Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2013
Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs.
There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. ⋯ Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.
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Frontiers in pharmacology · Jan 2013
Determinants of patient adherence: a review of systematic reviews.
A number of potential determinants of medication non-adherence have been described so far. However, the heterogenic quality of existing publications poses the need for the use of a rigorous methodology in building a list of such determinants. The purpose of this study was a systematic review of current research on determinants of patient adherence on the basis of a recently agreed European consensus taxonomy and terminology. ⋯ This study provides clear evidence that medication non-adherence is affected by multiple determinants. Therefore, the prediction of non-adherence of individual patients is difficult, and suitable measurement and multifaceted interventions may be the most effective answer toward unsatisfactory adherence. The limited number of publications assessing determinants of persistence with medication, and lack of those providing determinants of adherence to short-term treatment identify areas for future research.
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Frontiers in pharmacology · Jan 2013
A thermosensitive mutation alters the effects of lacosamide on slow inactivation in neuronal voltage-gated sodium channels, NaV1.2.
Epilepsy is a disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels (NaVs). The C121W mutation of the β1 subunit, in particular, gives rise to the thermosensitive generalized epilepsy with febrile seizures plus (GEFS+) phenotype. ⋯ Lacosamide was more effective in NaV1.2 associated with the WT-β1 than with C121W-β1 at either temperature. There is also a more potent effect by lacosamide on slow inactivation at elevated temperatures. Our data suggest a modulatory role is imparted by the β1 subunit in the interaction between the drug and the channel.
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Frontiers in pharmacology · Jan 2013
ReviewPathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN).
Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a "stocking and glove" distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. ⋯ In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves.