
ilant pharmacological monitoring because of the highly
selective nature of medications employed within sports
participants and the attendant effects on injury recovery
and athletic performance. The Guide to Physical Thera-
pist Practice1 identifies clinical pharmacology as an
essential component of appropriate patient monitoring,
treatment selection, and interprofessional communica-
tion. Privileges for writing drug prescriptions exercised
by select military therapists and the evolution of the
entire physical therapy profession compel consideration
of an expanded pharmacological role in physical thera-
py practice. Rehabilitation of the athlete following injury
is perhaps the most important aspect of treatment. To
optimize outcome, the physical therapist must integrate
information regarding the patient’s pharmacotherapeutic
care into clinical planning. Whether the practitioner
acts to monitor or prescribe drug agents, the importance
of a pharmacologically integrated approach to compre-
hensive management of the injured athlete cannot be
underestimated.
Contemporary models of physical therapy practice
involve monitoring of both over-the-counter (OTC) and
prescribed medication. An understanding of the pharma-
1
cological properties of drug agents commonly encoun-
tered in the treatment of athletes and the individual phar-
macokinetics of specific preparations will help the ther-
apist to screen athletic patients for potential side effects,
develop more effective plans of care, and, where
allowed, prescribe drug agents with greater sports-ori-
ented selectivity. This monograph seeks to encourage
practitioners to proactively incorporate both beneficial
and adverse drug effects into rehabilitation design.
Injured fitness, amateur, and competitive athletes are
highly motivated to recover and return rapidly to sport
activity. Compliance with prescribed pharmacological
regimens is usually excellent. Some athletes, however,
perceive drug agents as unnatural and are somewhat
resistant to use of medications based on a philosophy
that non-drug natural forms of healing are preferable. In
this case, the therapist must function as patient educator.
Other athletes fall into the “if a little is good, more is bet-
ter” thinking and may overuse medications, particularly
easily obtainable OTC medications, which are perceived
as safer, hoping for added benefit. Again, the therapist is
called upon to monitor and educate the patient.
PHARMACOTHERAPEUTICS: GENERAL
CONSIDERATIONS IN SPORTS
This monograph focuses on medications commonly
employed in treatment of athletic injury and does not
propose to discuss all medications that may be pre-
scribed to the active individual. Inclusion or exclusion of
a drug agent within this monograph is neither an
endorsement nor a condemnation. All medications used
to treat athletic injuries should be employed in a very
thoughtful fashion because of the narrow therapeutic
benefit-risk ratio often encountered within this special-
ized population.
Physical therapists participating in the medical care of
the recovering athlete should recognize specific drugs or
drug groups that may adversely affect athletes function-
ing in sport. Medications not intended for injury treat-
ment, but rather in the overall health care of an athlete,
may present particular risks or monitoring considerations
for athletes. Any therapeutic drug that produces photo-
toxic reactions, sedation, thermoregulatory alteration,
psychotropic effects, or diuretic depletion of blood vol-
ume, or medications that impact rate and rhythm should
be carefully monitored and potential adverse effects dis-
cussed with patients. Table 1 identifies example drugs to
be avoided or carefully monitored when use among ath-
letes and active individuals is necessary.
PHARMACOKINETICS AND THE ATHLETE
Pharmacokinetics, the study of drug absorption, dis-
tribution, metabolism, and excretion, is discussed in
detail within the first monograph of this series.2 An
understanding of these principles allows a means of rec-
ognizing or anticipating medication behavior, drug inter-
actions, and side effects that may cause or mimic disease
processes, thus generating rehabilitation treatment
Table 1. Drugs Requiring Special Monitoring in Athletes
Drug Effect Example Medications
Phototoxicity
Antibiotics -Tetracyclines, fluoroquinolones
Antifungal agents -Griseofulvin
Nonsteroidal anti-inflammatory drugs -Propionic acid derivatives (Table 2): ibuprofen, naproxen
Sedation
Analgesics
Narcotic agents -Vicodin, codeine, Darvon
Drugs for chronic pain -Neurontin, Elavil
Centrally acting skeletal muscle relaxants -Soma, Parafon, Valium
Antihistamines -Benadryl, Chlor-Trimeton
Anxiolytic agents -Librium, Xanax, Ativan
Sleep agents -Dalmane, Ambien, Sonata, alcohol
Antidepressants -Tricyclic antidepressants: amitriptyline, doxepin
Altered Thermoregulation
Stimulants (increase heat production) -Sympathomimetic agents: over-the-counter cough and cold medications con-
taining pseudoephedrine, over-the-counter and prescription diet medications
-Attention-deficit/hyperactivity disorder agents: amphetamines, Ritalin, Concer-
ta, Pemoline
-Caffeine
-Thyroid hormone
Drugs inhibiting autonomic function -Anticholinergic drugs: Dramamine, scopolamine
-Belladonna alkaloid anti-diarrheal agents
-Antihypertensive agents
-Tricyclic antidepressants
-Certain antipsychotic agents: haloperidol
Dehydration
Diuretic agents -Hydrochlorothiazide, furosemide, high dose of caffeine, theophylline
Cardiac Agents
Beta-blocking agents -Propranolol, atenolol, metoprolol
Calcium channel antagonists -Verapamil, diltiazem, nifedipine

choice or outcome issues for the patient. Physiological
changes induced by exercise can alter the pharmacoki-
netics of some drugs, creating novel monitoring require-
ments for the treating clinician. Recognition of exercise-
specific alterations in the pharmacokinetic behavior of
drug agents allows more precise rehabilitation modality
selection, scheduling, and delivery. A discussion of phar-
macokinetics involves 4 topics: absorption, distribution,
metabolism, and elimination of drug agents.
Absorption
Drug absorption can occur in the gastrointestinal (GI)
tract, subcutaneously, transdermally, intramuscularly,
and through the lungs via inhalation. Depending on the
route of delivery, drug pH, lipid solubility, and individual
physiology will all influence the amount of drug agent
actually absorbed by the body. In the case of orally
administered medications, despite these variables creat-
ing greater or lesser degrees of absorption in the stom-
ach, small bowel, or colon, the greatest absorption
occurs within the small intestine simply as a function of
vast surface area. With exercise, blood is directed away
from the GI tract and toward active muscles and skin.
Gastric emptying, however, may be unaffected until
exercise intensity reaches 70% of maximum oxygen
uptake (VO2max), at which point gastric emptying into
the small bowel slows and drug absorption may be
delayed.3 Conversely, drugs administered by intramuscu-
lar, transdermal, or subcutaneous methods may demon-
strate increased rates of absorption during intense exer-
cise with blood distribution changes. Subcutaneously
administered insulin, for example, will demonstrate sig-
nificant increased absorption within working muscle
cells. Transdermally administered nitroglycerin will
demonstrate a similar increase in rate of absorption.
The effect of high-intensity activity on drug kinetics is
known to vary among various agents, but exercise-specif-
ic information on many drugs is not yet available. During
periods of rest, conditioned athletes tend to show optimal
systemic vascular perfusion and organ function with
either normal (as anticipated) or increased hepatic metab-
olism, resulting in expected or shortened drug half-lives.
Distribution
A drug agent delivered by any route of administration
must arrive at the target tissue to exert its desired effect.

2
Physiological changes induced by sports training may
influence tissue-compartment distribution of drug agents
and, therefore, the effectiveness and potency of the med-
ication. Recall that potency refers to the qualitative (yes
or no) ability of a drug agent to produce the desired
effect, and efficacy refers to the amount (dosage)
required for that effect. Drug distribution depends on a
multitude of factors including vascular delivery to tissue
compartments, the ability of the drug to move through
tissue membranes, and the binding of the drug agent to
plasma proteins and target-cell receptors. All play a role
on the net impact (both potency and efficacy) of a med-
ication on the desired tissue and condition treated.
During exercise, the loss of water from the intravas-
cular compartment, due to increased perspiration and
increased osmolality of exercising tissue cells, results in
increased plasma protein concentration. As a result of
increased intravascular plasma concentration, a larger
drug fraction will be serum protein bound, shifting the
ratio of free (active drug) versus bound (inactive drug)
fractions, thus decreasing drug bioavailability and thera-
peutic effect. The active patient, therefore, may experi-
ence an overall decrease in anticipated pharmacologic
effect during exercise.
Additionally, the volume of distribution of some med-
ications is altered during exercise. Volume of distribution
is a calculation of the apparent volume in which a drug
is dissolved, assuming equal tissue-compartment distrib-
ution.4 If the drug, either as a product of its own physio-
chemistry or as a result of exercise-induced changes, is
not distributed equally to all tissue compartments, the
volume of distribution will change. For example, lipid-
soluble (lipophilic) drugs, an attribute of most prescrip-
tion medications, tend to concentrate within fatty tissues,
thus lowering the serum concentration and raising the
apparent volume of distribution. A decreased serum con-
centration indicates a large volume of distribution and a
greater serum concentration indicates a smaller volume.
Athletic activity induces alteration in tissue-compartment
distribution and, potentially, bioavailability and efficacy
of the drug agent. Examples of drugs known to be affect-
ed in this fashion include theophylline, propranolol,
verapamil, acebutolol, and oxprenolol. All show an
increase in plasma concentration and, therefore, a
decrease in organ tissue-compartment concentration
during exercise.
The implication for treatment is that published drug
pharmacokinetic behavior is typically investigated dur-
ing rest and not during active exercise. Patients are
therefore more appropriately directed to take prescribed
or OTC medications in a standard regimen that avoids
drug ingestion near times of maximal exertion as a
means of obtaining more predictable drug behavior and
monitoring.
Metabolism
Drug metabolism is the physiologic process of con-
verting the administered drug into another form or sub-
3
stance that can be conveniently excreted by the body.
Metabolism further serves to detoxify drug agents, thus
decreasing or negating pharmacological effect. The liver
is by far the most active organ in the drug metabolism
scheme, and its action is determined by hepatic blood
flow and competent biosynthesis of metabolic enzymes.
Exercise decreases hepatic perfusion by shifting blood
flow away from the liver to active muscles. The rate of
metabolism for medications particularly dependent upon
hepatic blood flow is reduced with exercise, and both
drug effect and duration may be increased.
Conversely, metabolism and bioconversion of drugs
with lower dependence on hepatic enzymatic metabo-
lism will be less affected by exercise-induced shunting of
blood flow away from the liver. Blood flow-induced
changes in hepatic metabolic activity occur only during
exercise; drug metabolism rates return to normal in the
resting state. The present information on drug metabo-
lism is normally based on resting state data. Drug effect
will be more reliable and predictable if medications are
not taken at times of maximal physical exertion.
Excretion
Excretion is the process of eliminating a drug from cir-
culation. Drugs may be excreted through urine, feces,
bile, sweat, expired air, breast milk, and seminal fluid.
Renal excretion is the primary mode of elimination of
most pharmacotherapeutic agents. Exercise decreases
renal filtration, as a product of decreased blood perfu-
sion, in proportion to the intensity of activity, by as much
as 30%. Renal blood, as measured by creatinine clear-
ance and urine volume, returns to normal within 30 to
60 minutes after exercise. Studies3 using procainamide
demonstrated a 1.7-fold increase in serum concentration
during exercise. These studies suggest that during periods
of exercise, the duration of drug activity will be extend-
ed and serum concentration of drug agents may increase.
Further investigation of specific drug agent pharmacoki-
netic changes with exercise is necessary.
In summary, multiple studies have demonstrated exer-
cise-induced alterations in drug pharmacokinetics that
impact the pharmacological monitoring of athletes. Exer-
cise may increase or decrease the rate of absorption of
drug agents, influence distribution of drugs with body tis-
sue compartments, and alter elimination rates. Therapists
must therefore be aware of normal drug parameters,
including time of onset, effect, half-life, normal and
adverse effects, and duration of action in order to antici-
pate and recognize pharmacokinetics among athletes.
