The use of opioids in the treatment of oncologic pain in the elderly

Ledismar José da Silva Diego Machado Mendanha Patrícia Pádua Gomes About the authors

ABSTRACT

BACKGROUND AND OBJECTIVES:

The use of opioids in cancer is already widespread and proven by several well-controlled clinical trials. However, the elderly with cancer pain are=un-dertreated due to the lack of knowledge in the management of these patients, the underestimation of pain, as well as the fear of complications arising in this age group. Therefore, the scientific community contributes to giving inputs to create possible clinical and health guidelines. The present study aimed to perform a systematic literature review of opioid treatments proposed for cancer-related pain in elderly patients.

CONTENTS:

The search on the literature included papers addressing cancer pain treatment with opioids among the elderly, published from 2008 to 2018, and available in Portuguese or English. Searches were conducted on Medical Literature, Analysis, and Retrieval System Online (MEDLINE) and Latin American and Caribbean Health Sciences Literature (LILACS) electronic databases using the keywords “cancer pain”, “opioids”, and “elderly” in both languages, combined with the Boolean operator “AND”. To analyze the quality of the method, the adapted Critical Appraisal Skills Programme was used. Of a total of 411 studies found, 32 were included. About 75% of the selected articles were published in the last five years.

CONCLUSION:

The results showed that opioids remain the pillar to treat cancer-related pain in the elderly. They can be used for better management of pain, but with caution due to the possible adverse effects. In addition, pain management in the elderly requires a multifactorial analysis, including comorbidities, polypharmacy, and patient functionality. Therefore, an individualized approach in the elderly patient is required in order to enhance results, reduce side effects, and improve quality of life.

Keywords:
Cancer pain; Elderly; Opioids

RESUMO

JUSTIFICATIVA E OBJETIVOS:

O uso de opioides em dor oncológica já é amplamente difundido e comprovado por diversos ensaios clínicos bem controlados. Entretanto, os idosos com dor oncológica são subtratados pela falta de conhecimento no manejo, a não valorização álgica nesses pacientes, bem como o receio das complicações advindas nesse grupo etário. Portanto, contribui a comunidade científica, dando substrato para a elaboração de possíveis diretrizes clínicas e de saúde. Este estudo teve como objetivo realizar uma revisão sistemática da literatura sobre o tratamento farmacológico com opioides proposto para dor oncológica em pacientes idosos.

CONTEÚDO:

A busca na literatura incluiu artigos sobre o uso de opioides para o tratamento da dor oncológica em idosos, publicados entre 2008 e 2018, disponíveis em português ou inglês. Foram conduzidas buscas nas bases eletrônicas de dados Medical Literature, Analysis, and Retrieval System Online (MEDLINE) and Latin American and Caribbean Health Sciences Literature (LILACS) utilizando os descritores “dor oncológica”,“opioides” e “idoso” em ambas as línguas, combinados com o operador booleano “AND”. Para a análise da qualidade metodológica, foi utilizado o Critical Appraisal Skills Programme adaptado. Do total de 411 estudos resultantes, foram incluídos 32. Cerca de 75% dos artigos selecionados foram publicados nos últimos cinco anos.

CONCLUSÃO:

Os resultados demonstraram que os opioides continuam sendo o pilar no tratamento da dor oncológica em idosos. Podem ser usados para o melhor gerenciamento da dor, mas com cautela por causa dos possíveis efeitos adversos. Além disso, o manejo da dor em idosos requer uma análise multifatorial incluindo as comorbidades, a polifarmácia e a funcionalidade do paciente. Portanto, é necessário tratar de modo individualizado o paciente idoso com o intuito de maximizar os resultados, diminuir os efeitos adversos e melhorar a qualidade de vida.

