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1.
Anticancer Drugs ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32107349

RESUMO

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.

2.
Sci Rep ; 9(1): 9312, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249357

RESUMO

Cisplatin (CDDP) combined with radiotherapy (RT) is employed in head and neck squamous cell carcinoma (HNSCC) with variable toxicities and clinical response. Glutathione S-transferases (GSTs) participate in CDDP excretion from cells, and genes encoding GSTs, GSTM1, GSTT1and GSTP1, are polymorphic in humans. This prospective study aimed to evaluate the roles of GSTM1, GSTT1, and GSTP1 Ile105Val polymorphisms in outcomes of HNSCC patients treated with CDDP chemoradiation. Ninety patients were genotyped by multiplex PCR. Urinary CDDP measurements were performed by HPLC. Treatment side effects and response were analysed by conventional criteria. Patients with GSTT1 genes showed 7.23- and 5.37-fold higher likelihood of presenting vomiting and ototoxicity, lower glomerular filtration rate (GFR), and lower elimination of CDDP in urine relative to patients with deleted genes. Patients harbouring the GSTP1 IleVal or ValVal genotypes showed 4.28-fold higher likelihood of presenting grade 2 or 3 vomiting and lower GFR with treatment than those harbouring the IleIle genotype. In multivariate Cox analysis, patients with the GSTP1 105ValVal genotype had 3.87 more chance of presenting disease progression than those with the IleIle or IleVal genotype (p < 0.01). Our findings provide preliminary evidence that inherited abnormalities in CDDP metabolism, related to GSTT1 and GSTP1 Ile105Val polymorphisms, alter outcomes of HNSCC patients treated with CDDP and RT.

3.
Crit Rev Oncol Hematol ; 137: 131-142, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014509

RESUMO

Cisplatin (CDDP) is a highly effective antineoplastic agent, widely used in the treatment of various malignant tumors. However, its major problems are side effects associated to toxicity. Considerable inter-individual differences have been reported for CDDP-induced toxicity due to genetic and epigenetic factors. Genetic causes are well described; however, epigenetic modifications are not fully addressed. In the last few years, many evidences were found linking microRNA to the development of CDDP-mediated toxicity, particularly nephrotoxicity. In this review, we described how genetic and epigenetic modifications can be important determinants for the development of toxicity in patients treated with CDDP, and how these alterations may be interesting biomarkers for monitoring toxicity induced by CDDP. Considering the validation in different studies, we suggest that miR-34a, -146b, -378a, -192, and -193 represent an attractive study group to evaluate potential biomarkers to detect CDDP-related nephrotoxicity.


Assuntos
Cisplatino/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/genética , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Epigênese Genética , Humanos , MicroRNAs/genética
4.
Cancer Med ; 8(5): 2020-2030, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977273

RESUMO

The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin-induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double-blind, placebo-controlled trial conducted in patients receiving high-dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro-, oto-, hepato-, myelo-, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty-seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low-dose oral NAC does not protect patients with head and neck cancer from cisplatin-induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.

5.
BMC Pregnancy Childbirth ; 19(1): 97, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894167

RESUMO

BACKGROUND: In clinical trials, pregnant women are potentially vulnerable, and the fetus is exposed to the intervention. This study aimed to identify the reasons that led pregnant women at a high risk of premature delivery to participate in a randomized clinical trial. METHODS: The women participating in the main trial were contacted by telephone postpartum and invited to answer an open questionnaire in a cross-sectional study. Data were collected by telephone and analyzed using thematic analysis. After the analysis categories were defined, all the answers were reviewed, categorized and grouped. A descriptive summary of the content of each category was then made. RESULTS: Overall, 208 women from different geographical regions of the country agreed to participate. Four categories were identified: 1) The risk of losing the baby; 2) A previous experience of premature delivery; 3) The role of the doctor and other health professionals, and 4) The availability of quality medical care and free medication. The main reason given for agreeing to participate was to reduce the risks associated with the baby being born prematurely, particularly when the woman herself or someone close to her had already experienced premature delivery. Other reasons were having received clear guidance and explanations from the doctor regarding prematurity and about the study and being given the opportunity to receive free treatment with greater access to the public healthcare system. CONCLUSIONS: The decision to participate in a clinical trial is not easy, particularly when the individual is vulnerable and in a critical situation as in the case of a pregnant woman at a high risk of delivering prematurely. Fears and uncertainties regarding the pregnancy outcome, as well as the woman's previous experiences and her awareness of the actual risks she faces will affect her decision regarding whether or not to participate. Recruitment challenges could be overcome by ensuring that the research team provides adequate information and support, thus creating a bond with participants that would foster a sense of safety and trust in the study proposals.


