Open access peer-reviewed chapter

Other Uses of Morphine

Written By

Shrenik Ostwal

Submitted: 10 July 2018 Reviewed: 12 February 2019 Published: 27 November 2019

DOI: 10.5772/intechopen.85165

From the Edited Volume

Opioids - From Analgesic Use to Addiction

Edited by Pilar Almela Rojo

Chapter metrics overview

1,106 Chapter Downloads

View Full Metrics


Worldwide many different strong opioids and their formulations are available to control pain. Of which, morphine is considered as global opioid of choice and is widely used to control moderate to severe pain. The World Health Organization (WHO) has recommended morphine as one of the essential drug. Apart from analgesic use, research has proven its effectiveness for relief and treatment of various debilitating and distressing conditions like breathlessness, mucositis (oral and vaginal) and cough. However, its role in diarrhea and opioid substitution therapy (OST) is still nonconfirmatory. This chapter illustrates all available literature supporting effectiveness of morphine in above conditions and its impact on quality of life.


  • morphine
  • dyspnoea
  • mucositis
  • chronic cough
  • opioid substitution therapy (OST)
  • diarrhea

1. Introduction

Preparations of the opium poppy Papaver somniferum have been used for many hundreds of years to relieve pain. Morphine remains as the gold standard for management of moderate to severe cancer pain. It has a five ringed structure with a characteristic T-shaped three dimensional form essential for activation of the opioid receptor.

Due to its strong affinity to mu receptors and action similar to endorphins, i.e., natural pain killers, morphine has been widely used globally. Apart from its analgesic action, it can be used widely for symptomatic relief of other distressing and debilitating conditions. This chapter depicts all available literature for various other uses of morphine.


2. Dyspnoea

2.1 Introduction

Dyspnoea, also termed as breathlessness, is a common and prevalent source of discomfort in patients with advanced cancer and non-cancer life limiting illnesses. Most people describe it as an uncomfortable sensation or increased work of breathing in terms of air hunger, increased effort, chest tightness, rapid breathing, incomplete exhalation or feeling of suffocation.

The American Thoracic Society defined dyspnoea as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity” [1]. This definition highlights key areas where dyspnoea can be measured, suggesting that dyspnoea is not merely a single sensation but a shared experience with physical and affective components. This is similar to concept of total pain or total suffering which constitutes other domains like psychological, social, spiritual and environmental.

The prevalence of dyspnoea varies according to disease primary site and stage of illness. Studies by Muers and Round [2]; Smith et al. [3] reported prevalence of dyspnoea in 75–87% patients with primary lung cancer. While, a systematic review by Solano et al. [4] reported dyspnoea prevalence of: 90–95% in patients with chronic obstructive pulmonary disease (COPD), 60–88% in patients with heart disease, 11–62% in patients with AIDS and 11–62% in patients with renal disease. COPD and chronic heart failure (CHF) constitutes major non-cancer causes of dyspnoea in patients [5, 6].

Dyspnoea due to its prevalence and associated suffering poses a significant burden to patients and caregivers, hence severely affecting quality of life.

2.2 Pathophysiology of dyspnoea

Normally during unconscious activity, respiration is managed by clusters of neurons in the medulla. They receive afferent input from several types of mechanoreceptors in respiratory muscles, airways, and lung parenchyma and chemoreceptors in aortic and carotid bodies and the medulla. Motor commands from the medulla or motor cortex by means of the medulla descend to respiratory muscles through efferent motor neurons [7, 8].

Differential diagnosis for dyspnoea in advanced cancer can be: (Table 1).

Malignant causesNon-malignant causes
Lung cancer/metastases to lungCOPD/interstitial lung disease
Pleural effusion/pericardial effusion/ascitesBronchiectasis
Superior vena caval obstructionCongestive heart failure
Pulmonary embolismArrhythmias
Pulmonary edemaMotor neuron diseases
Major airway obstructionMuscular dystrophy
Lymphangitis carcinomatosisAnaemia
Chest wall infiltrationAcidosis
Radiation induced pulmonary fibrosisAnxiety/panic attacks

Table 1.