Descritores:
Dor oncológica; Idosos; Opioides

INTRODUCTION

Aging is a worldwide phenomenon. Over the next 43 years, the number of people over 60 will be three times higher than the current one11 United Nations. World population prospects: the 2017 revision, key findings and advance tables. Working Paper No. ESA/P/WP/248. New York: UN Department of Economic and Social Affairs, Population Division; 2017. Disponível em: https://esa.un.org/unpd/wpp/Publications/Files/WPP2017_KeyFindings.pdf.
https://esa.un.org/unpd/wpp/Publications...
. The elderly population in Brazil has also been growing exponentially. By 2030 there will be 41.5 million older people or 18% of the population22 Figueiredo AH (Org.) Brasil: uma visão geográfica e ambiental no início do século XXI. Rio de Janeiro: IBGE, Coordenação de Geografia; 2016. Disponível em: https://biblioteca.ibge.gov.br/visualizacao/livros/liv97884.pdf.
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. Due to this, population aging has been one of the major public health challenges, because as people get older, they are more likely to develop or contract chronic diseases such as cancer, as risk factors accumulate for certain types of this disease33 Miranda GM, Mendes AC, Silva AL. O envelhecimento populacional brasileiro: desafios e consequências sociais atuais e futuras. Rev Bras Geriatr Gerontol. 2016;19(3):507-19.. Currently, more than 70% of cancer cases worldwide occur in the elderly44 Estapé T. Cancer in the elderly: challenges and barriers. Asia Pac J Oncol Nurs. 2018;5(1):40-2.. Therefore, there is an increase in the prevalence of chronic health problems and disabilities associated with the population of this age group, involving important specificities such as multimorbidities, polypharmacy, and their complications33 Miranda GM, Mendes AC, Silva AL. O envelhecimento populacional brasileiro: desafios e consequências sociais atuais e futuras. Rev Bras Geriatr Gerontol. 2016;19(3):507-19..

In elderly cancer patients, pain is the most prevalent symptom, as about 80% of them report some kind of painful sensation. Inadequate pain treatment can have serious consequences, both individually and socially55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7.

6 Reyes-Gibby CC, Anderson KO, Todd KH. Risk for opioid misuse among emergency department cancer patients. Acad Emerg Med. 2016;23(2):151-8.

7 Yen TY, Chiou JF, Chiang WY, Su WH, Huang MY, Hu MH, et al. Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study. Medicine. 2018;97(30):e11593.
-88 Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157-82..

Pain management should be performed according to the three-step analgesic ladder proposed by the World Health Organization (WHO) in the 1980s99 World Health Organization. Cancer pain relief. WHO: Geneva; 1986., in which opioids are recommended for the treatment of moderate to severe pain88 Paice JA, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157-82.,1010 Coluzzi F, Taylor R Jr, Pergolizzi JV Jr, Mattia C, Raffa RB. [Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering)]. Rev Bras Anestesiol. 2016;66(3):310-7. Portuguese, English.. In addition to limited evidence for opioid use in elderly patients, there are still barriers such as fears, myths, and stigmas regarding this type of prescription55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7.,1010 Coluzzi F, Taylor R Jr, Pergolizzi JV Jr, Mattia C, Raffa RB. [Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering)]. Rev Bras Anestesiol. 2016;66(3):310-7. Portuguese, English.

11 Wilson KG, Chochinov HM, Allard P, Chary S, Gagnon PR, Macmillan K, et al. Prevalence and correlates of pain in the Canadian National Palliative Care Survey. Pain Res Manag. 2009;14(5):365-70.
-1212 Galicia-Castillo M. Opioids for persistent pain in older adults. Cleve Clin J Med. 2016;83(6):443-51..

Therefore, this study aimed to conduct a systematic literature review addressing the use of opioids in the treatment of cancer pain in the elderly. The study also aimed to explore the repercussions of opioid use in pain treatment, as well as its main barriers to adequate management in this population.

