Jarosław Woroń

Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the study of pain and the Polish Neurological Society - part one.

Neuropathic pain may be caused by a variety of lesions or diseases of both the peripheral and central nervous system. The most common and best known syndromes of peripheral neuropathic pain are painful diabetic neuropathy, trigeminal and post-herpetic neuralgia, persistent post-operative and post-traumatic pain, complex regional pain syndrome, cancer-related neuropathic pain, HIV-related neuropathic pain and pain after amputation. The less common central pain comprises primarily central post-stroke pain, pain after spinal cord injury, central pain in Parkinson disease or in other neurodegenerative diseases, pain in syringomyelia and in multiple sclerosis. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on various types of neuropathic pain, with special focus on the available international guidelines, and has formulated recommendations on their diagnosis and treatment, in accordance with the principles of evidence-based medicine (EBM). High quality studies on the efficacy of various medicines and medical procedures in many neuropathic pain syndromes are scarce, which makes the recommendations less robust.

The role of naloxegol in the management of opioid-induced bowel dysfunction.

Opioid-induced constipation (OIC) and other gastrointestinal (GI) symptoms of opioid-induced bowel dysfunction (OIBD) significantly deteriorate patients’ quality of life and may lead to noncompliance with opioid schedule and undertreatment of pain. Although traditional oral laxatives are the first-line treatment of OIC, they do not address OIBD pathophysiology, and display numerous adverse effects. OIC treatment includes prokinetics (lubiprostone), opioid switch, and changing route of opioid administration. Targeted management of OIBD comprises the use of purely peripherally acting μ-opioid receptor antagonists (PAMORA): naloxegol and methylnaltrexone. Naloxegol (NKTR-118) is a polymer conjugate of the opioid antagonist naloxone. The polyethylene glycol limits naloxegol capacity to cross the blood–brain barrier (BBB). Naloxegol is substrate for the P-glycoprotein (P-gp) transporter. The central nervous system penetration of naloxegol is negligible due to reduced permeability and its increased efflux across the BBB, related to P-gp transporter. Naloxegol antagonizes μ- and κ-opioid receptors and displays low affinity to δ-opioid receptors in the GI tract, thereby decreasing OIBD symptoms without reversing central analgesic effects. Naloxegol is metabolised through CYP3A4 to six metabolites, with the majority of the dose (68%) excreted with faeces and less (16%) with urine. The dose of naloxegol equals 25 mg administered orally once daily on a fasting condition. Mild or moderate hepatic impairment has no impact on naloxegol dosing; naloxegol was not studied and is not recommended in patients with hepatic failure. Dose reduction (12.5 mg once daily) and caution is recommended in patients with moderate-to-severe renal impairment. Efficacy (bowel movement in 42–49% of patients not responsive to laxatives) and safety of naloxegol were confirmed in studies conducted in patients with OIC and nonmalignant pain. Naloxegol may be useful for cancer patients with OIC, although studies in this population are lacking.

Dihydrocodeine: safety concerns.

Dihydrocodeine (DHC) is a semi-synthetic analogue of codeine, which was formed by the hydrogenation of the double tie in the main chain of the codeine molecule - instead of a double bond between carbons 7 and 8 DHC possesses a single bond. DHC is used as an analgesic and antitussive agent and for the management of dyspnea and opioid addiction. Limited data is available on the potency of DHC to other opioids. The analgesic effect of DHC is similar to codeine and approximately twice as potent as tramadol for an oral route. In contrast to codeine and tramadol, DHC analgesia seem to be irrespective of CYP2D6 activity due to parent compound analgesic effects, multiple metabolic pathways and limited role of dihydromorphine in DHC analgesia. As the drug is commonly available appropriate titration and dosing and knowledge of its metabolism and possible adverse effects are important for safe prescription of DHC.

Treatment strategy of allergic rhinitis in the face of modern world threats

Allergic rhinitis (AR) is the most common form of allergy, which - as epidemiological research has shown - applies to nearly 25% of the population. AR significantly affects the quality of life of the patient, and the more severe the disease, the greater the risk of developing bronchial asthma. One of the factors affecting the severity of symptoms and the degree of their control is air pollution. In some patients, despite proper treatment, persistence or only partial remission of symptoms (uncontrolled allergic rhinitis) is observed. This can lead to an increase in comorbidities - inflammation of the paranasal sinuses, otitis media and asthma - both in children and in adults. The treatment of allergic rhinitis, in accordance with the standards, consists in: education of the patient, elimination of the allergen from the environment and factors intensifying the course of the disease, selection of proper pharmacotherapy and specific allergen immunotherapy. Many factors influence the selection of the antihistamine used, e.g., the opportunity of safe increase of the dosage.