Causes of dyspnoea.

2.3 Opioids in breathlessness

The primary site of action of opioids in breathlessness is through medulla oblongata, although various mechanisms may be involved on effect on perception of breathlessness. Box 1 suggests various mechanisms by which morphine acts on breathlessness [1].

Box 1.

Mechanism by which morphine reduces perception of breathlessness. Source: Adapted from American Thoracic Society guidelines on dyspnoea 2012.

  • Analgesia—reduction of pain induced respiratory drive.

  • Anxiolytic effects.

  • Reduce minute ventilation.

  • Cortical sedation (suppression of respiratory awareness).

  • Alteration of neurotransmission within medullary respiratory center.

  • Reduce central sensitivity and response to hypercarbia or hypoxia.

  • Decreased metabolic rate and ventilatory requirements—decrease in O2 consumption.

  • Vasodilatation and improved cardiac functions.

A study by Mahler et al. [9] in 2009 demonstrated threefold increase in beta endorphin levels in 17 COPD patients when compared from rest to end exercise. Patients were randomized to receive either normal saline or 10 mg of intravenous naloxone. Authors found significantly higher peak ratings and regression slope of breathlessness with naloxone as compared to normal saline. This study high-lighten role of endogenous opioids in dyspnoea modification in COPD patients.

Research has demonstrated role of oral morphine in breathlessness. However dosing schedule varies according to underlying condition. Box 2 depicts morphine dosing recommendations for breathlessness [10]:

Box 2.

Morphine dosing recommendations for breathlessness. Source: Adapted and developed from best practice for managing breathlessness in palliative care.

  • Opioids should be started when disabling dyspnoea persists despite maximal Management of underlying condition.

  • Check for renal, hepatic, pulmonary function, current and past opioid use.

  • Prescribe laxatives and other supportive medications.

  • Adopt policy of “Start Low and Go Slow” while titrating morphine dosage.

  • Titrate morphine dose (up to 25–50% of dose for continued mild to moderate dyspnoea; and by up to 50–100% of dose for continued moderate to severe dyspnoea) every weekly over 4 weeks until lowest effective dose is found.

  • Start with 2.5–5 mg/4 h. PO or 1–2.5 mg/4 h. SC of morphine in opioid naive patients.

  • For patients already prescribed morphine for pain, increase regular dose by 25–30%.

  • Consider long acting twice daily morphine dosing in patients with stable regular dose.

  • Consider 1/6th of regular dose prn for episodic breathlessness.

2.3.1 Morphine for breathlessness in cancer patients

There is good evidence for role of opioids in breathlessness [1, 5, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]. Most of studies illustrated beneficial effect of morphine in breathlessness in cancer patients. Out of eight studies which evaluated effect of morphine in cancer related dyspnoea, seven were randomized controlled, double blind trials [21]. Another study by Clemens et al. [22], a non-randomized prospective study in advanced terminal cancer patients with dyspnoea, reported beneficial effect of morphine in reducing intensity of dyspnoea when compared with oxygen. While, Charles et al. [23] also reported similar and rapid improvement in breathlessness with use of nebulised hydromorphone. Studies by Bruera et al. [15] and Mazocato et al. [24] compared role of subcutaneous morphine with placebo in patients with primary lung cancer or lung metastases, showing a significant decrease in breathlessness intensity on visual analogue scale (VAS) after 45 min of intervention when treated with morphine. This was supported by a meta-analysis by Ben-Aharon et al. [10] in patients with cancer related dyspnoea. Authors found positive effect of opioids in reducing breathlessness.

Another two studies by Davis et al. (1996) and Grimbert et al. [25] reported no significant improvement in VAS scores even after 60 min of intervention with nebulized morphine when compared with placebo, i.e., nebulised saline. In one study Bruera et al. [15] compared effect of subcutaneous morphine with nebulised morphine in lung primary patients, reporting no significant difference in dyspnoea intensity. However, this study reported patient’s preference with nebulised morphine. Lastly, Allard et al. [26] found no significant differences in VAS score with 25 or 50% increments in morphine dosages.

