The Impact of the CYP2D6 and CYP1A2 Gene Polymorphisms on Response to Duloxetine in Patients with Major Depression.

Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes.

Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region.

Over the Counter Pain Medications Used by Adults: A Need for Pharmacist Intervention.

BACKGROUND: The safety of pharmacotherapy for geriatric patients is an essential aspect of the demographic perspective in view of the increasing size of this population. Non-opioid analgesics (NOAs) are among the most popular and often overused over-the-counter medications (OTC). The reasons for drug abuse are common in the geriatric population: musculoskeletal disorders, colds, inflammation and pain of various origins. The popularity of self-medication and the ability to easily access OTC drugs outside the pharmacy creates the danger of their misuse and the incidence of adverse drug reactions (ADRs). The survey included 142 respondents aged 50-90 years. The relationship between the prevalence of ADRs and the NOAs used, age, presence of chronic diseases, and place of purchasing and obtaining information about the mentioned drugs were evaluated. The results of the observations were statistically analyzed using Statistica 13.3. The most commonly used NOAs among the elderly included paracetamol, acetylsalicylic acid (ASA) and ibuprofen. Patients consumed the medications for intractable headaches, toothaches, fevers, colds and joint disorders. Respondents indicated the pharmacy as the main location for purchasing medications, and the physician as the source of information for selecting the therapy. ADRs were reported most frequently to the physician, and less frequently to the pharmacist and nurse. More than one-third of respondents indicated that the physician during the consultation did not take a medical history and did not ask about concomitant diseases. It is necessary to extend pharmaceutical care to geriatric patients that includes advice on adverse drug reactions, especially drug interactions. Due to the popularity of self-medication, and the availability of NOAs, long-term measures should be taken to increase the role of pharmacists in providing effective, safe health care to seniors. We are targeting pharmacists with this survey to draw attention to the problem of the prevalence of selling NOAs to geriatric patients. Pharmacists should educate seniors about the possibility of ADRs and approach patients with polypragmasy and polypharmacy with caution. Pharmaceutical care is an essential aspect in the treatment of geriatric patients, which can contribute to better results in their existing treatment and increase the safety of medication intake. Therefore, it is important to improve the development of pharmaceutical care in Poland in order to enhance patient outcomes.

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers.

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.

Contrast Media Adverse Drug Reactions in Highly Polluted Environment.

Iodinated- (ICM) and gadolinium-based (GCM) contrast media are used in radiology imaging techniques, such as computer tomography (CT) and magnetic resonance (MR), respectively. The paper aims to analyze the adverse drug reactions of ICM and GCM on different sites of the body in a highly polluted environment. We analyzed the pharmacovigilance in contrast media on the basis of reports submitted to the Regional Center for Monitoring of Adverse Drug Reactions (ADR) at the Department of Clinical Pharmacology in Wroclaw. Safety profiles were compared between different ICM and GCM and at the system organ level using the proportional reporting ratio (PRR). We analyzed 124 reports of adverse reactions related to contrast agents between 2006 and 2021. Our findings revealed that ADR combinations occurred more frequently after the use of iodinated contrast agents (72.08%) than gadolinium contrast agents (27.92%). Iomeprol and Iopromide were identified as the most frequently reported media. Each medium presented a different safety profile. Skin disorders are the most common adverse drug reactions among patients using both iodine- and gadolinium-based contrast media. Gadolinium-based contrast agents are characterized by similar organ toxicity. Conversely, iodine-based contrast agents are more diverse-some of which show tissue specificity, such as Iodixanol for the gastrointestinal system or Iohexol for the respiratory tract. This study shows relatively high occurrence of respiratory tract related ADRs in Wroclaw. We also prove that it is possible to choose the most optimal contrast agent for patients with specific organ site problems to omit the possible complications.

Application of Novel Pharmacists' Risk in Pharmacotherapy (PHARIPH) Scale for Identification of Factors Affecting the Safety of Hospital Pharmacotherapy-An Observational Pilot Study.

