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Official websites use. Share sensitive information only on official, secure websites. The evaluation of pain and the subsequent issue of pain control is a clinical challenge that all healthcare providers face. Pain in the elderly population is especially difficult given the myriad of physiological, pharmacological, and psychological aspects of caring for the geriatric patient. Opiates are the mainstay of pain treatment throughout all age groups but special attention must be paid to the efficacy and side effects of these powerful drugs when prescribing to a population with impaired metabolism, excretion and physical reserve. The increasing use of opiates for pain management by healthcare practitioners requires that those prescribing opioids be aware of the special considerations for treating the elderly. This article will address the precautions one must take when using opiates in the geriatric population, as well as the side effects and ways to minimize them. The prevalence of pain in older adults is high. The care of older adults can occur in varied settings ranging from independent living to long term care and palliative care. It is important to assess for pain, evaluate, treat, and recognize side effects that may be associated with the pharmacologic management of pain in older adults. This can be very challenging due to the alterations in opiate pharmacokinetics which occur with normal physiologic aging. Other common problems that should be taken into consideration when caring for older adults include polypharmacy, multiple comorbities, and the potential of more side effects or treatment failures Linnebur et al It is important for those clinicians who provide care for elderly to have training in the recognition of pain and the subtle behaviors associated with those patients who may be in pain but are unable to communicate. Many geriatricians provide care to elderly patients as part of a palliative care treatment plan. According to the World Health Organization palliative pain management ladder, patients with moderate to severe pain should receive opioid analgesics as the mainstay of treatment WHO Opiates are indicated for management of both acute and chronic pain, as well as for the different classes of pain such as nociceptive and neuropathic pain. Meta-analysis done by Furlan and colleagues regarding effectiveness and side effects of opioids for chronic noncancer pain concluded that opioids have better outcome than placebo in reducing pain and improving functional activities, as well as being more effective for both nociceptive and neuropathic pain. Opiates are commonly used in clinical care. The guidelines also stressed the unacceptable risks associated with nonselective NSAID use in elderly due to gastrointestinal bleeding and new revisions by the AGS panel will be developed due to the withdrawal of some COX-2 from the US market. These guidelines also refer to opiates as possibly being appropriate in severe pain AGS Thus, it is imperative that providers be knowledgeable in the use of opiates and their side effects. Opiates are highly varied, however except for fentanyl and methadone, it is generally thought that they possess similar pharmacokinetic activity. In general young adults, opiates are rapidly absorbed in the gut, have high rate of first pass in the liver, are conjugated in the liver, have metabolites, and vary in distribution based on their differing protein affinity, and then are excreted via bile to feces or via kidneys. It is important to understand normal age-associated changes in the pharmacokinetic and pharmacodynamic action of drugs. Pharmacodynamic affects are complex and depend upon poorly measured variables such as receptor function and intracellular response which can alter drug action Hughes Pharmacokinetic actions of drug absorption, distribution, and elimination are more measurable. In general, the rate at which certain drugs are absorbed can be altered in the elderly because of decreased gastrointestinal transit time and increased gastric pH secondary to use of proton pump inhibitors, H 2 receptor antagonist, or antacids. With aging, there are changes in body composition: increase in adipose tissue, decrease in lean body mass and decrease in total body water. These changes can affect drug distribution. Therefore, lipophilic drugs tend to have greater volume of distribution, and it can take more time to be eliminated from the body Linnebur et al Aging can also bring reduction in hepatic blood flow and volume which can decrease metabolism of drugs Tegeder et al ; AGS Additional impairments in drug metabolism can occur with impaired Phase I reactions which include oxidation, hydroxylation, and dealkylation Tegeder et al This can specifically reduce the first pass affect of opiates in elderly Tegeder et al Elimination of drugs can be altered with age related reductions in renal blood flow and glomerular filtration rate. For opiates that have primary renal clearance, such as morphine and hydromorphone, decreases in GFR lead to more side effects Davies et al The above changes generally cause drugs used in elderly to be more potent and have a longer duration of action than predicted. Opioids that should be avoided in the older patients include meperidine, propoxyphene, and tramadol. Meperidine has active metabolites which can cause neuroexcitation, nervousness, and seizures. Prophoxyphene has not been shown to be more effective than placebo. Tramadol is not recommended in patients who are taking serotonergic medications or in those with underlying seizure disorders. Tramadol binds to opioid receptors and inhibits the reuptake of both norepinephrine and serotonin AGS Codeine can be used, however there should be recognition that there is individual variability in its effectiveness dependent upon drug metabolism into its seven active metabolites. Oral opioid medications are the most commonly prescribed medications in palliative care and geriatrics. Short-acting agents like oral morphine, hydromorphone, oxycodone, and codeine are used alone or in combination with acetaminophen, aspirin ASA , or ibuprofen. Peak analgesic effect occurs within 60 minutes and the effect lasts for 2—4 hours in patients with normal renal function. These medications can be dosed at a 4-hour interval if given alone or 6-hour intervals if used in combination APM ; PDR ; Thomson Dose escalation always depends on half life of the medications. Short-acting oral single agent opioids, can be safely escalated every 2 hours. Sustained release oral opioids can be escalated every 24 hours. For fentanyl patch, methadone or levorphanol, no earlier than 72 hours is recommended Weissman et al , ; Hanks et al The difference should be no more than 4 times the lowest dose. In the older population, start low and go slow monitoring side effects and pain tolerance. Debilitated patients or those with respiratory insufficiency are more at risk for hypoxia if over sedated. It is also a useful tool to document patient response to PRN dosing so as to more accurately tailor their pain regimen Gordon et al Opiate equianalgesic potency tables are not precise and vary slightly