2.3.2 Morphine for breathlessness in COPD patients

A systemic review and meta-analysis by Jennings et al., comparing opioids with placebo for the treatment of dyspnoea [21] showed out of 18 randomized controlled trials (RCT) involved, nine trials reported patients receiving either oral opioids (n = 8) or subcutaneous morphine (n = 1). Such patients experienced significant beneficial effect with parenteral opioids on reducing dyspnoea when compared with placebo (meanΔ: –0.40; CI: −0.32 to −0.17). However, exercise was used as provoking stimulus to dyspnoea in eight of these nine studies, whereas only one study could examine patients with dyspnoea at rest.

Another randomized, double blind, placebo-controlled crossover trial by Abernethy et al. [27] compared 4 days of 20 mg oral sustained-release morphine with 4 days of oral placebo. Thirty-eight (87.5%) participants who were opioid naive and had dyspnoea at rest in spite of optimal therapy for their underlying condition (mainly patients with COPD) completed the trial. Patients on morphine experienced significant improvements (i.e., less dyspnoea and improved sleep) on VAS scale. Hence, authors concluded that “sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.”

2.3.3 Morphine for breathlessness in heart failure patients

Only few published studies have demonstrated positive outcomes with use of morphine in CHF related dyspnoea. In a pilot study by Johnson et al. [28] aimed to measure effect of oral morphine on breathlessness in patients with CHF, authors found a significant decrease in median breathlessness in those who received 5 mg of oral morphine four times a day (p = 0.022), whereas no change was observed in patients treated with placebo.

Oxberry et al. [29] conducted a crossover RCT on 35 patients diagnosed with CHF (New York Heart Association Grade III–IV) comparing 4 days of morphine (5 mg four times daily), oxycodone (2.5 mg four times daily) and placebo followed by a washout period of 3 days. Patients were followed up for 3 months. Authors found a significant improvement in composite breathlessness in opioid group as compared to placebo (p = 0.017). However they did not find any statistically significant difference in breathlessness improvement in either intervention group. Hence, authors concluded need for long term trials to establish effectiveness of opioids.

Before stating opioids for dyspnoea in CHF patients, all possible etio-pathological causes should be taken into consideration. Non-pharmacological treatment options—salt and fluid restriction, diet modification, appropriate exercise training and weight reduction strategies, etc., should be used first. Pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), beta blockers, diuretics, digoxin and implant devices should be optimally considered. Other possible causes like anaemia and pleural effusion should be taken care of.

2.3.4 Morphine for breathlessness in other conditions

A recent double blind study by Shohrati et al. [30] on 40 patients presented with dyspnoea due to mustard gas induced bronchiolitis obliterans reported effectiveness of nebulised morphine (1 mg diluted in 4 cc normal saline). Patients experienced improvements in dyspnoea VAS score, cough, night time awakenings both due to dyspnoea and cough, heart rate, respiratory rate and overall quality of life.

A phase I clinical trial on six patients with interstitial lung disease (ILD) by Matsuda et al. [31] comparing two different doses of subcutaneous morphine injection demonstrated a tolerable dose of 2 mg to alleviate dyspnoea. However due to small sample size, results could not be reciprocated to general population and need for larger trials were recommended. On the other hand, Harris-Eze et al. [32] does not found any significant difference in exercise capacity and dyspnoea score in ILD patients treated with either 2.5 or 5 mg of nebulised morphine. This was supported by Cochrane review by Polosa et al. [33].

A single arm study of six patients with terminal amyotrophic lateral sclerosis (ALS) by Clemens et al. [22] showed effectiveness of morphine in reducing dyspnoea. Authors found a significant difference in respiratory rate and dyspnoea intensity at 120 min after morphine administration.