BACKGROUND: The widespread occurrence of medication errors (MEs) has become a global problem because it poses a serious threat to the health and lives of patients, can prevent the achievement of treatment goals, undermines patient trust in the health care system, and increases treatment costs. The purpose of this study was to develop an appropriate tool to identify key risk factors that hospital pharmacists believe threaten pharmacotherapy safety in the hospital. METHODS: A diagnostic survey method using the authors' PHARIPH (Pharmacists' Risk in Pharmacotherapy) scale and authorial questions was used to identify risks that may result in patient pharmacotherapy errors at the hospital pharmacist level. A total of 125 Polish hospital pharmacists participated in the study. RESULTS: The original authors' created PHARIPH scale was characterized by a Cronbach's alpha coefficient of 0.958. According to the surveyed pharmacists, the greatest threat to pharmacotherapy safety was misreading of a doctor's order (similar drug nomenclature) and preparing a wrong drug (similar drug packaging, similar drug nomenclature). Female pharmacists compared to male pharmacists attributed significantly higher importance to such risk factors such as pharmacist's ignorance of a list of drug substitutes (p = 0.047, risk 8), preparation from an expired/withdrawn drug (p = 0.002, risk 14), preparation from a drug stored in inappropriate conditions (p = 0.05, risk 15), preparation of drugs ordered in hospital and PODs (patients' own drugs) without checking for possible drug duplication (p = 0.011, risk 17) and their potential effect on patient safety. CONCLUSIONS: The PHARIPH scale could be applied as a novel tool for identification of pharmacotherapy risks.

Antibiotics and the Nervous System-Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?

Antibiotics as antibacterial drugs have saved many lives, but have also become a victim of their own success. Their widespread abuse reduces their anti-infective effectiveness and causes the development of bacterial resistance. Moreover, irrational antibiotic therapy contributes to gastrointestinal dysbiosis, that increases the risk of the development of many diseases, including neurological and psychiatric. One of the potential options for restoring homeostasis is the use of oral antibiotics that are poorly absorbed from the gastrointestinal tract (e.g., rifaximin alfa). Thus, antibiotic therapy may exert neurological or psychiatric adverse drug reactions which are often considered to be overlooked and undervalued issues. Drug-induced neurotoxicity is mostly observed after beta-lactams and quinolones. Penicillin may produce a wide range of neurological dysfunctions, including encephalopathy, behavioral changes, myoclonus or seizures. Their pathomechanism results from the disturbances of gamma-aminobutyric acid-GABA transmission (due to the molecular similarities between the structure of the ß-lactam ring and GABA molecule) and impairment of the functioning of benzodiazepine receptors (BZD). However, on the other hand, antibiotics have also been studied for their neuroprotective properties in the treatment of neurodegenerative and neuroinflammatory processes (e.g., Alzheimer's or Parkinson's diseases). Antibiotics may, therefore, become promising elements of multi-targeted therapy for these entities.

C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case-Control and Meta-Analysis Study.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn's disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

Pseudoephedrine-Benefits and Risks.

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.

Determinants of disease acceptance in renal transplantation patients assessed with the application of Acceptance Illness Scale (AIS).

PURPOSE: Kidney transplant patients require long-term pharmacotherapy with a significant risk of drug-related complications. The disease acceptance may significantly affect the effectiveness, safety, and patient adherence to their treatment. The purpose of this study was to evaluate, for kidney transplantation patients, the essential determinants for better disease acceptance, and whether a clinical pharmacist may influence its degree. METHODS: The study involved 201 renal graft patients aged 18-81 years. The diagnostic survey method with the questionnaire of the Acceptance Illness Scale (AIS) and authors' query was used to obtain sociodemographic and co-morbidities data, the number of medications taken, the therapy cost, a patient needs for more attention from medical staff, and their willingness to cooperate with a clinical pharmacist. RESULTS: The largest group (55.2%) of patients demonstrated a high level of acceptance of their health. However, in every disease acceptance score range (low, medium, high), the score was statistically lower in patients over 50 years of age (c2=7.27, p=0.026), occupationally inactive (c2 =13.8, p<0.001), over 5 medicines taken (c2=7.77, p=0.020), and declaring too much expenditure on the therapy (c2=14.3, p<0.001). The assessment established a statistically significant negative correlation between the number of chronic conditions and the AIS score (R=-0.32, p<0.001). The lower number of coexisting chronic diseases the better disease acceptance. Moreover, patients reporting the need for more attention from the health service and willing to consult a pharmacist cope in a statistically significant way worse with accepting their health (c2=15.1 and p<0.001, c2=6.76 and p=0.034 respectively).  Conclusion: For post-transplantation patients, factors affecting the acceptance of illness should be taken into consideration while planning medical care. The reported need for professional assistance indicates necessity for establishing a multidisciplinary therapeutic team in which a clinical pharmacist should play a special role.

