Side Effects of Pain Medications (Part 1)
By Larry C. Driver, MD
Associate Professor, The University of Texas M. D. Anderson
Cancer Center, Houston, Texas (Reprinted with permission from the Chronic Pain Report,
Volume I, Issue 4)
The intended effect of pain medications is obvious, to relieve
pain. However, desired effects are sometimes accompanied by
side effects that may be bothersome or even problematic themselves,
and may involve various organ systems. In this and future
articles, we will review some common side effects of the classes
of medications used as primary and adjuvant treatments for
chronic pain. This initial article will discuss opioid side
effects. Future installments will address steroids and non-steroidal
anti-inflammatory drugs (NSAIDs), medications used to treat
neuropathic pain including the tricyclic antidepressants (TCAs)
and anti-epileptic drugs (AEDs), skeletal muscle relaxants,
and drug used for anxiety and depression.
Opioid Side Effects
Opioids, often the foundation of a chronic pain medication
regimen, share common mechanisms of action, and also common
side effect profiles. Their impact on the central nervous
system (CNS), gastrointestinal (GI) function, and respiration
may be clear, with less obvious effects on other systems including
cardiovascular, urinary, skin and others. Side effects may
be related to a specific drug or combination of drugs, the
total daily opioid dose, to starting a drug or increasing
the amount taken, to drug byproducts, and to the patient’s
age and concurrent medical condition.
CNS effects may be inhibitory or excitatory, include alterations
in consciousness and cognition, and range from mild drowsiness
to profound sedation, euphoria to delirium with hallucinations.
Patients may have mild lightheadedness or sickening dizziness.
Excitatory effects include exaggerated sensitivity to pain,
muscle twitching or jerking, or seizures, all of which may
be related to excessive accumulation of the opioid or its
byproducts. Combining opioids with other substances such as
alcohol or benzodiazepine medications may aggravate CNS effects.
Older adults may be especially sensitive to both the effects
and side effects of opioids and other medications. Treatment
may include decreasing the opioid dose, changing to another
opioid, or adding another drug to address specific problems,
e.g. a psycho stimulant for drowsiness.
GI effects of nausea and constipation are predictable issues.
Acute nausea may complicate recovery following surgery, while
chronic nausea may be bothersome or even debilitating. Patients
may avoid taking pain medications because of fear of nausea.
Nausea and vomiting may lead to dehydration, which then worsens
the nausea. Nausea is due to opioid-induced slowed gastric
emptying and decreased gut motility, opioid activity in the
brain’s nausea centers, and perhaps increased sensitivity
in the inner ear causing vertigo-like symptoms.
Patients often develop tolerance to this problem within a
few days, but may need anti-emetics in the meantime, especially
when starting a new opioid or increasing dosage. Metoclopramide
is an anti-emetic that enhances gut motility and can be quite
useful in these situations. Nausea may also be caused or aggravated
by another GI side effect—constipation. Opioid-induced constipation
is due to impaired bowel motility and diminished intestinal
secretions. Unlike most other opioid side effects, tolerance
does not develop over time and constipation remains an ongoing
issue. The best approach to treatment is proactive use of
stool softeners and stimulant laxatives. For refractory constipation,
suppositories or enemas may be necessary.
Respiratory depression is a potentially dangerous situation,
but fortunately infrequent in the chronic pain patient taking
opioids on a long-term basis. Tolerance to this side effect
is generally protective. However, older patients and those
with underlying lung disease should nevertheless be cautious
in their use of opioids.
Cardiovascular effects of opioids are usually drug-specific
and not problematic for most chronic pain patients. Depression
of the heart and vascular dilation may be due to direct effects
of opioids, or mediated by histamine. Care in choice and dose
of opioid should be exercised.
Urinary retention, urgency, and bladder spasm may be problems,
particularly in older patients who usually develop tolerance
but may require a change in dose or drug or another intervention.
Itching as a side effect is poorly understood but may be related
to histamine. Thus, typical treatment includes using antihistamines,
but novel approaches may be useful.
Loss of body heat may occur due to opioid effects in the brain’s
temperature-regulatory centers, impairing the ability to maintain
constant body temperature.
Endocrine hormonal effects of opioids on brain centers may
result in diminished libido.
Allergy to opioids is uncommon. People may describe a “bad
experience” or side effects of opioids as an allergy, or they
may have some histamine type symptoms that are perceived as
“allergy.” Along with reassurance of the patient, careful
prescription of opioids can usually proceed.
Careful patient assessment and rational prescribing of appropriate
medications can successfully address most opioid side effects.
Dose adjustment or switching to an alternate opioid, or adding
another drug to treat the side effect is usually effective.
Proactive consideration of likely side effects along with
the pain treatment is the best approach.
Glossary
Adjuvant Treatments: treatment other than the primary treatment
of a condition or disease which compliments the primary treatment.
Tricyclic antidepressants: older class of antidepressant most
often used in low doses to control pain from neuropathic or
myofascial conditions by increasing levels of serotonin and
norepinephrine
Inhibitory: decreases activity in the central nervous system.
Excitatory: increases activity in the central nervous system.
Benzodiazepine: a class of medications most often used to treat
anxiety or sleep on a short term basis but occasionally used
to treat pain.
Anti-emetics: something, usually a medication, to reduce nausea
and/or vomiting.
Refractory constipation: constipation nor responsive to standard
treatment.
Libido: sex drive.
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