CONTENTS

This study was conducted as a systematic literature review following the guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-analyzes (PRISMA). In order to achieve a systematic literature review, the research question was initially established considering the proposed theme, i.e., the use of opioids in cancer pain treatment in the elderly, thus classifying individuals over 60 years. Then, between March and December 2018, searches were done in the Medical Literature, Analysis, and Retrieval System Online (MEDLINE) and Latin American and Caribbean Health Sciences Literature (LILACS) electronic databases, aiming at gathering and evaluating the main articles on the use of opioids for cancer pain treatment in the elderly, published between 2008 and 2018, available in Portuguese or English, using the descriptors “cancer pain,” “opioids”, and “elderly” and their respective Portuguese terms, all present in the Health Science Descriptors (DeCS) and Medical Subject Headings (MeSH), combined with the Boolean operator “AND”.

The criteria used for articles inclusion were: a) articles concerning the proposed theme, i.e., the use of opioids in cancer pain treatment in the elderly; b) articles published between 2008 and 2018; c) articles in Portuguese or English; d) articles available in full; e) articles on randomized studies, systematic reviews and observational studies; f) articles that met the criteria proposed by the Critical Appraisal Skills Program (CASP) checklist for qualitative research.

Exclusion criteria were a) articles addressing a non-phar-macological treatment of pain; b) articles describing animal studies; c) dissertations, theses and case reports; d) repeated articles among electronic databases.

The articles were categorized, allowing the gathering of information such as identification of the original article and its authors, journal, year of publication, database, methodological characteristics, level of evidence, measured interventions, and results found. The critical analysis of the data obtained in the studies was performed after the organization of the selected articles. The CASP instrument was applied to ensure the methodological rigor, relevance and credibility necessary for an integrative review of studies with different approaches. Searches in the MEDLINE and LILACS electronic databases resulted in 411 articles published between 2008 and 2018. The initial evaluation was performed by reading the title, excluding 321 articles that did not present the theme “opioids in cancer pain treatment in the elderly”. Then, the remaining 90 articles with inclusion potential were previously selected for evaluation of their abstracts according to the eligibility criteria. Three independent reviewers read the abstracts, and the publications that met the inclusion criteria were then fully assessed. In total, 32 articles were selected for this study; 75% were published in the last five years (Figure 1, Table 1).

Figure 1
Data collection
Table 1
Selected articles

DISCUSSION

The aging process is one of the factors that leads to the increased incidence of cancer, as there are inherent physiological changes that jointly cause molecular changes. These changes are combined with mitogenic factors that, associated with the insufficiency and dysregulation of the immune system that is characteristic of this age group, favor cell proliferation and, consequently, the onset of cancer3838 Sociedade Brasileira de Geriatria e Gerontologia. Dor: o quinto sinal vital - Abordagem prática no idoso. Rio de Janeiro: Sociedade Brasileira de Geriatria e Gerontologia, 2018. Disponível em: <http://www.amape.com.br/wp-content/uploads/2018/06/SBGG_guia-dor-no-idoso_2018-digital.pdf>.
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.

The physiological changes caused by aging also significantly affect the metabolism of administered drugs, especially opioids. Thus, healthcare professionals should be aware of the following factors: patient susceptibility to adverse drug effects, iatrogenic cascade, adverse drug reactions, hospitalization, and institutionalization, as well as polypharmacy commonly found in the practical reality of the elderly.

Usually, as a result of aging, organs and systems have less functional reserve. Therefore, they present particularities involving the pharmacokinetics and pharmacodynamics of drugs regarding absorption, distribution, metabolism and excretion variables (Table 2).

Table 2
Pharmacological changes due to aging

Pain is an unpleasant experience associated with tissue or potential injury, with sensory, emotional, cognitive, and social components. In turn, persistent pain is more complicated in the elderly than in younger patients. Up to 40% of elderly outpatients report pain, and this symptom affects 70-80% of patients with advanced cancer55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7..

