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  • CR: 5.17
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  • Springer  (100)
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  • 1980-1984  (89)
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  • 1991  (11)
  • 1983  (46)
  • 1980  (43)
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Publisher
  • Springer  (100)
  • Annual Reviews
  • Nature Publishing Group
  • Periodicals Archive Online (PAO)
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  • 1990-1994  (11)
  • 1980-1984  (89)
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  • 1
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    Computing 25 (1980), S. 317-335 
    ISSN: 1436-5057
    Keywords: AMS (MOS): 65L65 ; CR: 5.17 ; AMS (MOS): 65L65 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Description / Table of Contents: Abstract In this paper a general procedure to obtain spline approximations for the solutions of initial value problems for ordinary differential equations is presented. Several well-known spline approximation methods are included as special cases. It is common practice to partition the interval for which the initial value problem is defined into equidistant subintervals and to construct successively the spline approximation; thereby the spline function has to satisfy certain conditions at the knots. In the general procedure presented here additional knots are admitted in every subinterval. At these points which need not be equally spaced the spline approximation has to fulfill analogous conditions as at the original knots. Convergence and divergence theorems are proved; especially the influence of the additional knots on convergence and divergence of the method is investigated.
    Notes: Zusammenfassung In dieser Arbeit wird ein allgemeines Verfahren zur Erzeugung von Splineapproximationen für die Lösungen von Anfangswertproblemen bei gewöhnlichen Differentialgleichungen vorgestellt. Einige der bekannten Spline-approximationsmethoden sind als Spezialfälle enthalten. Eine gängige Vorgehensweise besteht darin, das Intervall, über dem das Anfangswertproblem gegeben ist, in äquidistante Teilintervalle zu zerlegen und dann sukzessive die Splineapproximation zu definieren. Hierbei wird gefordert, daß die Spline-approximation in den Knoten gewisse Bedingungen erfüllt. Bei dem hier betrachteten allgemeinen Verfahren werden in den einzelnen Teilintervallen noch zusätzliche Zwischenknoten eingeführt. In diesen Punkten, die nicht äquidistant sein müssen, werden für die Splineapproximation analoge Bedingungen wie in den Hauptknoten vorgeschrieben. Konvergenz- und Divergenzsätze werden bewiesen, insbesondere wird der Einfluß der Zwischenknoten auf Konvergenz und Divergenz des Verfahrens untersucht.
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  • 2
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    Numerische Mathematik 41 (1983), S. 373-398 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary The paper introduces a new semi-implicit extrapolation method especially designed for the numerical solution of stiff systems of ordinary differential equations. The existence of a quadratic asymptotic expansion in terms of the stepsize is shown. Moreover, the new discretization is analyzed in the light of well-known stability models. The efficiency of the new integrator is clearly demonstrated by solving a series of challenging test problems including real life examples.
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  • 3
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    Numerische Mathematik 41 (1983), S. 345-371 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Maximum-norm stability and error estimates of best approximation and nonsmooth data types are derived for the approximate solution of a parabolic equation in one space variable, using the continuous in time Galerkin method based on piecewise polynomial approximating functions on a quasi-uniform mesh.
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  • 4
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We study the difference equations obtained when a linear multistep method is applied to the scalar test equationdy/dt=λy and constant stepsizeh. LetS be the region of the absolute stability of the method, and letD be a closed subset ofS (on the Riemann sphere $$\mathbb{C}$$ ). It is shown that the solutions of these difference equations are bounded forn≧0, uniformly for λh∈D.S is itself closed in $$\mathbb{C}$$ iff ∂S is free of cusps. The question is studed by means of contractivity analysis and a matrix theorem, derived from the matrix theorem of Kreiss.
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  • 5
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    Numerische Mathematik 41 (1983), S. 399-422 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary The paper presents a new theory for joint order and stepsize control in extrapolation methods. This theory defines a locally optimal order that can be determined along any trajectory to be computed. In addition, Shannon's information theory is applied to derive some ideal convergence model that is expected to describe the behavior of an extrapolation method over a large set of test problems. Extensive numerical comparisons document a drastic acceleration in stiff integration and a mild acceleration in non-stiff integration by the new device. Moreover, a significant increase in reliability, robustness, and portability of the extrapolation codes is achieved.