Assuntos
Ensaios Clínicos como Assunto/psicologia , Gestantes/psicologia , Nascimento Prematuro/psicologia , Sujeitos da Pesquisa/psicologia , Adulto , Estudos Transversais , Tomada de Decisões , Feminino , Humanos , Gravidez , Nascimento Prematuro/prevenção & controle , Pesquisa Qualitativa
6.
J Clin Pharm Ther ; 44(3): 415-419, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30666679

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Polymyxins, especially polymyxin B, has become the last line of therapy against Gram-negative pathogens' carbapenemase producers. However, given increasing use of polymyxin B in clinical settings its therapeutic value has been evaluated worldwide due to its toxic effects. The aim of this study was to assess the efficacy and safety of antimicrobial therapy with polymyxin B in patients with multidrug-resistant bacteria in Brazil. METHODS: This was a prospective cohort study in a 403-bed academic tertiary care centre, located in the countryside of Brazil. Patients receiving polymyxin B intravenous treatment for at least 72 hours were eligible for the study. Antimicrobial susceptibility, adverse reactions and clinical outcomes were submitted for descriptive analysis. Main outcomes measure the following: Patients' conditions following treatment (Treatment Success, Mortality, Treatment Failure, Inadequate Empiric Treatment or Indeterminate Response) and toxicities induced by polymyxin B (nephrotoxicity and skin hyperpigmentation). RESULTS AND DISCUSSION: Among 247 patients, treatment success was achieved in 25.1%, while mortality was observed in 32.8%. Empirical therapy was prescribed for 26.3% of the patients. Nephrotoxicity was reported in 40.5%. The carbapenemase producer, Klebsiella pneumonia, was the bacterium most associated with mortality (22.2%). CONCLUSIONS: Even though polymyxin B is currently the main therapy against carbapenemase producers, its use demands robust criteria to lead to positive clinical outcomes.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Polimixina B/uso terapêutico , Administração Intravenosa , Antibacterianos/efeitos adversos , Brasil , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Hiperpigmentação/induzido quimicamente , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Polimixina B/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
7.
J Oncol Pharm Pract ; 25(7): 1665-1674, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30348073

RESUMO

Management and prevention of problems related to oncology drugs are particularly important due to the excessive cost, high toxicity, and narrow therapeutic index of the antineoplastic drugs, in addition to the patients' state of health. Therefore, the presence of the pharmacist as a member of the multidisciplinary team is essential to contribute to patient safety. In this work, the interventions performed were identified, quantified, and classified to characterize the work of the clinical oncology pharmacist. This is a prospective and quantitative study, conducted over a period of six months in the outpatient oncology and chemotherapy clinic of the University Hospital of the University of Campinas, Brazil. A total of 3526 medical prescriptions were evaluated for the 780 patients seen and, among these prescriptions, 220 (6.24%) contained errors, representing 6.24% of the total number. The most common error was dose-related with 79 (22.83%) cases of overdosing. Wrong-patient medication error was the least reported (0.29%). Thirty drugs were involved in the pharmaceutical interventions, Carboplatin and Ondansetron being the most frequent. Thirteen types of potential errors were evaluated according to the method proposed by Cardinal and Fernandes. Two (15.38%) included interventions of indication, contraindication, and therapeutic efficacy of a drug. Five of them (38.46%) are related to the treatment regimen, and two (15.38%) were related to prevention of potential adverse events. Four interventions (30.77%) concerned technical interventions in injectable drugs such as dilution, compatibility, and administration time. Of the 346 interventions performed, 1 (0.29%) was classified as potentially lethal, 114 as serious (32.95%), 140 as significant (40.46%), and 91 as minor (26.30%).