For cancer pain treatment, it is necessary to know its classification. Didactically, pain can be divided into two main types: 1) nociceptive, which represents tissue damage; 2) neuropathic due to nervous system’s injury or dysfunction as a result of abnormal activation of the nociceptive route. Also included in this analysis are the local effects of tumor growth and local invasion, as well as the effects of auxiliary therapies such as chemotherapy and radiotherapy, as well as other complications. Therefore, in cancer patients, mixed pain prevails55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7.,3838 Sociedade Brasileira de Geriatria e Gerontologia. Dor: o quinto sinal vital - Abordagem prática no idoso. Rio de Janeiro: Sociedade Brasileira de Geriatria e Gerontologia, 2018. Disponível em: <http://www.amape.com.br/wp-content/uploads/2018/06/SBGG_guia-dor-no-idoso_2018-digital.pdf>.
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. Pain complaints can be both precursors for cancer diagnosis as a consequence of the treatment adopted. Most of the time, pain is identified by the patient him/herself and not by health care professionals.

It is noteworthy that not only cancer involvement, but also the aging process lead to limitations in the body’s physiological functions. Thus, the elderly are more predisposed to dependence on other individuals for self-care, loss of autonomy, and deterioration of quality of life. In this environment, as the evaluation of painful conditions in the elderly is a multidimensional experience, it encompasses several domains, including sensory, cognitive, affective, behavioral and sociocultural ones. Given this, the importance of pain management using validated protocols and scales is evidenced in order to provide the most appropriate treatment according to the patients’ individual particularities55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7.,3939 Kim HJ, Kim YS, Park SH. Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care. 2015;14(1):41..

However, there is not yet a single and exclusive standard instrument for the elderly that allows for global pain assessment and is free of bias and measurement errors, as there are different variables involved, such as patient interpretations of pain, expectations regarding the problem and its treatment. Notably, good anamnesis, detailed physical examination, and analysis of external factors are fundamental for the adoption of appropriate conduct.

From a general perspective, the WHO99 World Health Organization. Cancer pain relief. WHO: Geneva; 1986. analgesic ladder is the most widely used. In specialized services, one-dimensional scales such as face and verbal numeric scales are employed, as well as multidimensional scales such as Geriatric Pain Measure (GPM), McGill Pain Questionnaire (MPQ), Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC), and Pain Assessment in Advanced Dementia (PAINAID)3838 Sociedade Brasileira de Geriatria e Gerontologia. Dor: o quinto sinal vital - Abordagem prática no idoso. Rio de Janeiro: Sociedade Brasileira de Geriatria e Gerontologia, 2018. Disponível em: <http://www.amape.com.br/wp-content/uploads/2018/06/SBGG_guia-dor-no-idoso_2018-digital.pdf>.
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.

Cancer pain can be controlled with simple treatments in more than 80% of cases. In the other 20%, however, it is necessary to adopt a multidisciplinary approach, with a careful reassessment of pain and the use of auxiliary drugs and/or non--pharmacological interventions for its control55 Rangel O, Telles C. Tratamento da dor oncológica em cuidados paliativos. Rev Hosp Universit Pedro Ernesto. 2012;11:32-7.,3838 Sociedade Brasileira de Geriatria e Gerontologia. Dor: o quinto sinal vital - Abordagem prática no idoso. Rio de Janeiro: Sociedade Brasileira de Geriatria e Gerontologia, 2018. Disponível em: <http://www.amape.com.br/wp-content/uploads/2018/06/SBGG_guia-dor-no-idoso_2018-digital.pdf>.
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. Regarding pharmacological treatment, opioids are among the most powerful and widely available drugs, constituting the pillar for the treatment of moderate to severe cancer pain77 Yen TY, Chiou JF, Chiang WY, Su WH, Huang MY, Hu MH, et al. Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study. Medicine. 2018;97(30):e11593.,1212 Galicia-Castillo M. Opioids for persistent pain in older adults. Cleve Clin J Med. 2016;83(6):443-51.,1919 Nunes BC, Garcia JB, Sakata RK. [Morphine as first medication for treatment of cancer pain]. Braz J Anestesiol. 2014;64(4):236-40. Portuguese. English..