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  • 6
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    Numerische Mathematik 42 (1983), S. 299-310 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary A new approach to the problem of numerically integrating stiff differential systems is described. In this approach a linear multistep method (the basic method) is split into a kind of predictor-corrector scheme, where the predictor is also implicit. If this splitting is done in an appropriate manner, the modified method has considerably better stability properties than the basic method. As a result, splitting methods are particularly useful for problems where conventional integration methods experience stability difficulties. In particular some highly stable split linear multistep methods based on backward differentiation formulae are derived and a highly stable variable step implementation is proposed.
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  • 7
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    Numerische Mathematik 42 (1983), S. 311-322 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65 N 30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary This paper presents Galerkin approximations for solutions of two dimensional interface problems by solving corresponding boundary integral equations. These are obtained by simple layer potential operators only. Due to the strong ellipticity of the integral equations the Galerkin procedure converges with optimal order. Smoothness of the given data implies high convergence rates for the layers.
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  • 8
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    Numerische Mathematik 42 (1983), S. 349-357 
    ISSN: 0945-3245
    Keywords: AMS(MOS) 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary In this paper theD-stability properties of some classes of perturbed collocation methods are investigated. Among others we show the implicit Runge-Kutta methods described by Ehle-Chipman to beD-stable. We also give implicit Runge-Kutta methods that are bothD-stable andA-stable but notB-stable. Finally we indicate in what senseB-stability is stronger thanA-stability together withD-stability. The results of this paper are based on recent results of Nørsett and Wanner on perturbed collocation methods.
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  • 9
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    Numerische Mathematik 34 (1980), S. 235-246 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary A class of extended backward differentiation formulae suitable for the approximate numerical integration of stiff systems of first order ordinary differential equations is derived. An algorithm is described whereby the required solution is predicted using a conventional backward differentiation scheme and then corrected using an extended backward differentiation scheme of higher order. This approach allows us to developL-stable schemes of order up to 4 andL(α)-stable schemes of order up to 9. An algorithm based on the integration formulae derived in this paper is illustrated by some numerical examples and it is shown that it is often superior to certain existing algorithms.
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  • 10
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    Numerische Mathematik 35 (1980), S. 127-142 
    ISSN: 0945-3245
    Keywords: AMS (MOS): 34G05, 65L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary A class of approximation schemes of arbitrary accuracy, generated by a two-step recurrence relation, is devised for evolution equations of the second order. The schemes are effected via a specially constructed family of rational approximations to cos τ for τ≧0 and yield computationally efficient methods for systems of second-order ordinary differential equations and semidiscrete approximations for initial-boundary value problems for second-order hyperbolic equations.
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  • 11
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    Numerische Mathematik 35 (1980), S. 143-162 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65M15, 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We study the error due to the discretization in time of a nonlinear parabolic problem by a multistep method. Error estimates are obtained if the method is of the orderp (p〉1) and stronglyA(Θ)-stable $$\left( {0〈 \Theta〈 \frac{\pi }{2}} \right)$$ . The method is also applied to the Navier-Stokes equations in two dimensions.
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  • 12
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    Numerische Mathematik 35 (1980), S. 231-240 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L10 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary The homotopy method is a frequently used technique in overcoming the local convergence nature of multiple shooting. In this paper sufficient conditions are given that guarantee the homotopy process to be feasible. The results are applicable to a class of two-point boundary value problems. Finally, the numerical solution of two practical problems arising in physiology is described.
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  • 13
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    Numerische Mathematik 35 (1980), S. 257-276 
    ISSN: 0945-3245
    Keywords: AMS(MOS) ; 65M10 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Description / Table of Contents: Résumé Considérons une équation d'évolution parabolique linéaire associée à un opérateur linéaireA(t) dépendant du tempst. Nous développons dans cet article une méthode de discrétisation, basée sur les méthodes linéaires à pas multiples, traitant de manière implicite une partie de l'opérateurA(t) indépendante du temps, l'autre partie est traitée de manière explicite. Nous étudions la stabilité et la convergence de cette méthode.
    Notes: Summary Let us consider a linear parabolic equation which is associated with a time dependent operatorA(t). In this paper, we present a method, which is founded on linear multistep methods, which discretize a time-independent part of the operatorA(t) in an implicit way, and the other part in an explicit way. We study stability and convergence for this method.
