NSAID Use from a Physical Therapist's Perspective
Jeff Robinson, PT, FAAOMPT
Introduction
The overwhelming majority of patients who are seeing a physical therapist in the
outpatient setting are on some type of drug.5 Drug therapy is the use of a drug in the
treatment of a patient with a specific disease or illness.6 “The goal of drug therapy is to
improve patient’s health and quality of life by preventing, eliminating or controlling diseases, or
symptoms.” 6 The study of the body's reaction to drugs is known as pharmacology. 10 To some
practitioners, the term “drug”, has a negative connotation. They prefer to use the term
“medication” or “medicine.” 15
Patients are often treated with drugs in combination with receiving physical therapy
treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular drugs in the
world in terms of utilization. 4 Seventeen percent of respondents surveyed in the United States
admitted to taking anti-inflammatory drugs.19 NSAIDs are often prescribed to patients who
receive outpatient physical therapy for an orthopedic condition. Boissonnault and Meek5
reported that 78.6% of patients seen for outpatient physical therapy treatment had used
aspirin or other OTC anti-inflammatory agents within the prior week.
Given these statistics, it is undeniable that physical therapists who work in the
outpatient orthopedic setting will be exposed to patients who are taking NSAIDs. According to
The Guide to Physical Therapist Practice, physical therapists are expected to take into account
the role of the medical history and medication use as it relates to physical therapy treatment.1
The purpose of this paper is to review the various aspects of pharmacology from a
general perspective and then to apply those aspects specifically to a particular NSAID,
ibuprofen. This will be accomplished in Part I of this paper. A case report will be included in
Part II of the paper. The case report is based on a 16 year old male athlete whose case was
published in the journal “Clinical Pediatrics.”2 Part II of this paper is written as if that patient
were referred to physical therapy. The goal of the case report is to solidify concepts presented
by applying pharmacological knowledge to a clinical scenario and to discuss various issues
related to the importance of physical therapists knowledge in the field of pharmacology.
1
Part I
Gladson defines pharmacology as “the study of how chemical substances affect living
tissue.” 8 Pharmacology is divided into pharmacotherapeutics and toxicology. 8
Pharmacotherapeutics is the use of chemicals to assist in curing or preventing disease.
Toxicology is how chemicals negatively impact living things. 8 Pharmacotherapeutics is further
broken down into pharmacodynamics and pharmacokinetics.
Pharmacodynamics “describes what the drug does to the body and its beneficial effects
at the cellular or organ level.” 8 Pharmacokinetics is “the study of how fast and how much of
the drug is absorbed into the body, how it is distributed to various organs, and how it is
ultimately metabolized and excreted by the body.” 8 In simple terms, pharmacodynamics is
what the drug does to the body and pharmacokinetics is what the body does to the drug.11
It’s not possible to understand the pharamacodynamics of ibuprofen without first
knowing something about prostaglandins. Prostaglandins are enzymes that are released from
the body when an injury occurs and are integral to the inflammatory process by causing
vasodilation. Prostaglandins are also responsible for pain afferent sensitization and many other
bodily functions. Prostaglandins are formed from arachadonic acid which is stored in the cell
membrane.
When an injury occurs, a series of events take place that cause arachadonic acid to form
into prostaglandins. The enzyme responsible for this conversion is the cyclooxygenase enzyme.
This enzyme has 2 forms, known as COX-1 and COX-2. COX-1 is found in the blood vessels,
stomach, and kidneys. COX-2 is found in the cells of the synovial lining, vascular endothelial
cells, and chondrocytes. 17
Ibuprofen acts to block the cyclooxygnease enzyme thereby preventing arachadonic
acid from being formed into prostaglandins. NSAIDs block both types of cyclooxygnease
enzymes, COX-1 and COX-2. Blocking COX-1 results in prostaglandins not being produced in
the GI tract and kidney which can ultimately affect function of these organs in a negative way.