Recent clinical guidelines and recommendations on the management of patients with advanced cancer emphasize the importance of adequate pain relief with the use of opioid analgesics to improve their quality of life. It is essential that patients are continuously informed about the goals of pharmacological therapy and regularly reevaluated during treatment77 Yen TY, Chiou JF, Chiang WY, Su WH, Huang MY, Hu MH, et al. Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study. Medicine. 2018;97(30):e11593..

The American Geriatrics Society has come to consider the use of opioids as an effective and sometimes indispensable option for treating pain in elderly patients. This is due, among other factors, to the potentially serious adverse events associated with the use of anti-inflammatory drugs, such as diclofenac and ibu-profen and COX-2 inhibitors (COXIB), such as celecoxib1212 Galicia-Castillo M. Opioids for persistent pain in older adults. Cleve Clin J Med. 2016;83(6):443-51.. Opioids mimic the action of endogenous opioid peptides. They may suppress the activation of presynaptic and post-synaptic tension-dependent calcium channels or activate post-synapse potassium channels. This suppression results in decreased excitability and suppression of neuron activity-dependent transmitter release or adenylyl cyclase action, reducing the impulses to the brain and spinal cord1212 Galicia-Castillo M. Opioids for persistent pain in older adults. Cleve Clin J Med. 2016;83(6):443-51.,1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49..

The four major opioid receptor subtypes are mu-opioid receptor (MOP), delta-opioid receptor (DOP), kappa opioid receptor (KOP), and nociceptin peptide factor (NOP). Clinically used opioids are mostly MOP selective, although they may also interact with other receptors if administered at high doses1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49.. Indeed, elderly cancer patients suffering from severe pain may benefit from the use of strong opioids such as fen-tanyl, morphine, oxycodone, hydromorphone, methadone, buprenorphine, among others (Table 3).

Table 3
Opioid analgesics

Fentanyl

Transdermal fentanyl is a potent, long half-life agonist opioid with lipophilicity. It is very suitable for patients unable to use the oral route due to odynophagia and/or dysphagia, with persistent nausea and vomiting, in situations that may lead to bronchoaspiration, intolerance to morphine and other opioids, and due to its ease of use. Its use is recommended in patients with constant pain but little episodic pain. After the patch placement, effective analgesia start lasts 12 to 24 hours. The action time of each patch is 72 hours, remaining for 12 to 18 hours after its removal. The transmucosal formulation has short action duration, non-invasive administration route, and tolerable safety profile1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49.,1717 Zeppetella G. Fentanyl sublingual spray for breakthrough pain in cancer patients. Pain Ther. 2013;2(1):1-9.,2525 Oosten AW, Abrantes JA, Jonsson S, De Bruijn P, Kuip EJM, Falcão A, et al. Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients. Eur J Clin Pharmacol. 2016;72(4):459-67.,2626 Reddy A, Tayjasanant S, Haider A, Heung Y, Wu J, Liu D, et al. The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients. Cancer. 2016;122(1):149-56.,3434 Guitart J, Vargas MI, De Sanctis V, Folch J, Salazar R, Fuentes J, et al. Efficacy and safety of sublingual fentanyl tablets in breakthrough cancer pain management according to cancer stage and background opioid medication. Drugs R D. 2018;18(2):119-28.,3535 Masel EK, Landthaler R, Gneist M, Watzke HH. Fentanyl buccal tablet for breakthrough cancer pain in clinical practice: results of the non-interventional prospective study ErkentNIS. Support Care Cancer. 2018;26(2):491-7..