3. Role of morphine in mucositis

Mucositis refers to erythematous, erosive and ulcerative lesion of mucosa observed in patients with cancer treated with chemotherapy and/or radiotherapy to fields involving areas of body. Accordingly it may involve oral cavity, gastrointestinal tract, vaginal mucosa or other areas. Hence, manifesting as burning pain in mouth, diarrhea, vaginitis, etc. Elting et al. [34] observed chemotherapy-induced mucositis in 303 out of 599 patients (51%). Oral mucositis was developed in 22% cycles while gastrointestinal (GI) mucositis in 7% cycles.

3.1 Pathophysiology of mucositis

The five-stage model depicts various steps involved in pathogenesis of mucositis. Stages involved are [35]:

  1. Stage of initiation of tissue injury

  2. Stage of signaling through up regulation of inflammation via generation of messenger signals

  3. Stage of amplification

  4. Stage of ulceration and inflammation

  5. Stage of healing

3.2 Morphine and oral mucositis

Oral mucositis poses a significant source of pain and distress to patients receiving chemotherapy or radiotherapy to head and neck area. It often manifests as burning pain, ulcers, erythematous lesions in mouth complicated by secondary infections—bacterial/fungal/viral. It significantly affects nutritional intake, oral hygiene and overall quality of life. Infections associated with oral mucositis may pose life-threatening conditions. Adequate oral hygiene and treatment of underlying cause helps to relieve symptoms and distress in patients [36, 37].

Various combination of local measures helps to take care of mucositis-related complications. Research has shown effectiveness of morphine gargles either alone (morphine rinse) or in combination with antacid, lignocaine viscous and dextromethorphan (magic mouth wash), in relieving pain and symptoms related to mucositis. A mini review by Dutta et al. [38] compared six studies using morphine as oral rinse. All studies showed satisfactory result in terms of pain control, mouth opening and patient preferences. This is supported by other studies which proved efficacy of morphine gargles [36, 37, 39, 40, 41, 42, 43, 44].

3.3 Morphine and vaginal mucositis

Vaginitis, also known as vaginal mucositis is an acute inflammation with erythema and erosion of vaginal mucosa leading to severe vaginal pain, per vaginal discharge and/or associated complications. It is commonly seen in patients with local infection or as a part of systemic infection, as a complication to radiotherapy to local areas or chemotherapy, recto-vaginal fistula, trauma, etc. Morphine, similar to its role in oral mucositis can be considered for vaginal mucositis. A case reported by Ostwal et al. [45] showed efficacy of morphine when combined with vaginal douche (magic vaginal douche—metronidazole, normal saline, povidone iodine solution, lignocaine viscous with 20 mg crushed tab morphine) in relief from symptoms of vaginal mucositis. However RCTs are not available and are required to prove its clinical efficacy.


4. Role of morphine in chronic cough

4.1 Introduction

Cough is found to be prevalent in around 65% patients with lung cancer [46] and 70% patients with COPD [47, 48]. Persistent or chronic cough can have various physical complications like musculoskeletal pain over chest wall, rib fracture, bowel and bladder incontinence, disturbed sleep and feeling of exhaustion. Patients usually experience psychological impacts, social isolation and decreased quality of life [48].

Cough reflex is regulated by vagal afferent pathways, nucleus tractus solitarius (NTS) in brainstem, and cough center in cerebral cortex. Common underlying patho-physiological causes for cough includes: (i) infection; (ii) lung cancer or secondary metastases to lung/pleura/mediastinum/pericardium/blood vessels; (iii) COPD, ILD, bronchiectasis; (iv) aspiration; (v) asthma/bronchospasm; (vi) esophageal reflux; (vii) tracheo-esophageal fistula; (viii) radiotherapy or chemotherapy induced pulmonary fibrosis; (ix) ACE inhibitors; (x) pulmonary edema/left ventricular failure, etc. Timely and proper assessment of cough with removal of underlying cause can decrease distress and improve patients’ quality of life.