Nephrotoxicity of Herbal Products in Europe-A Review of an Underestimated Problem.

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

Factors Influencing the Safety and Efficiency of Antifungal Prophylaxis with Posaconazole in Children with Hematological Diseases: From Genetics to Polypharmacotherapy.

The aim of this study was to determine the impact of ABCB1 polymorphism, BMI, age and drug co-administration on safety and efficiency of posaconazole (PCZ) oral suspension treatment in children with hematological diseases. Seventy children were included in the study. ABCB1 polymorphism in fifty-eight children was determined using a PCR-RFLP method. A protocol with data on the health condition, treatment and adverse events (AE), as well as a survey on treatment tolerance for the legal guardians was evaluated. Liver function tests were observed for the first 20 days, and AE during the complete medication period. For statistical analysis a χ2 test with Yates's correction, a Pearson's or Spearman's correlation test was performed (p < 0.05). Genetic testing showed 24% CC, 46% CT and 30% of TT variants. PCZ prophylaxis failed in twenty cases, where change in prophylactic treatment was needed. Fifty-two children suffered from at least one mild to moderate adverse event. Sixty-five legal guardians completed the survey, most of them reported the treatment to be well tolerated. ABCB1 polymorphism had no impact on AE occurrence and posaconazole prophylaxis efficiency. Age influenced the number of gastrointestinal (p = 0.02), visual (p = 0.05), neurological (p = 0.01), dermatological (p = 0.002) and flu-like (p = 0.02) complications. AST (p = 0.03) and LDH (p = 0.008) activity presented age dependency. The concomitant use of proton pump inhibitors (PPI) had impact on liver health parameters elevation (p = 0.009) and circulatory system complications (p = 0.008). High incidence of mild to moderate AE, and other factors influencing PCZ pharmacokinetics (PPI co-administration, obesity), suggest a need for careful pediatric onco-hematology patient evaluation.

Venlafaxine pharmacogenetics: a comprehensive review.

Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we reviewed studies which focused on the pharmacogenetics of VEN and found that there is a lack of guidelines for pharmacogenetic testing for VEN. Within investigated genetic polymorphisms, few of them can be indicated as potential predictors of VEN efficacy and tolerance. However, additional pharmacogenetic studies of VEN should be performed to reproduce already obtained results or explain contradictory ones. The individualization of pharmacotherapy is a key issue in providing patients with the highest possible quality of treatment, therefore pharmacogenetic studies should be one of the components of therapy optimization.

The importance of the polymorphisms of the ABCB1 gene in disease susceptibility, behavior and response to treatment in inflammatory bowel disease: A literature review.

Crohn's disease (CD) and ulcerative colitis (UD) are the 2 common clinical subtypes of idiopathic inflammatory bowel disease (IBD) characterized by chronic inflammation of the gastrointestinal tract. The multifactorial etiology and pathogenesis of IBD is still unknown; however, the interaction between genetic, environmental and immunological factors seems to be crucial. A member of the adenosine triphosphate (ATP)-binding cassette family, P-glycoprotein, encoded by the human ABCB1 gene, is among the most extensively studied transporters involved in drug disposition and effects. Single nucleotide polymorphisms (SNPs) located in exons 21, 26 and 12, i.e., G2677T/A, C3435T and C1236T, are of the greatest clinical importance. Functional defects of the intestinal epithelial barrier due to the lack of P-glycoprotein expression may constitute possible reasons for the development of colitis. Given that several drugs central to the therapy of IBD are also P-glycoprotein substrates, it has been hypothesized that its altered expression in IBD patients could modify the response to medical treatment. Nevertheless, there are conflicting reports of an association between these 3 SNPs and IBD. This article aims to review all relevant studies investigating the role of the polymorphisms of the ABCB1 gene in disease susceptibility, behavior and response to treatment in IBD.