Morphine

Morphine is indicated for pain classified as moderate to severe, with good results in pain of nociceptive or somatic origin, as 85% of them respond to this drug. It has a potent analgesic effect, short half-life, with therapeutic analgesia interval of 4 to 6 hours, without ceiling and linear effect, i.e., the higher the dose, the greater the analgesia. It is well-absorbed by the gastrointestinal tract, with action onset within 20 to 40 min. It undergoes hepatic metabolism and renal elimination, and only a small part is eliminated by the gallbladder. It does not generally accumulate in tissues and the free fraction in plasma is dialyzable. However, in patients with impaired renal function, it has a stronger effect and longer action duration, because there is an accumulation of active metabolites, especially mor-phine-6-glucuronide66 Reyes-Gibby CC, Anderson KO, Todd KH. Risk for opioid misuse among emergency department cancer patients. Acad Emerg Med. 2016;23(2):151-8.,1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49.,1919 Nunes BC, Garcia JB, Sakata RK. [Morphine as first medication for treatment of cancer pain]. Braz J Anestesiol. 2014;64(4):236-40. Portuguese. English.,2929 Haider A, Zhukovsky DS, Meng YC, Baidoo J, Tanco KC, Stewart HA, et al. Opioid prescription trends among patients with cancer referred to outpatient palliative care over a 6-year period. J Oncol Pract. 2017;13(12):e972-81.,3232 Nosek K, Leppert W, Nosek H, Wordliczek J, Onichimowski D. A comparison of oral controlled-release morphine and oxycodone with transdermal formulations of buprenorphine and fentanyl in the treatment of severe pain in cancer patients. Drug Des Devel Ther. 2017;11:2409-19.,3939 Kim HJ, Kim YS, Park SH. Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care. 2015;14(1):41..

Oxycodone

Oxycodone is a MOP agonist in the brain and spinal cord and has some activity in KOP. It goes through the first-pass metabo-lism2626 Reddy A, Tayjasanant S, Haider A, Heung Y, Wu J, Liu D, et al. The opioid rotation ratio of strong opioids to transdermal fentanyl in cancer patients. Cancer. 2016;122(1):149-56.. It is the preferred drug for change when morphine fails to provide effective pain relief but may also be recommended as a first-line drug for severe cancer pain control1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49.,3131 Lee KH, Kim TW, Kang JH, Kim JS, Ahn JS, Kim SY, et al. Efficacy and safety of controlled-release oxycodone/naloxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial. Clin J Cancer. 2017;36(1):74..

Hydromorphone

Hydromorphone hydrochloride is intended for single-dose administration. It is a potent MOP agonist, showing a poor affinity for KOP. It is the only opioid that has controlled single-phase release and promotes continuous dose-dependent analgesia during the 24 hours interval between two doses. It is moderately water-soluble, has hepatic metabolism and urinary excretion. Its primary metabolite is hydromorphone-3-glucuronide (H3G), in which concentrations are approximately 27-times higher than those of the original drug, indicating that H3G has a smaller volume of distribution and/or lower clearance77 Yen TY, Chiou JF, Chiang WY, Su WH, Huang MY, Hu MH, et al. Proportional dose of rapid-onset opioid in breakthrough cancer pain management: An open-label, multicenter study. Medicine. 2018;97(30):e11593.,1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49..

Methadone

The methadone is a synthetic opioid, agonist of MOP, KOP DOP, and N-methyl D-Aspartate (NMDA) receptor. It appears to block serotonin and norepinephrine reuptake. It is a lipophilic drug, which analgesic effect usually lasts from 6 to 8 hours and may reach up to 24 hours. Its analgesic power can be up to five to 10 times higher than morphine. Its oral absorption is quick and almost complete, and its metabolism occurs mainly in the liver. Methadone and its metabolites can be eliminated by feces and urine. Renal excretion of methadone decreases with time of use and can, therefore, be used in patients with chronic kidney disease. It causes less nausea, constipation and sedation than morphine. However, the interaction between methadone and other drugs is more frequent than with morphine1414 Hennemann-Krause L. Aspectos práticos da prescrição de analgésicos na dor do câncer. Rev Hosp Universit Pedro Ernesto. 2012;11:38-49.,4040 Ribeiro S, Schmidt AP, Schmidt SR. [Opioids for treatment non-malignant chronic pain: the role of methadone]. Rev Bras Anestesiol. 2002;52(5):644-51. Portuguese, English..

