Startseite A case-history illustrates importance of knowledge of drug-interactions when pain-patients are prescribed non-pain drugs for co-morbidities
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A case-history illustrates importance of knowledge of drug-interactions when pain-patients are prescribed non-pain drugs for co-morbidities

  • Harald Breivik EMAIL logo
Veröffentlicht/Copyright: 1. Oktober 2017
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Scandinavian Journal of Pain
Aus der Zeitschrift Scandinavian Journal of Pain Band 17 Heft 1

In this issue of the Scandinavian Journal of Pain Vigdis Solhaug and Espen Molden publish an interesting and important review of negative interactions between drugs we prescribe for patients suffering from chronic pain and other, non-pain drugs that patients take for other health problems [1]. They also describe how our genes can cause major differences in how individual patients react differently to analgesic drugs [1]. After one of Professor Espen Molden’s informative lectures on these topics, we discussed how we can understand the following conundrum in this chronic pain patient’s history:

1 An educational patient history

This 72 year old lady had multiple painful degenerative changes in her back, also a narrow spinal nerve canal at L2, causing radiating pain to her left hip and thigh region, our experienced neurosurgeon considered that her degenerated osteoporotic back skeleton would make it too risky to try to operate, even with micro-surgical technique. She also has a constantly painful left knee and leg after failed surgery for a fractured tibia; she developed a compartment syndrome, but this was not diagnosed until several extremely painful days later, and too late to save leg muscles. She has been wheelchair bound for more than 15 years. However, at home she was actively moving around with two crutches.

When she was referred to the Department of Pain Management and Research at Oslo University Hospital, her three main problems were (1) “nodding”, she fell asleep after a few minutes conversations with friends and relatives, being extremely sleepy all day so that social activities were almost impossible. (2) Extreme constipation almost unresponsive to large doses of various laxatives.(3) Hyperhidrosis, causing her bed to be wet in the morning and necessitating change of wet garments during the day.

From her general physician (GP) and from consultations with various specialists she was prescribed and used the following drugs:

Fentanyl patch 100 μg/h gave her reasonable pain relief when in her wheel-chair, but any activity outside the wheel-chair would precipitate severe pain attacks in her back, hip and knee, all on her left side.

Pregabalin 450 mg daily for her back and knee pain Diclofenac 50 mg ×3 daily for pain

Lanzoprazol 30 mg × 2 (sic) daily was effective in keeping her acid-dyspepsia under control

Atorvastatin 40 mg daily for reducing cholesterol

Acetylsalicylic acid 75 mg daily after a carotid artery stenosis-plaque-operation for transient ischaemic attacks (TIA) about 5 years ago.

We diagnosed several complications of her analgesic drugs:

  1. The extreme sleepiness and “nodding” caused by fentanyl and probably made worse by her high dose pregabalin (measured in the “toxic” plasma-concentration range)

  2. She clearly had a severe opioid-induced constipation (OIC), probably also opioid delayed gastric emptying of acid stomach content (from diclofenac, acetylsalicylic acid) so that she had to take the proton-pump-inhibitor (PPI) lanzoprazol.

  3. She had sever hyperhidrosis induced by the fentanyl.

  4. Cystatin C-based estimate of her kidney-function (GFR) documented that she has a significant kidney problem with eGFR only 33 ml/min, probably caused, or aggravated, by several years of high dose diclofenac.

2 Treatment

The easiest complication to “fix”, we reckoned, was her OIC because we now had available the PAMORA (peripherally acting my-opioid receptor antagonist) naloxegol. We prescribed naloxegol tablets 25 mg to be taken in the morning. We warned her that she should be close to the toilet. Naloxegol promptly caused a forceful bowel movement, and in spite of our warning, her wheelchair-problem made it too difficult for her to get to the toilet in time!

She continued taking naloxegol tablets every second day, taking the 25 mg tablet when she was already sitting safely on the toilet chair. This continued to help her empty her bowels well.

However, she complained that she felt “terrible”, her pain increased in intensity and also the attacks of radiating pain from her L2-root came more often. This did not make sense as she had continued with the transdermal fentanyl 100 μg/h administrations. She continued to feel “lousy” and therefore she stopped using the naloxegol tablets. After a few days without this peripherally acting my-opioid-antagonist, pain relief improved and her constipation worsened.