4.2 Morphine and cough

Research work by Kamei [49] showed involvement of mu opioid receptors in production of cough. Very limited studies are available for use of morphine on chronic cough [47, 50, 51, 52, 53, 54, 55, 56]. Strongest evidence for effectiveness of morphine in chronic cough was shown in a double blind placebo controlled trial by Morice et al. [57]. Twenty seven patients with chronic persistent cough were assigned to 4 weeks of slow release morphine sulfate (5 mg twice daily escalated to 10 mg twice daily) matched correspondingly with placebo. A significant improvement of 3.2 points over baseline, and 40% rapid reduction in cough frequency and severity was observed in slow release morphine group (p < 0.01). Dose comparison over 3 month period between 5 and 10 mg did not showed any significant difference, helping to conclude study with daily dose recommendation of slow release morphine sulfate from 5 to 10 mg twice daily.


5. Role of morphine in diarrhea

Diarrhea has been defined as “passage of ≥3 loose or watery bowel movements per day or passage of ≥200 g of stool per day based on typical diet.” Diarrhea can be acute (<14 days), persistent (>14 days but <30 days) or chronic (>30 days) based on its duration. Diarrhea poses a common and significant problem in patients with cancer. It may be due to either local infection, as a part of systemic inflammation/infection, as a complication to radiotherapy or chemotherapy [58], etc.

Mechanism for diarrhea can be attributed to increased intestinal motility [59, 60]. Hence drugs which act to decrease intestinal motility are found to be helpful in treatment. Morphine and other opiates (loperamide, diphenoxylate, codeine) act on intestinal mu-receptors and slow intestinal transit time, thus increasing net absorption [61, 62]. Though constipation is commonly seen as a side effect with morphine use, research considering use of this side effect to treat diarrhea has not been done. Clinical Practice guidelines by European Society for Medical Oncology (ESMO) has documented role of tincture of opium like morphine (10 mg/mL morphine) in treatment with diarrhea as an alternative to loperamide. The recommended dose of tincture morphine is 10–15 drops in water every 3–4 h [58, 63, 64]. Till date robust studies supporting this has not been available.


6. Morphine and opioid substitution therapy (OST)

Morphine has been known for its potential effect in analgesia since last few decades. However, it is also known for its potential to cause addiction and dependence. Opium, derived naturally from poppy plant is widely used for addiction. Opioid substitution therapy (OST) is an evidence-based intervention for opiate dependent persons that replaces illicit drug use with medically prescribed, orally administered opiates such as buprenorphine and methadone. OST reduces HIV risk behaviors and harms associated with injecting (such as abscesses, septicemia and endocarditis), overdose and participation in criminal activity, thereby improving the quality of life and health of injecting drug users (IDUs).

Work by Hämmig et al. [65] showed that slow release oral morphine (SROM) preparations can be used as OST for heroin addicted patients. Authors found higher treatment satisfaction, fewer cravings for drug and less mental stress with SROM. Cochrane review by Ferri et al. [65] found only three randomized controlled trials which included SROM for OST. Out of three, only two studies suggested possible role of SROM formulations; while remaining study was associated with adverse events like depressive symptoms [65, 66, 67, 68, 69, 70]. Hence authors concluded for necessity of more robust and clinically controlled trials.


7. Conclusion

Morphine, a potent and strong opioid, has shown its efficacy in relieving variety of distressing symptoms. Research has documented role of low dose morphine for treatment and relief from conditions like chronic, refractory breathlessness, cough, mucositis (oral/vaginal). However, more robust studies are required to establish its clinical efficacy in diarrhea and opioid substitution therapy.


