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

Antiemetics: 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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