3 For some reason her naloxegol penetrated her blood-brain-barrier (BBB) and caused opioid withdrawal

After consulting Professor Molden, we had the following likely explanation to this conundrum: Naloxegol is a large molecule that should not easily penetrate to the inside of the BBB. More important was probably that naloxegol is kept outside the BBB mostly by the Permeability-glycoprotein-transporter (Pgp) located in the endothelial cells of capillaries at the outside of the BBB. The activity of the Pgp is inhibited by several other drugs (see Table 1 in the Solhaug and Molden paper in this issue[1]), and in her case the lanzoprazol (a PPI) as well as the statin atorvastatin, both are Pgp-inhibitors. These two inhibitors of the Pgp made it possible for naloxegol to penetrate the BBB, enough to cause clear clinical withdrawal symptoms forthis patient. Renal impairment is another factor that can reduce the efficacy of the Pgp at the BBB[1].

We discontinued her diclofenac which is a likely cause of her renal impairment and also contributed to her very acid gastric content. We discontinued her statin, which contributed to her generalized muscle pain, and her lipid profile kept normal without this potent drug.

And we reduced the dose of pregabalin to 75 mg × 2 daily. Pregabalin is mostly excreted by the kidneys, explaining her toxic plasma-concentrations, and with this much reduced dose her plasma-concentration was normalized. This clearly contributed to her “awakening”.

We converted her high dose of fentanyl patch to sublingual buprenorphine, 1 mg Temgesic resoriblets daily. Buprenorphine is NOT excreted by the kidneys and is therefore an ideal opioid analgesic for patients with renal impairment. Buprenorphine has less sedative effects, less respiratory depressive effect. Buprenorphine also has less negative effects on endocrine organs than most other my-opioid-receptor agonists, less negative effect on androgen hormones, especially testosterone. Testosterone is well documented to decrease pain sensitivity and increase pain-tolerance. Buprenorphine is the ideal opioid for this patient [2,3]. For this patient buprenorphine 1 mg/24h had superior pain relief with less side-effects than fentanyl 2.4 mg/24 h plus diclofenac 150 mg/24 h (!).

This agrees well with her continued satisfaction with her pain-relief. She sleeps better at night, with less opioid aggravated obstructive sleep apnoea. Her cognitive functions are back to her normal. She has almost normal bowel movements and need laxatives only occasionally. She is more than satisfied with pain management at the Department of Pain Management and Research at Oslo University Hospital, also because we were able to understand her complex pharmacological drug interactions better, thanks to help from Professor Espen Molden[1]

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2017.09.009.

Oslo University Hospital, Department of Pain Management and Research, Pbox 4956 Nydalen, 0424 Oslo, Norway. Tel.: +47 23073691; fax: +47 23073690

  1. Ethical issues: The patient agreed to the publication of her pain history and pain management.

  2. Conflict of interest: None declared.

References

[1] Solhaug V, Molden E. Individual variability inclinical effect and to lerability of opioidan algesics-importance of drug interactions and pharmacogenetics. Scand J Pain 2017;17:193–200.Suche in Google Scholar

[2] Butler S. Buprenorphine-clinically useful but of tenmis understood. Scand J Pain 2013;4:148–52.Suche in Google Scholar

[3] Breivik H. Buprenorphine-theideal drug for most clinical indications for an opioid? Scand J Pain 2013;4:146–7.Suche in Google Scholar
Published Online: 2017-10-01
Published in Print: 2017-10-01

