Interactions between grapefruit juice and psychotropic medications: an update of the literature and an original case series.

INTRODUCTION: There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport. AREAS COVERED: Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided. EXPERT OPINION: The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.

Post-COVID-19 syndrome in everyday clinical practice: interdisciplinary expert position statement endorsed by the Polish Society of Civilization Diseases.

Post-COVID-19 syndrome, also known as long-COVID-19 syndrome, is a complex set of symptoms that persist for weeks or months after recovery from the acute phase of COVID-19. These symptoms can affect various body systems, including the respiratory, nervous, cardiovascular, and digestive systems. The most common complaints are fatigue, shortness of breath, joint pain, taste and smell disorders, as well as problems with memory and concentration. The pathogenesis of the post-COVID-19 syndrome is complicated and not fully understood, but it is likely related to an overactive immune system, disturbances in the intestinal microbiome, and cell and tissue damage caused by the virus. Incorporating a multidisciplinary approach to treating and rehabilitating patients and further research into this syndrome's underlying mechanisms and therapy is crucial for understanding and effectively treating this complex and multi-faced condition.

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.

Aim: We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. Methodology: A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms. Results: Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); Eleutherococcus senticosus: duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); Schisandra chinensis: bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); Tribulus terrestris: citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); Coptis chinensis: mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); Cimicifuga racemosa: mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); Bacopa monnieri: agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); Gynostemma pentaphyllum: duloxetine (back pain); Cordyceps sinensis: sertraline (upper gastrointestinal bleeding); Lepidium meyenii: mianserin (restless legs syndrome); and Scutellaria baicalensis: bupropion (seizures). Conclusion: Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.

The amount of calcium in calcium chloride - Is there a need to clarify emergency treatment of hyperkalaemia algorithm?

European Resuscitation Council (ERC) and American Heart Association (AHA) guidelines emphasize a rapid administration of calcium chloride (10 ml 10 % CaCl2) to protect the myocardium in the hyperkalaemia algorithm. However, calcium chloride preparations available in European markets vary from country to country. In our opinion, the drug dose recommended in the guidelines should not raise questions about the volume and amount of calcium in the intravenous supply and should be unambiguous to minimize the risk of error. Calcium dose should be given in terms of mmol/L or mEq or mg of calcium ions.

Unprescribed and unnoticed: Retrospective chart review of adverse events of interactions between antidepressants and over-the-counter drugs.

Aim: To systematically evaluate prevalence and clinical characteristics of adverse effects of antidepressants and OTC drugs interactions in a retrospective chart review. Methodology: Dataset of 1,145 registered adverse events were evaluated. Reports were selected for further analysis if pharmacoepidemiological avaluation indicated the presence of high probability of a causal relationship between antidepressants and OTC interaction and the occurrence of side effect. Following variables were extracted from the records: sex, age, medical comorbidities, antidepressant and other concomitant medications, clinical consequences ant the possible interaction mechanisms. Results: 368 showed causal relationship with the simultaneous use of antidepressant with another drug. 15 adverse events (4%) were related to the use of OTC medicine, particularly omeprazole, diphenhydramine, Japanese ginkgo biloba, ibuprofen, diclofenac and sildenafil. All of the analysed side effects were categorized as the result of pharmacokinetic interactions. Here we report identified OTC drugs with corresponding antidepressants and clinical manifestations of DDI. Omeprazole: agomelatine (nausea, abnormal dreams), fluoxetine (extrapyramidal symptoms, paresthesias), sertraline (vertigo, yawning), escitalopram (oral vesiculation). Diphenhydramine: sertraline (diaphoresis, insomnia, vertigo), paroxetine (pruritus, headache), duloxetine (oropharyngeal pain). Japanese ginkgo biloba: citalopram (bradycardia), trazodone (vertigo, taste pervesion), mianserine (restless legs syndrome). Diclofenac: escitalopram (oral vesiculation), and fluoxetine (restless legs syndrome). Ibuprofen: agomelatine (anxiety and nausea), sertraline and omeprazole (QTc prolongation). Sildenafil: fluoxetine (genital oedema) and sertraline (myocardial infarction). Conclusion: The use of OTC drugs by the patients should be monitored. Pharmacokinetic interactions between nonprescribed medicines and antidepressants may increase concentration and severity of side effects of latter ones.