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  • 14
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    Numerische Mathematik 35 (1980), S. 315-341 
    ISSN: 0945-3245
    Keywords: AMS(MOS) ; 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We present here some new families of non conforming finite elements in ℝ3. These two families of finite elements, built on tetrahedrons or on cubes are respectively conforming in the spacesH(curl) andH(div). We give some applications of these elements for the approximation of Maxwell's equations and equations of elasticity.
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  • 15
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    Numerische Mathematik 35 (1980), S. 381-404 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We study in this paper the convergence of a new mixed finite element approximation of the Navier-Stokes equations. This approximation uses low order Lagrange elements, leads to optimal order of convergence for the velocity and the pressure, and induces an efficient numerical algorithm for the solution of this problem.
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  • 16
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    Numerische Mathematik 41 (1983), S. 55-62 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary The finite element method with Laplace transform of time variable is proposed for the solution of hyperbolic equations. Error estimates in Hardy spaces of functions with values in Sobolev spaces are derived. Due to the isometric isomorphism of Hardy spaces with weighted Hilbert spaces these estimates are valid also for original formulations of hyperbolic equations.
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  • 17
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    Numerische Mathematik 41 (1983), S. 165-175 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65LO5 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary The extrapolated midpoint rule is a popular way to solve the initial value problem for a system of ordinary differential equations. As originally formulated by Gragg, the results are smoothed to remove the weak instability of the midpoint rule. It is shown that this smoothing is not necessary. A cheaper smoothing scheme is proposed. A way to exploit smoothing to increase the robustness of extrapolation codes is formulated.
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  • 18
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    Numerische Mathematik 41 (1983), S. 255-279 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L15 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Some methods for evaluating the characteristic exponents in connection with Newton's iteration are applied for solving the eigenvalue problem related to the finite Hill's differential equation or, in particular, Mathieu's equation. By using these methods a high accuracy is achieved, furthermore a complete error analysis, which yields rather realistic error bounds, is possible.
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  • 19
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    Numerische Mathematik 42 (1983), S. 15-30 
    ISSN: 0945-3245
    Keywords: AMS: 65L10 ; 34C25 ; 34K10 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary An iterative method is presented which starting from a lower or from an upper periodic solution, provides a monotone sequence converging to a periodic solution of (1). With some restrictions on the growth off, the method extends to functional differential equations of type (1′). Two numerical examples with an “a posteriori” error analysis are given.
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    Numerische Mathematik 42 (1983), S. 51-64 
    ISSN: 0945-3245
    Keywords: AMS (MOS): 65N99 ; 35L05 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Engquist and Majda [3] proposed a pseudodifferential operator as asymptotically valid absorbing boundary condition for hyperbolic equations. (In the case of the wave equation this boundary condition is valid at all frequencies.) Here, least-squares approximation of the symbol of the pseudodifferential operator is proposed to obtain differential operators as boundary conditions. It is shown that for the wave equation this approach leads to Kreiss well-posed initial boundary value problems and that the expectation of the reflected energy is lower than in the case of Taylor- and Padé-approximations [3, 4]. Numerical examples indicate that this method works even more effectively for hyperbolic systems. The least-squares approach may be used to generate the boundary conditions automatically.
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    Numerische Mathematik 42 (1983), S. 77-95 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N99 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Brakhage and Werner, Leis and Panich suggested to reduce the exterior Dirichlet boundary value problem for the Helmholtz equation to an integral equation of the second kind which is uniquely solvable for all frequencies by seeking the solution in the form of a combined double- and single-layer potential. We present an analysis of the appropriate choice of the parameter coupling the double- and single-layer potential in order to minimize the condition number of the integral operator.
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    Numerische Mathematik 42 (1983), S. 65-76 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65 N 20 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We consider here a general class of algorithms for the numerical solution of variational inequalities. A convergence proof is given and in particular a multi-grid method is described. Numerical results are presented for the finite-difference discretization of an obstacle problem for minimal surfaces
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    Numerische Mathematik 42 (1983), S. 119-123 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N10 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Many difference methods for the numerical solution of elliptic boundary value problems lead to systems of linear equations whose matrices areM-matrices and which therefore have nonnegative inverses. In this paper it is shown, that these difference methods are at most consistent of second order.