COMMON DRUG GROUPS IN SPORTS
REHABILITATION
Nonsteroidal Anti-inflammatory Drugs
By far the most frequently utilized and prescribed
drug agents in treatment of sports injury are the non-
steroidal anti-inflammatory drugs (NSAIDs). Of patients
seeing physical therapists, 25% to 40% are taking pre-
scription anti-inflammatory agents, with about 40% of
those using multiple NSAIDs concomitantly.5 Non-
steroidal anti-inflammatory medications are defined as a
diverse group of drugs with the shared ability to: (1)
relieve pain, (2) decrease inflammation, (3) decrease ele-
vated body temperature, and (4) decrease blood clotting
(nonselective NSAID agents only) by inhibition of
platelet aggregation.6 Nonsteroidal agents are distin-
guished from true steroid agents such as cortisone (corti-
sol), prednisone, triamcinolone, or methylprednisolone
and from the opiate-derived analgesics such as codeine,
oxycodone, morphine sulfate, and meperidine. Table 2
lists representative NSAIDs and summarizes their clinical
characteristics grouped by chemical classification.
The NSAIDs offer an impressive array of benefits to
injured athletes, particularly as analgesic and anti-
inflammatory agents, making them first-line drug choic-
es for treatment of mild to moderate pain and soft tissue
injury.7 Nonsteroidal anti-inflammatory drugs have a ten-
dency to produce adverse effects on multiple organ sys-
tems, with the major toxic effects being GI ulceration,
acute renal failure, and bleeding events. Other possible
side effects include dyspepsia, nausea, edema and fluid
retention, aphthous ulceration, and delayed wound heal-
ing. Nonsteroidal anti-inflammatory drugs may produce
central nervous system effects including tinnitus, dizzi-
ness, confusion, and stupor. Table 3 presents the adverse
effects of NSAIDs.
The pharmacology of aspirin is quite consistent with
that of other NSAID agents, and aspirin remains the pro-
totype for comparison of the efficacy and safety of new-

Table 2. Nonspecific and Cyclooxygenase-2-specific Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal Anti-inflammatory Drugs Half-life Onset Comments*†
(hours) (minutes)
Cyclooxygenase (COX)-2-specific Agents Inhibit biosynthesis of COX-2 prostaglandin products.
↓ gastrointestinal irritation.
Potential ↑ platelet aggregation (varies with agent).
Celecoxib (Celebrex) 11 30–60 ↓ cardiovascular risk than rofecoxib.
Rofecoxib (Vioxx) 24 45 No longer available.
Valdecoxib (Bextra) 8–11 60
Nonspecific Agents Inhibit biosynthesis of both COX-1 and COX-2
prostaglandin products.
Acetic Acid Derivatives
Etodolac (Lodine Tolmetin) 3–11 30 ↑ gastrointestinal tolerance.
Indomethacin (Indocin) 4.5 30 ↑ potency, ↑ toxicity.
Ketoralac (Toradol) 2.5 30–60 ↑ analgesic effect.
Sulindac (Clinoril) 8 60 ↓ potency and ↓ toxicity than indomethacin.
Tolmetin‡ (Tolectin) 2–5 10–30 ↑ patient tolerance.
Fenamic Acids No clear advantages.
Meclofenamate (Meclomen) 2.0 60–120 ↑ diarrhea.
Propionic Acid Derivatives ↑ patient tolerance.
Fenoprofen (Nalfon) 3 30 ↑ gastrointestinal tolerance.
Flurbiprofen (Ansaid) 3.8 60 ↑ gastrointestinal tolerance.
Ibuprofen (Motrin, et al) 2 10–30 ↑ gastrointestinal tolerance.
Ketoprofen (Orudis) 2-4 30 ↑ gastrointestinal tolerance.
Naproxen‡ (Anaprox, Naprosyn) 13 60–120 ↑ gastrointestinal tolerance.
Oxaprozin (Daypro) 58 60 Long acting.
Oxicam Derivatives
Piroxicam (Feldene) 50 15–30 Long onset, long acting.
Salicylates Active intermediate agent of aspirin.
Aspirin§‡ 0.25 10–30
Diflunisal§ (Dolobid) 16 30–60
*↑ indicates increased relative to acetylsalicylic acid.
†↓ indicates decreased relative to acetylsalicylic acid.
‡Extensively studied for use in children. Use in febrile viral illness precluded.
§Exerts drug effect as active metabolite salicylic acid.

4
Table 3. Potential Adverse Effects of Nonsteroidal Anti-inflammatory Drugs
Gastrointestinal Renal Central
Nervous
System
Nausea Sodium retention Tinnitus
Heartburn Edema Sedation
Dyspepsia Hyperkalemia Dizziness
Gastric ulcers Acute failure
Duodenal ulcers Nephritic syndrome
Perforations Papillary necrosis
Bleeding
Complications
er medications in the class. Aspirin continues to be the
first-line drug for a variety of conditions including relief
of mild pain and soft tissue inflammation. Other NSAID
agents differ from aspirin in modified pharmacokinetics,
duration of action, and patient tolerance, but overall effi-
cacy is very similar.
Mechanisms of action
Nonsteroidal anti-inflammatory drugs produce their
diverse effects by interfering with the enzymatic biosyn-
thetic effect of cyclooxygenase-1 (COX-1) and cyclooxy-
genase-2 (COX-2) on arachidonic acid. Arachidonic
acid is present on cell membranes throughout the body
and acts as a substrate for prostaglandin, prostacyclin,
and thromboxane synthesis. Prostaglandins (and other
arachidonic acid derivatives including prostacyclin,
thromboxane, and leukotrienes) are classed as
eicosanoids but are often included for convenience in
the prostaglandin category. They are among the most bio-
logically active substances known and account for the
complex pharmacodynamics of the NSAIDs and their
wide variety of effects in the body. A prostaglandin may
exhibit differing effects at different sites and under differ-
ent physiologic conditions. Prostaglandins are typical-
ly rapidly metabolized, local acting, and swiftly degrad-
ed in the lungs, preventing systemic arterial distribution.
Under normal conditions, COX-1 is constitutively
present in virtually all tissues. Notably, the COX-1 iso-
form is found in the endoplasmic reticulum of cells pro-
ducing prostaglandin (PGE2, PGG, PGI2) in the blood ves-
sels, stomach, and kidneys. In the GI tract, COX-1 pro-
motes synthesis of cytoprotective gastric mucus and
bicarbonate, and support for gastric mucosal blood flow.
In the renal system, COX-1 promotes vasodilation, result-
ing in increased renal perfusion. Cyclooxygenase-1
functions as a physiologic “housekeeping” enzyme in
most tissues, including the gastric mucosa and platelets.8
Conventional NSAIDs that exert a COX-1 (and COX-2)
inhibitory effect will deplete the body of specific
prostaglandins (PGI2 and PGE2) that, in healthy individu-
als, facilitate these normal maintenance purposes. An
increasing body of evidence has established that inhibi-
tion of COX-1 results in adverse events such as GI irrita-
tion and damage, platelet dysfunction, and bron-
Hematological Allergic Reactions
Hemorrhage Other nonsteroidal anti-inflammatory
Anemia drugs
Cardiovascular events Salicylin-containing foods: apples,
with cyclooxygenase-2 oranges, bananas
chospasms.9 Lichtenstein and Wolfe8 report that the role
of COX-1 in protecting the gastroduodenal mucosa is
supported by studies showing “the greatest degree of
damage is generally caused by NSAIDs that preferential-
ly inhibit COX-1.”(p.1298) All nonspecific (ie, conventional)
NSAIDs target COX-1 to some degree.
Cyclooxygenase-2 is typically not found on cell mem-
branes under baseline conditions but is induced and
upregulated by cytokines such as interleukin-1 in the
presence of cell stress or injury. Arachidonic acid is
released from cell membranes in response to physical,
chemical, hormonal, bacterial, or other stimuli. A syn-
thesis of PGE2 by COX-2 results in facilitation of the
inflammatory response to injury including pyresis,
chemotaxis, pain modulation, and potentiation of
bradykinen and histamine. Cyclooxygenase-2 upregula-
tion during inflammation is decreased by NSAIDs and
the steroid medications, which inhibit these vascular and
inflammatory responses. By interfering with the arachi-
donic acid cascade, both steroidal and nonsteroidal
agents will impede the action of various healing scheme
mediators, primarily inhibiting the substrate phase of
inflammation.
When looking at animal models of inflammation,
COX-2 was found in multiple cell types in the joint
including synovial lining cells, fibroblast-like cells, vas-
cular endothelial cells, infiltrating mononuclear cells,
chondrocytes, and adjacent bone marrow.10 Its enzymat-
ic activity leads to biosynthesis of prostaglandins includ-
ing PGE2 and prostacyclin (PGI2). Prostaglandin E2 medi-
ates pyresis, inflammation, and pain. Interestingly, PGE2
does not produce pain itself but hyperalgesia by sensitiz-
ing afferent C-fibers. The prostacyclin PGI2 is a vasodila-
tor and inhibitor of platelet aggregation.9 PGI2 addition-
ally functions to modulate the balance between its own
inhibition of platelet aggregation and thromboxane A2
enhanced platelet aggregation. Selective inhibition of
COX-2 diminishes this PGI2 modulating effect, perturb-
ing the equilibrium between thromboxane A2 thrombo-
genesis promotion and PGI2 thrombogenesis inhibition,
resulting in an overall shift toward platelet aggregation
and thrombus formation. Table 4 summarizes the effects
of COX-1 and COX-2.
5
Table 4. Effects of Cyclooxygenase-1 and Cyclooxygenase-2
Cyclooxygenase-1
- Enhanced platelet aggregation
- Gastrointestinal mucoprotection
- Renal homeostasis
- Vascular homeostasis: renal vasodilation, diuresis, electrolyte
and water excretion
- Uterine function, embryo implantation
- Regulation of sleep-wake cycle and body temperature
Platelet aggregation during the early phases of clot
formation is mediated by the influence of thromboxane
A2 on platelet aggregation factor. Nonsteroidal anti-
inflammatory drug inhibition of COX-1 impedes throm-
boxane A2 biosynthesis and platelet aggregation, result-
ing in decreased thrombus formation, which is the ratio-
nale for daily prophylactic aspirin to reduce stroke or
myocardial infarct risk. Aspirin in low-dose form (81
milligrams) used for this purpose has not been shown to
produce hemorrhagic events or other side effects that
would preclude its use among athletes.11 However, the
use of NSAIDs in therapeutic dosage in the immediate
postinjury period may increase risk of prolonged bleed-
ing, hemorrhage, or hematoma formation. Medications
that affect hemostasis should generally not be utilized
until hemostasis has been achieved. All NSAIDs impede
platelet aggregation and therefore potentially prolong
bleeding time.
The discovery of the 2 COX isoforms allows NSAIDs
to be clinically divided into 2 classes based on cyclooxy-
genase activity: (1) nonselective NSAIDs that inhibit both
COX-1 and COX-2, with some agents preferentially tar-
geting COX-2 with reduced COX-1 inhibition [eg,
etodolac (Lodine) and meloxicam (Meclomen)] and (2)
selective NSAIDs (the coxibs) that exclusively inhibit
COX-2 (eg, Vioxx, Bextra, and Celebrex) with little or no
effect on COX-1.
The newer selective COX-2 inhibitors, developed to
provide NSAID benefits without affecting the GI mucosa,
renal tissue, or platelet aggregation, have been a popular
topic in the medical news and general media. When
compared to traditional nonselective NSAIDs such as
naproxen and ibuprofen, coxibs achieve equal pain relief
while reducing upper GI dyspeptic symptoms by
15%.12,13 The use of celecoxib (Celebrex) is associated
with a lower incidence of symptomatic ulcers and ulcer
complications compared with conventional NSAIDs in
nonaspirin users.14 Clinically, the frequency of gastric
irritation or ulceration is lower, but not eliminated, with
use of coxibs compared to nonselective NSAIDs. Coxibs,
if prescribed, are used with caution in those persons with
pre-existing risk factors such as age or history of GI
ulcers.