Blocking of COX-1 also results in diminished ability for platelet aggregation. Blocking COX-2
results in the prostaglandins responsible for vasodilation and sensitization of afferent pain
fibers not being produced. This results in decreased inflammation, pain, and swelling.
The pharmacokinetics of any drug is broken down into 4 phases. Theses phases include:
absorption, distribution, metabolism, and excretion. Absorption is the process by which the
drug is taken into the body and disseminated to the general circulation. Ibuprofen is
administered orally and therefore enters the systemic circulation via the gastrointestinal tract.
Once in the circulatory system, ibuprofen is heavily bound (99%) to plasma proteins – mostly
2
albumins. The binding of ibuprofen to albumins renders it useless from a therapeutic point of
view as it is only the unbound medication that actually has a therapeutic effect on target cells.
Ibuprofen is distributed throughout the body once it is in the vascular system.
Distribution varies among various organs within the body. The brain, kidney, and liver often are
some of the first organs to receive the medication. Tissues which are more of interest to a
physical therapist like muscle, tendons, and ligaments take longer to be affected.
Ibuprofen, like other medications is metabolized by the liver. As ibuprofen is passed
through the liver the first time, a certain percentage of it will be metabolized and rendered
useless for therapeutic purposes. This is known as the “first pass effect.” Although the first
pass effect of ibuprofen is not as significant as other NSAIDs, one should be aware of this
common occurrence in the metabolism of all medications. The time that it takes for half of the
medication to clear the liver is known as the half-life. The half-life for ibuprofen is 2 hours. This
means a dosage of 2400 mg of ibuprofen will be reduced to 1200mg in 2 hours, 600 mg in 4
hours, 300mg in 6 hours and so on.
In order to be effective, ibuprofen must reach a “steady state” in the bloodstream. This
refers to the phenomena of there being the same amount of drug leaving the body as there is
entering the body. Consistent, accurate dosing of ibuprofen will ensure adequate
concentrations of the medication in the blood stream to deliver to the target tissues.
The most common modes of elimination of drugs is through feces and urine.8 After
ibuprofen is converted by the liver it eventually leaves the body via renal excretion.
The intended, beneficial effect of ibuprofen in the context of physical therapy treatment
is decreased pain and inflammation. This is known as the therapeutic effect and, as mentioned
previously, is accomplished by blocking prostaglandins. Because prostaglandins have a variety
of functions within the body, other non-therapeutic effects occur as well. These nontherapeutic effects are known as side effects or adverse effects. Generally a side effect is a
milder version of an adverse effect.
For example, ibuprofen’s role in blocking prostaglandins may result in altered
gastrointestinal (GI) function which can cause a side effect of abdominal pain. A GI bleed
resulting in the patient losing consciousness and requiring hospitalization would be considered
an adverse effect. Again, because prostaglandins play such an important role in many bodily
functions, many systems potentially can be affected. Biederman’s3 table of side/adverse effects
for ibuprofen by system is reproduced below:
System
Gastrointestinal
Side/Adverse Effects
Nausea, heartburn, dyspepsia, gastric
3
ulcers, duodenal ulcers, perforations,
bleeding complications
Sodium retention, edema,
hyperkalemia, acute failure, nephritic
syndrome, papillary necrosis
Tinnutis, sedation, dizziness
Renal
Central nervous
System
Hematological
Hemorrhage, anemia, COX-2 cardiovascular
events
Other NSAID- or salicylin-containing
foods: apples, oranges, banana
Allergic reactions
Weighing the risks of side effects and adverse effects versus the benefit of therapeutic
effects is known as the risk/benefit ratio. All health care providers who prescribe ibuprofen
must be able to analyze the risk/benefit ratio of each patient, taking into consideration all
possible therapeutic, side, and adverse effects. The end result of ibuprofen use can have a
huge impact on a patient’s quality of life – both in a positive and negative light.
Outside of expected therapeutic, side, and adverse effects, there are many variables
which can influence how a patient responds to ibuprofen, or to any medication, for that matter.
