RESUMO
BACKGROUND: Obese individuals have higher rates of cancer incidence and cancer- related mortality. The worse chemotherapy outcomes observed in this subset of patients are multifactorial, including the altered physiology in obesity and its impact on pharmacokinetics, the possible increased risk of underdosing, and treatment-related toxicity. AIMS: The present review aimed to discuss recent data on physiology, providing just an overall perspective and pharmacokinetic alterations in obesity concerning chemotherapy. We also reviewed the controversies of dosing adjustment strategies in adult and pediatric patients, mainly addressing the use of actual total body weight and ideal body weight. METHODS: This narrative review tried to provide the best evidence to support antineoplastic drug dosing strategies in children, adolescents, and adults. RESULTS: Cardiovascular, hepatic, and renal alterations of obesity can affect the distribution, metabolism, and clearance of drugs. Anticancer drugs have a narrow therapeutic range, and variations in dosing may result in either toxicity or underdosing. Obese patients are underrepresented in clinical trials that focus on determining recommendations for chemotherapy dosing and administration in clinical practice. After considering associated comorbidities, the guidelines recommend that chemotherapy should be dosed according to body surface area (BSA) calculated with actual total body weight, not an estimate or ideal weight, especially when the intention of therapy is the cure. CONCLUSION: The actual total body weight dosing appears to be a better approach to dosing anticancer drugs in both adults and children when aiming for curative results, showing no difference in toxicity and no limitation in treatment outcomes compared to adjusted doses.
Assuntos
Antineoplásicos , Neoplasias , Adulto , Adolescente , Humanos , Criança , Peso Corporal/fisiologia , Obesidade/tratamento farmacológico , Neoplasias/tratamento farmacológico , Preparações FarmacêuticasRESUMO
Medications are an important part of the management of patients with kidney disease. When used appropriately, pharmacotherapy can slow disease progression and reduce morbidity and mortality. Unfortunately, reduced kidney function can significantly alter the pharmacokinetics and pharmacodynamics of many medications, putting patients at risk for drug toxicity if modifications to therapy are not appropriately managed. Adding complexity to the appropriateness of medication and dosage selection is the difficulty in estimating kidney function and the discordance between the Cockcroft-Gault-derived dosing cut points in most medication package inserts and the estimations of glomerular filtration rate by newer and generally more accurate guideline-recommended equations. This installment of the AJKD Core Curriculum in Nephrology provides recent updates and practical considerations for designing optimal medication regimens. Given the prevalence of abnormal kidney function and its importance in medication selection and dose adjustment, additional focus and specific recommendations are provided for anticoagulant, anti-infective, analgesic, antidiabetic, and antihypertensive agents.
Assuntos
Currículo , Taxa de Filtração Glomerular/fisiologia , Nefropatias/tratamento farmacológico , Rim/fisiopatologia , Nefrologistas/normas , Humanos , Nefropatias/fisiopatologiaRESUMO
ABSTRACT Covid-19 has been identified as the cause of acute respiratory disease with interstitial and alveolar pneumonia, but it can affect several organs, such as kidneys, heart, blood, nervous system and digestive tract. The disease-causing agent (Sars-CoV-2) has a binding structure to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling entry into cells that express ACE2, such as the pulmonary alveolar epithelial cells. However, studies also indicate the possibility of damage to renal cells, since these cells express high levels of ACE2. Currently, there is no evidence to indicate a specific treatment for covid-19. Several drugs have been used, and some of them may have their excretion process altered in patients with abnormal kidney function. To date, there are no studies that assist health professionals in adjusting the dose of these drugs. Thus, this study aims to review and discuss the topic, taking into account factors associated with kidney injury in covid-19, as well as pharmacokinetic aspects and dose recommendations of the main drugs used for covid-19.
RESUMO A covid-19 foi identificada como a causa de doença respiratória aguda com pneumonia intersticial e alveolar, mas que pode afetar vários órgãos, como rim, coração, sangue, sistema nervoso e trato digestivo. O agente causador da doença (Sars-CoV-2) tem uma estrutura de ligação ao receptor da enzima de conversão da angiotensina 2 (ACE2), permitindo a entrada em células que expressam ACE2, como as células epiteliais alveolares pulmonares. Porém, estudos também indicam a possibilidade de lesão das células renais, uma vez que essas células expressam altos níveis de ACE2. Atualmente, não existem evidências para a indicação de um tratamento específico para a covid-19. Vários medicamentos vêm sendo utilizados, e alguns podem ter o processo de eliminação alterados em pacientes com comprometimento renal. Até o momento, não há estudos que auxiliem os profissionais de saúde no ajuste de dose desses medicamentos. Assim, este estudo tem como objetivo revisar e discutir o tema, levando em consideração os fatores relacionados à lesão renal na covid-19, bem como aspectos farmacocinéticos e recomendações de doses dos principais medicamentos utilizados para covid-19.
Assuntos
Humanos , COVID-19/complicações , COVID-19/tratamento farmacológico , Rim/fisiopatologia , Nefropatias/virologia , Enzima de Conversão de Angiotensina 2RESUMO
There are 2 major categories of patients with seizures and chronic kidney disease (CKD): patients who develop acute symptomatic seizures in the setting of CKD and patients with epilepsy who at some point develop CKD. The incidence of uremic seizures with kidney failure is â¼10%. These seizures are often nonconvulsive and may mimic uremic encephalopathy. Recognition and management of such situations may be challenging for treating physicians who are non-neurologists. Furthermore, practitioners caring for patients with seizures with or without an established diagnosis of epilepsy in the setting of CKD frequently encounter challenges in the selection, loading, titration, and maintenance of antiepileptic drugs (AEDs) due to potentially altered pharmacokinetics of the AEDs. We review the pathophysiology of uremia, uremic seizures, and other neurologic complications of kidney failure; management approaches to the treatment of such complications; the relevant mechanisms of action and pharmacokinetics of AEDs with their use in CKD; and in particular, the management of AEDs in patients requiring hemodialysis therapy.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Convulsões/complicações , Convulsões/tratamento farmacológico , Anticonvulsivantes/farmacocinética , Humanos , Uremia/etiologia , Uremia/metabolismo , Uremia/fisiopatologiaRESUMO
PURPOSE: In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring. METHODS: A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality. FINDINGS: Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis. IMPLICATIONS: Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.