CYP2D6 basic genotyping as a potential tool to improve the antiemetic efficacy of ondansetron in prophylaxis of postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after anesthesia and surgery. Ondansetron is one of the most widely used drugs in the prophylaxis of PONV and is extensively metabolized in humans. In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P450 enzymes. The cytochrome P450 (human hepatic cytochrome [CYP]) 2D6 inhibitor quinidine reduced in vitro hydroxylation of ondansetron, which indicates the important role of CYP2D6 in ondansetron metabolism. Genotyping these alleles allows the prediction of the extensive metabolizer (EM) and poor metabolizer (PM) phenotypes with approx. 90-96% accuracy. OBJECTIVES: The aim of our study was to evaluate whether the pharmacological prevention of PONV with ondansetron depends on the most common CYP2D6 alleles (CYP2D6*1, *3, *4, *5, and NxN [multiplication gene]). MATERIAL AND METHODS: Genotyping for the defective CYP2D6*3, CYP2D6*4 and CYP2D6*5 alleles among 93 surgical female patients was performed by polymerase chain reaction amplification and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genetically defined EMs and ultrarapid metabolizers (UMs) of CYP2D6 had a statistically significant (p < 0.02) higher frequency of nausea and vomiting after strumectomy (33.3%) than intermediate metabolizers (IMs) (10.3%) and PMs (0%). The relative risk (odds ratio [OR]) of PONV occurrence was 5 times higher for EMs/UMs than IMs/PMs. CONCLUSIONS: Our results suggest that PONV treatment with ondansetron could be improved by basic, widely available and inexpensive PCR-RFLP genetic tests.

Influence of CYP2C19 Genotypes on the Occurrence of Adverse Drug Reactions of Voriconazole among Hematological Patients after Allo-HSCT.

The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients' protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions. The observation and reporting of ADR took place from the -1 until the +20th day of VCZ therapy. For statistical analysis the χ2 test was used (p < 0.05). Among the examined patients 23 suffered from at least one side effect during VCZ therapy. Most frequent ADR were gastrointestinal disturbances (n = 15), nervous system (n = 11) and skin (n = 7) disorders. Patients with at least one loss of function allele (*2) were more likely to experience adverse drug reactions than those, with different genotypes. Due to the limited number of patients the result could not be proven with a statistical significance. Previous determination of CYP2C19 genotype may be a useful tool for prevention of adverse drug reactions during VCZ prophylaxis among patients after allo-HSCT.

ECONOMIC ISSUES IN THERAPEUTIC DRUG MONITORING.

The fact that resources for health care are limited has been found as a rationale for the development of pharmacoeconomics. Pharmacoeconomic analysis identifies, measures and compares the costs and the economic, clinical and humanistic outcomes of diseases, drug therapies and programmes directed to these diseases. As health care expenditures have escalated over the past decades, the number of its applications has increased. Taking into consideration outcome and economic issues and establishing their mutual relationship helps proper resource allocation. In the case of some effective and toxic drugs therapeutic drug monitoring has been proven to allow obtaining the desired clinical effects safely and thus to improve outcome. However, it requires the presence of clinical pharmacology or clinical pharmacy service within a hospital, which in turn is associated with some additional costs. This review sums up the results of pharmacoeconomic studies relevant to the use of therapeutic drug monitoring in case of the medicines for which it has been commonly performed so far.

Continuous vs. intermittent vancomycin therapy for Gram-positive infections not caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND: The aim of this study was to evaluate the effects of vancomycin pharmacokinetics (PKs) on effectiveness and safety in the treatment of Gram-positive infections due to pathogens other than methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Prospective study including septic patients received either continuous (N.=21) or intermittent (N.=21) infusions of vancomycin; the target drug concentration was 15-20 mg/L and target area under the curve of vancomycin concentrations over the minimum inhibitory concentration of the pathogen on day 1 (AUC24/MIC) >400. Clinical and microbiological responses, the development of acute kidney injury (AKI) and therapy costs were recorded. RESULTS: The median AUC24/MIC was 195(133-343) vs. 189(136-328) mg/L*h in the continuous and intermittent infusion groups. Target drug concentrations were achieved in 15/21 vs. 9/21 (P=0.12) patients and AUC24/MIC>400 in only 5/21 vs. 3/21 (P=0.35) patients of continuous and intermittent groups, respectively. High clinical cure (17/21 for continuous vs. 17/21 for intermittent, P=1.00) and microbiological eradication (17/21 vs. 15/21, P=0.47) were observed in both groups and not associated with drug concentrations or with AUC24/MIC. AKI was diagnosed during therapy in 5/21 patients in the continuous group and 8/21 in the intermittent group (P=0.32). The median total therapy costs were lower in the continuous than in the intermittent group (377 [304-485] vs. 552 [371-644] €, P=0.04). CONCLUSIONS: Vancomycin resulted in high clinical response during non-MRSA Gram-positive infections treatment even at drug concentrations lower than those for MRSA. A continuous infusion of vancomycin was associated with a significant reduction in therapy costs compared to intermittent infusions.

