Wednesday, October 29, 2014

Opiates and the elderly

Opiates and elderly

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Source - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546472/

Introduction

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. Studies report the prevalence of pain in community-dwelling elderly at 25%–50% and for nursing home residents as high as 70% (). The American Geriatrics Society (AGS) panel on persistent pain in older persons states that up-to 80% of long-term care residents have substantial pain (), and 25% of those received neither analgesic medication nor nonpharmacological treatment for their pain (). 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 (). 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 (). 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  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. A review of 300 randomly selected charts among the US veterans population noted that approximately 75% of patients with chronic pain were prescribed at least 1 analgesic, and most received 2 or more. While nonsteroidal anti-inflammatory drugs (NSAID) were the most commonly prescribed class of analgesics, 44% of those receiving an analgesic also received opioids (). The American Geriatrics Society  Guidelines for the Management of Persistent Pain in Older Adults recommendations included simplifying the pain regimen, avoiding polypharmacy, and beginning drugs at lower dosages and titrating upward as needed (). 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 (). Thus, it is imperative that providers be knowledgeable in the use of opiates and their side effects.


Physiologic changes with aging 

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 (). 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, H2receptor 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 (). Aging can also bring reduction in hepatic blood flow and volume which can decrease metabolism of drugs (). Additional impairments in drug metabolism can occur with impaired Phase I reactions which include oxidation, hydroxylation, and dealkylation (). This can specifically reduce the first pass affect of opiates in elderly (). 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 (). The above changes generally cause drugs used in elderly to be more potent and have a longer duration of action than predicted.
Because of pharmacokinetic and pharmacodynamic changes with aging, opioids should be started at the lower dose, about 25%–50% of the dose given to younger patients (). 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 (). 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. Up to 30% of the population has been reported to be poor (PM) hydroxylators of debrisoquine required for Codeine activation (Yue et al 2001).


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