The COX-2-specific drugs were also expected to
reduce or eliminate effects on renal function and were
thought to be useful, with caution, for those patients with
renal disease, whereas the nonselective NSAIDs are con-
6
Cyclooxygenase-2
- Produce pain, pyresis, chemotaxis, inflammation
- Modulation of thromboxane-enhanced platelet aggregation
vs prostacyclin inhibition of platelet aggregation
- Potentiation of histamine and bradykinin
- Vasodilation and inhibition of platelet aggregation
traindicated. However, this has not proven to be the
case, as COX-1 and COX-2 were subsequently found to
be present in the kidney in constitutive form. Overall, the
same precautions for patients at risk for adverse renal
effects apply to both nonselective NSAIDs and COX-2-
selective NSAIDs. Nonsteroidal anti-inflammatory drugs
interact with a variety of diuretic agents resulting in
hypertension, potassium retention, and acid-base shift.7
Therefore, athletes using diuretic agents, as prescribed or
inappropriately for weight loss, are at increased risk of
dehydration and renal complication with concomitant
usage of a COX-2-specific NSAID.
Evidence of an increased risk of thromboembolism
with use of coxibs led to withdrawal of several COX-2-
specific agents from the market. Some COX-2-specific
medications have greater antithrombotic properties than
others, and hemorrhagic and GI risk factors also appear
to vary among available agents. Kimmel15 reported rofe-
coxib was associated with higher odds of heart attack
compared with older NSAIDs but “no evidence for an
increased (heart attack) risk from Celecoxib/Celebrex,
again suggesting differences within the class of COX-2
inhibitors.”(p.1) Despite the recent media attention on
potential cardiovascular risk with use of these agents, the
risk of thrombus formation appears limited to long-term
(more than 18 months) use with specific coxibs. There is
controversy as to the correct interpretation of the cardio-
vascular-event incidence data with coxib use, and further
studies are underway. At present, available COX-2-spe-
cific agents remain an appropriate medication within
sports medicine and are used when specifically indicat-
ed and by contraindication to nonselective NSAIDs. As
a precaution, physical therapists should monitor for car-
diovascular complications in patients taking COX-2-spe-
cific medications until the degree of risk is more clearly
determined in future studies.
Algorithms of selection
The wide variety of NSAIDs on the market raises the
question of a “drug of choice” and second-choice or
third-choice agents for treatment of athletes. Nahlik16
states: “All currently marketed NSAIDs have been exten-
sively studied in clinical trials and there is little evidence
to suggest that one is significantly more effective than
another for the variety of rheumatic disorders for which
they are generally prescribed. Based on the evidence to
date, all NSAIDs, when given in equipotent doses, have
comparable efficacy. Given this equivalence, in choos-
ing a particular NSAID for an individual patient, tolera-
bility profiles remain potential ways in which it may be
possible to differentiate between different drugs.”(p.16)
Safavi and Hayward17 report that “preferences in NSAID
prescribing were mainly determined by which drugs
enhanced compliance or were used by other prescribing
personnel (the traditional choice) with cost to the patient
being less an influence in selection.”(p.33)
Practitioners tend to select among similar drugs on
the basis of 3 parameters: patient compliance, cost to
patient, and patient preference. Over-the-counter drugs
such as aspirin, ibuprofen, and naproxen are first-line
drugs based on cost and availability. Clinical experience
concurs with this finding: no one NSAID demonstrates
consistent superiority in effect or patient toleration.
Physicians may sequentially prescribe several agents
over time before deciding upon a particularly effective
drug for their patients. A strict algorithm for selection, as
found for antibiotic prescription for example, does not
exist for NSAIDs.
Yet some consistent themes are found in multiple
studies using differing methodologies and settings. Drugs
with longer half-lives such as piroxicam (Feldene) and
ketoprofen are associated with the highest risk for
adverse effect and, conversely, those agents with shorter
half-lives demonstrate lower risk. For example, ibupro-
fen, with a half-life of 2 hours, most consistently shows
lower risk for adverse GI events in standard dosage (less
than 1500 mg/day), although in higher dosage (greater
than 1500 to 2400 mg/day) the risk becomes comparable
to other NSAIDs taken at standard dosage. A simplified
method of drug selection is presented in Table 5.
The effect of a given NSAID will vary among individ-
ual patients, sometimes leading to trial of several differ-
ent agents in an effort to obtain the best therapeutic
effect. Nonsteroidal anti-inflammatory drugs are classi-
fied by chemical structure, allowing products of differing
chemical families to be selected as replacement for an
ineffective agent when seeking the most efficacious med-
ication. In clinical practice, 7 to 10 days is generally long
enough (with the exception of specific long-onset agents
such as Feldene) to ascertain the effect of a given drug.18
Patients should be encouraged to continue taking a trial
medication at least that long before concluding ineffec-
tiveness. Once an effective drug is identified, the dosage
may be gradually reduced to find the lowest effective
dose for the patient. Cyclooxygenase-2-specific
inhibitors should not be used as first-line agents unless
nonspecific agents are contraindicated (eg, by a history
of gastric disorder) and the patient is not at cardiovascu-
lar risk.
Nonsteroidal anti-inflammatory drugs versus
acetaminophen
Athletes frequently treat pain with OTC aceta-
minophen (Tylenol), warranting the treating therapist’s
consideration and comparison of this medication with
NSAIDs. Acetaminophen does not inhibit prostaglandin
synthesis in peripheral tissues and consequently lacks
anti-inflammatory properties; therefore, it is classified as a
nonopiate analgesic rather than an NSAID. Like the
NSAIDs, acetaminophen inhibits both COX-1 and COX-2
but is primarily centrally acting and exerts its peripheral
analgesic and antipyretic effects through an unknown
mechanism. However, since 1995 acetaminophen has
been recognized as the first-line agent (replacing aspirin)
for treatment of osteoarthritis by the American College of
Rheumatology. In comparing acetaminophen (given oral-
ly in divided doses of 4000 mg/day, the maximum recom-
mended dosage, at 1000 mg every 4 to 6 hours) to OTC
NSAIDs, acetaminophen is as beneficial as ibuprofen and
naproxen in reducing pain and enhancing joint function.
In high dose or with chronic usage, acetaminophen is
associated with hepatic toxicity, and with cumulative
lifetime use shows the same relationship to renal failure
as aspirin.19 The selection process between the 2 groups
depends on safety profile and patient risk factors. Aceta-
minophen is the analgesic of choice where NSAID use is
precluded by medical history, allergy, or hypersensitivity.

Table 5. Sports Injury Algorithm for Selection of Nonsteroidal Anti-inflammatory Drugs

Inflammation Alone Inflammation Pain Only
or or ⇓
Pain and Inflammation Pain and Inflammation Acetaminophen
⇓ ⇓
Assess risk factors for gastrointestinal Assess risk factors for gastrointestinal or renal toxicity
or renal toxicity ⇓
⇓ If Risk Factors Present
If no risk factors ⇓
⇓ Nonselective nonsteroidal anti-inflammatory drugs
Nonselective nonsteroidal anti-inflammatory drugs plus gastro-protective agent
or
Cyclooxygenase-2 selective agent

Gastrointestinal bleeding can still occur

7
Nonsteroidal anti-inflammatory drugs and wound
healing
By impeding COX-2 proinflammatory activity,
NSAIDs would appear beneficial to resolution of tissue
injury and inflammation. The overall result, however, has
proven inconsistent, with individual drug-specific and
tissue-specific results. Multiple studies suggest individual
NSAIDs may produce differing effects on tissue healing.
Some nonselective agents such as Piroxicam have been
shown to improve ligament healing and may be the drug
of choice in the treatment of ligament injury. This effect
cannot, however, be applied to all NSAIDs or other anal-
gesic agents. Ibuprofen, COX-2-specific agents, aceta-
minophen, and opiate analgesics (eg, codeine or
Vicodin) do not appear to affect ligament healing.20
Nonsteroidal anti-inflammatory drugs produce no alter-
ation in epithelial regeneration but induce a modest
delay in muscle strain healing during the acute (sub-
strate) phase of inflammation.21
In a tendon-healing study indomethacin (Indocin)
showed little effect on total collagen synthesis and may
have produced increased tensile strength in healing ten-
don during the proliferative phase,22 whereas ibuprofen
has been shown to inhibit tendon-cell proliferation.23
Hamstring injuries treated by physical therapists with
and without NSAID usage showed no difference in out-
come.24 In a study25 comparing rofecoxib with aceta-
minophen for treatment of acute muscle injury, no sig-
nificant difference was noted, indicating the anti-inflam-
matory effects of NSAIDs may not be an important fea-
ture of their action. Analgesia, a shared effect of NSAIDs
and acetaminophen, may be the primary benefit in ath-
letic rehabilitation.
Of concern to sports rehabilitation is growing evi-
dence of NSAID impairment of bone and cartilage heal-
ing, with a potential increase in the rate of nonunion and
delayed healing in those fractures that do unite.26 Glass-
man et al27 investigated the effect of clinically relevant
NSAID doses in patients with spinal fusion and reported
a fivefold increase in the rate of nonunion in patients tak-
ing 30 milligrams of ketorolac (Toradol) every 6 to 8
hours as needed for pain. A proposed mechanism for this
alteration in bone healing is NSAID interference with
endochondral ossification. Ketorolac, a powerful NSAID
analgesic with effect rivaling traditional narcotics such as
meperidine, is often used by both oral and intramuscular
routes to treat acute and chronic pain in amateur and
professional athletes.28
A consensus of multiple data suggests that NSAIDs do
produce a modest delay in healing during the acute
inflammatory phase, with no long-term difference in
healing outcome in epithelial, tendon, or ligament heal-
ing but significant induced delay of bone healing and
increased risk of nonunion. To provide the best environ-
ment for acute and chronic wound healing, therapists
should attempt to identify and correct any factors that
may impede success. Use of NSAIDs provides increased
8
comfort and reduced inflammation, which may enhance
some therapy modalities, but this must be balanced with
a modest delay of soft tissue healing, particularly during
the first few days of the inflammatory process, and possi-
ble long-term detriment to bone healing.
Adverse effects
Nonsteroidal anti-inflammatory drugs have a tenden-
cy to produce adverse effects on multiple organ systems
with the major shared toxic effects being GI ulceration,
acute renal failure, and bleeding in the GI tract and eyes.
The most common side effects seen clinically are nausea,
vomiting, and GI distress. Patients may also notice blood
in the urine and develop bladder infection when taking
NSAIDs. Other possible side effects include dyspepsia,
nausea, edema, fluid retention, aphthous ulceration, and
delayed wound healing. Nonsteroidal anti-inflammatory
drugs may produce central nervous system effects
including tinnitus, dizziness, confusion, and stupor.
Adults over the age of 60 taking NSAIDs have a fourfold
to fivefold higher risk of GI bleeding or ulceration than
younger individuals. In elderly patients and those with a
history of NSAID-induced ulcers, traditional nonselec-
tive NSAIDs should be used with caution, usually in low-
er dose, if at all. Potential adverse effects of NSAIDs are
listed in Table 3.
Coadministration of antacid agents will limit absorp-
tion of NSAIDs that are salicylate (aspirin, Disalcid,
Dolobid) based. Nonsteroidal anti-inflammatory drugs
are highly protein bound and may displace other drugs
(eg, Coumadin) from plasma proteins increasing free or
bioavailable drug, thus increasing effective dosage. The
more toxic NSAIDs include indomethacin, piroxicam,
and sulindac. The coxibs are prone to producing GI dis-
turbance, hypertension, fluid retention, dizziness, and
headache. They should not be used in pregnant patients.
Acetaminophen is hepatotoxic and with long-term
use shows the same adverse-effect risk as the NSAIDs.
However, most patients tolerate acetaminophen well,
and there is a greatly reduced incidence of GI distur-
bance, bleeding, or risk of ulceration compared to the
NSAIDs. Acetaminophen may also increase oral antico-
agulant effect and increase hepatotoxicity when used in
combination with alcohol, phenytoin, barbiturates, and
others. Acetaminophen is associated with skin rash,
hypoglycemia, and neutropenia on routine hematology
laboratory values.
