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Contemporary standard pharmacological care for the treatment of noncancer pain includes the use of opioid medications. The responsiveness of neuropathic pain to opioids has long been an area of controversy. Evidence from multiple randomized controlled trials indicates that opioids can relieve pain in a variety of neuropathic pain syndromes. Opioids are typically reserved for moderate to severe pain that cannot be relieved by the nonsteroidal anti-inflammatory drugs (NSAIDs). Opioids are often used in combination with other adjuvants or other analgesic agents. The advantage of opioids is the lack of a ceiling effect of the pure mu opioid agonists. The disadvantages of these drugs are a series of mechanism-based opioids-related side effects (e.g., nausea, drowsiness, constipation) and the potential issue of their abuse and misuse. Each patient needs to undergo a comprehensive evaluation and receive education on the treatment. The physician must be well conversant with the differential diagnosis and definitions of physical dependence, tolerance, pseudotolerance, aberrant behaviors, addiction, and pseudoaddiction. No specific opioid drug is intrinsically ''better'' than the others. Opioid rotation refers to the switch from one opioid to another when the degree of analgesia obtained is limited by the persistence of adverse effects or the occurrence of clinically relevant tolerance. This approach is based on the observation that a patient's response varies from opioid to opioid. At present, after 1) appropriate selection of patients and 2) longitudinal patient care with routine assessment of degree of analgesia, functional daily activities, adverse events and aberrant behaviors is carried out, opioid therapy can be the safest and most effective treatment measure for quality of life improvement in the chronic pain patient.
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PMID:Opioid therapy for chronic noncancer pain: practice guidelines for initiation and maintenance of therapy. 1601 15

The aim of this article is to summarize the current evidence base about interventions that improve symptoms at the end of life. Moderate to severe symptoms are highly prevalent in the weeks and months before death: 1.4 million individuals have dyspnea; and 1 million have pain. Of those with pain, 300,000 want more pain relief. 700,000 may need more relief, but do not receive it because of the myth of opioid addiction; their physicians do not know how to manage the adverse effects of pain relieving therapies, or they don't know the various options that are available for pain relief. Of the 1 million Americans who die in hospitals, 324,000 had fatigue, 280,000 anorexia, 244,000 dyspnea, 232,000 xerostomia, 208,000 cough, 196,000 pain, 148,000 confusion, 148,000 depression, 140,000 nausea, 92,000 insomnia in 23, and 88,000 vomiting. This is caused in part by clinician ignorance. In a representative sample of oncologists, the most important source of information about symptom control was trial-and-error in practice. In addition, large, well-designed, well-controlled studies of patients at the end of life have not been performed. Clinical practice is guided by extrapolation of data from other populations and from anecdote. The system of care provided by hospice programs in the U.S. provides improved symptom control as compared with hospitals, home health agency, and nursing home systems. Population-based studies of prevalence are needed to gauge outcomes of the implementation of measures to relieve symptoms. Well-powered, definitive studies of both existing and new approaches in terminally ill patients with the most common symptoms are needed. The health care system interventions that are effective in hospice care must be studied so that they can be broadly applied to the care of all dying Americans.
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PMID:Interventions to manage symptoms at the end of life. 1649 73

Although the incidence of occupational and adult lead poisoning has declined, the problem still exists. We encountered three patients with lead poisoning in Iran, all of whom associated with presented with diffuse abdominal pain, which was at times colicky in nature, anemia, constipation, nausea, vomiting, and slightly abnormal liver biochemistries. A history of opium ingestion was present in each of these patients. None of the patients reported known occupational exposure to toxins. Diagnoses of lead poisoning were confirmed through the detection of elevated blood lead levels. The cause of lead poisoning was attributed to the ingestion of contaminated opium. Opium adulterated with lead had not been previously recognized as a source of lead poisoning in Iran. It is, therefore, pointed out that lead poisoning should be considered as a differential diagnosis for acute abdominal colic of unclear cause in patients with opium addiction.
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PMID:Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran. 1664 84

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.
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PMID:Mechanisms of acupuncture analgesia for clinical and experimental pain. 1673 14