Sudden Cardiac Arrest in a Patient With COVID-19 as a Result of Severe Hyperkalemia After Administration of Succinylcholine Chloride for Reintubation. A Case Report.

Background: We present a case study of a man with coronavirus disease 2019 (COVID-19) who developed cardiac arrest as a result of hyperkalemia following administration of chlororsuccinylcholine during endotracheal intubation. Case Summary: A patient with a severe course of COVID-19, hospitalized in the Intensive Care Unit, underwent reintubation on day 16. The applied scheme was rapid sequence induction and intubation with administration of chlororsuccinylcholine. Immediately after intubation, there was a sudden cardiac arrest due to hyperkalemia (cK + 10.2 meq/L). Treatment was initiated as per guidelines, which resulted in a return to spontaneous circulation after 6 min. Conclusion: Chlorsucynylcholine may cause life-threatening hyperkalemia. We recommend using rocuronium as a neuromuscular blocking agent in critically ill COVID-19 patients due to its more optimal safety profile.

Topical clonidine for neuropathic pain in adults.

BACKGROUND: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs has been gaining interest since the beginning of the century, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated for almost 20 years in clinical trials. This is an update of the original Cochrane Review published in Issue 8, 2015. OBJECTIVES: The objective of this review was to assess the analgesic efficacy and safety of TC compared with placebo or other drugs in adults aged 18 years or above with chronic neuropathic pain. SEARCH METHODS: For this update we searched the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid), and Embase (Ovid) databases, and reference lists of retrieved papers and trial registries. We also contacted experts in the field. The most recent search was performed on 27 October 2021. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in adults with chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. Any discrepancies were resolved by discussion or by consulting a third review author if necessary. Where required, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with P values. We used Review Manager Web software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model.  The review primary outcomes were: participant-reported pain relief of 50% or greater; participant-reported pain relief of 30% or greater; much or very much improved on Patient Global Impression of Change scale (PGIC); and very much improved on PGIC. Secondary outcomes included withdrawals due to adverse events; participants experiencing at least one adverse event; and withdrawals due to lack of efficacy. All outcomes were measured at the longest follow-up period. We assessed the certainty of evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies in the review (two new in this update), with a total of 743 participants with painful diabetic neuropathy (PDN). TC (0.1% or 0.2%) was applied in gel form to the painful area two to three times daily. The double-blind treatment phase of three studies lasted 8 weeks to 85 days and compared TC versus placebo. In the fourth study, the double-blind treatment phase lasted 12 weeks and compared TC versus topical capsaicin. We assessed the studies as at unclear or high risk of bias for most domains; all studies were at unclear risk of bias for allocation concealment and blinding of outcome assessment; one study was at high risk of bias for blinding of participants and personnel; two studies were at high risk of attrition bias; and three studies were at high risk of bias due to notable funding concerns. We judged the certainty of evidence (GRADE) to be moderate to very low, downgrading for study limitations, imprecision of results, and publication bias. TC compared to placebo There was no evidence of a difference in number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.78 to 1.86; 179 participants; 1 study; low certainty evidence). However, the number of participants with participant-reported pain relief of 30% or greater during longest follow-up period (8 to 12 weeks) was higher in the TC group compared with placebo (RR 1.35, 95% CI 1.03 to 1.77; 344 participants; 2 studies, very low certainty evidence). The number needed to treat for an additional beneficial outcome (NNTB) for this comparison was 8.33 (95% CI 4.3 to 50.0). Also, there was no evidence of a difference between groups for the outcomes much or very much improved on the PGIC during longest follow-up period (12 weeks) or very much improved on PGIC during the longest follow-up period (12 weeks) (RR 1.06, 95% CI 0.76 to 1.49 and RR 1.82, 95% CI 0.89 to 3.72, respectively; 179 participants; 1 study; low certainty evidence). We observed no evidence of a difference between groups in withdrawals due to adverse events and withdrawals due to lack of efficacy during the longest follow-up period (12 weeks) (RR 0.34, 95% CI 0.04 to 3.18 and RR 1.01, 95% CI 0.06 to 15.92, respectively; 179 participants; 1 study; low certainty evidence) and participants experiencing at least one adverse event during longest follow-up period (12 weeks) (RR 0.65, 95% CI 0.14 to 3.05; 344 participants; 2 studies; low certainty evidence).  TC compared to active comparator There was no evidence of a difference in the number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (RR 1.41, 95% CI 0.99 to 2.0; 139 participants; 1 study; low certainty evidence). Other outcomes were not reported. AUTHORS' CONCLUSIONS: This is an update of a review published in 2015, for which our conclusions remain unchanged. Topical clonidine may provide some benefit to adults with painful diabetic neuropathy; however, the evidence is very uncertain. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine whether it is possible to predict who or which groups of people will benefit from TC.