© 2017 Scandinavian Association for the Study of Pain

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  28. COMBAT study – Computer based assessment and treatment – A clinical trial evaluating impact of a computerized clinical decision support tool on pain in cancer patients
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  30. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain
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  32. Spatial summation of pain and its meaning to patients
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  34. Effects of validating communication on recall during a pain-task in healthy participants
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  42. Quantitative sensory tests (QST) are promising tests for clinical relevance of anti–nociceptive effects of new analgesic treatments
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  44. Pregabalin as adjunct in a multimodal pain therapy after traumatic foot amputation — A case report of a 4-year-old girl
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  65. Editorial comment
  66. Why can multimodal, multidisciplinary pain clinics not help all chronic pain patients?
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  68. Individual variability in clinical effect and tolerability of opioid analgesics – Importance of drug interactions and pharmacogenetics
  69. Editorial comment
  70. A new treatable chronic pain diagnosis? Flank pain caused by entrapment of posterior cutaneous branch of intercostal nerves, lateral ACNES coined LACNES
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  72. PhKv a toxin isolated from the spider venom induces antinociception by inhibition of cholinesterase activating cholinergic system
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  74. Lateral Cutaneous Nerve Entrapment Syndrome (LACNES): A previously unrecognized cause of intractable flank pain
  75. Editorial comment
  76. Towards a structured examination of contextual flexibility in persistent pain
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  78. Context sensitive regulation of pain and emotion: Development and initial validation of a scale for context insensitive avoidance
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  80. Is the search for a “pain personality” of added value to the Fear-Avoidance-Model (FAM) of chronic pain?
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  82. Importance for patients of feeling accepted and understood by physicians before and after multimodal pain rehabilitation
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  91. Observational study
  92. The use of rapid onset fentanyl in children and young people for breakthrough cancer pain
  93. Original experimental
  94. Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm
  95. Original experimental
  96. Swearing as a response to pain: A cross-cultural comparison of British and Japanese participants
  97. Clinical pain research
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  106. Coping with pain in intimate situations: Applying the avoidance-endurance model to women with vulvovaginal pain
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  117. Clinical pain research
  118. Hospitalization due to acute exacerbation of chronic pain: An intervention study in a university hospital
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  120. A novel miniature, wireless neurostimulator in the management of chronic craniofacial pain: Preliminary results from a prospective pilot study
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  122. Implicit evaluations and physiological threat responses in people with persistent low back pain and fear of bending
  123. Original experimental
  124. Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty
  125. Original experimental
  126. Initial validation of the exercise chronic pain acceptance questionnaire
  127. Clinical pain research
  128. Exploring patient experiences of a pain management centre: A qualitative study
  129. Clinical pain research
  130. Narratives of life with long-term low back pain: A follow up interview study
  131. Observational study
  132. Pain catastrophizing, perceived injustice, and pain intensity impair life satisfaction through differential patterns of physical and psychological disruption
  133. Clinical pain research
  134. Chronic pain disrupts ability to work by interfering with social function: A cross-sectional study
  135. Original experimental
  136. Evaluation of external vibratory stimulation as a treatment for chronic scrotal pain in adult men: A single center open label pilot study
  137. Observational study
  138. Impact of analgesics on executive function and memory in the Alzheimer’s Disease Neuroimaging Initiative Database
  139. Clinical pain research
  140. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [11C]-D-deprenyl PET/CT
  141. Original experimental
  142. Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway
  143. Topical review
  144. Psychoneuroimmunological approach to gastrointestinal related pain
  145. Letter to the Editor
  146. Do we need an updated definition of pain?
  147. Narrative review
  148. Is acetaminophen safe in pregnancy?
  149. Book Review
  150. Physical Diagnosis of Pain
  151. Book Review
  152. Advances in Anesthesia
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  154. Atlas of Pain Management Injection Techniques
  155. Book Review
  156. Sedation: A Guide to Patient Management
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  158. Basics of Anesthesia
https://doi.org/10.1016/j.sjpain.2017.09.023