Assuntos
Oncologia/normas , Erros de Medicação/prevenção & controle , Segurança do Paciente/normas , Farmacêuticos/normas , Papel Profissional , Brasil/epidemiologia , Feminino , Hospitais Universitários/normas , Hospitais Universitários/tendências , Humanos , Masculino , Oncologia/tendências , Erros de Medicação/tendências , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/normas , Equipe de Assistência ao Paciente/tendências , Farmacêuticos/tendências , Estudos Prospectivos
8.
Int J Clin Pharm ; 41(1): 74-80, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30552622

RESUMO

Background The emergence and rapid spread of multidrug-resistant gram-negative bacteria related to nosocomial infections is a growing worldwide problem, and polymyxins have become important due to the lack of new antibiotics. Objectives To evaluate the outcomes and pharmacoeconomic impact of using colistin and polymyxin B to treat nosocomial infections. Setting Neurosurgical, cardiovascular, or transplantation intensive care unit (ICU) at the Clinical Hospital of the University of Campinas (São Paulo, Brazil). Method A retrospective cohort study was conduct in patients in the ICU. The renal function was determined daily during treatment by measuring the serum creatinine. A cost minimization analysis was performed to compare the relative costs of treatment with colistin and polymyxin B. Main outcomes measure The outcomes were 30-day mortality and frequency and onset of nephrotoxicity after beginning treatment. Results Fifty-one patients treated with colistin and 51 with polymyxin B were included. 30-day mortality was observed in 25.49% and 33.33% of patients treated with colistin and polymyxin B, respectively; Nephrotoxicity was observed in 43.14% and 54.90% of patients in colistin and polymyxin B groups, respectively; and onset time of nephrotoxicity was 9.86 ± 13.22 days for colistin and 10.68 ± 9.93 days for polymyxin B group. Colistin treatment had a lower cost per patient compared to the cost for polymyxin B treatment (USD $13,389.37 vs. USD $13,639.16, respectively). Conclusion We found no difference between 30-day mortality and nephrotoxicity between groups; however, colistin proved to be the best option from a pharmacoeconomic point of view.


Assuntos
Antibacterianos/economia , Colistina/economia , Infecção Hospitalar/economia , Farmacoeconomia , Unidades de Terapia Intensiva/economia , Polimixina B/economia , Adulto , Idoso , Antibacterianos/uso terapêutico , Brasil/epidemiologia , Estudos de Coortes , Colistina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Custos de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimixina B/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
9.
Pediatr Emerg Care ; 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30106866

RESUMO

OBJECTIVES: The objectives of this study were to analyze adverse drug events (ADEs) related to admissions to a pediatric emergency unit and to identify the associated risk factors. METHODS: This was a prospective study. Demographic data and details of medications were collected for each patient admitted. Case studies were performed by clinical pharmacists and the clinical team to discuss whether the admission was due to an ADE and to characterize the ADE. Multivariate logistic regression was used for statistical analysis. RESULTS: In total, 1708 pediatric patients were included in this study. Adverse drug events were the cause of hospital admission in 12.3% of the studied population. The majority of patients presenting with an ADE were in the age group of 0 to 5 years (61.6%), had a mean ± SD age of 4.9 ± 3.9 years, were female (51.2%), were Caucasian (72.0%), and had infectious disorders (49.3%). High frequencies of medication errors (68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs of mild severity (75.3%) were reported. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological (odds ratio [OR], 4.63; 95% confidence interval [CI], 2.38-8.99), dermatological (OR, 3.16; 95% CI, 1.93-5.18), and respiratory (OR, 3.02; 95% CI, 1.89-4.83) disorders. CONCLUSIONS: A high frequency of ADE-related admissions to the pediatric emergency unit was observed. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological, dermatological, and respiratory disorders. Clinical pharmacists play an important role in the identification of ADEs and the education of child caregivers and health care providers concerning pediatric medication.