Summary of rehabilitation considerations
1. Nonsteroidal anti-inflammatory drugs may be divid-
ed into 2 major groups: the nonselective and selec-
tive agents. Nonselective agents impact both COX-1
and COX-2, whereas selective agents target only
COX-1.
2. There is no accepted algorithm for agents of first,
second, or third choice, but an overall scheme sug-
gests using short half-life nonselective agents initial-
 ly because they demonstrate an overall lower
adverse reaction profile. However, long-acting
agents, taken only once or twice daily, offer
increased convenience and ease of patient compli-
ance. The therapist should balance these choices in
consideration of drug toleration and patient schedul-
ing needs.
3. Cyclooxygenase-2-specific agents are effective and
indicated for use in athletes with GI, renal, or other
contraindications to nonspecific agents.
4. Nonsteroidal anti-inflammatory drugs delay the
healing process, particularly during the acute phase.
Multiple studies, however, do not demonstrate long-
term deleterious effects to soft tissue healing, and at
times, with certain agents and tissues, NSAIDs may
prove advantageous to healing. Specific agents (eg,
Ketorolac) have been shown to increase the rate of
nonunion in fracture healing.
5. Acetaminophen, not classified as an NSAID, is rec-
ommended as a first-choice agent for relief of mild to
moderate pain and may be used in those athletes
with a history of GI disorders.
Steroid Agents
Glucocorticoids (steroids) inhibit both inflammatory
and immunological function and are indicated and pre-
scribed for either purpose. The steroid medications, as
typified by cortisone or prednisone, are potent anti-
inflammatory agents commonly prescribed for the treat-
ment of athletic injures. Given orally or by injection, cor-
ticosteroids exert a more intense anti-inflammatory effect
than any other anti-inflammatory drug group. In sports
medicine, steroid agents are used to obviate inflamma-
tion, reduce pain, decrease edema, and improve inflam-
matory-derived limitation of motion. Steroid agents are
available in oral, intramuscular, intravenous, and topical
preparations.
The use of glucocorticosteroids drugs in sports medi-
cine is both common and controversial. Well-researched
protocols for administration of steroid agents in treat-
ment of athletic disorders are still being developed, and
dosage and treatment regimens employed by individual
practitioners are often arbitrary.29 Administration of glu-
cocorticoid agents to any athlete should involve careful
assessment of treatment goals, target tissues, and risk-
benefit analysis. There is general agreement that steroid
injections around tendons should be approached with
caution due to reports of subsequent tendon rupture, par-
ticularly at the Achilles tendon.30
Many physicians additionally limit the number of
injections and the interval between injections to tendon,
ligament, or synovial regions. Pending patient response,
injections may be repeated up to 5 times at intervals of
weeks to months. Additional studies to determine maxi-
mal outcome and safety are needed. The literature does
report tendon rupture as a potential complication of con-
nective tissue weakening effects produced by steroid
9
agents. Development of atrophy in skin, subcutaneous
tissues, and connective tissue (often noted as a grayish
coloration of skin with dimpling over the atrophic sub-
cutaneous tissues) is not uncommon and warrants dis-
continuation of steroid therapy and modification of phys-
ical therapy modality selection. Atrophic regions will
regenerate following injection but may require a year or
more for partial or complete tissue restoration.
Rehabilitation specialists should consider the number
of injections, agent used, and injection interval carefully
when choosing treatment modalities. There is also debate
regarding appropriate restriction of activity following
injection to differing anatomic areas. A period of 7 to 14
days is commonly recommended.29 A large variable in
all of these considerations is the potency and duration of
action of the steroid agent employed. Table 6 lists steroid
agents by potency.
Table 6. Relative Potency of Representative Cortico-
steroid Agents
Compound Anti-inflammatory Duration of
Potency Action
Cortisol 0.8 Short
(8 to 12 hours)
Hydrocortisone 1 Short
Fludrocortisone 10 Short
Prednisone 4 Intermediate
(18 to 36 hours)
Prednisolone* 4 Intermediate
Triamcinolone 5 Intermediate
Betamethasone 25 Long
(26 to 54 hours)
Dexamethasone 25 Long
*Metabolically active form of prednisone.
Classification of steroid agents
The steroid agents encompass a large group of med-
ications designed for differing modes of administration
and therapeutic effects. All are derivatives of endogenous
steroids that can be divided into 2 main groups depend-
ing on their relative metabolic-regulating (glucocorti-
coids represented by cortisol or cortisone) versus elec-
trolyte-regulating (mineralocorticoids such as aldos-
terone) activity. Almost every cell in the body will
respond to these medications. Monitoring athletes for
glucocorticoid effects is complicated by the fact that
available compounds affect both metabolism and elec-
trolyte balance, but one effect is usually more prevalent
than the other. Table 7 summarizes the relative glucocor-
ticoid versus mineralocorticoid effect of representative
steroid agents.
Glucocorticoid agents in sports medicine are usually
employed for their specific anti-inflammatory effects.
Sex hormone steroids may be utilized in treating amen-
orrhea among women athletes. Less commonly encoun-
Table 7. Relative Actions of Steroid Medications
➜ with positive rehabilitation-
Glucocorticoid Agents Equal ➜
Glucocorticoid/Mineralocorticoid
Effect
Dexamethasone (Decadron) Cortisol, cortisone
Prednisone betamethasone Hydrocortisone
Methylprednisolone (Kenalog)
Prednisolone, prednisone
Triamcinolone (Aristocort)
Betamethasone (Celestone)
tered, especially within the athletic population, the min-
eralocorticoids are used for management of fluid and
electrolyte disorders. Anti-inflammatory glucocorticoid
agents are further classified by duration of action and rel-
ative potency.
Oral glucocorticoids used in sports medicine (eg,
methylprednisone or prednisone) are lipid soluble and
thus well absorbed from the GI tract. Peak plasma con-
centrations may occur in as little as 2 hours.18 Clinicians
may anticipate noticeable drug effects within hours to
days with duration of effect lasting days to many weeks.
Oral preparations are convenient and effective. In short-
term use, oral agents demonstrate minimal untoward
patient reaction. However, the drug is diluted systemi-
cally, which reduces the effect at the target anatomic
region and may produce less improvement than intrale-
sional injection.
Injectable forms of steroids administered intramuscu-
larly, intralesionally, or intra-articularly are available in
short-acting, intermediate-acting, and long-acting prepa-
rations. Onset varies from hours with short-acting agents
to 2 to 3 days for long-acting agents. Duration of action
varies from 1 week with short-acting phosphate-based
preparations to over a month with long-acting acetate-
based agents. Table 8 identifies sample steroid agents by
rate of onset and duration of action. Intralesional injec-
tion offers a key benefit compared to oral agents in that
the injection targets involved tissue with greatly reduced
systemic distribution, effect, and adverse effect. The drug
agent is also concentrated in the desired anatomic loca-
tion; the beneficial effect tends to be more dramatic, as
does potential atrophy of surrounding tissues. It is impor-
tant to identify which steroid preparation has been used
for intra-articular or intralesional injection because
extended duration of drug anti-inflammatory pain-reduc-
ing action may be confused
Mineralocorticoid
modality outcome.
Agents
A major factor in the overall
potency of steroid agents is
Fludrocortisone
their relative dependence on
Aldosterone
liver metabolism. The interme-
diate-acting and long-acting
agents are structurally modi-
fied to decrease their rate of
hepatic degradation. Athletes
with liver disease, therefore,
will show increased action and duration of effect with
these medications. Liver function test values should be
evaluated (eg, LDH, ALT/SGOT, and AST/SGPT) when
working with athletes prescribed long-term steroid regi-
mens. Table 8 lists steroid agency by potency.
Glucocorticoid mechanism of action
Inflammation and the immune response are closely
linked, and both are impeded by steroid drugs. The
inflammatory response focuses on the release of humoral
agents to affect a given site. The immune response refers
to the mobilization and interactions of various immune
cells including lymphocytes, macrophages, neutrophils,
eosinophils, basophils, and mast cells. Glucocorticoids
inhibit migration of leukocytes to inflammatory sites,
interfere with their function, and suppress the production
and effects of humoral agents. Impacted cytokines are
myriad: complement 5a; leukotrienes; interleukin 1, 2, 3,
and 6; transforming growth factor-β; basophil release of
histamine; and TNF-α that initiate, augment, and perpet-
uate the inflammatory response.18,31 Additionally,
steroids, like NSAIDs, impede biosyntheses of arachi-
donic acid to prostaglandins and leukotrienes.
Of clinical note, glucocorticoids exert their primary
effect on acute-phase (substrate) reactants, noted in the
initial phase of inflammation. When treating injured ath-
letes, it is important to recognize the delay in healing (tar-
geted at the acute inflammatory phase) produced by cor-
ticosteroid agents. Steroid agents do not promote soft tis-
sue healing but rather interfere with normal tissue healing
and maintenance by decreasing normal cellular turnover
and replacement, potentially resulting in delayed wound
healing and atrophy of surrounding tissues.
Glucocorticoids bind to their cell-membrane receptor
site and ultimately gain access to the cell DNA where

Table 8. Onset and Duration of Injectable Corticosteroid Agents

Rapid onset–Short acting
- Betamethasone sodium phosphate (Selestoject)
- Betamethasone (Celestone)
- Dexamethasone sodium phosphate (Decadron)
- Hydrocortisone sodium succinate (Cortef)
- Hydrocortisone sodium acetate (Cortef)
Intermediate onset–Duration
- Betamethasone phosphate + acetate
(Celestone Soluspan)
- Methylprednisolone (Medrol)
- Prednisolone
- Prednisone (Deltasone)
- Triamcinolone acetonide (Aristocort)
Slow onset–Long acting
- Methylprednisolone acetate
- Dexamethasone acetate
- Prednisone acetate
- Triamcinolone acetonide (Kenalog)

10
they alter RNA transcription and synthesis of receptor
proteins. As is true with most second-messenger system-
mediated medications, this mechanism may produce
delayed onset of action (hours to days) and extended
duration cellular changes after the drug is discontinued.
The mineralocorticoids have a specific receptor site that
demonstrates high affinity for aldosterone but also low
affinity for endogenous glucocorticoids (cortisol), thus
creating a crossover effect. Of clinical significance, inter-
mediate-acting and long-acting steroid agents tend to
show weaker or absent affinity for the mineralocorticoids
receptor site and thus exert a mostly anti-inflammatory
effect.18
Glucocorticoid effects on carbohydrate, fat, and
protein metabolism are responsible for both desirable
and adverse effects. Glucocorticoid agents stimulate
gluconeogenesis, with a resulting catabolic effect on
lipids and proteins, and decreased glucose use. Thyroid
secretion is suppressed, calcium absorption from the
GI tract decreased, and osteoblastic activity suppressed.
All of these effects combined produce drug agents
that offer near wonder-drug benefits to athletes, with a
long list of potential problems to be considered before
prescribing.
Preparations available
Anti-inflammatory steroids are available in oral
preparations and for intramuscular, intravenous, and
intralesional use. Steroid medications may be classed by
their duration of action, which is a function of their
chemical structure. Oral steroid medications are used
for short-term anti-inflammatory therapy, where
increased potency, as compared to NSAIDs, is desired.
Exogenous steroid intake will induce adrenal suppres-
sion; therefore, to avoid risk of temporary endogenous-
steroid deficiency; steroid agents should not be abruptly
discontinued. Oral agents for short-term therapy (eg,
methylprednisolone 4 milligrams) are often prescribed
in a decreasing dose schedule (Figure 1), which begins
with 6 tablets on the first day, 5 tablets on the second
day, 4 tablets on the third day, and so on, or are
Figure 1. Methylprednisolone 6-day decreasing dose
packet.
11
prescribed upon discontinuation of long-term steroid
therapy as a tapered decrease in drug dose to allow
gradual resumption of endogenous adrenal gland secre-
tion.