Drugs containing extracts from Ruscus in chronic venal disease therapy - what's new we know about their effects?

Pharmacotherapy of venous insufficiency is based on the use of drugs which, through their mechanism of action, contribute to the complex pathomechanism of this disease. One of the drugs used in the treatment of CVD are extracts of Ruscus. Numerous studies have demonstrated a multidirectional mechanism of action involving the effect of the drug on the adrenergic and cholinergic systems and the intracellular calcium metabolism. All these mechanisms are responsible for the multidirectional mechanism of action of the drug.

Management Decisions: The Effectiveness and Size of the Emergency Medical Team.

In Poland, often for economic reasons, the staffing of medical rescue teams is limited to the legally required minimum. This gives rise to problems related to the effectiveness and efficiency of medical rescue teams. A literature review did not find any sources addressing the issue of the verification of the effectiveness of paramedic teams depending on the personnel composition of units. The aim of the study was to analyze the effectiveness of resuscitation depending on the size of the medical rescue team, comparing the work of two- and three-person teams. In total, 100 two-person teams and an analogous number of three-person units were studied. Statistical analyses were performed using the IBM SPSS Statistics 24 package. The results showed that the assessment of the condition of the victim as well as the ability to assess the heart rhythm and monitor the condition during advanced measures were more effective in three-person teams; three-person teams also used oxygen more frequently during advanced life support (ALS). Most of the elements influenced the quality of resuscitation and it can be unequivocally stated that the work of three rescuers is more efficient and definitely more effective.

Experts and national consultants' recommendations regarding management of patients treated for migraine with comorbid depression. Epidemiology. Pathomechanism. Comorbidity. Part 1. / Zalecenia ekspertów i konsultantów krajowych dotyczace postepowania u pacjentów leczonych z powodu migreny ze wspólwystepujaca depresja. Epidemiologia. Patomechanizm. Wspólchorobowosc. Czesc 1.

Coexistence of migraine and depression is a significant clinical problem. Health examination surveys indicate that patients who suffer from migraine are more likely to develop depression than the general population. The inverse relationship is also observed. The etiopathogenesis of both migraine and depression is not fully understood and is probably multifactorial and complex. Neurotransmission disorders, the immune system, and genetic predisposition are considered in the literature. The authors present etiopathogenetic theories of both diseases and their prevalence. They analyze data on the comorbidity of these conditions and discuss likely underlying factors. They describe clinical predictors of depression onset in people with migraine.

Experts and national consultants' recommendations regarding management of patients treated for migraine with comorbid depression. Diagnosis. Therapeutic strategies. Part 2. / Zalecenia ekspertów i konsultantów krajowych dotyczace postepowania u pacjentów leczonych z powodu migreny ze wspólwystepujaca depresja. Diagnoza. Strategie terapeutyczne. Czesc 2.

