|
28 June 2010
Overview
Opioids are one of the most commonly prescribed medications for pain. In pain management settings, as much as 90% of patients with chronic pain are on an opioid1. The use of opioids in the US has exponentially increased, sales of hydrocodone increased by 244% from 1997 to 20062. Opioid therapy has been show to be superior to placebo (no treatment) for patients being treated for non-cancer related chronic pain3.
Indications for Opioids
Opioids in general are used as an analgesic (pain reliever). Opioids are used in the following common conditions4:
- acute pain
- trauma-related pain
- post-operative pain
- cancer pain
- chronic non-cancer pain i.e. osteoarthritis, low back pain, neuropathic pain
Mechanism of Action4
Opioids bind to opioid receptors which are mainly found within the central nervous system and gastrointestinal tract (stomach and intestines). There are three types of opioid receptors: mu, kappa, and delta. The majority of opioid medications bind to mu receptors. Side effects of the medication are dependent upon which opioid receptor it binds to. When the medication attaches to the receptor it prevents pain signals from traveling from the peripheral nervous system to the spinal cord to the brain thereby preventing the perception of pain. The medication also promotes a signal to suppress pain and changes the limbic system in your brain which is responsible for certain behaviors, emotions, and memory.
Commonly Prescribed Opioids
- morphine (MS Contin)
- oxycodone (OxyContin)
- tramadol (Ultram)
- hydromorphone (Dilaudid)
- codeine
- meperidine (Demerol)
Short Term Side Effects3-5
Sedation:
This is a common side effect experienced by most patients when either beginning a new opioid medication or increasing the dose of an opioid. The sedation generally resolves between 3 to 7 days. Chronic (long-term) sedation is reported in a small percentage of patients.
Elderly patients are more prone to the sedative effects of opioids.
Nausea:
Similar to sedation, the nausea and vomiting associated with opioids usually resolves shortly after the initiation of the treatment. If a patient is prone to nausea and vomiting an antiemetic(anti-nausea and vomiting) medication like Zofran(ondansetron) can be given during the first few days of opioid therapy.
Constipation:
Opioids decrease gastric motility and intestinal secretions leading to constipation. Constipation does not resolve with time. A stool softener and a laxative is recommended for all patients using opioids. Dietary changes such as increasing fiber and drinking more water can help improve the constipation.
Confusion:
Confusion occurs mainly in patients who are on high doses or on opioids for an extended period of time that also have poor kidney function. Opioids can also increases confusion in elderly patients that already have a central nervous system disease that causes confusion i.e. Alzheimer's.
Itching(pruritis):
Pruritus occurs due to a release of histamine when taking an opioid. This can be resolved by taking an anti-histamine like Benedryl.
Dry Mouth(xerostomia):
Opioids decrease saliva production. Patients with severe dry mouth should be switched to a different medication or dosage schedule to prevent dental carries (cavities).
Long Term Side Effects3-5
A review of multiple studies published showed that approximately 22.9% of patients taking oral opioids discontinue therapy due to common side effects like constipation, nausea, and sedation but very few discontinued therapy due to severe side effects including addiction and hypogonadism6. Another study confirmed that after 5 weeks of opioid therapy the statistically and clinically significant side effects were constipation and nausea3.
Constipation:
Although stool softeners and laxatives can help improve the constipation this side effect does not resolve over time and is the most common reason for discontinuation of opioid therapy3.
Tolerance:
Tolerance is when a patient is on an opioid and overtime the patient's body becomes used to the medication so a higher dose of medication is needed in order to achieve the same pain relief as the previous dose. Tolerance occurs in patients taking opioids chronically (long-term).
Physical Dependence:
Physical dependence is defined as an adaptation of the body's homeostasis or equilibrium thus when the opioid is stopped abruptly or the dose is decreased rapidly the patient can experience withdrawal symptoms. Dependence occurs in all patients using opioids for a prolonged period. In order to avoid withdrawal symptoms, the dose of the medication will slowly be decreased over time.
Addiction:
Addiction is a common fear of patients when first starting pain medications. Addiction is when the patient becomes compulsive about the use of the drug or attempts to seek more medications to abuse the effect of the medication. This is a behavioral issue that is separate from dependence and tolerance. Dependence and tolerance are the body's natural response to long term use of opioids as opposed to addiction which is a change in the patient's behavior. For example, patients with cancer have a significant amount of pain requiring high doses of opioids for an extended period of time. This causes the patient to have a tolerance and dependence on opioids; however, the patient is not addicted to the opioids because the patient is using the medications correctly and not abusing them. In a pain practice approximately 3-5% of patients develop an addition to opioids7,8. Therefore, addiction should be monitored for but is not a common occurrence among people taking opioids.
