Potent analgesics are more expensive for patients in developing countries: a comparative study

Opioids are some of the most important analgesic medications for the management of both moderate to severe pain and several are included on the World Health organization (WHO) list of essential drugs. Opioid costs in developing countries have been reported to be higher than those in developed nations. This study documents retail prices and availability of several potent opioids in a number of developing and developed countries. Pain and Palliative Care specialists currently working in their countries were asked to collect data on the retail cost of a 30 day supply of 15 different opioid preparations in 5 developing and 7 developed countries. Data were analyzed to compare costs and costs as a percentage of gross national product (GNP) per capita per month. Opioid costs and availability varied widely in both developing and developed countries. Forty five of 75 opioid preparations were available in developing countries (40% of medications studied were not available) and 76 of 105 preparations were available in the developed countries (28% not available). In US dollars, the median cost of opioids differed between developed and developing countries ($53 and $112 respectively) The median costs of all opioid preparations as a percentage of GNP per capita per month were 36% for developing and 3% for developed nations; the difference was statistically significant (p < 0.001). In developing countries 23 of 45 (51%) of opioid dosage forms cost more than 30% of the monthly GNP per capita, versus only three of 76 (4%) in developed countries. The relative cost of opioids to income is higher in developing countries. Our data suggest that in developing countries opioid access for the majority of patients is likely to be limited by cost, and development of palliative care programs will require heavy or total subsidization of opioid costs.     

Assessment and management of breakthrough pain in cancer patients: Current approaches and emerging research

Cancer pain is highly prevalent and often severe. Fortunately, most cancer pain can be readily managed, with up to 90% of patients responding well to standard interventions. However, breakthrough cancer pain—brief flares of severe pain superimposed on baseline pain—is common, difficult to manage, and often negatively impacts patients’ quality of life. Breakthrough cancer pain is traditionally managed with oral, immediaterelease opioids. However, because of its sudden onset and severity, oral opioids often fall short of providing adequate control. Research into novel approaches to pain management has identified several innovative strategies for this difficult cancer pain problem. We describe current approaches to assess, define, characterize, and treat breakthrough cancer pain, and summarize recent clinical research on novel agents, novel routes of drug delivery, and other advances in its management.     

Managing Breakthrough Pain

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate intensity in patients on regularly administered analgesic treatment. This review provides updated information about the classification, assessment, and treatment of BTcP, with special emphasis on the use of opioids. Due to its slow onset to effect, oral opioids cannot be considered an efficacious treatment of BTcP. More recently, different technologies have been developed to provide fast pain relief with potent opioid drugs, such as fentanyl, delivered by noninvasive routes. Transmucosal, buccal, sublingual, and intranasal fentanyl have been shown to provide rapid analgesia in comparison with oral morphine or placebo and are available for clinical use in most countries. All the studies performed with these delivery systems have recommended that these drugs should be administered to opioid-tolerant patients receiving doses of oral morphine equivalents of at least 60 mg. The need of titrating opioid doses for BTcP has been commonly recommended in all the controlled studies, but never has been substantiated in appropriate studies.     

Improving the availability and accessibility of opioids for the treatment of pain: The International Pain Policy Fellowship

Opioid analgesics are simultaneously indispensable medicines for the treatment of moderate to severe pain and are harmful when abused. The challenge for governments is to balance the obligation to prevent diversion, trafficking, and abuse of opioids with the equally important obligation to ensure their availability and accessibility for the relief of pain and suffering. Over the last 30 years, significant progress has been made toward improving access to opioids as measured by increasing global medical opioid consumption. However, this progress is marked by ongoing large disparities among countries, with most increases in medical opioid consumption attributed to high-income countries, not low- and middle-income countries (LMICs). The International Pain Policy Fellowship (IPPF) was developed by the Pain & Policy Studies Group, with the central goal of developing national leaders from LMICs and empowering them to improve availability and accessibility of opioids for the treatment of pain. To date, two classes of fellows have been selected, representing 17 fellows from 15 countries. Progress achieved by the leadership of three fellows from Sierra Leone, Colombia, and Serbia is highlighted in this paper. The fellows from each country were successful at initiating collaboration with relevant governmental bodies, national authorities, and professional societies, which resulted in a new supply of oral opioids in Sierra Leone and Serbia, and improvements in the distribution of already available opioids in Colombia. All fellows were instrumental in facilitating evaluation of national policy. The IPPF program empowers fellows with the necessary knowledge, skills, and guidance to improve the availability and accessibility of opioids for the treatment of pain.     