Health care providers must be familiar with these variables when prescribing ibuprofen
Any disease state of the liver like cirrhosis or hepatitis is a variable which can influence
the amount of ibuprofen in a patient’s circulation. In these patients, serum albumin levels are
decreased. This decreases the amount of albumin available for ibuprofen to bind, thereby
increasing the amount of “free” drug available. Any type of kidney disease can influence the
ability of the patient to eliminate the drug and can also increase the amount of “free” drug
available in the circulation.
Ibuprofen’s strong binding capabilities to protein (mostly albumin) can displace more
weakly bound medications and increase the amount of “free” displaced drug. Hypoglycemic
agents like diabinese and glucatrol as well as anti-clotting agents like warfarin and
methotrexate all are displaced by ibuprofen.9 Ibuprofen can also interact with diuretics in a
negative way, albeit a different mechanism. Since ibuprofen decreases prostaglandin
production and the kidney requires prostaglandins to maintain adequate perfusion, increased
blood volume could result, which could ultimately lead to increased blood pressure. 8
Age is an important variable in patients taking ibuprofen. “Adults over the age of 60
taking NSAIDs have a 4- to 5-fold higher risk of GI bleeding or ulceration than younger
individuals.” 3 Since older patients take more medications and are more likely to have other
diseases, the risks of drug-drug interactions and interactions with other diseases are increased.
4
Albumin in the serum decreases with age and, as with liver and kidney disease states
mentioned previously, this decreases the number available to bind to protein which in turn
results in additional “free” drug in the circulation.
Genetics can play a role in how medication affects individuals. Some individuals may
metabolize drugs differently because of certain enzyme deficiencies or chemical reactions more
prevalent in certain ethnic groups. 8 Daly et al7suggest genetic factors may mediate the
formation of reactive metabolites in those taking NSAIDs. The formation of these metabolites
could lead to adverse effects in patients taking ibuprofen.
Diet may affect drugs. The therapeutic effect of ibuprofen may be extended by eating
acidic foods versus alkaline foods. This has to do with ibuprofen not being excreted as easily in
acidic environments and therefore remaining in the systemic circulation. 3 Grapefruit juice is a
well known inhibitor of liver enzymes which can increase the amount of “free” drug in the
bloodstream. 8
Since ibuprofen is an over the counter medication (OTC) and readily available, it is not
uncommon for it to be used in a non-therapeutic way. Compliance to proper dosing in order to
reach a steady state of medication in the bloodstream is extremely important in reaping
benefits. Non-compliance to proper dosing in the form of overdosing may result in adverse
effects. When used properly, ibuprofen can be an extremely effective medication in patients
who are concurrently receiving physical therapy.
Part II
A 16 year old male baseball pitcher entered the physical therapy clinic with a chief
complaint of right shoulder pain. The patient presented a prescription from his pediatrician
with a diagnosis of shoulder tendonitis and instructions to “evaluate and treat.” The patient
described his pain as a constant dull aching pain located diffusely around the shoulder with
referral to the brachium during overhead movements. The patient denied neck pain, left upper
extremity pain, thoracic and scapular pain, and pain distal to the right elbow. The patient also
denied numbness and tingling.
The patient described his right shoulder pain developed over a period of time, but had
gotten worse over the course of the last 2 weeks of the season after participating in weekend
baseball tournaments for 2 weekends in a row. The pain got to the point where the patient had
difficulty lifting his arm above his head without pain.
The patient stated his mother took him to see his pediatrician who prescribed ibuprofen
at a dose of 400mg every 8 hours for 2 weeks. The patient completed his medication regime,
but still had pain and therefore was referred to physical therapy. Physical therapy was initiated
5
approximately 4 weeks after first seeing his pediatrician. The patient denied any previous
history of right shoulder pain or any trauma or past history of any other upper quarter injuries.