A patient discontinuing glucocorticoids abruptly may
display Addison disease-like symptoms, which are relat-
ed more to mineralocorticoid deficiency than to inade-
quate glucocorticoids and clinically manifest as hypoten-
sion, weakness, vomiting, abdominal pain, and lethargy
that may progress to coma in severe cases.
A distinction among parenteral preparations is intro-
duced by chemical modification such as sodium phos-
phate, acetate, acetonide, dipropionate, sodium succi-
nate, and valerate additions seen in inhalant, oral, and
topical preparations. Treating clinicians must identify the
preparation used for intralesional or intra-articular injec-
tion because the wide variation in duration of effect will
affect both rehabilitation-modality selection and out-
come assessment. Commonly employed phosphate-
based injectable steroids, such as dexamethasone phos-
phate (Figure 2), are visually clear liquid solutions that
clinically produce short onset times (1 day) and duration
of action (1 week) usually with minimal local tenderness
or irritation following intralesional or intra-articular
injection.
Figure 2. Triamcinolone acetate (Kenalog) and dexam-
ethasone phosphate.
Acetate-based, acetonide-based, and other injectable
steroids (eg, methylprednisolone acetate) are white-col-
ored suspensions that show longer onset time (2 to 3
days), long duration (2 to 3 months), and have the
propensity to produce steroid flare, a painful local inflam-
matory response of approximately 24-hour duration that
typically begins 1 day after injection. Clinical experience
and observation suggest that these flares may occur more
frequently with preparations utilizing suspensions of larg-
er particle size. Steroid flares are self-limited, do not cor-
relate with the outcome of the injection, and can be
treated with a short course of NSAIDs, warm compresses,
and rest. Therapists may reassure patients experiencing
this response of its temporary and benign, if painful,
nature. Active therapy may need to be suspended for 1 to
2 days until the flare calms and the patient notes onset of
a therapeutic effect. A common practice intended to
minimize flares and take advantage of steroid character-
istics is to inject a mixture of short-acting and long-acting
agent, often combined with a local anesthetic, to create a
rapid-onset, long-duration effect.
Adverse effects
Steroid agents impact nearly every organ system in
some fashion, potentially with negative implications to
the recovering or active athlete. Because steroid agents
alter tissue wound recovery by interfering with the
inflammatory process at numerous physiologic points,
vigilance in monitoring for deleterious effects and inte-
gration of pharmacological data into treatment planning
for athletes is a substantial process.
Undesirable drug effects influencing recovery of the
athlete include those previously discussed as well as
weight gain, euphoria, psychoses, glucose intolerance,
skin fragility, acne, myopathy or muscle weakness, avas-
cular necrosis, osteoporosis in men and women but
more so in postmenopausal women, tissue atrophy,
opportunistic infections, and limitation of growth in chil-
dren. Glucocorticoid agents affect glucose metabolism,
producing hyperglycemia, which should be monitored in
patients with diabetes. Urine glucose readings may be
elevated. A diuretic effect is also possible along with cen-
tral nervous system effects including an enhanced sense
of well-being or, less commonly, euphoria. In short-term
use, such as with 6-day regimens, the incidence of side
effects that affect therapy is minimal, although the rigor
of modalities should be modified with respect to the
injury and noted drug effects.
Patients may rapidly demonstrate suppression of
inflammation and improved comfort and mood, produc-
ing the sense of greater performance capability in the
presence of pharmacologically blunted healing. Vigorous
and active regimens applied to chronically inflamed con-
nective tissues, such as those with tendinitis, tendinosis
(defined as chronic tendinitis with synovial hypertrophy
often visible on magnetic resonance imaging), myopathy,
and synovitis, should be moderated following steroid
injection, typically for 10 to 14 days. Injection to weight-
bearing joints should be followed with 24 to 48 hours of
rest. In those cases where long-term oral drug use or
repeat injections generate systemic effects, the therapy
implications become considerable, thus requiring coor-
dination with all members of the treatment team.
Summary of rehabilitation considerations
1. Glucocorticoid agents are widely used in manage-
ment of athletic injury, but standardized protocols
for indication, dosage, and duration of treatment are
still in development.
2. Steroid agents exhibit broad-spectrum inhibition of
inflammation and alteration of normal bone and soft
tissue healing and maintenance. Adverse effects
involving all organ systems are possible.
12
3. Patients with diabetes should be monitored for
hyperglycemia.
4. Steroid agents used in sports medicine may be clas-
sified by potency and duration of action. Knowledge
of the characteristics of the preparation used for
sports injury is important to patient monitoring,
modality selection, and outcome evaluation.
5. Intra-articular steroid injections, particularly with
long-acting agents, are prone to self-limited steroid
flares 1 to 2 days after injection, which may tem-
porarily impair patient performance and capability
in a physical therapy setting.
6. Oral steroids should be discontinued in a decreasing
dose schedule.
7. Visible local atrophy is common following intrale-
sional injection and may require a year or more for
resolution.
Analgesic Agents
Somewhat unique to modern Western culture, and
perhaps more so among the athletic population, is the
consideration of pain as an enemy rather than a benefi-
cial physiologic signal. Pain is considered an unaccept-
able hindrance to performance that should be eliminat-
ed, sometimes by inadvisable means, to avoid losing
training time or sport participation. To be sure, rehabili-
tation efforts may be brought to a standstill and valuable
recovery time lost with ineffective pain control. The mon-
itoring or prescribing therapist will integrate pharmaco-
logical characteristics of analgesic agents into treatment
planning and delivery. Considerations include effectual-
ly scheduled care with respect to the onset and duration
of pain relief as well as recognizing drug effects necessi-
tating changes in rehabilitation design. The skillful clin-
ician will balance these factors to produce the best treat-
ment outcome.
Analgesic agents are divided into 2 major groups: the
opiates (and derivatives) and the nonopiates. Minor to
moderate pain may be managed with the nonopiate
analgesics, which include NSAIDs and acetaminophen.
Moderate to severe pain is controlled with more potent
opiate agents or combinations of analgesic agents.
Opiate analgesics
Opium is derived from the juice of the seedpods of the
common poppy plant and contains 2 main ingredients:
morphine (10%) and codeine (0.5%). Opiate medications
have been employed for centuries for their analgesic,
antidiarrheal, and euphoric effects. Middle Easterners
traded opium with the merchants of Venice, and its use
then spread, primarily by physicians, through Europe. The
morphine (named after Morpheus, the god of dreams)
component of opium was first isolated in 1803. When
extracted morphine became available, it was subject to
more societal control than opium, which was still loosely
prescribed by physicians. As a result, the opiates became
very popular street, pub, and food store drugs in England
during the early 1800s. Opiates were used even more
extensively in the United States, so much that addiction to
opium was known as the army disease during the Civil
war. Opiate dependency was eventually recognized as a
serious social problem, leading to the Harrison Narcotic
Act in 1914, which banned nonprescription use of opium
among a number of addiction-prone drugs.
Heinrich Dreser (who interestingly also isolated
aspirin) experimented with morphine while working for
Bayer of Germany, and eventually produced heroin.
Heroin is a semisynthetic morphine that is 10 times more
lipid soluble than opium. Heroin (German for heroisch,
meaning “heroic” to imply concentrated power) pro-
duces less nausea and better mucosal absorption, mak-
ing it a more convenient and effective drug agent than
opium. Bayer believed it was not addictive, and so did
the United States government, which explains why it was
excluded from the Harrison Act. With the loss of opium
and morphine from the general market, heroin, which
was still legal and available, became popular. Further
pharmaceutical research of the opiates led to develop-
ment of an array of safer and effective analgesic opiate
derivatives that are now everyday pain-relieving agents
seen by therapists treating athletes.
Opiates produce analgesia by increasing the pain
threshold and reducing anxiety and fear. Opiate recep-
tors are widespread within the central nervous system
including the limbic region, which is responsible for
emotional interpretation of sensory input to the brain.
The experience of pain is individual and subjective. How
patients respond to pain is, in part, a learned behavior. As
a result, therapists may encounter patients receiving nar-
cotic analgesics who remain in deceptively good spirits
while simultaneously reporting pain. An understanding
of opiate pharmacology explains this paradox and begins
with discussion of brain and spinal cord receptor sites
involved in the transmission of pain sensation to the
brain. Stimulation of the brainstem periaquaductal gray
matter, periventricular gray matter, or nucleus raphe
results in release of enkephalins or monoamines (sero-
tonin, dopamine, epinephrine, and norepinephrine) and
ultimately analgesia.
Receptors that respond to naturally occurring endoge-
nous opioid peptide hormones (as opposed to the plant-
derived opiates) include enkephalins, beta-endorphins,
and dynorphins, collectively called the endorphins. The
term endorphin describes any endogenous opiate-like
neurotransmitter that exhibits pharmacological proper-
ties of morphine. Endorphins mediate pain and regulate
mood. The opiate analgesics are endorphin agonists.
Systemic administration of opiates, such as morphine,
excites periaquaductal and periventricular areas, thus
enhancing their natural neuronal activity. This increase in
activity suppresses (at times pharmacologically confus-
ing, an agonist effect may include suppression or inhibi-
tion of neuron activity, in which case the action or ago-
nist effect is sedation) neurons in the spinal and
medullary posterior horns that transmit painful informa-
tion, resulting in the production of analgesia.32 Opiates
13
also inhibit substance P in the interneurons of the spinal
cord. Direct delivery of morphine into the spinal cord
produces potent analgesia useful for surgical or obstetric
procedures. Opioids are most effective in relieving the
constant dull pain associated with trauma, surgery,
inflammation, and cancer. Clinicians should advise
patients to take opiate analgesics before onset of pain for
maximum relief rather than waiting until pain becomes
intense or intolerable.
The mechanism by which opioids produce euphoria,
tranquility, and alteration of mood is still being investi-
gated. Opioids activate mu receptors in the ventral
tegmental, and its dopamine projections to the nucleus,
the mesolimbic dopamine pathway, is known to be
responsible for portions of substance dependency and
reinforcement neurology.33 The mesolimbic pathway is of
extreme importance because it is this dopamine pathway
that appears to play a major role in the neurology of sub-
stance and behavioral addictions. Given the propensity
of opiate analgesics, especially with extended usage, to
produce euphoria and physical dependency, an under-
standing of receptor activity is important to pharmaco-
logical monitoring.
Opioid receptor groups
Most of the actions of narcotic analgesics, including
euphoria and dependency, are mediated by opiate mu
receptors. Mu receptors are located in all pain-conduct-
ing regions of the spinal cord and various brain areas,
excluding the cortex and cerebellum, and respond to
endogenous opioid neurotransmitters. In the hindbrain,
mu receptors affect respiratory, nausea, and vomiting
centers. Drugs that act as mu-receptor agonists are
responsible for the Edinger-Westphal response, which
produces the classic opioid pinpoint pupils. Activation of
mu receptors by endorphins and the opiate analgesics
appears to reduce or inhibit neurotransmission of pain
using a G protein-receptor system and may ultimately
alter Ca+ or K+ channels and cell membrane polarity.
Additionally, endorphins interfere with release of norep-
inephrine, dopamine, and acetylcholine, thus acting as
neuromodulators by influencing the presynaptic mem-
branes of other neurons.
Opioid drugs create their effect by affecting 3 differ-
ent receptor types: mu, kappa, and delta:
• Mu-1 receptors are located outside the spinal cord
and are responsible for the central interpretation of
pain.
• Mu-2 receptors produce euphoria, respiratory
depression, and spinal analgesia.
• Kappa receptors appear to be affected by mixed ago-
nist-antagonist drugs, producing analgesia with less
respiratory depression than produced by mu-recep-
tor agonists. Kappa-receptor agonists also produce
miosis. Kappa agonists produce strong dysphoria,
mild analgesia, and respiratory depression.
• Delta receptors are endogenous enkephalin recep-
tors that also produce analgesia. Delta receptors are
 found in the limbic system and may play a role in the
emotional response to opioids. Delta receptors may
additionally modulate the activity of mu receptors.