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    Numerische Mathematik 42 (1983), S. 173-194 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary We consider the stationary Navier-Stokes equations, written in terms of the primitive variables, in the case where both the partial differential equations and boundary conditions are inhomogeneous. Under certain conditions on the data, the existence and uniqueness of the solution of a weak formulation of the equations can be guaranteed. A conforming finite element method is presented and optimal estimates for the error of the approximate solution are proved. In addition, the convergence properties of iterative methods for the solution of the discrete nonlinear algebraic systems resulting from the finite element algorithm are given. Numerical examples, using an efficient choice of finite element spaces, are also provided.
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    Numerische Mathematik 42 (1983), S. 271-290 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65J10, 65L20, 65M10 ; CR: 5.17
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Notes: Summary Consider a linear autonomous system of ordinary differential equations with the property that the norm |U(t)| of each solutionU(t) satisfies |U(t)|≦|U(0)| (t≧0). We call a numerical process for solving such a system contractive if a discrete version of this property holds for the numerical approximations. A givenk-step method is said to be unconditionally contractive if for each stepsizeh〉0 the numerical process is contractive. In this paper a general theory is given which yields necessary and sufficient conditions for unconditional contractivity. It turns out that unconditionally contractive methods are subject to an order barrierp≦1. Further the concept of a contractivity threshold is studied, which makes it possible to compare the contractivity behaviour of methods with an orderp〉1 as well. Most theoretical results in this paper are formulated for differential equations in arbitrary Banach spaces. Applications are given to numerical methods for solving ordinary as well as partial differential equations.
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    Numerische Mathematik 42 (1983), S. 359-377 
    ISSN: 0945-3245
    Keywords: AMS 65L05 ; 65L07 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary This paper is concerned with the stability of multistep methods for ordinary initial-value problems on grids with variable mesh-sizes. A necessary and sufficient condition for stability is given from which generalizations of recent results by Gear et al. and by Zlatev can be obtained as special cases. As an application the stability of the variable BDF-formulas is treated.
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    Numerische Mathematik 42 (1983), S. 379-389 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L20 ; 15A60 ; 65M20 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary If the field of values of a matrixA is contained in the left complex halfplaneH and a functionf mapsH into the unit disc then ∥f(A)∥2≦1 by a theorem of J.v. Neumann. We prove a theorem of this type, only the field of values ofA is used for functions which are absolutely bounded by one in only part ofH. An extension can be used to show norm-stability of single step methods for stiff differential equations. The results are applicable among others to several subdiagonal Padé approximations which are notA-stable.
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    Numerische Mathematik 34 (1980), S. 171-187 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary Difference methods for the numerical solution of linear partial differential equations may often be improved by using a weighted right hand side instead of the original right hand side of the differential equation. Difference formulas, for which that is possible, are called “Mehrstellenformeln’ or Hermitian formulas. In this paper the Hermitian formulas for the approximation of Laplace's operator are characterized by a very simple condition. We prove, that in two-dimensional case for a Hermitian formula of ordern at leastn+3 discretization points are necessary. We give examples of such optimal formulas of arbitrary high-order.
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    Numerische Mathematik 34 (1980), S. 457-467 
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    Keywords: AMS(MOS): 65L05, 65Q05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary By employing a numerical method which uses only rather classical tools of Numerical Analysis such as Newton's method and routines for ordinary differential equations, unstable periodic solutions of differential-difference equations can be computed. The method is applied to determine bifurcation diagrams with backward bifurcation.
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    Numerische Mathematik 35 (1980), S. 13-20 
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    Keywords: AMS (MOS): primary 65M05 ; 65M10 ; 65M15 ; secondary: 35M05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary We consider the numerical solution of the Tricomi problem. Using a weak formulation based on different spaces of test and trial functions, we construct a new Galerkin procedure for the Tricomi problem. Existence, uniqueness, and uniform stability of the approximate solution is proven, and a priori error bounds are given.
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    Numerische Mathematik 35 (1980), S. 21-33 
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    Keywords: AMS(MOS): 65B05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary The trapezoidal rule with deferred corrections using uncentered end formulas is shown to converge. While the proof technique is more specialized than the standard asymptotic expansion approach, it has some advantages. In addition to providing a more complete theoretical justification for current implementations of deferred corrections with the trapezoidal rule, the approach given here will hopefully apply for several other discretization methods.
