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Pharmacological plasticity-How do you hit a moving target?

ABSTRACT: Paul Ehrlich's concept of the magic bullet, by which a single drug induces pharmacological effects by interacting with a single receptor has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm-synchronizing procedures to optimize drug therapy.

SUBMITTER: Parnham MJ

PROVIDER: S-EPMC6868654 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Pharmacological plasticity-How do you hit a moving target?

Parnham Michael J MJ Geisslinger Gerd G

Pharmacology research & perspectives 20191121 6

Paul Ehrlich's concept of the magic bullet, by which a <i>single drug</i> induces pharmacological effects by interacting with a <i>single receptor</i> has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with li ...[more]

PMID: 31768257

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Project description:BackgroundWith the advent of percutaneous coronary intervention, specifically the bare metal stent and subsequently, the drug-eluting stent, the scope of interventional cardiology has greatly increased. Aspirin, in combination with a thienopyridine is the present-day cornerstone of oral antiplatelet therapy after coronary artery stent placement. Continuing this chronic antiplatelet therapy, to mitigate a perioperative major adverse cardiac event, can be challenging and remains controversial in patients with a coronary artery stent undergoing non-cardiac surgery. We describe here the rationale for and successful use of an alternate approach to formulating local institutional management protocols for patients with a coronary artery stent, undergoing an elective surgical procedure.DiscussionA recent systematic review identified 11 clinical practice guidelines for the perioperative management of antiplatelet therapy in patients with a coronary stent who need non-cardiac surgery. However, there is significant variance and inadequacy with these current applicable professional society guidelines. Moreover, persistently variable success has been experienced in translating even well-grounded national clinical guidelines into local practice, including in the perioperative setting. Under the auspices of a broadly multidisciplinary institutional task force and applying the Consensus-Oriented Decision-Making model, we created two evidence-informed and local expert opinion-supported standardized clinical assessment and management plans for the preoperative management of antiplatelet therapy in patients with a coronary artery stent.SummaryPatient care can be optimized via evidence-based, yet locally developed and reiterative standardized clinical assessment and management plans for patients with coronary artery stents undergoing surgical procedures. Such standardized clinical assessment and management plans can result in greater consistency in care, providing a positive feedback loop in which the care plan itself can be continuously reevaluated, improved, and brought up to date with the most recent available data and knowledge.

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Pharmacological plasticity-How do you hit a moving target?

Publications

Pharmacological plasticity-How do you hit a moving target?

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