Depressive disorders are currently diagnosed based on the ICD-10 and DSM-5 diagnostic criteria and include axial depressive symptoms and additional symptoms that must coexist for at least two weeks. Migraine is diagnosed based on the International Classification of Headache Disorders. It is generally divided into migraine with and without aura, and with regard to the frequency of attacks into episodic and chronic migraine. The therapeutic strategy in the treatment of depression is pharmacotherapy combined with psychotherapy, whereas in the treatment of migraine the strategy depends on the frequency of headache attacks (episodic migraine vs. chronic migraine) and comorbidities. A novelty is the introduction of monoclonal antibodies directed against CGRP or the receptor of CGRP. There are numerous reports which indicate specific usefulness of monoclonal antibodies that modify the action of CGRP in the treatment of migraine in people suffering from depression.

The volume of infusion fluids correlates with treatment outcomes in critically ill trauma patients.

Background: Appropriate fluid management is essential in the treatment of critically ill trauma patients. Both insufficient and excessive fluid volume can be associated with worse outcomes. Intensive fluid resuscitation is a crucial element of early resuscitation in trauma; however, excessive fluid infusion may lead to fluid accumulation and consequent complications such as pulmonary edema, cardiac failure, impaired bowel function, and delayed wound healing. The aim of this study was to examine the volumes of fluids infused in critically ill trauma patients during the first hours and days of treatment and their relationship to survival and outcomes. Methods: We retrospectively screened records of all consecutive patients admitted to the intensive care unit (ICU) from the beginning of 2019 to the end of 2020. All adults who were admitted to ICU after trauma and were hospitalized for a minimum of 2 days were included in the study. We used multivariate regression analysis models to assess a relationship between volume of infused fluid or fluid balance, age, ISS or APACHE II score, and mortality. We also compared volumes of fluids in survivors and non-survivors including additional analyses in subgroups depending on disease severity (ISS score, APACHE II score), blood loss, and age. Results: A total of 52 patients met the inclusion criteria for the study. The volume of infused fluids and fluid balance were positively correlated with mortality, complication rate, time on mechanical ventilation, length of stay in the ICU, INR, and APTT. Fluid volumes were significantly higher in non-survivors than in survivors at the end of the second day of ICU stay (2.77 vs. 2.14 ml/kg/h) and non-survivors had a highly positive fluid balance (6.21 compared with 2.48 L in survivors). Conclusion: In critically ill trauma patients, worse outcomes were associated with higher volumes of infusion fluids and a more positive fluid balance. Although fluid resuscitation is lifesaving, especially in the first hours after trauma, fluid infusion should be limited to a necessary minimum to avoid fluid overload and its negative consequences.

Analysis of the Way and Correctness of Using Automated External Defibrillators Placed in Public Space in Polish Cities-Continuation of Research.

Immediate resuscitation is required for any sudden cardiac arrest. To improve the survival of the patient, a device to be operated by witnesses of the event-automated external defibrillator (AED)-has been produced. The aim of this study is to analyze the way and correctness of use of automated external defibrillators placed in public spaces in Polish cities. The data analyzed (using Excel 2019 and R 3.5.3 software) are 120 cases of use of automated external defibrillators, placed in public spaces in the territory of Poland in 2008-2018. The predominant location of AED use is in public transportation facilities, and the injured party is the traveler. AED use in non-hospital settings is more common in male victims aged 50-60 years. Owners of AEDs inadequately provide information about their use. The documentation that forms the basis of the emergency medical services intervention needs to be refined. There is no mention of resuscitation performed by a witness of an event or of the use of an AED. In addition, Poland lacks the legal basis for maintaining a register of automated external defibrillators. There is a need to develop appropriate documents to determine the process of reporting by the owners of the use of AEDs in out-of-hospital conditions (OHCA).