Under the headline "drug addiction" the medical world has exclusively been interested in psychoactive drugs. For diagnosis of substance dependence (addiction), DSM-IV-TR has determined seven criteria, and fulfilling at least tree of them signifies addiction. When studied salt intake according to these criteria it is seen that most of them are fulfilled, showing that sodium chloride, which is not classified under the psychoactive drugs, is capable of producing addiction. Namely: at the beginning of salt abstinence, anorexia and slight nausea during meal time (withdrawal symptoms); about 1000-fold difference of per capita salt consumption between several human societies, and life-long continuation of discretional salt intake behaviour (high dose and very long duration of use); difficulty of restriction of salt intake (unsuccessful efforts to cut down or control); lack of success of salt restriction campaigns in hypertensive patients (substance use despite health problem). Additionally, the decrease of salt preferences of individuals whose salt intake are restricted for some time, and vice versa, signifies tolerance. On the other hand, it is evident that as the main culprit of developing systemic hypertension and as producing or promoting some other important health problems, salt intake causes millions of deaths in the world yearly. The recognition of addicting property of salt will facilitate combating these health problems.
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PMID:Salt addiction: a different kind of drug addiction. 1679 Mar 20

Effective pain relief, especially at the end of life, is a primary ethical obligation based upon the principles of beneficence, nonmaleficence, patient autonomy, and particularly the concept of double effect. The pragmatic foundation of pain management begins with a complete assessment, which incorporates "WILDA" (words, intensity, location, duration, aggravating/alleviating factors) and considers the components of total pain: physical, emotional, social, and spiritual pain. Opioids are the pharmacologic sine qua non of pain management in life-limiting illness and should be prescribed based on the severity of pain, considering the functional and psychological significance of that severity. Numerous misunderstandings present a barrier to effective pain management. These misconceptions include the idea that opioids are highly addictive, that dependence or tolerance are forms of addiction, that respiratory depression is common with opioids, that opioids have a narrow therapeutic range, and that opioids are ineffective by mouth and cause too much nausea. In reality, opioids are the safest and most effective pain medicine for most moderate to severe pain in most patients. Aspects of basic opioid pharmacology, such as dosage, route of administration, rotation of drugs, and the avoidance of toxicity and complications, should be considered when initiating and maintaining therapy. Failure to pay attention to the basic rules can lead to errors in opioid management.
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PMID:Ethical and practical issues with opioids in life-limiting illness. 1725 34

Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.
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PMID:Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. 1743 82

Opioids are given for acute intra- and postope-rative pain relief or for chronic cancer pain. In the literature there are only rare and contradictory reports on the oral administration of opioids for chronic non-malignant pain. However, there is no reason to withhold strong analgesics for patients with severe pain. When all other thrapeutic measures fail to control pain, patients with non-malignant pain can also be treated by opioids. We report 70 patients with severe pain who were given opioids as the ultima ratio in pain therapy: 50 received buprenorphine sublingual tablets, 13 received morphine sustained release tablets and the remaining 7 were treated with other opioids. The mean daily dose was 1.45 mg buprenorphine or 87.6 mg morphine. The dosage increased in 12 of the 50 patients treated with buprenorphine while 5 of the 13 morphine patients needed increasing dosage. The other patients had a constant dosage after the initial period of dose-finding. In more than 50% the pain could be effectively controlled by oral opioids. The general performance status (Karnofsky) increased from 63.6% to 74.1%. The typical side effects were constipation and nausea. Prophylaxis of constipation is most important during opioid therapy. No case of respiratory depression or opioid addiction was registered. Our results show that patients with musculo-skeletal and deafferentation pain respond better to opioids than patients with headache. Negative results were observed in some patients with neuropathic pain. The results of the study show that opioids are justifiable for the treatment of non-malignant pain and can be given without danger over a long period of time. Side effects are controlled by additional medication. The principle of opioid administration is prophylaxis of pain -therefore, they should be given "by the clock". Opioids are not only indicated in malignant illness, but also according to severity of pain and by the failure of other measures to control pain.
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PMID:[Oral opioids in patients with non-malignant pain.]. 1841 9