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    Numerische Mathematik 35 (1980), S. 57-68 
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    Keywords: AMS(MOS): 65L05 ; 65M20 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary This paper discussesrational Runge-Kutta methods for stiff differential equations of high dimensions. These methods are explicit and in addition do not require the computation or storage of the Jacobian. A stability analysis (based onn-dimensional linear equations) is given. A second orderA 0-stable method with embedded error control is constructed and numerical results of stiff problems originating from linear and nonlinear parabolic equations are presented.
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    Numerische Mathematik 36 (1980), S. 253-266 
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    Keywords: AMS(MOS): 65LO5 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary Single step exponentially fitted integration formulae of orders 4 and 6 are derived. The final approximation to the required solution is obtained via a linear combination of asymptotically less accurate solutions obtained using conventional implicit integration formulae. This linear combination is performed in such a way that the final integration formula, as well as having an increased order of accuracy, integrates a certain pre-determined ordinary differential equation exactly. The algorithms developed are illustrated by means of some numerical examples.
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    Numerische Mathematik 34 (1980), S. 29-40 
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    Keywords: AMS(MOS): 65N25 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary A method is constructed which yields a strip containing the full solution sets of nonlinear eigenvalue problems of the formu=λTu. The strip can be narrowed iteratively, and the method applies for both stable and unstable branches. Its high degree of accuracy is demonstrated by numerical examples. In particular, a lower bound is given for the critical value at which criticality is lost in the thermal ignition problem for the unit ball.
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    Numerische Mathematik 34 (1980), S. 41-62 
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    Keywords: AMS(MOS): 65N30 ; CR: 5.17
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    Notes: Abstract This paper presents a new approach to the analysis of finite element methods based onC 0-finite elements for the approximate solution of 2nd order boundary value problems in which error estimates are derived directly in terms of two mesh dependent norms that are closely ralated to theL 2 norm and to the 2nd order Sobolev norm, respectively, and in which there is no assumption of quasi-uniformity on the mesh family. This is in contrast to the usual analysis in which error estimates are first derived in the 1st order Sobolev norm and subsequently are derived in theL 2 norm and in the 2nd order Sobolev norm — the 2nd order Sobolev norm estimates being obtained under the assumption that the functions in the underlying approximating subspaces lie in the 2nd order Sobolev space and that the mesh family is quasi-uniform.
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  • 36
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    Numerische Mathematik 34 (1980), S. 143-154 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65L65 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary In the first part [1] a general procedure is presented to obtain polynomial spline approximations for the solutions of initial value problems for ordinary differential equations; furthermore a divergence theorem is proved there. Sufficient conditions for convergence of the method are given in the second part [2]. The remaining case which has not been considered in [1] and [2] is treated in the present paper. In this special case the procedure is equivalent to an unstable two-step method with special initial values; nevertheless, convergence can be proved. Finally,A 0-stability of the method as well as the influence of rounding errors are investigated.
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  • 37
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    Numerische Mathematik 34 (1980), S. 1-13 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 34A45, 34A50, 65L05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary In this paper Lie series are presented in Chebyshev form and applied to the iterative solution of initial value problems in differential equations. The resulting method, though algebraically complicated, is of theoretical interest as a generalisation of Taylor series methods and iterative Chebyshev methods. The theory of the method is discussed and the solutions of some simple scalar equations are analysed to illustrate the behaviour of the process.
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  • 38
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65M25, 35L20 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary The ALGOL-procedure1 char2 presented in this paper can be applied to the initial or initial-boundary value problem of a quasilinear hyperbolic differential equation of second order. A method of characteristics is combined with extrapolation to the limit. Thus, the results are very accurate. The same accuracy can also be obtained if the initial values are only piecewise smooth.
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  • 39
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    Numerische Mathematik 36 (1980), S. 1-25 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65 N 30 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary We begin in this paper the study of a general method of approximation of solutions of nonlinear equations in a Banach space. We prove here an abstract result concerning the approximation of branches of nonsingular solutions. The general theory is then applied to the study of the convergence of two mixed finite element methods for the Navier-Stokes and the von Kármán equations.