Aggravating factors included raising his arm above his head as in combing his hair,
putting on his belt, and lying on the right side. Easing factors included resting his shoulder. The
patient denied any neck movements causing right shoulder pain.
The patient denied currently taking any sort of medication except for infrequent
ibuprofen as needed. His general health was good with no history of any medical problems
whatsoever. The patient denied taking any steroid medication in the past and denied any
lightheadedness or dizziness (ruling out vertebral artery dysfunction).
His main recreational activities included sports. The patient had completed summer
baseball, but was now participating in football practice where he was the quarterback. He also
participated in basketball in the winter months. His main goal was to get to being able to throw
without pain.
The patient’s exam was significant for pain with resisted shoulder tests, positive
impingement tests, and decreased range of motion at end ranges of flexion, abduction, and
external and internal rotation. The patient also presented with a tight posterior capsule. The
patient’s treatment plan included manual therapy and exercise.
The patient was progressing well, but presented to the clinic on visit #4 (2 weeks into his
physical therapy course) with a distinct yellowing of the skin and whites of his eyes. He also
complained of dark urine for 2 days prior to the onset of jaundice. Having experienced
patients with these types of symptoms in other practice settings, the treating therapist
immediately recognized these symptoms as being derived from the liver.
Initial thoughts as to what specifically was causing these symptoms were directed to
some sort of acute hepatitis, but before contacting the referring physician, the therapist
decided to research further the only medication the patient had taken in the recent past –
ibuprofen. The therapist considered the patient may be having some sort of drug reaction to
ibuprofen. It is not uncommon for patients who receive physical therapy to have
gastrointestinal (GI) complaints to the point of GI bleeds, but the therapist was less familiar
with patients who developed liver symptoms from ibuprofen use.
The clinic where the therapist works does not have a Physician’s Desk Reference (PDR)
and so the internet was used to further research ibuprofen and its side effects. When using the
internet to obtain reliable information on medications, the therapist understood there are
several factors to keep in mind in determining quality of websites. Medline plus, a database
which “brings together authoritative information from the NLM (National Library of Medicine),
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the National Institutes of Health (NIH), and other government agencies and health-related
organizations” 12 offers guidelines to evaluate the quality of health related websites. Medline
plus identifies several key questions to ask when seeking health information from websites. 14
Questions such as who runs the site, what is its purpose, is the site trying to sell something, are
articles reviewed before posting and are they referenced, is the source of data and research
identified, and is the site updated frequently and recently are some of the most important
questions to ask.
The therapist first went to the www.drugs.com website. This is a website which meets
much of the criteria for what is considered a “good” website and was deemed an appropriate
website for the purpose of identifying side effects, adverse effects, dosing guidelines, and drug
reactions. This website did list liver related symptoms as potential, but rare side effects.11 A
search on www.medicenet.com13 (a website owned by webMD.com) and www.rxlist.com also
listed the specific liver related side effects with which the patient was presenting. 16
Because this patient was taking no other medications or supplements, the therapist was
not as concerned with drug interactions and did not read into detail the drug interaction
sections. Information on dosing was relevant to this patient. The patient did follow
appropriately initial dosing recommendations in order to achieve a “steady state” of medication
in his system, however after further questioning the patient, the patient did admit to
independently continued ibuprofen usage in a non-therapeutic way after the initial prescription
period ended (more than the “infrequent” amounts he first admitted to during the initial
evaluation). The patient stated he continued to take 200-400 mg sporadically after the initial
prescription period ended.
With this knowledge, the therapist contacted the referring MDs office and was
eventually able to discuss the patient’s presentation with the MD. The MD agreed the patient
needed to be seen immediately. The PT session was discontinued and the patient was
instructed to go directly the referring MDs office.
The patient’s pediatrician ordered liver function tests (LFTs) which turned out to be
abnormal. The patient was eventually referred to a hepatology specialist at a large teaching
hospital. The patient’s condition did not improve quickly and actually worsened with
development of persistent, severe pruritis. This was treated with pharmacologic intervention.
Approximately 2 weeks after the onset of symptoms, the patient underwent a liver biopsy
which confirmed drug induced liver damage. No specific intervention was performed, but the
patient was observed over several weeks. The patient gradually improved over a 3 month
period with a gradual lessening of symptoms and a normalization of LFTs. The cause of the
patient’s negative response to ibuprofen was not completely resolved, but a genetic
component likely contributed to this particular patient’s ibuprofen-induced liver injury.
7
Discussion
This case offers an excellent example of the health care team working together for the
benefit of the patient. Physical therapists must recognize signs and symptoms that are not
considered normal and refer to the appropriate medical personnel. The therapist initiated the
referral back to the referring physician demonstrating the physical therapist’s role within the
treatment team in terms of appropriately using pharmacologic knowledge to channel the
patient’s healthcare in the right direction.
Physical therapists can serve a vital role within the treatment team by using our
pharmacologic knowledge to make healthcare delivery more efficient. In this case the therapist
was able to quickly rule out drug interactions or other medical issues as possible causes of the
patient’s symptoms. For other patients, the therapist’s knowledge of drug interactions and the
relaying of this information to the referring physician or healthcare practitioner can increase
the speed and efficiency of diagnosing the patient’s condition.
In this case the therapist was able to clearly and concisely inform the referring physician
that the patient had no history of kidney or liver problems and was not taking any other
medications. This information was used by the referring physician to direct his thinking as to
what may have been causing the patient’s symptoms.
Under normal circumstances, the use of ibuprofen can have a significant positive impact
on the outcome of patients who are receiving physical therapy. In the case of this patient, the
initial relief of pain and inflammation assisted the patient in being able to perform therapeutic
exercise and to tolerate manual therapy interventions that he may not have been able to
perform or tolerate as well otherwise. In retrospect, the patient may have been benefitting
from pain relief after the initial therapeutic dosage was complete due to continuing to take
ibuprofen independently.
Potentially, as in this case, there is a chance of any medication having a negative impact
on the outcome of patients who are receiving physical therapy. The negative impact is usually
due to some form of side or adverse effect. One of the most common side effects of ibuprofen
is the development of GI problems. Symptoms associated with GI problems include upset
stomach, nausea, vomiting, and heartburn. Symptoms of a GI bleed are black, tarry stools or
vomiting that looks like coffee grounds. 18 The discomfort caused by GI problems may affect
the patient’s ability to participate in physical therapy and have a negative impact on outcome.
This could also result in needing to cease taking ibuprofen, leading to poor control of pain and
inflammation.
In many cases, the practicing physical therapist spends more time with the patient than
any other health care provider. This places physical therapists in a unique position to monitor
8
the effects of medications on patients. The knowledge by physical therapists of the
therapeutic effects and side/adverse effects of medications allows the practicing physical
therapist to monitor the patient closely and act upon situations where the patient is not
responding as expected. This may require the physical therapist to notify the referring
physician in cases of an adverse effect or in cases of no effect. When the prescribed medication
does not produce any effect, it is known as therapeutic failure. 15
As this case demonstrates, knowledge of pharmacology is an extremely important skill
for the current practicing physical therapist. Most states allow patients access to physical
therapy services without a physician referral. The American Physical Therapy Association
continues to lobby for Medicare to recognize physical therapist’s ability to see patients on a
direct access basis. Physical therapists roles will most likely continue to expand in today’s
healthcare environment.
Although this particular case was not an example of a patient receiving physical therapy
from a direct access route, one could imagine a scenario where this type of patient may have
entered the clinic taking self directed or parent directed ibuprofen. The physical therapist must
be armed with accurate information or know where to locate and understand accurate
information as it relates to pharmacology. Physical therapists can then educate patients about
the expected therapeutic effects as well as the side and adverse effects they may experience.
Physical therapists must then refer to the appropriate medical provider in cases where the
patient does not respond as expected.
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