Constipation In Cancer Patients

Constipation In Cancer Patients

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Constipation In Cancer Patients

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Constipation In Cancer Patients

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Question:
Write an Essay on “Management of Constipation in Cancer Patients on Morphine”.
 
 
Answer:

Introduction:
There are a myriad of different lateral complications that cancer patients in advanced stages go through, and constipation is one of the most common co-lateral medical constipation that the cancer patients suffer with. Studies suggest that close to 50% of the cancer patients suffer from constipation and 16% of them report it to be extremely severe (Candy, Jones, Larkin, Vickerstaff, Tookman, & Stone, 2015). According to the most of research studies, the onset of constipation in the advanced stages of cancer might lead to a number of more complex health adversities like urinary dysfunction, overflow diarrhea and anorexia (Mercadante, et al., 2017). And that is the reason why this particular health complexity in the cancer patients leads to the most of emergency department visits in the health care sectors band enhances the hospital costs for the patients as well.
Although the underlying reason behind the onset of constipation in the cancer patients is not yet understood completely, however substantial number of research studies argue that the side effects generated by the opoid medication plays an important role in the pathogenesis of constipation in the cancer patients (Coyne, LoCasale, King, Margolis, & Ahmedzai, 2016). This assignment will present a literature review on the role of morphine on facilitating constipation in the cancer patients and the management techniques that can be opted for the predicament.
Constipation in cancer patients:
The pathogenesis process of constipation can be considered multi- factorial, as there are various physiological and biochemical factors associated with the entire mechanism. However, constipation is considered to be one of the primary grievances expressed by the cancer patients in the severe or advanced stages. According to the article by Gonzalez and Halm (2016), almost 50% of the entire emergency room visits for the cancer patients are due to constipation and the related complexities that it comes accompanied with (Gonzalez & Halm, 2016). According to the Droney et al. (2013), there are many health care complications that are facilitated by the onset of constipation (Droney, et al., 2013). It has to be mentioned in this context that the disrupted bowel movements leads to urinary dysfunctions and overflow diarrhea. Another pharmacological side effect of the constipation in the cancer patients is the decreased drug absorptions, nausea, vomiting, and intestinal obstruction. Now it must not escape notice that for the cancer patients the burden of the terminal disease and its extreme treatments already affects the quality of life and the trouble of constipation facilitates an added bonus of distressing and debilitating elements into their life. On a more elaborative note, the constipation facilitates feelings of pain, confusion, anxiety, insomnia and spiritual distress in the cancer patients (Riley, et al., 2015). Although there are various kinds of effects of the constipation on the cancer patient, the magnitude of the effects generally depends on the severity of constipation that the cancer patient might be having. For instance, constipation in the cancer patients can range from mild to intermittent to chronic in terms of severity; the effect imparted on the quality of life for the cancer patient will also depend completely on the severity scale. Although, regardless of the severity of the constipation the patient might be having, the management technique depends entirely upon the etiology and patho- physiology of the condition (Ahmedzai, et al., 2015).
 
Role of opioids in pathogenesis of constipation:
In cancer patients, the use of opoids has been considered to be the main underlying contributing factor behind the onset of restricted bowel movements (Oosten, et al., 2016). Now opioids can be considered as the major class of analgesics that is used abundantly in the management of acute pain. And as the cancer patients in the advanced stages experience bouts of excruciating pain during their stay in the palliative units, opioids are the most common class of pin management medication administered to the patients. However all classes of opioid analgesic drugs, the most frequently observed side effects observed is constipation, with the probability index of almost 40% to 80% depending on the dosage and severity statistics of the patient population. As the most commonly used opioid drug used for acute pain management for cancer patients in morphine, the drug is also known to induce onset of constipation in the highest probability (Zhu, Gong, Hu, Wei, Kong, & Peng, 2017).
On a more elaborative note, constipation that is caused by the side effect of the opioid analgesic is known to originate outside of the colon. According to the Asna et al. (2017), the opioids that are taken by the patient bind to the receptors that are present on the gastrointestinal tract of the patient along with the nervous system, effectively reducing or restricting the normal bowel motility of the patient (Asna, Shemesh, Arbel, Yosef, Batash, & Schaffer, 2017). There are two methods by which the opioids like morphine can cause bowel obstruction, it is either by direct or anti-cholinergic mechanisms. Elaborating more on the same context, the detailed biochemical method of constipation is complex. According to Camilleri et al. (2014), there are three classes of opioid receptors involved in the procedure of gastrointestinal or GI signaling procedure, µ, ? and δ. ? and δ receptors are mainly expressed in the stomach and proximal colon where as the µ receptors are expressed widely throughout the gastrointestinal tract (Camilleri, Becker, Webster, Davies, & Mawe, 2014). And due to this ubiquitous distribution of the µ receptors in the GI tract, these receptors are play crucial roles in the gut functions, and hence, are extremely vulnerable to be affected by the opiod agents. Now in the presence of the opioid agents the µ opioid receptors, analogous to the regular ones, are activated that in known to induce OBD kinase functions and contribute largely to the bowel obstruction activating OIC or opioid induced constipation in the cancer patients (Nosek, Leppert, Nosek, Wordliczek, & Onichimowski, 2017).
 