Cognitive Impairment:
Many studies have looked at the effect of opioids on cognitive function and psychomotor tasks and found the cognitive impairments are minimal9,10. One study performed looked at the long-term effects of opioids on patients with low back pain. Patients were evaluated over a 180 day time period in which they were taking the opioids. Patients scores of motor speed, attention, and intellectual tasks significantly improved over the 180 day period thus suggesting that mental-clouding or confusion is not associated with long-term use of opioids11. Often chronic pain itself can cause mental impairments thus some patients may experience an improvement in cognition with the use of opioids.
Opioid Endocrinopathy:
A review of studies recently published revealed that long-term opioid therapy can sometimes lead to opioid endocrinopathy or hypogonadism. Hypogonadism symptoms include decreased libido, infertility, fatigue, depression, anxiety, loss of muscle strength and/or mass, increased risk of osteoporosis, and menstrual irregularities in women. Opioids can bind to receptors in the hypothalamus and inhibit the secretion of gonadotropin-releasing hormone (GnRH) which regulates sex hormones i.e. testosterone and estrogen production in the body. Patients on long-term opioid therapy should be monitored for these symptoms and have routine blood work to monitor their endocrine function. This is a potential side effect and does not occur in all patients. However, there are few studies showing the actual incidence and prevalence of opioid induced hypogonadism. If hypogonadism is suspected in a patient, the patients could be switched to a non-opioid pain medication, consider other pain management options, switch to an opioid rotation schedule, or receive sex hormone supplementation5,12.
Immunosuppression:
The use of certain opioids may increase the risk of infection and suppress the cellular immune response and antibody production. However, severe pain itself has a significant negative impact on the immune system as well so a balance of pain relief and immunosuppression must be met. A consensus statement of an international expert panel in 2008 included that the immunosuppressant effects of opioids in the elderly is not fully understood; therefore, an opioid to provide adequate pain relief in addition to having few significant adverse events and minimal immunosuppression should be used5,13.
Opioid Induced-Hyperalgesia(OIH):
OIH is when a patient taking opioids for pain becomes more sensitive to a certain painful stimuli. The pain may or may not be different from the original reason for taking a pain medication. The cause of this is poorly understood but it is believed to be a result of peripheral and central nervous system changes which leads to sensitization of pain pathways14. One small study used patients that had never been exposed to opioids but had chronic pain. The patients were given oral morphine for one month. The study found significant hyperalgesia (increased sensitivity to pain) in response to painful cold stimuli but not to heat stimuli15. There are few studies published on OIH and the studies that have been published are inadequate for generalizing the findings to all patients using opioids15. Thus, the physician and patient must communicate and be vigilant when examining the patient's chronic and acute pain.
References:
1. Trescot A, Glaser SE, Hansen H, Benyamin R, Patel S, Machikanti L. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician. 2008;11:S181-200.
2. Manchikanti L, Singh A. Thgerapeutic opioids: A ten-year persepective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids. Pain Physician. 2008;11:S68-88.
3. Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E. Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. Can Med Ass J. 2006;174:1589–1594.
4. Carver A. "Pharmacologic Management of Pain." ACP Medicine. eds Federman DD, Nabel EG. 2010. New York,NY: BC Decker Inc.
5. Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, & Vallejo R. Opioid complications and side effects. Pain Physician. 2008;11:S105–S120.
6. Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM. Long-term opioid management for chronic non-cancer pain. Cochrane Database of Systematic Reviews. 2010;1.
7. Fishbain DA, Cole B, Lewis J, Rosomoff HL, Rosomoff RS. What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review. Pain Med. 2008;9:444–459.
8. Fleming MF, Balousek SL, Klessig CL, Mundt MP, Brown DD. Substance use disorders in a primary care sample receiving daily opioid therapy. J Pain. 2007;8:573–582.
9. Brown RT, Zuelsdorff M, Fleming M. Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. J Opioid Manag. 2006;2:137–146.
10. Byas-Smith MG, Chapman SL, Reed B, Cotsonis G. The effect of opioids on driving and psychomotor performance in patients with chronic pain. Clin J Pain. 2005;21:345–352.
11. Jamison RN, Schein JR, Vallow S, Ascher S, Vorsanger GJ, Katz NK. Neuropsychological effects of long-term opioid use in chronic pain patients. J Pain Symptom Management. 2003;26(4):913-921.
12. Katz N & Mazer NA. The impact of opioids on the endocrine system. Clinical J of Pain. 2009;25(2):170-175.
13. Pergolizzi J, Boger RH, Budd K, Bahan A, Erdine S, Hans G, et al. Opioids and the management of chornic severe pain in the elderly: Consesus statement of an international expert panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Physician. 2008;8(4):287-313.
14. Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: Molecular mechanisms and clinical considerations. Clin J Pain. 2008;24:479–496.
15. Chu LF, Clark DJ, Angst MS. Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. J Pain. 2006;7:43-48.
The content on this website is for educational purposes only, and is in no way intended to replace your physician's advice. Please always consult your doctor before taking any advice learned here or on any other website.
Comments
RSS feed for comments to this post