Drug-induced diseases in otolaryngology - causes, clinical signs, treatment.

In the daily practice of an otolaryngologist, we encounter cases where the symptoms are not the result of disease but result from pharmacotherapy. In the case of symptoms such as hearing loss, tinnitus, or dizziness, polytherapy may be used as the basis for their occurrence, which, due to the lack of rationality in combining drugs, leads to symptoms that the patient and the doctor very often interpret as a new disease syndrome. The aim of the study is to show and to raise awareness of the fact that the symptoms of hearing organ impairment are frequently drug-related and only a modification of the currently used pharmacotherapy is a rational procedure in such cases. This paper describes 30 cases who developed side effects of polypharmacy in the form of hearing disorders, dizziness, and tinnitus. The causes of drug-related complications were discussed, as well as effective methods of their prevention.

Drug-induced diseases in otolaryngology - causes, clinical signs, treatment.

<b>Introduction:</b> In the daily practice of an otolaryngologist, we encounter cases where the symptoms are not the result of disease but result from pharmacotherapy. In the case of symptoms such as hearing loss, tinnitus, or dizziness, polytherapy may be used as the basis for their occurrence, which, due to the lack of rationality in combining drugs, leads to symptoms that the patient and the doctor very often interpret as a new disease syndrome. <br><b>Aim:</b> The aim of the study is to show and to raise awareness of the fact that the symptoms of hearing organ impairment are frequently drug-related and only a modification of the currently used pharmacotherapy is a rational procedure in such cases. <br><b>Material:</b> This paper describes 30 cases who developed side effects of polypharmacy in the form of hearing disorders, dizziness, and tinnitus. The causes of drug-related complications were discussed, as well as effective methods of their prevention.

Adverse effects of interactions between antipsychotics and medications used in the treatment of cardiovascular disorders.

BACKGROUND: High level of comorbidity between bipolar disorder or schizophrenia and cardiovascular diseases (CVD) in clinical practice may contribute to drug-drug interactions between medications used in these conditions. The aim of this study was to evaluate harmful interactions between antipsychotics and medications used in treatment of CVD. METHODS: The analysis of 52 cases of adverse reactions with a clinical picture indicates that they were the result of the combination of antipsychotic with cardiovascular medications. RESULTS: The highest number of interactions with antipsychotics was recorded among beta-blockers (n = 13, 25% of all cases), including cardiac arrhythmias [atrial fibrillation (n = 1): risperidone plus atenolol; bradycardia (n = 1): perphenazine with metoprolol; ventricular arrhythmias: sertindole with metoprolol (n = 1) and ziprasidone with sotalol (n = 3)] and hypotension [chlorprotixene with nebivolol or metoprolol (n = 2)]. 12 cases concerned statins-myalgia, myopathy, or creatine kinase elevation appeared after combination of atorvastatin with haloperidol (n = 1), quetiapine (n = 3) or risperidone (n = 1), and simvastatin with quetiapine (n = 5) or risperidone (n = 2). There were also cases of interactions observed for the use of antipsychotics with anti-arrhythmic drugs (amiodarone, flecainide, propafenone) (n = 11), calcium channel blockers (n = 6), and other cardiac medications: clonidine, dabigatran, doxazosin, ivabradine, and losartan (n = 10). CONCLUSIONS: Due to a high risk of interactions and related adverse effects, particular attention should be paid while using cardiovascular medications with antipsychotics. Clinical decisions should be preceded by a detailed analysis of safety, risk-benefit ratio to search for, as safe as possible, drug combinations.

Postoperative pain relief in general surgery - recommendations of the Association of Polish Surgeons, Polish Society of Anaesthesiology and Intensive Therapy, Polish Association for the Study of Pain and Polish Association of Regional Anaesthesia and Pain Treatment.