Interventions and management of constipation:
Although the signaling mechanism of the opiod induced constipation is complex, the =re have been many a management techniques that have been identified in the last few years. According to the article by Gonzalez and Halm (2016), there are various classes of pharmacological treatment or interventions identified for the management of opioid induced constipation in the patients. The authors in this article have described 4 classes of interventional drugs. The very first drug that has been discussed is the osmotic laxative, including PEG and lactulose drugs (Gonzalez & Halm, 2016). According to the Laugsand et al. (2017), these well tolerated yet poorly absorbed agents draw and hold eater in the intestinal lumen and facilitates better bowel movements (Laugsand, et al., 2015). Although one restricting factor with this intervention is the fact that lactulose can facilitate abdominal pain, gas, and bloating in some patients, the article does not discusses the interventions taken in clinical setting to avoid these side effects. The second class of intervention agents that are discussed in this paper are µ opioid receptor antagonists, Naloxegol and methylnaltrexone, that peripherally act as opioid receptors and effectively antagonize the action of regular opiod receptor and release the obstruction on bowel movements. The second last example of interventional management discussed involves lubricants and enemas, which are mainly utilized in the ED setting (Gonzalez & Halm, 2016). Both these intervention techniques soften the stool and ease the way for it to be passed. And last example of intervention shared by this paper are the bulk forming agents, that are nothing but gentle laxatives making the fecal material retain more water and n=making the feces softer and easy to pass. Although it has to be mentioned in this context that this article has explained a number of intervention techniques to help treat the OIC in cancer patients, though it fails to incorporates crucial details about safe implementation of these techniques in the article.
The effect of methylnaltrexone, a key µ opioid receptor has also been discussed in the article by Mori et al. (2017), Now this particular µ-opioid receptor cannot cross the blood-brain barriers and hence is a key peripherally acting receptor antagonist that as a key role in relieving the bowel obstruction in cancer patients due to morphine or another opioid ingestion (Mori, Ji, Kumar, Ashikaga, & Ades, 2017). The authors have discussed in this article that this particular antagonist is much more effective in patients with severe OIC and requiring higher dosage of opioids but were not in terminal or end of life stage of the disease. Along with that the authors also discovered that the this particular drug could revive the bowel movements of the patient regardless of the trajectory or the disease as long as the patient is not in the terminal stage. However the key findings of this article have to be fact that the methylnaltrexone therapy in conjunction with the minor laxatives could effectively soften the stool making it far easier for it to pass than used alone. However the authors only generated a promising hypothesis based results for this study, and the lack of a multicenter clinical trial with routine screening of cancer patients on opioids reduces the external validity of the study.
The article by Chey et al. (2014), on the other hand keeps the focus on the effect of naloxegol, the other µ-opioid receptor antagonist on treating the OIC in cancer patients. In this study the authors have analyzed the efficacy of this µ-opioid receptor antagonist by the help of control trials with two particular dosage of the medication, 25 mg and 12.5 mg. the results of this study argues with the statement by the previous article, as the effect of naloxegol elicited best outcome for patients who were non- responsive to the osmotic and stimulant laxatives (Chey, Webster, Sostek, Lappalainen, Barker, & Tack, 2014). The authors also discussed the use of pegylated µ-opioid receptor antagonist in restoring the bowel movements of the patents with OIC due to morphine or other opioid treatments yielded the best results in reviving the bowel movements without actively taking away from the analgesic action of the opioid (morphine).
 
In the article by Camilleri et al. (2014), a few contemporary and comparatively new intervention techniques are utilized that are not so frequently used in the clinical settings. Along with the common laxatives and µ-opioid receptor antagonist, this article discusses the efficiency of chloride channel activators and the Selective 5-HT4 agonist prucalopride (Camilleri, Becker, Webster, Davies, & Mawe, 2014). First and foremost, the interventional management involving lubiprostone, a specific activator of intestinal CIC2 chloride channel can affectively increase the transport of fluids intestine countering the antisecretory effects of the opioids like morphine in the intestine. The prucalopride in turn accelerates colonic transit that in turn activates the contraction in the colon and facilitates the normal bowel movements. Although, it has to be mentioned that both the contemporary intervention techniques highlighted in the article are indirect mechanisms of intervention for OIC, and there are no significant evidence of usage of this techniques in cancerous patients.
The last article by Yokota et al. (2017), discusses the use of naldemedine in treating the opioid induced constipation in the cancer patients, which is another peripherally acting µ-opioid receptor antagonist. The authors carried out a randomized double- blind placebo-controlled study and the most notable outcome of the study had been that fact that the use of nalmedine conspicuously improved the bowel movement statistics in the patients when compared to the placebo sample population (Yokota, Katakami, Harada, Tada, Narabayashi, & Boku, 2017). Although the article fails to reveal any detail regarding the mechanism of action, stability of the intervention program and the extent of side effects of the treatment. Although a brief mention of the Diarrhea occurring in the few patients had been discussed, there is no clear detailed data mentioned about the results of the study which subsequently decreases the reliability and external validity of the study. Although, the honest effort from the authors in evaluating the effect of nalmedine, a rather undiscovered µ-opioid receptor in research, should be appreciated.
 