Schmerztherapie in der Finalphase maligner Erkrankungen

Most patients with very advanced cancer suffer from severe pain, and many studies have demonstrated how this pain can be sufficiently controlled. It is of great importance to find out if the findings are also true during the final stage of cancer and how the treatment must be adapted. We therefore examined the methods and efficacy of providing pain relief for dying cancer patients. This study included 160 patients with cancer in different sites. The pain treatment and pain severity during the last few days and hours of their lives are described and discussed. Analgesic drugs administered orally in 53% and parenterally in 39% of the patients were the mainstay of therapy. Non-opioid analgesics alone were effective in 10% and in combination with weak opioids in 15% of the patients. In 68% strong opioids were necessary to achieve sufficient pain reduction. Morphine was the most frequently used opioid for 96 patients. Oral doses of morphine were 86+/-60 mg/day (15-240 mg/day), and parenteral doses 89+/-74 mg/day (15-360 mg/d). Additional adjuvant drugs to treat specific types of pain or other symptoms of cancer disease were described for 80% of the patients. Non-pharmacological measures, such as radiation, nerve blocks or neurosurgery, were of no real importance. Only 4% of the patients treated in the way described experienced severe pain during the final stage of cancer. Systemic administration of drugs is very effective in relieving pain in dying patients. No signs of tolerance to opioids could be observed, even in patients who had been taking opioids for a longer period of time (average 39 days).     

Opioid formulations: tailoring to the needs in chronic pain

Opioids are one of the standard therapies used in the management of chronic pain. They were first widely adopted for the treatment of chronic pain associated with cancer and are now considered important in the alleviation of non-cancer and neuropathic pain. Around-the-clock (ATC) medication has been found to be an effective approach in treating chronic pain. Guidelines issued by the American Pain Society (1999) note that in most cases the preferred route of administering opioids is oral, because of convenience, flexibility, and relative steadiness of the opioid concentrations in the blood. The advantages of ATC therapy and oral medication are some of the reasons for the development of controlled-release, oral formulations of opioids (e.g. morphine, oxycodone, hydromorphone, and hydrocodone). The reduced dosing frequency makes the oral medication more convenient for patients, making it easier for them to comply with the dosing regimen. ATC therapeutic coverage and the possible increased compliance afforded by controlled-release formulations can make opioids even more effective in managing chronic pain.     

Controlling cancer pain in primary care: the prescribing habits and knowledge base of general practitioners

During recent years, the national policy of the United Kingdom has increasingly recognized the central place of general practitioners (GPs) in the care of cancer patients, from screening and early diagnosis through to palliative care and bereavement. There are, however, continuing reports of poor control of pain and other symptoms in the community. To investigate general practitioners' prescribing habits and knowledge of some key pain control issues in advanced cancer, a postal questionnaire surveyed a random sample of 450 East Anglian GPs. The response rate was 73.3%. Most respondents were familiar with the modern management of cancer pain, including the World Health Organization approach, the use of oral opioids, and the management of bone pain. There was less awareness of the drug options available for more uncommon situations, especially the dose conversion of oral morphine to subcutaneous diamorphine and drugs that may be used in syringe drivers. GPs in the UK are familiar with the management of the more common pain control problems. However, it is not appropriate to expect GPs to know the details of management of more unusual cancer pain problems. Specialist clinicians need to make themselves readily available to advise their generalist colleagues. The educational implications for GPs are discussed.     

Continuous morphine infusions for cancer pain in resource-scarce environments: comparison of the subcutaneous and intravenous routes of administration

Acute onset of severe pain in cancer patients may be due to multiple causes. Irrespective of the etiology, adequate analgesia has to be provided as quickly as possible. The standard practices of relieving pain by using syringe pumps (syringe drivers) or infusion pumps may not be feasible in resource-scarce developing nations where many cancer patients first present at advanced stages of disease for management. This study compared the efficacy of the subcutaneous and intravenous routes of morphine administration continuously using a simple and economic technique for cancer pain management. Both routes were found to be equally effective in producing good analgesia without side effects. The drip method is a cost-effective way of providing subcutaneous morphine infusion for cancer patients and is applicable for both inpatients and home care.     

Methadone use in cancer patients with pain: a review

In recent years a better understanding of the pharmacologic and pharmacokinetic properties of methadone, including equianalgesic ratios has led to its increased use as a second line opioid for the treatment of pain in patients with cancer. Methadone may be an important alternative for those who have side effects related to the use of other opioids because it has no known active metabolites, is well absorbed by oral and rectal routes, and also has the advantage of very low cost. However, it has a long, unpredictable half-life, which can result in accumulation and toxicity in some patients. In addition, rotation to methadone as a second line agent is more complex than with other opioids because of its increased potency in those patients who are opioid tolerant, particularly those who have been on higher doses of other opioids. Future research should address the use of methadone as a first-line agent in the management of cancer pain, its use in patients with neuropathic pain, and in those who develop rapid tolerance to other opioids. In some patients with cancer the long half-life of methadone offers the advantage of extended dosing intervals to 12 and even 24 hours, further research is also needed in this area.     