It is estimated that there are over 310 million surgeries performed in the world every year. Appropriate analgesic management in the perioperative period constitutes a fundamental right of every patient, significantly reducing the number of postoperative complications and the time and costs of hospitalization, particularly in the high-risk group of patients (ASA III-V) subject to extensive surgical procedures and hospitalized in intensive care units. Despite such significant arguments speaking for the conduct of effective analgesia in the perioperative period, nearly 79% of patients operated in hospitalization settings and 71% of patients operated in outpatient settings (so-called first day surgery) experienced postoperative pain of moderate, strong or extreme intensity. Hence, effective relief of postoperative pain should constitute one of the priorities of integrated, modern perioperative management, the components of which apart from adequate analgesia involve early nutrition through the alimentary canal, early patient activation and active physiotherapy. In the currently published "Guidelines", a team of authors has updated the previous "Recommendations" primarily in terms of methods for optimizing postoperative pain relief and new techniques and drugs introduced for postoperative pain therapy in recent years. The algorithms of postoperative pain management in different treatment categories were also updated.

Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders. / Niepozadane efekty interakcji leków psychotropowych z produktami leczniczymi stosowanymi w chorobach ukladu sercowo-naczyniowego.

OBJECTIVES: To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders. METHODS: The analysis of 66 cases of adverse reactions with a clinical picture indicating, to a degree that is probable or certain, that they were the result of the combination of antidepressant with cardiovascular medication. RESULTS: The most common side effect (n = 25, 37.9%) was bradycardia (and other side effects of beta blockers) as a consequence of addition of metoprolol or propranolol to SSRI or bupropion. In one case combination of fluoxetine with propranolol resulted in cardiac arrest. We observed 8 cases of intensified side effects of amlodipine (swelling of lower limbs, headaches) after its combination with: fluoxetine, sertraline and paroxetine, and occurrence of myalgia, elevated aminotransferase levels, polyuria and hypotension after combination of lercanidipine with some of the SSRIs. We also found i.a. worsening of propafenone tolerance in combination with venlafaxine or bupropion, 2 cases of granulopenia associated with duloxetine-propafenone combination, 2 cases of hemorrhagic complications associated with the combination of vortioxetine-warfarin, 1 case of hyponatremia associated with the combination of vortioxetine and hydrochlorothiazide, as well as antagonizing clonidine's hypotensive effect by mirtazapine, and peripheral thrombosis following the combination of warfarin with trazodone. CONCLUSIONS: Because of ahigh risk of interactions and related adverse effects, especially in older patients, each decision regarding combination of a particular antidepressant with a medication used in treatment of cardiovascular disorders should be preceded by a detailed analysis of safety and risk-benefit ratio, and also be associated with the search for the safest, alternative combinations of the above-mentioned medications.

Pharmacotherapy of pain in cancer patients - recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons.

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, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. 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 management of crisis situations. In the final part of the recommendations, the issues of pain and care in dying patients are discussed. Recommendations are addressed to physicians of different specialties involved in the diagnostics and treatment of cancer in their daily practice. It is the hope of the experts who took part in the development of these recommendations that the recommendations would become helpful in everyday medical practice and thus contribute to the improvement in the quality of care and the efficacy of pain treatment in this group of patients.

Perioperative Immunosuppression and Risk of Cancer Progression: The Impact of Opioids on Pain Management.

Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially immunosuppressive effects of opioid analgesics and their serious consequences, including the risk of cancer progression. The identification of these risks has prompted a search for other effective, and most importantly, safer methods of perioperative analgesic management. Regional analgesia techniques, which allow for a significant reduction in opioid dosing and thus diminish the risk of immunosuppression associated with these drugs, seem to offer substantial hope in this respect. A number of studies available in the literature assess the effects of regional analgesia techniques on cancer progression; however, it is often difficult to interpret their results owing to several perioperative factors (such as surgical trauma, inadequate pain and stress relief, and hypothermia) which are also attributed immunosuppressive effects and tend to be implicated in increased risk of cancer progression. Further research is needed to verify the available data on both the potential adverse effects of opioids and the possible protective effects of regional analgesia techniques on cancer patients.