Buprenorphine

The buprenorphine is a thebaine derivative, 25 to 40 times more potent than morphine. Its action mechanism is suggested to occur by partial agonist effects on MOP and KOP, as well as antagonistic action on DOP. It is found in intravenous, sublingual and transdermal presentations, the latter being the only one available in Brazil. The patches come in the 5, 10 and 20 pg/h presentations, which are released within seven days. It has no systemic accumulation and its elimination occurs mainly through the intestinal tract and is therefore considered safe in patients with renal failure66 Reyes-Gibby CC, Anderson KO, Todd KH. Risk for opioid misuse among emergency department cancer patients. Acad Emerg Med. 2016;23(2):151-8..

FINAL CONSIDERATIONS

Considering the main strong opioids described, it is noteworthy that pain intensity is not adequately assessed in approximately 50% of cancer patients. Besides, adverse effects of opioids, such as nausea, vomiting and constipation, may be limiting factors for the use of these drugs, leading to their early discontinuation and consequent inadequate analgesic efficacy. Therefore, in order to achieve proper pain management in cancer patients, it is necessary to simultaneously minimize both the pain and the adverse effects of opioids employed for its control1212 Galicia-Castillo M. Opioids for persistent pain in older adults. Cleve Clin J Med. 2016;83(6):443-51.,3636 Peng Z, Zhang Y, Guo J, Guo X, Feng Z. Patient-controlled intravenous analgesia for advanced cancer patients with pain: A retrospective series study. Pain Res Manag. 2018;2018.7323581.,3939 Kim HJ, Kim YS, Park SH. Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care. 2015;14(1):41.,4040 Ribeiro S, Schmidt AP, Schmidt SR. [Opioids for treatment non-malignant chronic pain: the role of methadone]. Rev Bras Anestesiol. 2002;52(5):644-51. Portuguese, English..

It is essential that health professionals assess the barriers that prevent or hinder the use of opioids in the elderly when treating cancer pain. In several situations, these patients are undertreated due to the lack of knowledge about cancer pain management, due to their pain complaints not being adequately taken into account, due to the fear of the complications arising from the use of opioids and due to bureaucratic and cultural difficulties in the implementation of this type of pharmacological therapy.

Some points are important to elucidate the difficulties in prescribing opioids when treating cancer pain, such as inadequate pain assessment, as only a small number of physicians reported applying pain management guidelines in their practice; 23 to 31% of physicians tend to delay the adoption of strong opioids until patients reach the terminal stage of their disease, or until their pain becomes intractable due to the difficulty in managing adverse effects; 25 to 40% of physicians are concerned about opioid addiction, and there is even greater fear in patients with a family history of addiction. Moreover, although oncologists have shown excellent basic knowledge about the use of opioids to treat cancer pain than physicians in other specialties, there is still a significant information deficit within their specialty1515 Madadi P, Hildebrandt D, Lauwers AE, Koren G. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada. PLoS One. 2013;8(4):e60600.,2424 Lin CP, Hsu CH, Fu WM, Chen HM, Lee YH, Lai MS, et al. Key opioid prescription concerns in cancer patients: a nationwide study. Acta Anaesthesiol Taiwan. 2016;54(2):51-6.,2727 Barbera L, Sutradhar R, Chu A, Seow H, Howell D, Earle CC, et al. Opioid prescribing among cancer and non-cancer patients: Time trend analysis in the elderly using administrative data. J Pain Symptom Manage. 2017;54(4):484-92.e1.,3737 Yamada M, Matsumura C, Jimaru Y, Ueno R, Takahashi K, Yano Y. Effect of continuous pharmacist interventions on pain control and side effect management in outpatients with cancer receiving opioid treatments. Biol Pharm Bull. 2018;41(6):858-63.,3939 Kim HJ, Kim YS, Park SH. Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care. 2015;14(1):41.,4141 Nguyen LMT, Rhondali W, De La Cruz M, Hui D, Palmer L, Kang DH, et al. Frequency and predictors of patient deviation from prescribed opioids and barriers to opioid pain management in patients with advanced cancer. J Pain Symptom Manage. 2013;45(3):506-16..