10.
Oncotarget ; 9(51): 29538-29547, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-30038702

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT. DNA from peripheral blood was analyzed by PCR-based methods to obtain genotypes. It was observed 4.27-fold and 4.69-fold increased risks of presenting pronounced nephrotoxicity with treatment in patients with MSH3 GG and EXO1 rs9350 CC genotypes compared with patients with GA or AA and CT or TT genotypes, respectively. MSH3 GG or GA and GT haplotype of EXO1 rs1047840 and rs9350 SNPs conferred to patients 10.29 and 4.00 more chances of presenting pronounced ototoxicity after treatment than MSH3 AA genotype and other EXO1 haplotypes, respectively. Patients with EXO1 rs1047840 GA or AA genotype and AC haplotype of EXO1 rs1047840 and rs9350 SNPs had both 9.55-fold increased risks of achieving partial response or stable disease instead of complete remission after treatment than patients with EXO1 GG genotype and other EXO1 haplotypes, respectively. For the first time, our data show preliminary indication that inherited alterations of DNA MMR pathway, related to MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 SNPs, modify toxicity and response to chemoradiation in HNSCC, and may contribute to future personalized treatment of patients.

12.
Mol Cell Biochem ; 440(1-2): 139-145, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28828710

RESUMO

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, H2DCF-DA, and Amplex® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O 2•- ), hydrogen peroxide (H2O2), and general reactive oxygen species production occurred. A higher production of H2O2 was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H2O2 production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, H2O2 production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.


Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Peróxido de Hidrogênio/sangue , Nefropatias , Leucócitos Mononucleares , Estresse Oxidativo/efeitos dos fármacos , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/patologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade
15.
BMC Cancer ; 17(1): 831, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29212535

RESUMO

BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Laríngeas/tratamento farmacológico , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/radioterapia , Perna (Membro)/irrigação sanguínea , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/patologia , Vasculite Leucocitoclástica Cutânea/complicações , Vasculite Leucocitoclástica Cutânea/patologia
16.
Basic Clin Pharmacol Toxicol ; 121(6): 520-525, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28686330

RESUMO

Cisplatin (CDDP) chemotherapy associated with radiation (RT) has been used in advanced head and neck squamous cell carcinoma (HNSCC) patients, and vomiting is a common side effect during treatment. This prospective study aimed to identify the roles of GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-1168G>T, CASP9 c.-1339A>G, CASP8 c.-937_-932delAGTAAG, FAS c.-1378G>A and c.-671A>G, and FASL c.-157-687C>T single nucleotide polymorphisms, involved in CDDP metabolism, in vomiting severity in 88 HNSCC patients treated with CDDP and RT. Ondansetron and dexamethasone were administered as anti-emetic therapy. Patients with GSTP1 c.313AG or GG genotype alone and combined with XPD c.934GA or AA, XPF c.2505TC or CC, and CASP9 c.-1339AG or GG genotypes had 4.28, 5.00, 5.45 and 5.38 more chances of presenting moderate/severe vomiting than patients with others genotypes. Our data suggest, for the first time, that inherited abnormality in apoptosis pathway alone or combined with inherited abnormalities in DNA repair pathway, is capable of modulating emesis in HNSCC patients under CDDP chemoradiation and may be used for selecting patients who should receive pre-emptive anti-emetic therapy.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Predisposição Genética para Doença/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Vômito/induzido quimicamente , Vômito/genética , Adulto , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/farmacocinética , Carcinoma de Células Escamosas/complicações , Cisplatino/farmacocinética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Vômito/tratamento farmacológico
17.
J Glob Antimicrob Resist ; 10: 195-199, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28735057