Best practice of pain management with opioids

Opioids are main drugs in pain management for terminal cancer patients. In these days, we have to choice suitable opioids for the terminal cancer patients with severe pain by opioids rotation. Morphine is a basic drug in opioids. To know about character of morphine make us easy for using other opioids. In this article, character and some points in using opioids were described in detail. For example, timing for administrating opioids, titration, rescue dose, and side effects were included in this article. We don't have to remember the aim of pain management. Pain control is not a purpose, but a way for keeping QOL of the terminal cancer patients.     

Schmerzbehandlung bei Karzinompatienten

Freedom from cancer pain is one of the four priorities of the WHO Cancer Control Programme. Every day 3.5 million people are suffering from cancer pain, and most do not receive adequate relief. A lack of training in cancer pain management at most nursing and medical schools is the principal reason for this, coupled with limited availability of oral strong opioids in many countries. Education is the key to progress in cancer pain management. Health workers must appreciate that: 1. Attention must be paid to all aspects of suffering -physical, psychological, social and spiritual. 2. In advanced cancer, most patients with pain have multiple pain. 3. Pain experienced in carcinoma is not always caused by the tumour. 4. There is more to pain management than the use of analgesics. 5. In the case of opioid-responsive pains, analgesics should be administered by mouth according to a regular time-schedule and with dose increments. 6. Adjuvant medication is generally necessary. 7. Opioid-resistant pains require other forms of treatment. 8. Pain is the physiological antagonist to the central depressant effects of opioids. 9. Opioid tolerance is not a problem in practice. 10. Psychological dependence does not occur in patients receiving opioids for pain relief. 11. Patients receiving analgesics must be carefully monitored. 12. Teamwork is necessary for good results.     

Role of epidural and intrathecal narcotics and peptides in the management of cancer pain

The spinal administration of opioids may provide analgesia of long duration to patients with bilateral or midline lower abdominal or pelvic cancer pain. However, cross-tolerance to orally and parenterally administered narcotics and the rapid development of tolerance to spinal narcotics have limited their usefulness. Opioids have extensive distribution in the CSF and plasma when administered into the epidural or intrathecal space, and delivery of drug to brain stem sites may account for many of the toxic and therapeutic effects of spinal opioids. Further clinical and pharmacokinetic studies are required to provide the information regarding: the optimal opioids for use as spinal analgesics; equieffective dose ratios of spinal opioids in comparison to parenteral or oral opioids; strategies useful to forestall the development of tolerance of spinally administered opioids; the analgesic efficacy of this therapy in opioid-tolerant patients; and the role of spinally administered nonopioid analgesics in the management of cancer pain in the tolerant patient. These questions will need resolution before this therapy can be recommended for routine use in the management of cancer pain.     

Medikamentöse Therapie von Tumorschmerzen

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.     

Patient education in cancer pain management with opioids

It is important for pharmacists to remove patients' anxiety and misunderstanding about cancer pain management with opioids. Furthermore, we need to explain how to take opioids as well as its effects and side-effects and make sure they are correctly understood so that patients and their family members adequately use the medicine. Here describes the patient education which aims to remove patients' anxiety and misunderstanding about opioids and urge patients to be proactively involved in cancer pain management.     

Opioids for the Management of Dyspnea in Cancer Patients: Evidence of the Last 15 Years—A Systematic Review

The objective of this study was to review the evidence on the use of opioids for treatment of the dyspnea in adult cancer patients. A systematic literature review was conducted in the databases MEDLINE, CINAHL (EBSCO), ScienceDirect, and Cochrane Library of trials testing the effect of opioids in relieving dyspnea in cancer patients. Fourteen trials met the criteria for inclusion in the review. Eight randomized trials and six nonrandomized trials. All randomized clinical trials analyzed present risks of bias. Morphine has been the most studied strong opioid showing efficacy in alleviating dyspnea when administered, either orally or subcutaneously, in cancer patients. The potential benefit of the strong opioids in the alleviation of dyspnea in cancer patients is modest and limited to some opioids. More studies are needed to sufficiently support the role of opioids in dyspnea at rest, at exertion, and for breakthrough dyspnea and to clarify the safety issues.     

Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n = 855), step II (n = 509) and step III (n = 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used non-opioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or co-analgesics used by >1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; i.v. or s.c. morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.