Conflicts of interest



  1. 1. Parshall MB et al. An official American thoracic society statement: Update on the mechanisms, assessment, and management of dyspnoea. American Journal of Respiratory and Critical Care Medicine. 2012;185(4):435-452
  2. 2. Muers MF, Round CE. Palliation of symptoms in non-small cell lung cancer: A study by the Yorkshire Regional Cancer Organisation thoracic group. Thorax. 1993;48(4):339-343
  3. 3. Smith EL et al. Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer. Journal of Pain and Symptom Management. 2001;21(4):323-329
  4. 4. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. Journal of Pain and Symptom Management. 2006;31(1):58-69
  5. 5. Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest. 1986;89(2):234-236
  6. 6. Higginson I, McCarthy M. Measuring symptoms in terminal cancer: Are pain and dyspnoea controlled? Journal of the Royal Society of Medicine. 1989;82(5):264-267
  7. 7. Mahler DA, O’Donnell DE. Recent advances in dyspnea. Chest. 2015;147(1):232-241
  8. 8. Nishino T. Dyspnoea: Underlying mechanisms and treatment. British Journal of Anaesthesia. 2011;106(4):463-474
  9. 9. Mahler DA et al. Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD. The European Respiratory Journal. 2009;33(4):771-777
  10. 10. Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Interventions for alleviating cancer-related dyspnea: A systematic review. Journal of Clinical Oncology. 2008;26(14):2396-2404
  11. 11. Cabezón-Gutiérrez L, Khosravi-Shahi P, Custodio-Cabello S, Muñiz-González F, Cano-Aguirre M d P, Alonso-Viteri S. Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease. Supportive Care in Cancer. 2016;24(9):4045-4055
  12. 12. Currow D et al. A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, exertion and morphine sulfate (BEAMS) study protocol On behalf of the Australian National Palliative Care Clinical Studies Collaborative (PaCCSC). BMJ Open. 2017;7:18-100
  13. 13. Barnes H, McDonald J, Smallwood N, Manser R. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database of Systematic Reviews. 31 Mar 2016;3:CD011008. DOI: 10.1002/14651858.CD011008.pub2
  14. 14. Afolabi TM, Nahata MC, Pai V. Nebulized opioids for the palliation of dyspnea in terminally ill patients. American Journal of Health-System Pharmacy. 2017;74(14):1053-1061
  15. 15. Bruera E, Macmillan K, Pither J, MacDonald RN. Effects of morphine on the dyspnea of terminal cancer patients. Journal of Pain and Symptom Management. 1990;5(6):341-344
  16. 16. Kloke M, Cherny N. Treatment of dyspnoea in advanced cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology. 2015;26(5):69-73
  17. 17. Thomas JR, von Gunten CF. Clinical management of dyspnoea. The Lancet Oncology. 2002;3(4):223-228
  18. 18. Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Interventions for alleviating cancer-related dyspnea: A systematic review and meta-analysis. Acta Oncologica. 2012;51(8):996-1008
  19. 19. Mahler DA. Opioids for refractory dyspnea. Expert Review of Respiratory Medicine. 2013;7(2):123-135
  20. 20. Tian C, Wang JY, Wang ML, Jiang B, Zhang LL, Liu F. Morphine versus methylprednisolone or aminophylline for relieving dyspnea in patients with advanced cancer in China: A retrospective study. Springerplus. 2016;5(1):1945
  21. 21. Jennings A-L, Davies AN, Higgins JPT, Gibbs JSR, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2002;57(11):939-944
  22. 22. Clemens KE, Quednau I, Klaschik E. Is there a higher risk of respiratory depression in opioid-naïve palliative care patients during symptomatic therapy of dyspnea with strong opioids? Journal of Palliative Medicine. 2008;11(2):204-216
  23. 23. Charles MA, Reymond L, Israel F. Relief of incident dyspnea in palliative cancer patients: A pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline. Journal of Pain and Symptom Management. 2008;36(1):29-38