Artikel in diesem Heft

  1. Observational study
  2. Perceived sleep deficit is a strong predictor of RLS in multisite pain – A population based study in middle aged females
  3. Clinical pain research
  4. Prospective, double blind, randomized, controlled trial comparing vapocoolant spray versus placebo spray in adults undergoing intravenous cannulation
  5. Clinical pain research
  6. The Functional Barometer — An analysis of a self-assessment questionnaire with ICF-coding regarding functional/activity limitations and quality of life due to pain — Differences in age gender and origin of pain
  7. Clinical pain research
  8. Clinical outcome following anterior arthrodesis in patients with presumed sacroiliac joint pain
  9. Observational study
  10. Chronic disruptive pain in emerging adults with and without chronic health conditions and the moderating role of psychiatric disorders: Evidence from a population-based cross-sectional survey in Canada
  11. Educational case report
  12. Management of patients with pain and severe side effects while on intrathecal morphine therapy: A case study
  13. Clinical pain research
  14. Behavioral inhibition, maladaptive pain cognitions, and function in patients with chronic pain
  15. Observational study
  16. Comparison of patients diagnosed with “complex pain” and “somatoform pain”
  17. Original experimental
  18. Patient perspectives on wait times and the impact on their life: A waiting room survey in a chronic pain clinic
  19. Topical review
  20. New evidence for a pain personality? A critical review of the last 120 years of pain and personality
  21. Clinical pain research
  22. A multi-facet pain survey of psychosocial complaints among patients with long-standing non-malignant pain
  23. Clinical pain research
  24. Pain patients’ experiences of validation and invalidation from physicians before and after multimodal pain rehabilitation: Associations with pain, negative affectivity, and treatment outcome
  25. Observational study
  26. Long-term treatment in chronic noncancer pain: Results of an observational study comparing opioid and nonopioid therapy
  27. Clinical pain research
  28. COMBAT study – Computer based assessment and treatment – A clinical trial evaluating impact of a computerized clinical decision support tool on pain in cancer patients
  29. Original experimental
  30. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain
  31. Editorial comment
  32. Spatial summation of pain and its meaning to patients
  33. Original experimental
  34. Effects of validating communication on recall during a pain-task in healthy participants
  35. Original experimental
  36. Comparison of spatial summation properties at different body sites
  37. Editorial comment
  38. Behavioural inhibition in the context of pain: Measurement and conceptual issues
  39. Clinical pain research
  40. A randomized study to evaluate the analgesic efficacy of a single dose of the TRPV1 antagonist mavatrep in patients with osteoarthritis
  41. Editorial comment
  42. Quantitative sensory tests (QST) are promising tests for clinical relevance of anti–nociceptive effects of new analgesic treatments
  43. Educational case report
  44. Pregabalin as adjunct in a multimodal pain therapy after traumatic foot amputation — A case report of a 4-year-old girl
  45. Editorial comment
  46. Severe side effects from intrathecal morphine for chronic pain after repeated failed spinal operations
  47. Editorial comment
  48. Opioids in chronic pain – Primum non nocere
  49. Editorial comment
  50. Finally a promising analgesic signal in a long-awaited new class of drugs: TRPV1 antagonist mavatrep in patients with osteoarthritis (OA)
  51. Observational study
  52. The relationship between chronic musculoskeletal pain, anxiety and mindfulness: Adjustments to the Fear-Avoidance Model of Chronic Pain
  53. Clinical pain research
  54. Opioid tapering in patients with prescription opioid use disorder: A retrospective study
  55. Editorial comment
  56. Sleep, widespread pain and restless legs — What is the connection?
  57. Editorial comment
  58. Broadening the fear-avoidance model of chronic pain?
  59. Observational study
  60. Identifying characteristics of the most severely impaired chronic pain patients treated at a specialized inpatient pain clinic
  61. Editorial comment
  62. The burden of central anticholinergic drugs increases pain and cognitive dysfunction. More knowledge about drug-interactions needed
  63. Editorial comment
  64. A case-history illustrates importance of knowledge of drug-interactions when pain-patients are prescribed non-pain drugs for co-morbidities
  65. Editorial comment
  66. Why can multimodal, multidisciplinary pain clinics not help all chronic pain patients?
  67. Topical review
  68. Individual variability in clinical effect and tolerability of opioid analgesics – Importance of drug interactions and pharmacogenetics
  69. Editorial comment
  70. A new treatable chronic pain diagnosis? Flank pain caused by entrapment of posterior cutaneous branch of intercostal nerves, lateral ACNES coined LACNES
  71. Clinical pain research
  72. PhKv a toxin isolated from the spider venom induces antinociception by inhibition of cholinesterase activating cholinergic system