Pharmacotherapy of pain in cancer patients– recommendations of the Polish Association for the Studyof Pain, Polish Society of Palliative Medicine, Polish Societyof Oncology, Polish Society of Family Medicine, and PolishSociety of Anaesthesiology and Intensive Therapy

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, and Polish Society of Anaesthesiology and Intensive Therapy. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as “pain”, “cancer”, “pharmacotherapy”, “analgesics”, and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the pharmacotherapy of pain in cancer patients with organ dysfunctions (circulatory failure, chronic obstructive pulmonary disease,

Use of opioids as one of the causes of fever in patients with advanced cancer

Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). https://doi.org/10.1177/0394632016686088 International Journal of Immunopathology and Pharmacology 2017, Vol. 30(1) 98 –104

The role and choice criteria of antihistamines in allergy management – expert opinion

Allergic diseases are the most common chronic conditions lasting throughout the patient’s life. They not only cause significant deterioration in the quality of life of patients but also lead to significant absenteeism and reduced productivity, resulting in very high costs for society. Effective and safe treatment of allergic diseases is therefore one of the main challenges for public health and should be carried out by all the specialists in family medicine, internists and paediatricians in collaboration with allergists, otorhinolaryngologists and dermatologists. Antihistamines are most commonly used in the treatment of allergies. Several dozen drugs are available on the pharmaceutical market, and their generic forms are advertised widely as very effective drugs for the treatment of allergic diseases. What is the truth? What are the data from clinical trials and observational studies? Are all drugs equally effective and safe for the patient? According to a panel of experts representing various fields of medicine, inappropriate treatment of allergies can be very risky for patients, and seemingly equally acting medications may differ greatly. Therefore, a panel of experts gathered the latest data from the entire scientific literature and analysed the latest standards and recommendations prepared by scientific societies. This paper provides a summary of these studies and highlights the importance for the patient of the proper choice of drug to treat his allergies.

660 SAFETY OF PAIN PHARMACOTHERAPY IN POSTOPERATIVE PERIOD

Lornoxicam (Xefo) is a potent balanced COX-1/COX-2 inhibitor whose short half-life of 4 hours may beneficially influence safety and tolerability. The following analysis compared the tolerability of lornoxicam with that of comparator analgesics, NSAIDs or placebo. Meta-analysis of adverse event (AE) data from randomised, active comparator – (NSAIDs or other analgesics) and/or placebocontrolled non-phase I trials of lornoxicam in pain and rheumatology disorders. Time to first AE was modelled by Cox’s proportional hazard regression with treatment as explanatory variable. Primary outcome measure was relative risk (hazard ratio) of AEs with a focus on gastrointestinal AEs. The meta-analysis considered patient data from 50 clinical trials encompassing 10,520 patients. Risk of experiencing any AE was significantly lower in patients taking lornoxicam relative to patients taking comparator analgesics (0.839 [0.774–0.910], p = 0.00001), and risk of experiencing any AE for patients taking lornoxicam relative to patients taking placebo was not significantly different (1.122 [0.959–1.313], p = 0.1510). The risk of experiencing any AE was also comparable between patients taking lornoxicam and those taking other NSAIDs (0.944 [0.837–1.065], p = 0.3). Relative risk of experiencing a gastrointestinal AE was significantly lower for patients taking lornoxicam relative to patients taking comparator analgesics (0.773 [0.696–0.858], p = 0.00001), whereas risk of experiencing a gastrointestinal AE was comparable between lornoxicam and placebo (1.103 [0.870–1.398], p = 0.4194). Age had no impact on the risk of experiencing an AE with lornoxicam. Lornoxicam was associated with a significantly lower risk of AEs compared with comparator analgesics and carried no increased risk of AEs versus placebo. Professor Pleiner and Professor Nell act as consultants for Nycomed Group. Dr Simin-Geertsen is an employee of Nycomed. Professor Branebjerg and Professor Ilias have also received honoraria from Nycomed Group.