T W Wilson1, D W Quest. 1. Cardiovascular Risk Factor Reduction Unit, Royal University Hospital, Saskatoon, Saskatchewan.
Abstract
OBJECTIVE: To compare clinically relevant pharmacokinetic, pharmacodynamic and toxico logical characteristics of calcium-modulating compounds used in ischemic heart disease. DATA SOURCES: A MEDLINE search (1990 pt B to 1991 pt A revised for 1993; 1991 pt B to 1992 revised for 1993; and January to May 1993) combining the search phrases 'calcium channel blockers', 'myocardial ischemia', 'pharmacodynamics' and 'pharmacokinetics', and a search in Compact Cambridge Drug Information Source vol-6 (revised 1992, fourth quarter) using the search phrase 'calcium antagonists' and medical subject headings (MeSH) 'pharmacokinetics' and 'pharmacodynamics' were used to obtain title and abstract information on available current literature. STUDY SELECTION: Review articles, proceedings and studies published in English and available within the University of Saskatchewan library system, as they appeared to relate closely to the objective, were obtained for closer evaluation. In addition, primary references were examined, and journal reprints were selected from the authors' files. DATA EXTRACTION: The focus was on studies and objective reviews that profiled one or more representative compounds in a manner suitable for deriving background and comparative information pertaining to the objective. Data from multiple studies, or from studies that employed multiple methodological approaches, were preferentially extracted and summarized for presentation. DATA SYNTHESIS: The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells. With a focus on verapamil, diltiazem and 1,4-dihydropyridines currently employed in the treatment of cardiovascular disorders, a general survey of their sites of action, tissue selective pharmacodynamics, pharmacokinetic properties and side effects was undertaken in a comparative context. CONCLUSIONS: Calcium antagonists are employed in the treatment of angina, certain cardiac arrhythmias and hypertension. They are a chemically and pharmacologically heterogeneous group of compounds that act principally to inhibit the influx of calcium across certain voltage-dependent membrane channels. Concepts pertaining to calcium mobilization in the pathophysiology of myocardial ischemia, particularly at the molecular level, have evolved remarkably over the past decade. The repertoire of agents having calcium-regulating properties has expanded in parallel. The task of integrating new knowledge in both of these areas requires further attention in order to determine optimal approaches to treatment.
OBJECTIVE: To compare clinically relevant pharmacokinetic, pharmacodynamic and toxico logical characteristics of calcium-modulating compounds used in ischemic heart disease. DATA SOURCES: A MEDLINE search (1990 pt B to 1991 pt A revised for 1993; 1991 pt B to 1992 revised for 1993; and January to May 1993) combining the search phrases 'calcium channel blockers', 'myocardial ischemia', 'pharmacodynamics' and 'pharmacokinetics', and a search in Compact Cambridge Drug Information Source vol-6 (revised 1992, fourth quarter) using the search phrase 'calcium antagonists' and medical subject headings (MeSH) 'pharmacokinetics' and 'pharmacodynamics' were used to obtain title and abstract information on available current literature. STUDY SELECTION: Review articles, proceedings and studies published in English and available within the University of Saskatchewan library system, as they appeared to relate closely to the objective, were obtained for closer evaluation. In addition, primary references were examined, and journal reprints were selected from the authors' files. DATA EXTRACTION: The focus was on studies and objective reviews that profiled one or more representative compounds in a manner suitable for deriving background and comparative information pertaining to the objective. Data from multiple studies, or from studies that employed multiple methodological approaches, were preferentially extracted and summarized for presentation. DATA SYNTHESIS: The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells. With a focus on verapamil, diltiazem and 1,4-dihydropyridines currently employed in the treatment of cardiovascular disorders, a general survey of their sites of action, tissue selective pharmacodynamics, pharmacokinetic properties and side effects was undertaken in a comparative context. CONCLUSIONS:Calcium antagonists are employed in the treatment of angina, certain cardiac arrhythmias and hypertension. They are a chemically and pharmacologically heterogeneous group of compounds that act principally to inhibit the influx of calcium across certain voltage-dependent membrane channels. Concepts pertaining to calcium mobilization in the pathophysiology of myocardial ischemia, particularly at the molecular level, have evolved remarkably over the past decade. The repertoire of agents having calcium-regulating properties has expanded in parallel. The task of integrating new knowledge in both of these areas requires further attention in order to determine optimal approaches to treatment.