  73. Clinical pain research
  74. Lateral Cutaneous Nerve Entrapment Syndrome (LACNES): A previously unrecognized cause of intractable flank pain
  75. Editorial comment
  76. Towards a structured examination of contextual flexibility in persistent pain
  77. Clinical pain research
  78. Context sensitive regulation of pain and emotion: Development and initial validation of a scale for context insensitive avoidance
  79. Editorial comment
  80. Is the search for a “pain personality” of added value to the Fear-Avoidance-Model (FAM) of chronic pain?
  81. Editorial comment
  82. Importance for patients of feeling accepted and understood by physicians before and after multimodal pain rehabilitation
  83. Editorial comment
  84. A glimpse into a neglected population – Emerging adults
  85. Observational study
  86. Assessment and treatment at a pain clinic: A one-year follow-up of patients with chronic pain
  87. Clinical pain research
  88. Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of L-4-chlorokynurenine in healthy volunteers
  89. Clinical pain research
  90. Prevalence and characteristics of chronic pain: Experience of Niger
  91. Observational study
  92. The use of rapid onset fentanyl in children and young people for breakthrough cancer pain
  93. Original experimental
  94. Acid-induced experimental muscle pain and hyperalgesia with single and repeated infusion in human forearm
  95. Original experimental
  96. Swearing as a response to pain: A cross-cultural comparison of British and Japanese participants
  97. Clinical pain research
  98. The cognitive impact of chronic low back pain: Positive effect of multidisciplinary pain therapy
  99. Clinical pain research
  100. Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia
  101. Topical review
  102. Targeting cytokines for treatment of neuropathic pain
  103. Original experimental
  104. What constitutes back pain flare? A cross sectional survey of individuals with low back pain
  105. Original experimental
  106. Coping with pain in intimate situations: Applying the avoidance-endurance model to women with vulvovaginal pain
  107. Clinical pain research
  108. Chronic low back pain and the transdiagnostic process: How do cognitive and emotional dysregulations contribute to the intensity of risk factors and pain?
  109. Original experimental
  110. The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury
  111. Educational case report
  112. Erector spinae plane (ESP) block in the management of post thoracotomy pain syndrome: A case series
  113. Original experimental
  114. Hyperbaric oxygenation alleviates chronic constriction injury (CCI)-induced neuropathic pain and inhibits GABAergic neuron apoptosis in the spinal cord
  115. Observational study
  116. Predictors of chronic neuropathic pain after scoliosis surgery in children
  117. Clinical pain research
  118. Hospitalization due to acute exacerbation of chronic pain: An intervention study in a university hospital
  119. Clinical pain research
  120. A novel miniature, wireless neurostimulator in the management of chronic craniofacial pain: Preliminary results from a prospective pilot study
  121. Clinical pain research
  122. Implicit evaluations and physiological threat responses in people with persistent low back pain and fear of bending
  123. Original experimental
  124. Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty
  125. Original experimental
  126. Initial validation of the exercise chronic pain acceptance questionnaire
  127. Clinical pain research
  128. Exploring patient experiences of a pain management centre: A qualitative study
  129. Clinical pain research
  130. Narratives of life with long-term low back pain: A follow up interview study
  131. Observational study
  132. Pain catastrophizing, perceived injustice, and pain intensity impair life satisfaction through differential patterns of physical and psychological disruption
  133. Clinical pain research
  134. Chronic pain disrupts ability to work by interfering with social function: A cross-sectional study
  135. Original experimental
  136. Evaluation of external vibratory stimulation as a treatment for chronic scrotal pain in adult men: A single center open label pilot study
  137. Observational study
  138. Impact of analgesics on executive function and memory in the Alzheimer’s Disease Neuroimaging Initiative Database
  139. Clinical pain research
  140. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [11C]-D-deprenyl PET/CT
  141. Original experimental
  142. Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway
  143. Topical review
  144. Psychoneuroimmunological approach to gastrointestinal related pain
  145. Letter to the Editor
  146. Do we need an updated definition of pain?
  147. Narrative review
  148. Is acetaminophen safe in pregnancy?
  149. Book Review
  150. Physical Diagnosis of Pain
  151. Book Review
  152. Advances in Anesthesia
  153. Book Review
  154. Atlas of Pain Management Injection Techniques
  155. Book Review
  156. Sedation: A Guide to Patient Management
  157. Book Review
  158. Basics of Anesthesia
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