based on the source; they should be used only as guides. A new opiate to the market in is oxymorphone. Elderly patients can have increased plasma levels and systemic effects Guay Few studies published on the equianalgesic potency of oxymorphone report that it has an equianalgesic dose ratio of compared with oxycodone Gabrail et al Cross-tolerance effects can cause the new opiate to have more adverse effects and analgesic properties. Conversion to fentanyl should be based on the manufacturer guidelines. Methadone conversion should be done by experienced providers as the relationship is non linear to the prior dose of opiates Chau and Mason It is preferred that one opiate be used and titrated to effect instead of multiple small doses of varying opiates. As elderly take many concomitant drugs, prescribers of opiates should also recognize potential drug interactions such as antifungals and methadone that can lead to elevated levels of opiates and toxicity Thomson In cognitively impaired residents, activities or treatments that have caused pain in the past should be anticipated as causing pain in the future. Pain should also be anticipated: cognitively impaired elders should be premedicated Hutt et al Dementia is prevalent and may impair the perception of pain, ability to report pain, ability to recall pain sensation for evaluating relief, and the ability to communicate about relief. The mechanism of action of opioid-induced nausea is through the direct stimulation on chemoreceptor trigger zone CTZ , which detects noxious chemicals in the blood and sends signals to the vomiting center VC in the medulla and initiates the vomiting reflex. The other mechanisms are through the direct stimulation of the vestibular apparatus and anticholinergic effects on the gastrointestinal system Gordon et al Opioid peptides and opioid receptors are distributed along the gastrointestinal GI tract, indicating endogenous opiates released peripherally may modulate GI motor and secretory functions. Most opiates that have a selective or predominant mu agonist activity inhibit gastric motility and delay gastric emptying by acting centrally; delta and kappa agonist are inactive when injected systemically. This increase in colonic motility and the delay in colonic transit are associated with a reinforcement of tonic contractions and reduced propulsive waves. This in turn leads to opiate induced constipation Bueno and Fioramonti Management of constipation is important in patients who are taking opioids which can sometimes lead to serious complications. Unlike other side effects of opioids, there is no tolerance effect on constipation, so treatment of constipation should be initiated preventively at the same time when opioid therapy is started. Combined use of stool softeners and stimulant laxatives are recommended Walsh Urinary retention is the anticholinergic side effect of opioids and can be secondary to opioid-induced constipation Meier et al Sedation and mild cognitive impairment are the other common side effects of opioids in elderly Hayes et al Combinations of opioids and other central nervous system CNS depressant drugs such as barbiturates, benzodiazepines, antidepressants, and antipsychotics may have additive effects on sedation. Since most of the elderly are on polypharmacy, a careful review of medications is crucial while they are on opioid therapy Cherny et al Myoclonus is the other CNS adverse effect and occurs in patients with chronic opioid therapy. It appears to be dose related and more common with oral morphine than parenteral which suggests it may be due to a production of morphine metabolites by the liver Cherny et al This generally resolves within one week. However; it is also the cause of an unwanted side effect which is the marked depression of breathing that can complicate their clinical administration and be potentially life threatening when opiates are abused McCrimmon and Alheid The degree of respiratory depression depends upon the serum level of opioids. First, patients become somnolent, and then they become less arousable and finally obtunded. The pattern of respiration becomes shallower and slower. This is done to avoid pain crisis and acute withdrawal symptoms Ferrell ; AGS Patients who are receiving increasing doses of opioids may have opioid-induced hyperlagesia. This is the phenomenon of increasing sensitivity to both pain hyperlagesia and nonpainful stimuli allodynia. Since it is due to the effect of toxic metabolites, the other opioid hyper excitability effects such as myoclonus, delirium or seizures can also be present Kranz et al QT prolongation and torsades de pointes were found to take place in individuals infected with HIV and treated with methadone Clark Methadone dose correlated positively with the QTc interval prolongation. This finding supports the possibility that methadone contributed to the development of arrhythmias Gil et al Opioids have effects on two levels in the endocrine system: hypothalamic-pituitary-adrenal axis and also on the hypothalamic-pituitary-gonadal axis resulting in reduced serum luteinizing hormone, cortisol levels and increased prolactin levels Ballantyne and Mao Diminished bone density, decreased libido and impaired sexual performance are reported with chronic opiate use. Heroin use results in acute suppression of luteinizing hormone LH release from the pituitary followed by a secondary drop in plasma testosterone levels Mirin et al If pain is well controlled, but there are adverse effects, a reduction in dose of opioids gradually will help in resolving the adverse effects while maintaining pain relief. Some adverse effects such as drowsiness, delirium, and myoclonus occur in direct relation to the dose which may be reversed by dose reduction. If the dose reduction interferes with efficacy of pain control, it is recommended to add adjuvant therapy such as steroids, neurontin, or low dose tricyclic antidepressants Cherny et al Knowledge about pain therapy can assist in achieving the goals of pain management. The elderly population is especially challenging when one has to consider all of the pharmacodynamic changes that occur with normal aging. The side effect profile of opiates is similar for all age groups; however the elderly population is at a greater risk for these side effects given their comorbidities and high incidence of polypharmacy. Using opiates appropriately and at the most efficacious dosage for the severity and type of pain becomes crucial in the elderly. Knowing how to increase medications and to move between the different classes is also necessary in the safe and successful management of pain. Adjuvant therapy with other nonopioid pain relievers should be encouraged and in fact a standard practice in pain management. Properly evaluating and treating pain in all types of elderly patients and clinical scenarios should be the goal of all clinicians. As a library, NLM provides access to scientific literature. Clin Interv Aging. Find articles by Diane L Chau. Find articles by Vanessa Walker. Find articles by Latha Pai. Find articles by Lwin M Cho. Issue date Jun. All rights reserved. Similar articles. 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