Comparison of clinical pharmacology of voriconazole and posaconazole.

Despite greater knowledge and possibilities in pharmacotherapy, fungal infections remain a challenge for clinicians. As the population of immunocompromised patients and those treated for their hematologic ailments increases, the number of fungal infections grows too. This is why there is still a quest for new antifungal drugs as well as for optimization of pharmacotherapy with already registered pharmaceutics. Voriconazole and posaconazole are broad-spectrum, new generation, triazole antifungal agents. The drugs are used in the pharmacotherapy of invasive aspergillosis, Candida and Fusarium infections. Voriconazole is also used in infections caused by Scedosporium. Posaconazole is used in the treatment of coccidioidomycosis and chromoblastomycosis. Besides some similarities, the two mentioned drugs also show differences in therapeutic indications, pharmacokinetics (mainly absorption and metabolism), frequency and severity of adverse drug reactions, drug-drug interactions and dosage. As both of the drugs are used in the treatment of invasive fungal infections in adults and children, detailed knowledge of the clinical pharmacology of antifungal agents is the main factor in pharmacotherapy optimization in treatment of fungal infections. The goal of the article is to present and compare the clinical pharmacology of voriconazole and posaconazole as well as to point out the indications and contraindications of using the drugs, determine factors influencing their pharmacotherapy, and provide information that might be helpful in the treatment of fungal infections.

Evaluation of the toxicity of anticancer chemotherapy in patients with colon cancer.

BACKGROUND: Modern anticancer chemotherapy can cause numerous adverse effects in the organism, whose functioning has already been disrupted by the neoplastic process itself. OBJECTIVES: The aim of the study was to evaluate and compare the frequency and severity of the toxicity of FOLFOX-4 and CLF-1 anticancer therapy in patients with colon cancer, and to analyze certain factors that might have increased the toxicity of the chemotherapy. MATERIAL AND METHODS: The study involved 64 patients suffering from generalized colon cancer, including 48 patients treated according to the FOLFOX-4 regimen and 16 patients treated according to the CLF-1 regimen. The toxicity of each regimen was analyzed on the basis of a confidential questionnaire formulated by the authors and laboratory research according to the extended WHO toxicity criteria. RESULTS: The analysis of the symptoms of toxicity symptoms associated with the use of the FOLFOX-4 and CLF-1 therapeutic regimens revealed that the most common side effects included nausea and vomiting, despite ondansetron premedication, and neurotoxicity. Disruption of the functioning of the nervous system under the FOLFOX-4 regimen statistically significant exacerbation that increased with the number of chemotherapy cycles administered; this was more common and more severe in women. Paresthesia was also revealed to be a neurotoxic effect of the FOLFOX-4 regimen after termination of therapy. A statistically significant relationship was observed between the use of vitamin supplements and the incidence and severity of the toxicity of the FOLFOX-4 regimen. CONCLUSIONS: The findings of the current study regarding the toxicity of the FOLFOX-4 and CLF-1 therapy regimens should be taken into consideration when monitoring chemotherapy safety in colon cancer. The patients' tolerance of the administered medication and the side effects reported by patients should be constantly evaluated, which will help prevent these side effects, apply appropriate therapy and contribute to the improvement of the patients' quality of life. The functioning of the central nervous system should be carefully evaluated when planning the anticancer therapy, especially if repeated administration of neurotoxic drugs is necessary in cases of a recurrence of the disease. Chemotherapy should be thoroughly monitored for safety, especially in women over 65 years of age suffering from coexisting diseases. Colon cancer patients and their families should be informed of the risks of nutritional supplements before the start of the anticancer chemotherapy, and may need to dispense with their use.