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  • 40
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    Numerische Mathematik 36 (1980), S. 33-52 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary A modified variational formulation, recently introduced by Taylor, Beresford and Wilson for solving second order problems, using the nonconforming Wilson element is here analysed. It is shown that the Patch Test is satisfied and that stresses and displacements are respectively first and second order accurate for arbitrary quadrilateral meshes.
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  • 41
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    Numerische Mathematik 36 (1980), S. 73-98 
    ISSN: 0945-3245
    Keywords: AMS: 35R35, 65P05, 76S05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary A new numerical method is used to solve stationary free boundary problems for fluid flow through porous media. The method also applies to inhomogeneous media, and to cases with a partial unsaturated flow.
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  • 42
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    Numerische Mathematik 36 (1980), S. 267-290 
    ISSN: 0945-3245
    Keywords: AMS(MOS): 65N30 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary In this paper, we present a finite element lumped mass scheme for eigenvalue problems of circular arch structures, and give error estimates for the approximation. They assert that approximate eigenvalues and eigenfuctions converge to the exact ones. Some numerical examples are also given to illustrate our results.
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  • 43
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    Numerische Mathematik 36 (1980), S. 319-331 
    ISSN: 0945-3245
    Keywords: AMS (MOS) ; 65L05 ; CR: 5.17
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    Topics: Mathematics
    Notes: Summary Burrage and Butcher [1, 2] and Crouzeix [4] introduced for Runge-Kutta methods the concepts ofB-stability,BN-stability and algebraic stability. In this paper we prove that for any irreducible Runge-Kutta method these three stability concepts are equivalent.
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  • 44
    ISSN: 1432-1041
    Keywords: Atenolol ; hypertension ; ß-adrenoceptor blockade ; blood pressure ; heart rate ; ambulatory ; circadian rhythm
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  • 45
    ISSN: 1432-1041
    Keywords: Insulin secretion ; Nifedipine ; non insulin-dependent-diabetes mellitus- ; hyperglycaemia ; plasma insulin ; hypertension
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic β-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg·dl−1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P〈0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.
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  • 46
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    European journal of clinical pharmacology 40 (1991), S. 131-134 
    ISSN: 1432-1041
    Keywords: trimazosin ; hypertension ; alpha1-adrenoceptor blocker ; essential ; exercise ; extracellular fluid volume ; haemodynamics ; plasma volume ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The long-term haemodynamic effect of sustained-release trimazosin (mean daily dose 418 mg) at rest and during exercise has been examined in 14 male patients (age 30–61 y) with previously untreated mild or moderate essential hypertension. Cardiac output (dye dilution), heart rate and intra-arterial blood pressure were measured supine and sitting at rest, and during bicycle exercise. After 11 months of trimazosin treatment the mean casual blood pressure was reduced from 165/106 mm Hg to 147/92 mm Hg. The intra-arterial systolic and diastolic pressure was reduced by 3–7% at rest and during 50, 100 and 150 W exercise. Total peripheral resistance was reduced by 8–14% and cardiac output was slightly higher (2–8%) in all situations. Stroke volume and heart rate remained unchanged, as did body fluid volumes (isotope dilution) and body weight. Side effects were minor and transient. Thus, the haemodynamic responses to trimazosin are similar to but weaker than those of other alpha1-adrenoceptor blockers. The efficacy of the sustained-release formulation of trimazosin was low and daily doses above 600 mg are likely to be needed by many patients.
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  • 47
    ISSN: 1432-1041
    Keywords: Fibrinolysis ; hypertension ; atenolol ; doxazosin ; tissue plasminogen activator ; plasminogen activator inhibitor ; cholesterol
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disturbances in the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the fibrinolytic system have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the fibrinolytic system in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.
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  • 48
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    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Keywords: sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
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  • 49
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    European journal of clinical pharmacology 18 (1980), S. 225-229 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The treatment of hypertension with a single daily-dose of a beta-blocker gives rise to high peak-plasma concentrations 1.5 h after ingestion. After slow release-preparations of beta-blockers, the peak concentrations are half those produced by the conventional preparation at the same oral dose. A frequently occurring side-effect of beta-blocker therapy is fatigue. In this study the effect of a single dose of metoprolol 300 mg, 200 mg, 200 mg slow-release and a placebo on maximal exercise power was tested in 6 healthy subjects, 1.5 h and 24 h after ingestion. Maximal exercise power was significantly reduced 1.5 h after ingestion of metoprolol 300 mg and 200 mg. No change was found 1.5 h after 200 mg of a slow-release preparation. The possible reasons for reduced maximal exercise power are discussed. It is concluded that use of a beta-blocker for the treatment of hypertension in a single daily-dose regimen may be a reason to prefer a slow-release preparation.