  24. 24. Mazzocato C, Buclin T, Rapin CH. The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: A randomized double-blind controlled trial. Annals of Oncology: Official Journal of the European Society for Medical Oncology/ESMO. 1999;10(12):1511-1514
  25. 25. Grimbert D et al. Dyspnea and morphine aerosols in the palliative care of lung cancer. Revue des Maladies Respiratoires. 2004;21(6):1091-1097
  26. 26. Schwartzman RJ, Patel M, Grothusen JR, Alexander GM. Efficacy of 5-day continuous lidocaine infusion for the treatment of refractory complex regional pain syndrome. Pain Medicine. 2009;10(2):401-412
  27. 27. Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ [British Medical Journal]. 2003;327(7414):523-528
  28. 28. Johnson MJ, Mcdonagh TA, Harkness A, Mckay SE, Dargie HJ, Infirmary GR. Morphine for the relief of breathlessness in patients with chronic heart failure—A pilot study. The European Journal of Heart Failure. 2002;4:753-756
  29. 29. Oxberry SG, Bland JM, Clark AL, Cleland JG, Johnson MJ. Repeat dose opioids may be effective for breathlessness in chronic heart failure if given for long enough. Journal of Palliative Medicine. 2013;16(3):250-255
  30. 30. Shohrati M, Ghanei M, Harandi AA, Foroghi S, Harandi AA. Effect of nebulized morphine on dyspnea of mustard gas-exposed patients: A double-blind randomized clinical trial study. Pulmonary medicine. 2012;2012:1-6
  31. 31. Matsuda Y et al. Low-dose morphine for dyspnea in terminally ill patients with idiopathic interstitial pneumonias. Journal of Palliative Medicine. 2017;20(8):879-883
  32. 32. Harris-Eze AO, Sridhar G, Clemens RE, Zintel TA, Gallagher CG, Marciniuk DD. Low-dose nebulized morphine does not improve exercise in interstitial lung disease. American Journal of Respiratory and Critical Care Medicine. 1995;152(6):1940-1945
  33. 33. Polosa R, Simidchiev A, Walters EH. Nebulised morphine for severe interstitial lung disease. Cochrane Database of Systematic Reviews. 2002;3:CD002872
  34. 34. Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy: Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98(7):1531-1539
  35. 35. Lalla RV, Sonis ST, Peterson DE. Management of oral mucositis in patients who have cancer. Dental Clinics of North America. 2008;52(1):61-77
  36. 36. Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO Clinical Practice Guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453-1461
  37. 37. Joanna Briggs Institute. Prevention and treatment of oral mucositis in cancer patients. Best Practice. 1998;2(3):1-6
  38. 38. Dutta K, Garg R, Garg R. Palliative medicine and hospice care morphine mouthwash in oral mucositis: A mini review. The American Journal of Hospice & Palliative Care. 2016;2(2):26-29
  39. 39. Saroja G, Devi PS, Namrata R. Oral morphine solution as an oral rinse or mouth gargle for mucositis pain. Indian Journal of Palliative Care. 2010;16(1):54-55
  40. 40. Sarvizadeh M, Hemati S, Meidani M, Ashouri M, Roayaei M, Shahsanai A. Morphine mouthwash for the management of oral mucositis in patients with head and neck cancer. Advanced Biomedical Research. 2015;4(1):44
  41. 41. Saunders DP et al. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients. Supportive Care in Cancer. 2013;21(11):3191-3207
  42. 42. Quinn B. Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: A review of current data. European Journal of Cancer Care. 2013;22(5):564-579
  43. 43. Cerchietti LCA et al. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002;95(10):2230-2236
  44. 44. Chan A, Ignoffo RJ. Survey of topical oral solutions for the treatment of chemo-induced oral mucositis. Journal of Oncology Pharmacy Practice. 2005;11(4):139-143
  45. 45. Anandi Q , Ostwal S, Patel H, Sanghavi P. Magic vaginal douche for severe vaginal mucositis: A case-based approach. International Journal of Palliative Nursing. 2018;1(1):17-18
  46. 46. Kvale PA. Chronic cough due to lung tumors ACCP evidence-based clinical practice guidelines. Chest. Jan 2006;129(1 Suppl):147S-153S. DOI: 10.1378/chest.129.1_suppl.147S
  47. 47. Molassiotis A et al. Clinical expert guidelines for the management of cough in lung cancer: Report of a UK task group on cough. Cough. 2010;6(1):9
  48. 48. Molassiotis A, Bailey C, Caress A, Tan JY. Interventions for cough in cancer. Cochrane Database of Systematic Reviews. 2010;9:CD007881
  49. 49. Kamei J. Role of opioidergic and serotonergic mechanisms in cough and antitussives. Pulmonary Pharmacology. 1996;9(5-6):349-356
  50. 50. Dudgeon DJ. Managing dyspnea and cough. Hematology/Oncology Clinics of North America. 2002;16(3):557-577
  51. 51. An HJ, Kim I-K, Lee JE, Kang Y-J, Kim CH, Kim H-K. Nebulized morphine for intractable cough in advanced cancer: Two case reports. Journal of Palliative Medicine. 2015;18(3):278-281
  52. 52. Gibson P, Wang G, McGarvey L, Vertigan AE, Altman KW, Birring SS. Treatment of unexplained chronic cough chest guideline and expert panel report. Chest. 2016;149(1):27-44
  53. 53. Wee B et al. Management of chronic cough in patients receiving palliative care: Review of evidence and recommendations by a task group of the Association for Palliative Medicine of Great Britain and Ireland. Palliative Medicine. 2012;26(6):780-787
  54. 54. Stein WM, Min YK. Nebulized morphine for paroxysmal cough and dyspnea in a nursing home resident with metastatic cancer. American Journal of Hospice and Palliative Medicine. 1997;14(2):52-56
  55. 55. Borja-Cacho D, Matthews J. NIH public access. Nano. 2008;6(9):2166-2171
  56. 56. Badri H, Satia I, Woodcock A, Smith J. The use of low dose morphine for the management of chronic cough in a tertiary cough clinic background: Objective: Methods. American Journal of Respiratory and Critical Care Medicine. 2015;191:A4117
  57. 57. Morice AH et al. Opiate therapy in chronic cough. American Journal of Respiratory and Critical Care Medicine. 2007;175(4):312-315
  58. 58. Bush SH et al. Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology. 2018;29(4):iv126-iv142
  59. 59. Porreca F, Heyman JS, Mosberg HI, Omnaas JR, Vaught JL. Role of mu and delta receptors in the supraspinal and spinal analgesic effects of [D-Pen2, D-Pen5] enkephalin in the mouse. The Journal of Pharmacology and Experimental Therapeutics. 1987;241(2):393-400
  60. 60. Wood JD, Galligan JJ. Function of opioids in the enteric nervous system. Neurogastroenterology and Motility. 2004;16(s2):17-28
  61. 61. Kaufman PN et al. Role of opiate receptors in the regulation of colonic transit. Gastroenterology. 1988;94:1351-1356
  62. 62. Sternini C, Patierno S, Selmer I-S, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterology and Motility. 2004;16(s2):3-16
  63. 63. Cherny NI. Evaluation and management of treatment-related diarrhea in patients with advanced cancer: A review. Journal of Pain and Symptom Management. 2008;36(4):413-423
  64. 64. Schiller LR, Pardi DS, Sellin JH. Chronic diarrhea: Diagnosis and management. Clinical Gastroenterology and Hepatology. 2017;15(2):182-193
  65. 65. Hämmig R et al. Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence. Journal of Substance Abuse Treatment. 2014;47(4):275-281
  66. 66. Ferri M, Minozzi S, Bo A, Amato L. Slow-release oral morphine as maintenance therapy for opioid dependence. Cochrane Database of Systematic Reviews. 2013;6:CD009879. DOI: 10.1002/14651858.CD009879.pub2
  67. 67. Eder H, Jagsch R, Kraigher D, Primorac A, Ebner N, Fischer G. Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy. Addiction. 2005;100(8):1101-1109
  68. 68. Kraigher D et al. Use of slow-release oral morphine for the treatment of opioid dependence. European Addiction Research. 2005;11(3):145-151
  69. 69. Giacomuzzi S, Kemmler G, Ertl M, Riemer Y. Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants. Substance Use & Misuse. 2006;41(2):223-244
  70. 70. Beck T et al. Maintenance treatment for opioid dependence with slow-release oral morphine: A randomized cross-over, non-inferiority study versus methadone. Addiction. 2013;109:617-626

Written By

Shrenik Ostwal

Submitted: 10 July 2018 Reviewed: 12 February 2019 Published: 27 November 2019