Classification of opiate medications
A variety of opiate medications (also known as nar-
cotic analgesics) have been developed by the pharma-
ceutical industry. Opiate medications are classed into 3
groups by their receptor actions: agonists (morphine and
codeine), antagonists (naloxone and Antabuse), and
mixed agonist-antagonists (Talwin and Stadol).
Opiate agonist agents are further classified and select-
ed for use according to their relative potency, which is a
function of mu-receptor activation. Potent agents such as
morphine or hydromorphone (Dilaudid) are full agonists
at target mu receptor sites. Partial agonists such as
codeine phosphate or oxycodone (OxyContin) and other
moderately potent agents are unable to fully activate mu
receptors. Weak agonists include propoxyphene (Dar-
von) and Darvocet. Mixed agonist-antagonist agents pro-
duce an agonist effect at one receptor subtype and an
antagonist effect, in which the drug occupies the recep-
tor but exerts no effect, at another subtype. The opioid
antagonists block opiate activity at all receptor types.
Table 9 lists opiate agents by preferential receptor affini-
ty and potency.
The agonist agents are the most commonly utilized in
clinical practice. Effective monitoring of athletic patients
prescribed these drugs requires recognition of drug
effects, onset time, duration of action, and offset time; all
such data are readily available in pharmacological texts
or other references such as the Physicians’ Desk Refer-
ence. Clinical integration of this information also allows
efficient scheduling of therapy. For example, morphine
shows peak effect in 30 to 90 minutes with duration of 3
to 7 hours, while meperidine (Demerol) peaks at 30 to 60
minutes with duration of 2 to 4 hours, and codeine
preparations peak at 60 minutes with duration of 4 to 6
Table 9. Classification of Opiate Agents by Level of Pain
Agonist Agents Mixed Agonist-Antagonist
Agents
Severe pain: Severe pain:
- morphine - dezocine (Dalgan)
- hydromorphone (Dilaudid)
- fentanyl (Sublimaze)
Moderate to severe pain: Moderate to severe pain:
- meperidine (Demerol) - pentazocine (Talwin)
- fentanyl (Sublimaze) - nalbuphine (Nubain)
- hydrocodone (Vicodin) - butorphanol (Stadol)
- oxycodone (OxyContin)
- oxycodone and aspirin
(Percodan)
Mild to moderate pain:
- propoxyphene (Darvon)
- codeine
- tramadol (Ultram)
hours. Therapy can be scheduled at a time of maximum
patient comfort balanced with adverse side effects that
may impair modality delivery, such as sedation.
As a clinical side note, onset time often correlates
with offset time (ie, a drug with rapid onset likely will
demonstrate rapid offset). Those drugs with rapid offset
are more prone to production of withdrawal symptoms.
Offset refers to the rapidity of drug effect loss; it is not a
direct function of drug half-life, which measures the
amount of drug onboard rather than the rate of declining
effect. Heroin, as an example, shows rapid onset and
offset and, obviously, significant withdrawal problems.
The substitution of methadone, a similar narcotic that has
a slow offset rate and decreased withdrawal symptoms,
is done in hopes of easing the process of drug abuse ces-
sation.
In context of athletic injury, developing drug depen-
dence after administration of narcotic analgesics is
uncommon for both medical and psychosocial reasons.
Therapists can minimize dependency issues with assistive
patient education and pain-management modalities
designed to minimize drug requirement. Ideally this pro-
duces short-term use of narcotics for acute pain, careful
monitoring based on conversation with patients and pre-
scribing clinicians, and transition to nonopiates (ie, aceta-
minophen or NSAIDs) as soon as reasonably possible.
Patients demanding extended use of narcotic agents
or overutilizing prescriptions should be appropriately
discussed with other treating medical professionals, cre-
ating a team approach to dependency avoidance. With-
drawal symptoms are relatively simple to identify; they
tend to be opposite the drug’s normal effects. Opiates, for
example, produce euphoria, sedation, and dry mucus
membranes, among other effects. Withdrawal signs
include the opposite: dysphoria, agitation, and runny
nose, respectively. A review of opiate effects allows
recognition of opposite or reversed effects suggestive of
withdrawal.
Individual narcotic
Indication and Mode of Action analgesics also vary con-
siderably in effect based
Antagonist Agents
on mode of administra-
tion and pharmacokinetic
Reversal of opiate agonist effects: characteristics. Meperi-
- naloxone (Narcan)
dine effect, for example,
- naltrexone (ReVia)
is very predictable with
intramuscular administra-
tion but is quite inconsis-
tent when used orally.
Fifty to 100 milligrams
orally may be required
to equal a 25-milligram
intramuscular dose. Mep-
eridine’s duration of
action may be limited
with oral administration;
some sources indicate a
14
half-life as brief as 45 minutes in young healthy patients.
Careful questioning of the patient regarding drug effec-
tiveness is important to individualizing care. Patients
should additionally be monitored for appropriate dosage
based on analgesic effect. Not uncommonly, patients are
undermedicated because of cautious prescribing habits
or, in some athletes, large body size. Standard doses are
calculated based on a 70-kilogram body weight; there-
fore, a 220-pound patient will require approximately
50% greater dosage for proper analgesic effect. Commu-
nication with the patient and prescribing clinician regard-
ing analgesic effect will help in proper dosage selection
and the rehabilitation capability of the patient.
Tylenol with codeine is a ubiquitously prescribed nar-
cotic preparation. The amount of codeine in the medica-
tion can be obscured by persistence of the ancient
apothecary system. In the apothecary system, grain is
equal to roughly 60 milligrams. Tylenol with codeine no.
4 contains 1 grain or 60 milligrams of codeine; Tylenol
with codeine no. 3 contains one-half grain or 30 mil-
ligrams; Tylenol with codeine no. 2 contains one-quarter
grain or 15 milligrams. A Tylenol with codeine no. 3
tablet is roughly equivalent in analgesic effect to 30 to 50
milligrams of oral (recall meperidine is less effective oral-
ly than parenterally) Demerol, 25 milligrams of intra-
muscular Demerol, or 2 milligrams of morphine. Drug
potency equivalency is quantified in a number of phar-
macology reference texts available to the therapist. In
addition, codeine, unlike most opiates, confers an anti-
tussive effect. Athletes taking cold or cough medications
containing codeine are subject to all opiate side effects,
and possible disqualification from sport. Any athlete pre-
scribed any narcotic medication should carefully evalu-
ate sports organization medication protocols to avoid
disqualification from participation.
The mixed agonist-antagonist opiate analgesics pre-
sent an interesting paradox by simultaneously stimulat-
ing and antagonizing opiate receptors. Representative
medications seen in practice are pentazocine (Talwin),
nalbuphine (Nubain), and butorphanol (Stadol). All are
indicated for moderate to severe pain. These agents are
an attempt to maintain an opiate analgesic effect with
reduced dependency and toxic effects. Mixed agonist-
antagonist medications are typically well tolerated and
produce a very good analgesic effect, but some patients
will experience dysphoria, often as unpleasant dreams,
and wish to change medications. Also note that a mixed
agonist-antagonist drug will inhibit the analgesic effect of
an agonist agent when administered simultaneously; the
2 should not be mixed. Mixed agonist-agonists are also
dependency prone medications, although less so than
the pure agonists, and require the same level of monitor-
ing vigilance as the agonists.
Two other agents seen in the treatment of athletes are
propoxyphene (Darvon) and tramadol (Ultram). Darvon
(Darvocet when combined with acetaminophen) is a
weak narcotic agonist prescribed for mild pain, often fol-
15
lowing discontinuation of more potent agents. Its narcot-
ic derivation may be overlooked; it is roughly equivalent
to codeine in effect, patient tolerance, and adverse
effects. Ultram is different from other opioids in that it is
not a controlled substance. It shows lower affinity to mu
receptors with less effectiveness than true mu agonist
agents. Ultram does offer analgesia through a weak mu
agonist effect and alternate mechanisms and, important-
ly, demonstrates greatly reduced respiratory depression
and potential for dependency.
Adverse effects
Athletes for whom narcotic agents are prescribed are
subject to a variety of adverse effects on sport and reha-
bilitation performance. The most common reactions are
predicted by the pharmacological actions of morphine at
mu receptors: nausea and vomiting (which tends to
decrease after initial doses), constipation, urinary reten-
tion, itching, and hypertension. All impair athletic per-
formance. Patients with concomitant respiratory condi-
tions may be seriously impaired by opiate-induced respi-
ratory depression. Alcohol potentiates respiratory
depression when used concomitantly with narcotic anal-
gesics and can prove fatal. The amount of narcotic
required to produce a toxic or fatal effect is markedly
reduced by the concomitant use of alcohol. Patients must
be advised to avoid use of alcoholic beverages when pre-
scribed narcotic analgesics.
Additionally, opiates act as bronchodilators but in
some patients may produce bronchoconstriction with seri-
ous consequences. Active therapy modalities may be
employed but with caution or assistive guarding until the
opiate’s effects on the patient are determined. Opiates are
contraindicated in athletes with head injury because they
increase carbon dioxide retention, thus dilating the
intracranial blood vessels and increasing intracranial pres-
sure. Also opiates produce euphoria and decreased per-
ception of pain, which could lead an athlete to overzeal-
ous training, further injury, and delayed recovery. The
mixed agonist-antagonists increase blood pressure and
cardiac workload. Table 10 lists adverse effects of opiates.
Table 10. Adverse Effects of Opiates
Central Nervous System: physical dependence, sedation,
somnolence, clouded sensorium, euphoria, dysphoria,
paradoxical anxiety, tremor, dizziness, seizures, headache,
hallucinations, syncope, light-headedness
Cardiovascular: hypotension, bradycardia, tachycardia,
cardiac arrest, shock
Gastrointestinal: constipation, dry mouth, nausea, vomit-
ing, biliary spasms
Genitourinary: urinary retention
Musculoskeletal: muscle twitching
Respiratory: respiratory depression, respiratory arrest
Dermatological: pain at injection site, pruritus, urticaria,
diaphoresis
Summary of rehabilitation considerations
1. Opiates are classed by relative potency, which is a
function of mu-receptor agonist effect.
2. Opiate agonists may produce euphoria while mixed
agonist-antagonist agents may produce unpleasant
dreams and dysphoria, especially in athletic patients
not accustomed to drugs.
3. All opiate analgesics may induce drug dependency.
They are intended for acute pain and short duration
of use.
4. Adverse effects include euphoria, dysphoria, seda-
tion, nausea, constipation, urinary retention, respira-
tory depression, and varied impact on the bronchio-
lar tree.
5. Opiates are contraindicated in patients with head
injury.
6. Miosis, the Edinger-Westphal response, may be used
for substance-abuse monitoring.
7. All opiates will interact with other opiates, central
nervous system depressants, sedatives, tranquilizers,
tricyclic antidepressants, and monoamine oxidase
inhibitors with additive effect. These agents should
be used together with extreme caution.
8. Assisted walking using a gait belt with patients pre-
scribed opiates may be initially warranted until the
patient’s capabilities are assessed.
9. Opiate half-life and duration vary widely among
agents. Discussion with the patient to identify time
periods of maximal drug benefit and adverse effects
will assist selection of effective treatment schedules.
Skeletal Muscle Relaxants
Muscle spasm, the product of involuntary contraction
of a muscle or of muscle groups, is often seen following
trauma and may initially produce as much pain and dis-
ability to the injured athlete as the primary injury. Skele-
tal muscle spasms occur in fractures, sprains, bursitis,
arthritis, and low back pain. Spasm is generated by
excess alpha motor neuron outflow resulting from noci-
ceptor efferent activation by traumatized or inflamed tis-
sues. This results in tonic con-
traction of the involved muscles, Table 11. Drugs Used for Treatment of Spasticity and Spasm
creating pain and a self-perpetu-
Treatment of spasticity:
ating cycle of further spasm.