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  • 50
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    European journal of clinical pharmacology 18 (1980), S. 399-401 
    ISSN: 1432-1041
    Keywords: prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
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    European journal of clinical pharmacology 18 (1980), S. 105-108 
    ISSN: 1432-1041
    Keywords: renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism.
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  • 52
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    European journal of clinical pharmacology 18 (1980), S. 135-139 
    ISSN: 1432-1041
    Keywords: hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
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  • 53
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    European journal of clinical pharmacology 18 (1980), S. 231-235 
    ISSN: 1432-1041
    Keywords: molsidomine ; hypertension ; hypotension ; angina pectoris
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.
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  • 54
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of nifedipine (10–20 mg t.i.d.) given alone, or in combination with a beta-adrenoceptor blocking drug, was related to the observed plasma concentration during one dosage interval at steady-state (Pl-Nifss). The study was carried out as a within-patient comparison of treatment with nifedipine or placebo for 4 weeks. A highly significant reduction in blood pressure was obtained during monotherapy, as well as during combined treatment. The blood pressure reduction when nifedipine was added to beta-adrenoceptor blockade was of the same magnitude as that observed on nifedipine monotherapy. A considerable variation in Pl-Nifss was noted (range: 2–70 ng/ml). No significant correlation was found between the percentage reduction in blood pressure and Pl-Nifss in either of the two groups. There was a close relationship between Pl-Nifss and the concentration found 4 h after the morning dose. Side-effects were common during nifedipine monotherapy and were the reason for discontinuation of treatment in 4 of 18 patients. In contrast, none of the 9 patients on combined treatment dropped-out. In neither of the treatment groups was there any evidence for sodium retention and volume expansion during the first 4 weeks expressed as weight gain or signs of cardiac insufficiency. However, in 13 patients who continued on long-term treatment for 3–14 months, a definite need for concomitant diuretic therapy was found. The results indicate that nifedipine is effective in lowering blood pressure in patients with mild to moderate essential hypertension, either when given alone or in addition to beta-adrenoceptor blockade. It appears best tolerated as combination therapy. Long-term treatment requires addition of a diuretic. Pl-Nifss did not seem to be a major determinant of the magnitude of the hypotensive response.
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    European journal of clinical pharmacology 18 (1980), S. 375-382 
    ISSN: 1432-1041
    Keywords: calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.
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    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
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    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Keywords: metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
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    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
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    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Keywords: indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
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    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; plasma concentration ; blood pressure response
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  • 61
    ISSN: 1432-1041
    Keywords: furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
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    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
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  • 63
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    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Keywords: beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
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  • 64
    ISSN: 1432-1041
    Keywords: prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
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  • 65
    ISSN: 1432-1041
    Keywords: atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
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  • 66
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    European journal of clinical pharmacology 17 (1980), S. 239-241 
    ISSN: 1432-1041
    Keywords: timolol ; hypertension ; dose ranging ; double-blind trial
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demonstrating that many but not all hypertensives can be controlled with daily administration of timolol.
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  • 67
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    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Keywords: propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
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  • 68
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    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Keywords: hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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  • 69
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    European journal of clinical pharmacology 24 (1983), S. 1-5 
    ISSN: 1432-1041
    Keywords: hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
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  • 70
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    European journal of clinical pharmacology 24 (1983), S. 301-305 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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  • 71
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    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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  • 72
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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  • 73
    ISSN: 1432-1041
    Keywords: captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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  • 74
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    European journal of clinical pharmacology 24 (1983), S. 145-150 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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  • 75
    ISSN: 1432-1041
    Keywords: Captopril ; Diabetes ; nephropathy ; hypertension ; glucose tolerance ; plasma lipids ; blood pressure ; long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng·ml−1·h−1, and so did serum potassium (from 4.57 to 4.83 mEq·l−1). Serum aldosterone fell from 161 to 70.9 pgm·ml−1 and from 27.3 to 15.3 μg·24 h−1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile.