From the patient’s perspective, other potential barriers to the use of opioids may include lack of communication with physicians, resulting in insufficient notification of symptoms; misconceptions about the pain drug due to the fear of adverse effects, dependence, tolerance, and reduced immunity; and fatalistic beliefs, i.e., if the pain is increasing, the idea of inevitable and uncontrollable progression of the disease is created. Patients with drug concerns and misconceptions have worse adherence to treatment. In addition, pain intensity is associated with a higher level of psychological distress, including depression, anxiety, hostility, and mood disorders. Therefore, there is a need for psychiatric and psychological follow-up to complement and increase the efficiency of pharmacological treatment1010 Coluzzi F, Taylor R Jr, Pergolizzi JV Jr, Mattia C, Raffa RB. [Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering)]. Rev Bras Anestesiol. 2016;66(3):310-7. Portuguese, English.,1313 Passik SD. Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc. 2009;84(7):593-601.,2222 Reticena KO, Beuter M, Sales CA. Vivências de idosos com a dor oncológica: abordagem compreensiva existencial. Rev Esc Enferm USP. 2015;49(3):419-25.,2323 Cella IF, Trindade LCT, Sanvido LV, Skare TL. Prevalence of opiophobia in cancer pain treatment. Rev Dor. 2016;17(4):245-7..

Also, bureaucratic difficulties imposed on the prescription by government agencies, as well as on the access to these drugs and their price, were reported. Regulatory restrictions on opioid prescribing differ widely across countries. Thus, in developed countries, physicians have access to a wide range of opioids, while those in developing countries have limited treatment options2020 Rocha LS, Beuter M, Neves ET, Leite MT, Brondani MC, Perlini NM. Self-care of elderly cancer patients undergoing outpatient treatment. Texto Contexto Enferm. 2014;23(1):29-37.

21 Kim YC, Ahn JS, Calimag MM, Chao TC, Ho KY, Tho LM, et al. Current practices in cancer pain management in Asia: a survey of patients and physicians across 10 countries. Cancer Med. 2015;4(8):1196-204.
-2222 Reticena KO, Beuter M, Sales CA. Vivências de idosos com a dor oncológica: abordagem compreensiva existencial. Rev Esc Enferm USP. 2015;49(3):419-25..

In order to solve or alleviate these problems mentioned above, there are several strategies, including the use of validated pain scales for patient pain selection and monitoring; multicomorbidities assessment; multidimensional assessment; choice of opioids according to the particularities and pathophysiology of pain; anticipation and treatment of adverse effects; referral to other specialties when necessary; education of patients, families and, especially, caregivers; provision of psychosocial support; information to patients that most cancer pain can be alleviated; establish realistic and objective expectations regarding pain. In addition to this, it is necessary to promote educational lectures to disseminate strategies to be adopted for better pain management by health professionals and to increase the availability of opioids.

CONCLUSION

The results showed that opioids remain the pillar in cancer pain treatment in the elderly. They can be used for better pain management, but with caution due to the possible adverse effects. In addition, pain management in the elderly requires a multifactorial analysis, including comorbidities, polypharmacy, and patient functionality. Therefore, it is necessary to treat the elderly patient individually in order to maximize results, reduce adverse effects and improve quality of life.

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Publication Dates

  • Publication in this collection
    06 Mar 2020
  • Date of issue
    Jan-Mar 2020

History

  • Received
    23 June 2019
  • Accepted
    10 Dec 2019
Sociedade Brasileira para o Estudo da Dor Av. Conselheiro Rodrigues Alves, 937 Cj2 - Vila Mariana, CEP: 04014-012, São Paulo, SP - Brasil, Telefones: , (55) 11 5904-2881/3959 - São Paulo - SP - Brazil
E-mail: dor@dor.org.br