Specific drug agents, the oral - diazepam (Valium)
skeletal muscle relaxants, may - baclofen (Lioresal)
be used for the relief of muscle - dantrolene (Dantrium)
spasm as part of an overall Treatment of spasm:
program that includes physical - carisoprodol (Soma)
therapy. - chlorzoxazone (Paraflex, Parafon Forte) - drowsiness, liver toxicity
Spasticity is an upper motor - cyclobenzaprine (Flexeril)
neuron disorder resulting from - diazepam (Valium)
brain or spinal cord injury.
- metaxalone (Skelaxin)
Although the term spasticity is
- methocarbamol (Robaxin, Skelaxin)
often used synonymously with
- orphenadrine (Norflex, Flexoject)
spasm, it is a specific and dis-
tinct pathology representing
either excessive activation of
gamma motor neurons increasing activity of type 1a
muscle spindle fibers, and ultimately alpha motor neu-
rons, or a generalized failure of descending cortical reg-
ulation of spinal cord inhibitory neurons. Medications
used to treat muscle spasm and spasticity share a com-
mon therapeutic goal: reduction of muscle hypertonicity.
These agents fall into 2 major groups: the peripherally
acting agents and the centrally acting agents.
Mechanisms of action
Centrally acting agents regularly prescribed to treat
acute muscle spasm are listed in Table 11 and include
such agents as carisoprodol (Soma), diazepam (Valium),
and cyclobenzaprine (Flexeril). Central agents are fre-
quently combined with the analgesics aspirin or aceta-
minophen. For example, Parafon Forte is the trade name
for chlorzoxazone with acetaminophen and Soma Com-
pound is carisoprodol with aspirin. With the exception
of cyclobenzaprine (Flexeril), these agents are similar to
anxiolytic or sedative-hypnotic agents in action, drug
interactions, and side effects. For this reason, short-term
use rather than long-term use is the norm. Cyclobenza-
prine (Flexeril) is related to the tricyclic antidepressant
agents such as amitriptyline (Elavil), which is also indi-
cated for chronic pain, or imipramine (Tofranil), and it
does not demonstrate drug dependency or altered sleep
patterns as do the other agents.
The actual skeletal muscle-relaxing effect and mech-
anism of action of these agents is unclear and is consid-
ered to be a byproduct of central nervous system seda-
tion and overall decrease in body tone. Diazepam (Vali-
um), a benzodiazepine, and baclofen (Lioresal) simulate
the endogenous neurotransmitter gamma amino butyric
acid, which acts at neuron sodium ion channels to
hyperpolarize neurons, thus raising the threshold of
depolarization and yielding an overall reduction in brain
neuronal activity. Diazepam, in common with other ben-
zodiazepines, produces central nervous system sedation,
anxiolytic effect, and anticonvulsant activity, and can
impede anterograde memory assimilation, making it dif-
Side effects:
- sedation, depression
- diminished deep tendon reflexes
- generalized weakness
Side effects:
- drowsiness
- liver toxicity
- sedation, depression
- liver toxicity
- not recommended for patients with epilepsy
- anticholinergic effects: avoid use in glauco-
ma, urinary retention, myasthenia gravis, or
tachycardia

16
ficult for patients to recall oral instruction given by ther-
apists. Diazepam is indicated for treatment of both
spasm and spasticity and has been shown to act as an
effective adjuvant to morphine, serving to decrease mus-
cle spasm and acting as an opioid-sparing agent.34
Cyclobenzaprine (Flexeril), shown in Figure 3,
relieves muscle spasm of local origin without interfering
with muscle function. It has been shown in animal mod-
els to reduce muscle hyperactivity. In common with tri-
cyclic antidepressant agents, it also produces some anti-
cholinergic, antihistaminic, and alpha-1 antagonism.
Therapists may therefore observe dry mouth, sedation,
and orthostatic hypotension accordingly. The adverse-
reaction profile of cyclobenzaprine is otherwise very
similar to that of diazepam (Valium).
Figure 3. Flexeril and generic cyclobenzaprine.
The mechanism of skeletal muscle relaxation for most
central agents such as Parafon and Soma has not been
clearly identified, but in animal models these medica-
tions block interneuronal activity and depress transmis-
sion of polysynaptic neurons in the spinal cord and
descending reticular formation of the brain.35 Clinically,
the source of skeletal muscle relaxation may be primari-
ly a function of central nervous system sedation.
Peripherally acting agents
Dantrolene (Dantrium), the sole peripherally acting
agent, is the only available agent that acts directly on
skeletal muscle. It is chemically and pharmacologically
unrelated to the other skeletal muscle relaxants. It is used
to treat malignant hyperthermia, a life-threatening genet-
ic sensitivity of skeletal muscles to volatile unaesthetic
agents and depolarizing neuromuscular blocking agents.
It is also indicated for treatment of Ecstasy intoxication
and neuroleptic malignancy syndrome and in rehabilita-
tion for skeletal muscle spasticity. As seems customary
for the skeletal muscle relaxants, the precise mechanism
of action of dantrolene and its molecular targets are, as
yet, incompletely understood.36 Dantrolene depresses
the intrinsic mechanisms of excitation-contraction cou-
pling in skeletal muscle by impeding calcium release
from the sarcoplasmic reticulum of muscle cells, thus
limiting myofilament cross-bridging and the ability of the
sarcomere to contract.
17
Central nervous system depressants, including alco-
hol, act additively with dantrolene, resulting in increased
sedation, lack of coordination, and respiratory depres-
sion. Athletes taking birth control pills should be aware
that estrogens can increase the risk of dantrolene-
induced hepatotoxicity and that dantrolene is associated
with photosensitivity; hats, sunscreen, and protective
clothing are to be advised when participating in outdoor
activity.
Adverse effects
Sedation and drowsiness are the most frequently
encountered adverse consequences of skeletal muscle
relaxants. Light-headedness, dizziness, vertigo, ataxia,
dysarthria, and headache are also possible. Patients for
whom centrally acting agents are prescribed may appear
lethargic and poorly motivated. Athletes may find seda-
tion advantageous, particularly with therapist education
and encouragement, in enhancing rest and recovery, or
they may object to the resultant loss of energy and alert-
ness. Clinically, many patients report both the adverse
effects and beneficial effects of these agents to be mini-
mal. There is a low incidence of drug dependency
among patients using central agents for extended periods
(weeks to months) that must be kept in mind while mon-
itoring. The centrally acting agents are usually dispensed
for treatment of acute spasm, whereas chronic or inter-
mittent spasm or spasticity is more appropriately treated
using baclofen, diazepam, and tizanidine.
Dantrolene produces generalized muscle weakness
as a primary adverse effect but also may be associated
with central nervous system sedation and dizziness.
Patients with pre-existing weakness are particularly at
risk for amplified strength impairment with dantrolene.
All skeletal muscle relaxants, both central and peripher-
al, may produce nausea and diarrhea.
Therapy implications
Physical therapists treating athletes taking skeletal
muscle relaxants should evaluate for sedation and
decreased capacity to participate in active modalities.
The potential for weakness, dizziness, or orthostatic
hypotension warrants precaution and, if necessary, assis-
tive guarding during treatment.
A fine balance must be sought between rehabilitation
benefit and attendant undesirable sedation or muscle-
weakening effect. Sedation and impairment of memory
assimilation should be considered in patients taking
diazepam for spasm or other benzodiazepines pre-
scribed for sleep or injury-related anxiety. Informing
patients of potential adverse effects helps alleviate
patient concerns and allows maximum drug benefits. The
therapist may wish to give written instruction to all
patients taking muscle relaxants.
Summary of rehabilitation considerations
1. All centrally acting agents may produce sedation,
dizziness, and vertigo.
2. Dizziness upon standing may be minimized by rising
slowly and avoiding sudden position changes (“start
low and go slow”).
3. Advise patients that centrally acting agents should
not be combined with alcohol or other central ner-
vous system depressants such as anxiolytic agents.
4. There is question as to the overall effectiveness of the
centrally acting agents in reducing skeletal muscle
spasm.
5. Most centrally acting agents are indicated for acute
rather than chronic muscle spasm.
6. Dantrolene, the sole peripherally acting agent, may
produce or accentuate muscle weakness.
Topical Agents in Sports Medicine
Therapists have long used specific steroid agents (eg,
dexamethasone phosphate and local anesthetics) topi-
cally in the treatment of injury. Numerous studies have
investigated, with positive findings, the effectiveness of
iontophoresis as a drug-delivery vehicle for dexametha-
sone with or without lidocaine or tetracaine for athletic
injury.37 Dosage calculation and reliable delivery can be
difficult because of myriad variables in absorption. Topi-
cal drug agent penetration depends, in part, upon the
partition coefficient of drug: the propensity of the drug to
separate from its solution and move into the skin. Sec-
ondly, the skin acts as a 2-way (both in and out) limited
barrier to drug penetration, with most barrier function
provided by the hydrophilic cells and hydrophobic inter-
cellular spaces of the epidermal stratum corneum.
Consideration of topical agent use begins with the
somewhat tricky assessment of dosage. As a precaution,
one should assume that all drug agents placed on the
skin are absorbed with rate and amount of absorption
influenced by the following variables:
• Regional variation: permeability varies inversely to
thickness of the stratum corneum; higher penetration
is seen in the face and intertriginous areas, especial-
ly the perineum. There is increased risk of sensitiza-
tion, irritation, and with steroid use, atrophy in these
regions. On the face use only low-potency (eg, cor-
tisone) steroids and only for short-term therapy.
• Hydration of the skin increases drug absorption.
• Drug-vehicle variations affect absorption: soaks,
lotions, solutions, creams, and ointments are avail-
able. Absorption increases in that order.
• Age: children have a greater surface to mass ratio, so
the systemic dose increases.
• Drug concentration in medium to higher concentra-
tions yields greater absorption but in a nonlinear
fashion.
• Altered barrier function: diseases such as psoriasis
will increase absorption.
• Lipid solubility of the drug and small particle size
favor absorption.
Therapists treating injured athletes or supervising
trainers and other personnel are familiar with several
18
OTC topical agents used in sports injury. The OTC
agents are available in 2 main groups: the salicylates and
the counterirritants. Counterirritants include menthol,
camphor, allyl isothiocyanate, and capsaicin. Methylsal-
icylate and trolamine salicylates are components of
many products and exert a mild NSAID effect. Methyl-
salicylate is also a counterirritant. The counterirritants
exert no direct analgesic effect but rather produce sensa-
tions of cooling or warmth caused by mild superficial
vasodilation that may be perceived by the patient as
enhancing comfort.
Topical NSAID use appears to avoid typical side
effects and relieve muscle soreness following athletic
workouts.38 Researchers compared a cream version of the
NSAID drug ketoprofen (Orudis KT) with a placebo skin
cream. Subjects who used the anti-inflammatory cream
reported up to 45% less muscle soreness than those who
used the placebo cream. Other NSAIDs have not demon-
strated equal effectiveness when used topically. Ibupro-
fen showed virtually no topical effect. Topical salicylate
(aspirin) creams do not work well for most kinds of
chronic pain but may be of adjunct use in treating sore
muscles after exercise. Topical salicylates additionally
serve to distract from the perception of pain by produc-
ing intense sensations of heat or cold.
A new counterirritant of much interest is capsaicin,
which is derived from hot chili peppers and available
OTC in topical form. Capsaicin is not commonly pre-
scribed for treatment of athletic injury but as a topical
treatment for osteoarthritis, herpes zoster, and trigeminal
neuralgia. Capsaicin, similar to other OTC balms, func-
tions as a counterirritant. Its OTC availability leads to
growing trial among athletes for treatment of sore joints
and muscles. Capsaicin appears to alter pain conduction
and requires consistent application over 1 to 2 weeks for
onset of analgesia. It produces hypesthesia by stimulating
release of neuropeptides, including substance P, initially
producing a burning or scraped-skin sensation. Cap-
saicin stimulates release of substance P from peripheral
type C sensory fibers to central neurons. Depletion of
substance P causes cell death and gradual desensitiza-
tion to the nociceptor stimulation, eventually resulting in
a numbing effect at targeted sensory neurons. It is used
no more than twice daily, not in conjunction with ion-
tophoresis, and patients should be advised not to place
tight or occlusive dressings over applied capsaicin to
avoid excess penetration and skin irritation. Additionally
a skin-burning sensation may be sustained in patients
using the drug more than twice per day.