Analgesic pharmacotherapy represents one of the major approaches to the treatment of cancer pain, since it is used in almost every patient. A thorough evaluation of the physical and mental status of the patient and of the pain is as necessary as a sound understanding of the pharmacokinetic and pharmacodynamic characteristics of the analgesics selected. The World Health Organization (WHO) has issued a basic 3 stage progression for the treatment of cancer pain, the "WHO Analgesic Ladder". Assignment to the stages depends mainly on the intensity of the pain rather than on its specific aetiology. Mild to moderate pain is treated with non-opioid drugs; moderate to severe pain, with a combination of a "weak" opioid and a non-opioid; and "strong" opioids should be used in combination with a non-opioid in the case of severe pain. Adjuvant drugs can be added if specifically indicated. Nonopioid analgesics include non-acidic compounds, e. g. paracetamol and metamizole, and acidic non-opioids, e. g. acetylsalicylic acid and newer non-steroidal anti-inflammatory drugs (NSAID). In contrast to most of the opioid analgesics, they have a ceiling effect for analgesia. Addiction and tolerance are extremely rare concerns. Opioids can be subgrouped into "weak" (e. g., codeine, dextropropoxyphene) and "strong" opioids (e. g., morphine) and also into drugs interacting with different opioid-receptor subtypes. Whereas pure agonists (e. g., morphine) produce increasingly intense analgesia with increasing dose, partial agonists and agonist-antagonists have a ceiling effect for analgesia and therefore have only a minor role in the treatment of chronic pain in cancer patients. Adverse effects occur in most patients in a dose-dependent manner. The most common of these is constipation; nausea, vomiting and sedation occur mostly at the start and can usually be treated effectively. The appropriate dosage, route of administration and dosage scheme of analgesics needs to be worked out for each individual patient in intensive work with the patient and a close follow-up, for years if necessary. Some analgesics may not be available in some countries, or only in specific preparations.
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PMID:[Drug therapy for tumor pain I. Properties of non-opioids and opioids.]. 1841 58

The adequate use of opioids in the treatment of chronic cancer pain requires sound knowledge of selection criteria for the various opioids, the routes of administration, dosages, dosing schemes and possible side effects. Drug selection depends on the intensity of pain rather than on the specific pathophysiology. Mild to moderate pain can often be treated effectively by so-called "weak" opioids. These include codeine, dihydrocodeine and dextropropoxyphene. Non-opioid analgesics, like acetylsalicylic acid or paracetamol can be added according to the "analgesic ladder" proposed by the World Health Organization (WHO). If adequate pain relief is not achieved "strong" opioids are required. The route of administration that is the safest and the least invasive for the patient should be chosen. Non-invasive (oral, rectal, sublingual, transdermal and intranasal) and invasive routes (intravenous, subcutaneous, spinal and epidural) are available (Table 8). Noninvasive routes are preferred, and most patients can be maintained on oral opioids. Alternatively, in some patients pain can be managed by the sublingual (buprenorphine) route. A transdermal preparation exists for fentanyl, but has not yet been approved for the German market. If the oral route cannot be used or if large doses are required, it will be necessary to change to an invasive route. Intravenous bolus injections provide the fastest onset of analgesic action. They are mostly used in very severe pain. Repeated injections can be avoided by using intravenous or subcutaneous infusions. Various types of pumps delivering analgesics at constant basal infusion rates with the option of rescue doses in case of breakthrough pain are available (patient-controlled analgesia=PCA). Opioids frequently used for s. c. infusion are morphine and hydromorphone. Adjuvant drugs (antiemetics, anxiolytics) can be added. Epidural or intrathecal administration of opioids should only be used in intractable pain or if severe side effects, such as sedation and confusion, will arise with systemic opioids. Morphine, hydromorphone, fentanyl and sufentanil have been used, as have other additional compounds (e.g. local anaesthetics, clonidine). Intracerebroventricular application of morphine has been used only occasionally. In all cases, opioids should be given on to a fixed time schedule thereby, preventing pain from recurring. Additional rescue doses (approximately 50% of baseline single dose) are given for break-through pain. The most frequent side effect of opioids is constipation, and the administration of laxatives is often recommended (Table 5). Nausea, vomiting, sedation and confusion mostly occur in the beginning of opioid therapy. In contrast to constipation, tolerance to these effects develops within days or weeks. True dependence or psychological addiction rarely occurs in patients with chronic cancer pain. In most cases, progression of the underlying disease associated with increasing tissue damage and increasing pain is found. Fear of dependence and addiction often contributes to undertreatment of patients suffering from chronic cancer pain.
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PMID:[Pharmacotherapy of cancer pain : 2. Use of opioids.]. 1841 94


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