RESUMO

OBJECTIVE: The aim of this study was to determine the impact of two resolutions to restrict antibiotic use (RDCs no. 44/2010 and 20/2011) in the Campinas metropolitan area (Sao Paulo, Brazil) on antibiotic consumption, resistance rates, and trends in Escherichia coli-causing community-acquired urinary tract infection (UTI). METHODS: The annual retail sale information of antibiotics from drugstores in the Campinas metropolitan area between 2008 and 2012 were obtained through the Intercontinental Medical Statistics Health of Brazil. The daily-defined dose (DDD)/1000 inhabitants/day was calculated from these data to measure consumption. To examine resistance rates, we performed an observational retrospective study in a Campinas teaching hospital, where urinary cultures from outpatients with a clinical suspicion of UTI between October 2009 and September 2015 were analyzed. RESULTS: We observed an increase in rates of antibiotic sales from 2008 to 2011 (cephalosporin: 216.8%, quinolones: 170.9%, aminopenicillins: 140.9%), followed by a decrease in sales in 2012 (cephalosporin: 19.4%, quinolones: 12.7%, aminopenicillins: 11.1%). Sale of nitrofurans, however, did not significantly change during this period. In the retrospective analysis, we observed a significant increasing trend of E. coli resistance for all antibiotic classes, except nitrofurans and folate pathway inhibitors. CONCLUSIONS: We found changes in antibiotic consumption, with an initial increase, followed by a decrease in sales after implementation of the resolutions. However, bacterial resistance does not appear to be affected by the RDCs.


Assuntos
Antibacterianos/normas , Comércio/normas , Farmacorresistência Bacteriana , Uso de Medicamentos/normas , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Brasil , Comércio/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
18.
Saudi Pharm J ; 25(5): 724-733, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28725145

RESUMO

Background: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient's response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group. Methods: We conducted a prospective controlled intervention study with patients paired by gender and initial T CD4+ lymphocyte (CD4) count. HIV-infected patients of a public outpatient service were enrolled for the study by consecutive and convenience sampling. Patients selected for the study were divided into a control group and an intervention group. Both groups were followed for one year; however, only the intervention group received pharmaceutical care. The primary outcome was the drug related problem (DRP) analysis for the intervention group. Secondary outcomes were CD4 count and viral load evaluation for both groups. Results: There was a total of 143 patients enrolled in this study, with 53 (37.06%) patients in the control group and 90 (62.94%) patients in the intervention group. A total of 202 pharmacist interventions with 193 pharmacist-patient and 9 pharmacist-physician interventions were proposed. After one year of pharmaceutical care, a reduction of 38.43% between the initial and final DRP was found (p = 0.0001). The most common DRPs found were related to medication safety. The intervention group showed a mean increase of 84% for the CD4 count in comparison with that observed in the control group. The viral load was not significantly different between the final and initial mean values for both groups. Conclusion: Pharmacist appointments enabled identification, prevention, and solving of drug related problems, especially those related to drug safety. Also, pharmacist interventions improved adherence and increased HAART effectiveness as suggested by the higher elevation in the CD4 count seen in the intervention group in comparison with the control group.

19.
Cancer Chemother Pharmacol ; 80(2): 223-233, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28612092

RESUMO

PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure. CONCLUSIONS: We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Sistema Enzimático do Citocromo P-450/metabolismo , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP4A/metabolismo , Humanos , Nefropatias/induzido quimicamente , Nefropatias/enzimologia , Espécies Reativas de Oxigênio/metabolismo
20.
Daru ; 25(1): 12, 2017 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438219

RESUMO

BACKGROUND: Cisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer. METHODS: Outpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80-100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0-4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0-12, 12-24, and 24-48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine. RESULTS: In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 µg/mg creatinine at 0-12, 12-24, and 24-48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs. CONCLUSIONS: The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0-12 h after chemotherapy, and cisplatin excretion could not predict toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Anemia/induzido quimicamente , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Antineoplásicos/urina , Quimiorradioterapia/métodos , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Cisplatino/urina , Feminino , Humanos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias Faríngeas/terapia , Estudos Prospectivos
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