Epilepsy and bone health in adults.
ABSTRACT Adults taking antiepileptic drugs (AEDs) have an augmented risk for osteopenia and osteoporosis because of abnormalities of bone metabolism associated with AEDs. The increased fracture rates that have been described among patients with epilepsy may be related both to seizures and to AEDs. The hepatic enzyme-inducing AEDs phenytoin, phenobarbital, and primidone have the clearest association with decreased bone mineral density (BMD). Carbamazepine, also an enzyme-inducing drug, and valproate, an enzyme inhibitor, may also adversely affect bone, but further study is needed. Little information is available about specific effects of newer AEDs on bone. Physicians are insufficiently aware of the association between AEDs and bone disease; a survey found that fewer than one-third of neurologists routinely evaluated AED-treated patients for bone disease, and fewer than 10% prescribed prophylactic calcium and vitamin D. Physicians should counsel patients taking AEDs about good bone health practices, and evaluation of bone health by measuring BMD is warranted after 5 years of AED treatment or before treatment in postmenopausal women.
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ABSTRACT: Introduction: Adverse drug effects and drug−drug interactions (DDIs) can be elicited by the activation of several nuclear receptors (NRs). Of the NRs that regulate expression of drug metabolizing enzymes and transporters and alter cellular processes, the most important are pregnane X receptor, constitutive androstane receptor and aryl hydrocarbon receptor. Screening for the activation of these receptors can be achieved during drug discovery by using various high-throughput analyses including ligand binding and transactivation assays. Areas covered: This review focuses on the importance of screening for NR activation during drug discovery and includes a discussion of the various assays to evaluate activation of NRs by xenobiotics. It also describes screening for species-specific NR activation to attenuate the use of animals in toxicology studies and to identify complications associated with drug metabolism and clearance that may occur during pharmacokinetic analyses. Expert opinion: Given the potential for adverse drug effects and DDIs during all phases of drug elimination, NR screening should occur early in drug discovery. Such screening could be used in structure–activity relationship studies to guide chemists in altering compound structures to eliminate the NR-binding and activation properties on priority compounds. Early screening can also reduce the risk of adverse drug effects, identify novel therapeutic agents and decrease the number of animals used in drug development. Overall, performing these types of assays described here could decrease drug development costs, alleviate the liability associated with drugs that activate NR and prevent unsafe drugs from entering the marketplace.Expert Opinion on Drug Discovery 01/2014; 9(6). · 2.30 Impact Factor
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ABSTRACT: Vitamin D deficiency is a highly prevalent condition. Low vitamin D levels have long been associated with bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults. However, it has become apparent in recent years that adequate vitamin D levels are also important for optimal functioning of many organs and tissues throughout the body, including the cardiovascular system. Evolving data indicate that vitamin D deficiency is associated with an increased risk of cardiovascular disease (CVD). Studies have shown that low vitamin D levels are associated with hypertension, diabetes, metabolic syndrome, left ventricular hypertrophy, and chronic vascular inflammation, all of which are risk factors for CVD. This paper reviews the definition and pathophysiology of vitamin D deficiency, clinical evidence linking vitamin D and CVD risk, diabetes and its complications, and metabolic syndrome.Journal of Diabetes Research 01/2013; 2013:243934. · 3.54 Impact Factor
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ABSTRACT: Mentally and physically handicapped patients with epilepsy may have an increased risk of osteoporosis due to different reasons: alimentary problems, lack of sport, chronic medication, especially antiepileptic drugs. Patients with special syndromes have an elevated risk for osteoporosis, especially people with Down syndrome. Other reasons may play a role: comorbidity, lack of sunlight exposure, lack of information about osteoporosis.Zeitschrift für Epileptologie 18(3).