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.

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.

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.

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.

Genetic polymorphism of ABCB1 gene (C3435T) in patients with inflammatory bowel diseases. Is there any gender dependency?

BACKGROUND: In recent years, an increasing incidence of inflammatory bowel disease (IBD) has been reported, mainly as Crohn's disease (CD) and ulcerative colitis (UC). The individual susceptibility, the disease's course and response to the applied therapy is likely due to genetic factors such as ABCB1 gene mutations, exemplified by C3435T polymorphism. The aim of the study was to evaluate the distribution of C3435T polymorphism regarding the gender in IBD patients and control subjects from Lower Silesia region and its possible association with IBD susceptibility. METHODS: The research was conducted in groups of 61 IBD patients and 101 healthy subjects from the Lower Silesia region. Polymorphism of C3435T was determined using PCR-RFLP method. RESULTS: Frequency distributions of C3435T genotype and of 3435T or 3435C gene alleles of IBD, CD or UC patients were compared to control group; each treated as a whole or split further by gender. The statistically significant correlation was discovered between gender and C3435T genotype both for IBD and CD patients, with 3435CT heterozygote prevailing in IBD and CD males. Odds ratio calculations revealed statistically significant difference for the 3435CT genotype between control and: IBD group considered as a whole; IBD males; CD males; and for 3435TT variant between control and IBD males. Conclusions. The 3435CT genotype could be a risk factor for IBD and CD in men. The 3435TT genotype in males seems to be associated with the lower chance of IBD presence.

Pharmacokinetics of treosulfan and its active monoepoxide in pediatric patients after intravenous infusion of high-dose treosulfan prior to HSCT.

Pro-drug treosulfan (TREO) is currently evaluated in randomized phase III clinical trials as a conditioning agent prior to HSCT. In the present paper pharmacokinetics of both TREO and its biologically active monoepoxide (S,S-EBDM) was investigated in pediatric patients for the first time. The studies were carried out in 16 children (median age 7.5 years) undergoing TREO-based preparative regimen prior to HSCT, who received 10, 12 or 14 g/m(2) of the drug as a 1h or 2h intravenous infusion. Plasma concentrations of TREO as well as S,S-EBDM were determined using the validated HPLC-MS/MS method. The changes in S,S-EBDM concentration over time followed TREO levels. The area under the curve (AUC) of TREO was 100-fold higher than AUC of S,S-EBDM. No statistically significant dependency of the dose-normalized AUC of either TREO or S,S-EBDM on the patients' age and body surface area was stated. Moreover, plasma C(max) as well as AUC of S,S-EBDM demonstrated linear correlation with the C(max) and AUC of TREO, respectively. The biological half-lives of TREO and S,S-EBDM were similar. This indicates that S,S-EBDM was completely eliminated from the patients' blood within relatively short time, comparable to TREO.

The investigation of specific biochemical markers in monitoring kidney function of drug addicts.

INTRODUCTION: An increasingly important issue in the Polish population is drug abuse. It leads to extensive damage of parenchymal organs, including kidney. Establishing early markers of organ damage and their monitoring during rehabilitation therapy is therefore of pivotal importance. This study evaluated the utility of highly specific and selective markers (NGAL, IL-18, a and π-GST isoenzyme, and ß2-M). The influence of opioid drugs and other factors on kidney function (HIV and HCV infections, duration and the kind of drugs abused) was determined. MATERIALS AND METHODS: Urine collected from 83 subjects who abused drugs and 33 healthy volunteers was tested with ELISA using specific antibodies (IBL, Biotron, Bioporto-Diagnostics). HIV infection was confirmed with western-blotting and HCV with PCR. CD4 lymphocytes were quantified with flow cytometry. RFLP and PCR were used to determine the viral load of HIV and HCV (genotype). RESULTS: A significant increase of IL-18, NGAL and ß2M activity in heroin addicts compared to the control group was noted as well as the influence of HIV infection on NGAL and ß2M excretion. A statistically significant (p=0.04) correlation between the viral load and IL-18 concentration was noted while no significant influence of the duration and the kind of drugs abused, the route of intake or the age of addicts was seen. Only the NGAL concentration was sex dependent and significantly higher in women. DISCUSSION: This study showed the specific, clinical utility of IL-18, NGAL, and ß2M in the evaluation of renal function in drug addicts. Early detection of nephropathy with biochemical indicators might help prevent severe conditions that require hospitalization and intensive care.

Influence of anticancer therapy on oxidation phenotype and acetylation phenotype in patients with acute myeloblastic leukemia.

The aim of this study was to determine whether antineoplastic cytostatic therapy induces changes in the oxidation or acetylation phenotypes in patients with acute myeloblastic leukemia (AML). The investigations involved 22 patients with AML undergoing chemotherapy with daunorubicin, cytosine arabinoside, etoposide and mitoxantrone. The oxidation phenotype prior to therapy and after termination of induction was examined in all 22 patients and was examined in 10 patients after termination of the first consolidation cycle. The acetylation phenotype was examined prior to therapy and after termination of induction in 21 patients and after termination of the first remission consolidation cycle in 9 patients. The oxidation phenotype was determined by means of the method by Eichelbaum and Gross. The acetylation phenotype was determined using Varley's modification of the Bratton-Marshall method. Anticancer therapy affected the oxidation phenotype, causing decreased activity of the cytochrome P450 isoenzyme CYP2D6. This decrease suggests that daunorubicin, cytosine arabinoside, etoposide and mitoxantrone may impair the metabolism of other active substances metabolized by this isoenzyme, which should be taken into consideration in planning the dosage scheme in individual patients and considering interactions between drugs. Evaluation of the effect of administered cytostatic drugs on acetylation phenotype revealed no statistically significant decrease in the rate of sulfadimidine acetylation.

[Anticancer chemotherapy containing cisplatin in patients with lung cancer and kidney function]. / Chemioterapia przeciwnowotworowa zawierajaca cisplatyne u chorych na raka pluca a czynnosc nerek.

To carry out safe anticancer chemotherapy one should consider the kidney function. Insufficiency of that main organ responsible for drugs excretion, caused either by neoplastic disease or by chemotherapy, can diminish the possibility or even make impossible of carrying out a complete treatment cycle. The aim of our work was to evaluate the kidney function in patients with lung cancer during anticancer chemotherapy containing cisplatin. The tubular function was studied by estimation the activity of N-acetyl-beta-D-glucosaminidase in urine and glomerular function was studied by estimation the concentration of creatinine in urine, urea, uric acid and electrolytes in plasma. The observations have recorded that neoplastic process, as well as chemotherapy impaired the tubular function. It has showed that it does exist a necessity of detailed estimation of kidney excretory function before, during and after the end of anticancer therapy. Determination of NAG activity in urine may be helpful for the recognition of the patients at high nephrotoxicity risk, who need special care.