Conclusion:
On a concluding note, it can be stated that the constipation generated in the cancer patients due to extended use of opioid like morphine is the cause of the most of the discomfort and distress for the cancer patients. Along with that, the onset of constipation in the cancer patients can also lead to a number of other more complicated adversities further deteriorating the condition of the patient, if the constipation is not managed actively and effectively in the early stages. This literature review provided an assortment of a variety of different management or intervention techniques highlighted in the previously published literature. Although, there is no standardized or definite protocol for management of OIC in the patients that are on the extended morphine treatment for acute pain. Although the use of methylnaltrexone coupled with stimulant laxatives can be considered one of the most effective techniques for managing OIC in non-terminal patients.  Hence, there is need for more extensive and outcome oriented research on this antagonist so that a standardized and safe intervention technique can be identified for the management of OIC in the all cancer patients, avoiding the probability of alteration of the analgesic effect of the opioid used.
 
Bibliography
Ahmedzai, S. H., Leppert, W., Janecki, M., Pakosz, A., Lomax, M., Duerr, H., et al. (2015). Long-term safety and efficacy of oxycodonenaloxone prolonged-release tablets in patients with moderate-to-severe chronic cancer pain. Supportive Care in Cancer , 823-830.
Asna, N., Shemesh, N., Arbel, L., Yosef, R. B., Batash, R., & Schaffer, M. (2017). Effect of the Sedative Combination of Ketamine, Morphine and Midazolam on the Quality-of-Life in the Final Days of Terminally Ill Cancer Patients. Archives of Medicine , 9(2).
Camilleri, M. D., Becker, G., Webster, L. R., Davies, A. N., & Mawe, G. M. (2014). Emerging treatments in neurogastroenterology: A multidisciplinary working group consensus statement on opioid?induced constipation. Neurogastroenterology & Motility , 1386-1395.
Candy, B., Jones, L., Larkin, P. J., Vickerstaff, V., Tookman, A., & Stone, P. (2015). Laxatives for the management of constipation in people receiving palliative care. The Cochrane Library , 584-615.
Chey, W. D., Webster, L., Sostek, M., Lappalainen, J., Barker, P. N., & Tack, J. (2014). Naloxegol for opioid-induced constipation in patients with noncancer pain. New England Journal of Medicine , 2387-2396.
Coyne, K. S., LoCasale, R. J., King, F. R., Margolis, M. K., & Ahmedzai, S. H. (2016). Opioid-induced constipation among a convenience sample of Patients with cancer Pain.  Frontiers in oncology , 6.
Droney, J. M., Gretton, S. K., Sato, H., Ross, J. R., Branford, R., Welsh, K. I., et al. (2013). Analgesia and central side?effects: two separate dimensions of morphine response. British journal of clinical pharmacology , 1340-1350.
Gonzalez, C. E., & Halm, J. K. (2016). Constipation in cancer patients. Oncologic Emergency Medicine , pp. 327-332.
Laugsand, E. A., Skorpen, F., Kaasa, S., Sabatowski, R., Strasser, F., Fayers, P., et al. (2015). Genetic and non-genetic factors associated with constipation in cancer patients receiving opioids. Clinical and translational gastroenterology , 6(6), e90.
Mercadante, S., Masedu, F., Maltoni, M., Giovanni, D. D., Montanari, L., Pittureri, C., et al. (2017). The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study. Current Medical Research and Opinion , 1-6.
Mori, M., Ji, Y., Kumar, S., Ashikaga, T., & Ades, S. (2017). Phase II trial of subcutaneous methylnaltrexone in the treatment of severe opioid-induced constipation (OIC) in cancer patients: an exploratory study. International journal of clinical oncology , 397-404.
Nosek, K., Leppert, W., Nosek, H., Wordliczek, J., & Onichimowski, D. (2017). 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 Design, Development and Therapy , 2409.
Oosten, A. W., Matic, M., van Schaik, R. H., Look, M. P., Jongen, J. L., Mathijssen, R. H., et al. (2016). Opioid treatment failure in cancer patients: the role of clinical and genetic factors. Pharmacogenomics , 1391-1403.
Riley, J., Branford, R., Droney, J., Gretton, S., Sato, H., Kennett, A., et al. (2015). Morphine or oxycodone for cancer-related pain? A randomized, open-label, controlled trial.  Journal of pain and symptom management , 161-172.
Yokota, T., Katakami, N., Harada, T., Tada, Y., Narabayashi, M., & Boku, N. (2017). O-9 Phase 3 study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation (OIC) in cancer patients. 858-885.
Zhu, H. D., Gong, Z., Hu, B. W., Wei, Q. L., Kong, J., & Peng, C. B. (2017). The Efficacy and Safety of Transcutaneous Acupoint Interferential Current Stimulation for Cancer Pain Patients With Opioid-Induced Constipation: A Prospective Randomized Controlled Study. Integrative Cancer Therapies , 934-1115.

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