Summary of rehabilitation considerations
1. When using topical agents, with or without ion-
tophoresis, resultant systemic dosage varies with the
drug agent carrier and the thickness and integrity of
the stratum corneum.
2. Clinicians should consider absorption variables
when calculating absorbed dosage.
3. Topical effects, especially with steroid agents, will
increase in thin stratum corneum areas or in areas of
skin-integrity compromise.
4. Topical NSAIDs, specifically ketoprofen, show
promise in treatment of athletic injury.
5. Topical capsaicin is demonstrated as an effective
analgesic agent.
6. Topical counterirritants offer no objective analgesic
effect.
CONCLUSIONS
Exercise has significant consequence for both the
choice of pharmacotherapeutic agents and their effect on
the physically active patient. Alterations in pharmacoki-
netics during strenuous activity is not well researched for
many medications at this time, but sufficient data exist to
warrant consideration of, and monitoring for, pharmaco-
kinetic changes in all medications as a result of athletic
activity. The environment in which the athlete functions
also necessitates change in drug choices or increased
patient education regarding potential effects of drugs
affecting autonomic function, analgesics, anti-inflamma-
tory drugs, skeletal muscle relaxants, photosensitizing
agents, and many other medications that may create
health risks for the athlete. Additionally, many medica-
tions interact with other unrelated medications, altering
their physiological behavior, efficacy, and incidence of
adverse effect, and necessitating vigilant monitoring by
the physical therapist.
The modern practice of physical therapy is actively
assuming a much greater role in the monitoring and pre-
scribing of medications to the injured athlete. Learning
the vast amount of pharmacological information avail-
able is formidable, if not impossible, making familiariza-
tion with pharmacological reference sources such as the
Physicians’ Desk Reference, drug-interaction texts and
software, online sites, and PDA software necessary. This
monograph has focused on the more commonly encoun-
tered medications used in the treatment of the athletic
patient and hopefully serves to stimulate further study of
pharmacology and augment the continuous advance-
ment of rehabilitation practice.
CASE STUDIES
Case Study 1
History
A 55-year-old man who is a moderately overweight
college professor is referred to physical therapy with a
chief complaint of pain at the right Achilles tendon pre-
sent over the past 3 to 4 months. Over the past 2 months,
in an effort to lose weight, the patient began walking and
jogging approximately 2 miles for 2 to 3 days per week,
resulting in exacerbation of the symptoms. Past treatment
by the patient’s primary care physician consisted of a
one-quarter-inch felt heel lift placed in the shoe and
ibuprofen (800 milligram tablets, 1 tablet 3 times daily
for a total daily dose of 2400 milligrams for 1 month),
19
which produced only slight improvement. On his last
visit to his physician’s office, an injection of 5 milligrams
of triamcinolone acetate (Kenalog) mixed with 4 mil-
ligrams of dexamethasone phosphate and 1cc 2% lido-
caine plain (without epinephrine) was placed in the peri-
tendinous area.
Two weeks following initiation of physical therapy,
the patient sustained a rupture of the right Achilles ten-
don. A diagnosis of partial rupture 2 to 3 centimeters
proximal to the calcaneal insertion was confirmed with
magnetic resonance imaging studies showing the tendon
to be 50% intact but in lengthened position. The patient
was not a candidate for surgical repair and elected to
decrease activity rather than undergo serial cast immobi-
lization treatment.
Evaluation
Given the chronic nature of the problem, the tendon
would be weakened simply as a result of inflammatory
tissue effect. There is controversy over the use of steroids
in tendons, particularly the Achilles tendon, but the liter-
ature does not demonstrate a strict contraindication to
this treatment. Injection to the tendon itself, as opposed
to the peritendinous area, is contraindicated. The effect
of the injection is difficult to isolate from that of obesity,
a relatively recent increase in activity, the normal inci-
dence of tendoachilles rupture in active persons, and the
tendon-weakening effect of chronic inflammation.
Intervention
As the patient is not a surgical candidate and refuses
conservative treatment with many weeks of serial cast-
ing, the therapist will select modalities to enhance heal-
ing, strengthen the tendon, maintain muscle strength in
the new lengthened position, and limit the chance of
repeat injury. The therapist realizes that the dexametha-
sone, although a more potent steroid than triamcinolone,
is in the form of dexamethasone phosphate, a short-act-
ing preparation that is likely no longer influencing tissue
healing. However, the presence of Kenalog, a long-act-
ing steroid, decreases inflammation and stunts healing,
potentially for 2 to 3 months. The injury may show less
pain and inflammation than normally anticipated as a
result, and the therapist will modify therapy to avoid
excess tendon strain.
Case Study 2
History
A 52-year-old woman with an unremarkable medical
history is referred to physical therapy with a chief com-
plaint of radiating pain at the back of the right hip, thigh,
and calf that began 2 days after completing a rigorous
backpacking trip. During the trip, the patient hiked
approximately 30 miles over 3 days at high elevations
while carrying a 30-pound pack. She notes walking sev-
eral miles on a steeply sloped mountainside first with the
right leg on the down slope and then, on the return trip,
with the left leg on the down slope. During the return
trip, the patient fell on loose rock onto the right hip. At
the time of the fall, she noticed only moderate temporary
pain at the hip but developed aching in the right buttock
that night. Two days later, upon rising from bed in the
morning, radiating pain in the right leg was present,
aggravated by hip flexion and knee extension, coughing,
and sitting.
Radiographs were negative for fracture; the patient
ambulates normally but with hip and posterior leg sore-
ness after the initial morning pain subsides. She notes
that the pain is most severe when sitting in a crossed-leg
position while putting on her shoes and socks. Paresthe-
sias developed at the plantar aspect of the lateral 3 digits
of the right foot about 4 weeks after onset of the leg pain.
The patient was prescribed a core strengthening pro-
gram, Vicodin ES for pain, a 6-day decreasing dose pack
of methylprednisolone 4-milligram tablets, and 10-mil-
ligram diazepam tablets to be taken at night before sleep
for muscle relaxation. Little if any improvement was not-
ed on her return visit 2 weeks later. At that time, she was
prescribed indomethacin, 50 milligrams to be taken 2 to
3 times daily as needed. The patient reported 80%
improvement with indomethacin but a full return of
symptoms when discontinuing the medication. The
diazepam appeared to improve symptoms upon rising,
but the overall effect was considered questionable so the
patient was instructed to use diazepam on an as needed
basis. The patient was referred to physical therapy.
Evaluation
The literature demonstrates questionable effect of
steroids in treatment of sciatica. In short-term use, a 6-
day decreasing schedule dosage (Medrol Dosepak or
generic methylprednisolone 4-milligram decreasing dose
pack) would be commonly prescribed here. The effect
would be of short duration, so at the time of physical
therapy initiation the steroid would no longer be a factor.
Indomethacin is a potent and toxic NSAID with all of the
side effects of NSAIDs to be considered. Indomethacin is
additionally more prone than most NSAIDs to the central
nervous system effects of dizziness or sedation that may
impede or limit modality selection. The therapist obtains
a thorough medical history to ensure no contraindication
to nonselective NSAID use or indication for COX-2-
selective agents based on a history of GI and renal disor-
ders or history of thromboembolic event.
Intervention
Discussion with the referring physician regarding pos-
sible discontinuation of indomethacin and administering
a less toxic NSAID for long-term use is indicated. The
decision for employing a long-acting NSAID versus a
short-acting agent will be based on compliance and
patient toleration of any adverse side effect. The patient
should be advised that full anti-inflammatory effect might
not be realized for 7 to 10 days after beginning use of any
NSAID agent. The concern of delayed healing, which is
20
minimal in the case of soft tissue injury, will be balanced
against the comfort, improved modality toleration, and
mobility provided by the drug agent.
Diazepam (Valium) is a potentially helpful agent for
relief of skeletal muscle spasm. Studies show that its use
may decrease the need for narcotic analgesics, but Vali-
um-induced sedation will be additive to that of Vicodin.
The patient’s ability to participate in therapy modalities is
possibly limited. This drug regimen should be short term
only, with consideration of changing the skeletal muscle
relaxant, if still desired, to Flexeril, which as a tricyclic
antidepressant-like agent shows decreased propensity to
sedation. The goal of therapy is to improve comfort and
change to a carefully targeted, less sedating skeletal mus-
cle relaxant.
Vicodin is a moderate-strength narcotic analgesic
with all typical adverse effects possible. The patient may
demonstrate sedation, constipation, and urinary reten-
tion along with all other adverse effects of opiates. When
Vicodin is used concomitantly with the NSAID
indomethacin and the skeletal muscle relaxant
diazepam, significant central nervous system effects are
much more likely to be encountered. In this case, the
patient is prescribed 3 drug agents, all with central ner-
vous system effects, which produce an additive effect.
Additionally, long-term use of Vicodin raises concern
over development of drug dependency. Moving the
patient toward an NSAID or acetaminophen pain relief is
a primary goal. The therapist will monitor Vicodin use in
reference to the prescribed regimen and include pain
relief, with the intent to eliminate the Vicodin require-
ment, as a priority in therapy planning and delivery.
Case Study 3
History
A 22-year-old man who is 6 feet, 3 inches tall, 225
pounds in weight, and a competitive track athlete con-
sulted his team physician and reported a chief complaint
of left side neck and shoulder pain present for the past 3
months. The patient reported progressively increasing
shooting electrical pains produced by neck rotation and
shoulder motion. No injury was recalled other than a fall
to the left side while running on a wet track surface dur-
ing a typical practice. He was able to complete all prac-
tice drills with mild neck and side soreness and consid-
ered this to be only a minor injury at the time.
Evaluation
Mild to moderate spasm of the posterior and lateral
neck musculature were noted at the time of examination.
The patient demonstrated local muscle pain in the affect-
ed neck region and radicular pain in a C5-C6 distribution.
Plain-film x-rays were negative for fracture or osseous
deformity at the neck but demonstrated loss of normal
cervical curvature. The past medical, family, and social
history is unremarkable with the exception of depression,
which has progressed since the injury. Initial medications
dispensed were Tylenol with codeine no. 3 to be taken 4
times daily and gabapentin (Neurontin) in 400-milligram
tablets to be taken 2 times daily for relief of radicular
pain. Rest and moist heat were recommended and a soft
neck splint dispensed. Little relief was noted after 2
weeks, so the primary care physician advised the patient
to discontinue sports training and prescribed 50 mil-
ligrams of amitriptyline (Elavil) for worsening depression.
The patient was then referred to physical therapy.
Intervention
During the physical therapy evaluation, the therapist
reviewed the medication history with the patient to
ascertain effectiveness and any adverse effects that might
modify therapy planning or delivery. The patient reported
moderate improvement in symptoms to the physical ther-
apist but noted feeling “dizzy” with difficulty walking
especially upon standing. He stated the Tylenol with
codeine prescribed for pain had been refilled twice
because he continued to be uncomfortable.
The patient’s weight of 225 pounds is nearly twice the
normal 70-kilogram weight used for drug calculations.
The therapist realized the prescribed Tylenol with
codeine no. 3 taken 4 times daily was inadequate for this
patient’s body size; this may explain the failure to obtain
pain relief. Patient compliance with instruction indicat-
ed no issue with abuse to be present. The prescribing
physician was informed that the pain relief provided by
the Tylenol dosage appeared to be inadequate during
therapy and was asked for options regarding analgesia
that would benefit the patient’s rehabilitation process.
Neurontin and Elavil are drugs that require special
monitoring in athletes. Both are drugs seen in physical
therapy practice that have significant effects on athletes
and sport performance. Investigation of each drug agent
by the therapist using various textual, online, and soft-
ware reference sources reveals a great deal of clinically
useful information that will serve the therapist and the
patient.
Neurontin is used for post-herpetic pain and also may
be prescribed for neuropathic pain. Although not a first-
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