British journal of clinical pharmacology
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Br J Clin Pharmacol · Mar 2015
ReviewImproving antibiotic prescribing for children in the resource-poor setting.
Antibiotics are a critically important part of paediatric medical care in low- and middle-income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. ⋯ The World Health Organization initiatives, such as 'Make medicines child size', the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence-based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing.
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Br J Clin Pharmacol · Mar 2015
Randomized Controlled TrialMetabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1.
The rare association of flupirtine with liver injury is most likely caused by reactive quinone diimines and their oxidative formation may be influenced by the activities of N-acetyltransferases (NAT) that conjugate the less toxic metabolite D13223, and by glucuronosyltransferases (UGT) and glutathione S-transferases (GST) that generate stable terminal glucuronides and mercapturic acid derivatives, respectively. The influence of genetic polymorphisms of NAT2, UGT1A1 and GSTP1 on generation of the terminal mercapturic acid derivatives and analgesic effects was evaluated to identify potential genetic risk factors for hepatotoxicity of flupirtine. ⋯ Formation of mercapturic acid derivatives is a major elimination route for flupirtine in man. However, the theoretically toxic pathway is not influenced by the frequent polymorphisms of UGT1A1, NAT2 and GSTP1.
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Br J Clin Pharmacol · Feb 2015
Comparative StudyAngiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink.
This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors. ⋯ A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users.
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Br J Clin Pharmacol · Feb 2015
Meeting the societal need for new antibiotics: the challenges for the pharmaceutical industry.
The rise of antibiotic resistance is leading to clinicians being increasingly faced with clinical failure due to the lack of effective and safe treatment options. New antibiotics are needed now for current multi-drug resistant infections but also in preparation for emerging and anticipated threats. There are significant challenges for the pharmaceutical industry to discover and develop new antibiotics including a business model that balances reasonable reimbursement with appropriate use. This summary reviews the key challenges and collaborative interventions that may contribute to addressing a societal problem.
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Anaesthesiologists adjust drug dosing, administration system and kind of drug to the characteristics of the patient. They then observe the expected response and adjust dosing to the specific requirements according to the difference between observed response, expected response and the context of the surgery and the patient. The approach above can be achieved because on one hand quantification technology has made significant advances allowing the anaesthesiologist to measure almost any effect by using noninvasive, continuous measuring systems. ⋯ Similarly, cases in which the dissociation process of the drug-receptor complex is slow compared with other processes relevant to the time course of the anaesthetic effect are not frequent in anaesthesia, where in addition to a rapid onset, a fast offset of the response is required. With respect to the characterization of PD drug interactions different response surface models are discussed. Relevant applications that have changed the way modern anaesthesia is practiced are also provided.