Identifiers: NCT03105232
Unique Protocol ID: N28/11/16
Brief Title: Opioid-Redox Study (ORS)
Multicentre prospective observational clinical trial
Brief Summary:
Side effects of opioids can from practical view be divided into short-termand long-term. Nervous system disorders are manifested by psychologicalstatus changes of the patient and may cause confusion, mental and somaticdependency, dizziness and so on. Influencing the vegetative and cardiovascularsystem hypotension can occur what is manifestation of vasodilation anddecreased myocardial inotropic activity. Another clinical sign is bradycardiaand is characterized by general weakness, sweating, collapse can develop.Effects of opioids may cause respiratory depression, bronchospasm andbronchoconstriction. Side effects on the gastrointestinal tract are nausea,vomiting, constipation and less frequently dry mouth. The constipation doesnot develop tolerance and has to be avoided (dietary modification, laxativesprevention) respectively during long-term opioid treatment obstipation shouldbe affected by blocking peripheral opioid receptors in the gastrointestinal tractby application of an opioid antagonist methylnaltrexone, which does not crossthe blood brain barrier, or using naloxone, which is metabolized by “first-pass”metabolism in the liver for example combined preparation containing oxycodoneand naloxone (Kulichová, 2012). Known side effects on parenchymatousorgan especially on liver is restricted biliary excretion caused by spasm ofthe biliary tract. Skin manifestations caused by the effects of opioids areurticaria, dermatitis, and pruritus. Renal and urinary disorders may developas urinary retention and ureteral spasm. Rarely can occur disorders of theimmune system, which through the development of hypersensitivity may leadto the development of anaphylactic shock (Kulichová, 2012). Opioids have anegative effect and the endocrine system. Various studies have demonstratedthe influence of opioids on regulatory mechanisms. Fundamental changesoccur in hypothalamic-pituitary complex, which directs the activities of all theendocrine system. Secretion of hormones of the pituitary gland regulates thenervous system through the hypothalamus, which is the coordination centerof autonomic function. The pituitary gland has coordinating function in relationto other endocrine glands, and by production of their hormones affects theperipheral endocrine organs and the targeting tissues (Kulichová, 2012),(Colameco, 2009).Opioids decrease the secretion of gonadotropin-stimulating hormone, resultingin reduced levels of luteinizing hormone. The result of these changes isreduced secretion of testosterone and estradiol what results in symptoms ofhypogonadism. Chronic administration of exogenous opioids decreases thelevels of adrenocorticotropic hormone and cortisol, as well as their circadianrhythms. The result is a reduction in the response to stress. Effect on prolactinis not entirely clear. Opioids can stimulate the hypothalamus through the thyroidstimulating hormone, which may cause prolonged and increased response toopioids in patients with hypothyroidism. Chronic use of opioids is associatedwith weight gain, hyperglycemia and diabetes can worsen (Kulichová, 2012).It may be related to central effects through the sympathetic nervous systemand impaired insulin secretion. New laboratory measurements show the- Page 2 of 5 [DRAFT] –
development of oxidative stress in patients receiving morphine and relateddrugs (Merdin, 2016).The consequences of these biochemical changes further negatively affect theclinical outcome of the patients. They may become predisposed to excessiveprogression of previously latent diseases whose manifestations in patientspreviously were not apparent and there is emergence of new diseases. Thepresent data are essential to create a clinical prospective observational studiesto clarify this issue and its conclusions would be essential for new therapeuticoptions for adjuvant therapy in patients suffering from chronic pain.
Cooperative institutions:
Clinic of Anaesthesiology and Intensive Care Medicine, East Slovak Institute of Cardiovascular Disease, Košice, Slovak Republic
ALGMED s.r.o., PainClinic, Košice, Slovak Republic
1st Clinic of Anaesthesiology and Intensive Care Medicine, Louis Pasteur University Hospital, SNP 1, 040 11 Košice, Slovak Republic
Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafarik University in Košice, Slovak Republic
F. D. Roosevelt University Hospital in Banská Bystrica, Slovak Republic