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  • 76
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    European journal of clinical pharmacology 17 (1980), S. 329-332 
    ISSN: 1432-1041
    Keywords: reserpine ; hydrochlorothiazide ; pituitary hormones ; gonadal hormones ; hypertension ; serum concentration ; antihypertensive therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sex histories and serum samples were obtained from 27 hypertensive men before and after 3 months of therapy with either 100 mg of hydrochlorothiazide or 0.25 mg of reserpine daily. Sera were analyzed for testosterone, dihydrotestosterone, estradiol, luteinizing hormone and prolactin. Both drugs effectively lowered blood pressure. The incidence of impaired sexual performance was low and insignificantly different in the two treatment groups. There were no significant changes in serum hormone concentrations as a result of drug therapy.
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  • 77
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    European journal of clinical pharmacology 17 (1980), S. 409-413 
    ISSN: 1432-1041
    Keywords: penbutolol ; hypertension ; propranolol ; double-blind crossover comparison ; blood pressure ; heart rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penbutolol is a potent long-acting non-cardioselective beta-adrenergic blocker with partial agonist activity. A double-blind cross-over comparison of penbutolol given in a single daily dose and propranolol given twice daily in the treatment of ambulant patients with moderate hypertension is described. Fourteen patients completed the study and were treated with each drug for 12 weeks. Penbutolol in daily doses of 20–120 mg and propranolol in daily doses of 80–400 mg produced similar significant reductions in both supine and erect blood pressure. Penbutolol did not reduce heart rate to the same extent as propranolol, in equivalent doses. Penbutolol appears to produce adequate control of moderate hypertension when administered once a day, and this effect appears to be equivalent to divided doses of propranolol. No serious adverse effects were reported, although one patient receiving penbutolol experienced severe eye pains at a dose of 40 mg which resolved on crossing over to treatment with propranolol.
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  • 78
    ISSN: 1432-1041
    Keywords: papaverine ; propranolol ; pindolol ; hypertension ; isoprenaline ; haemodynamic effects ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of two β-adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p〈0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p〈0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the β-blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both β-blockers. While the β-blockers inhibited the β-adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the α-adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the α-and β-adrenoceptor effects of noradrenaline.
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  • 79
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    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Keywords: metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 80
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    European journal of clinical pharmacology 25 (1983), S. 467-473 
    ISSN: 1432-1041
    Keywords: hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
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  • 81
    ISSN: 1432-1041
    Keywords: guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
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    European journal of clinical pharmacology 25 (1983), S. 713-715 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; calcium antagonist ; plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p〈0.05) and diastolic (p〈0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (〈160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.
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    European journal of clinical pharmacology 25 (1983), S. 835-837 
    ISSN: 1432-1041
    Keywords: tienilic acid ; hydrochlorothiazide ; amiloride ; blood pressure control ; biochemical effects ; serum uric acid ; serum potassium ; prolonged treatment ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.
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  • 84
    ISSN: 1432-1041
    Keywords: bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
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  • 85
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    European journal of clinical pharmacology 25 (1983), S. 581-583 
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; hydrochlorothiazide ; drug combination ; adverse reactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 27 hypertensive patients whose blood pressure could not be adequately controlled with 200 mg metoprolol Durules alone, the effect of a double dose of metoprolol Durules® (400 mg once daily) was compared with a fixed combination of 200 mg metoprolol and 25 mg hydrochlorothiazide (Selokomb®). The study followed a double-blind cross-over schedule in 2 parallel groups. The reduction in diastolic blood pressure (p〈0.01) was comparable in the two groups. A significant fall (p〈0.01) in systolic blood pressure occurred with the metoprolol/hydrochlorothiazide combination. The subsequent change from the double dose of metoprolol Durules to the combination therapy also resulted in a fall in systolic blood pressure (p〈0.05). Mean serum potassium and blood glucose levels did not change after each alteration in therapy. Most of the side-effects mentioned were mild and transient in character.
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  • 86
    ISSN: 1432-1041
    Keywords: Cadralazine ; hypertension ; prazosin ; metoprolol ; combined therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) ≥ 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds. 108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine). Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min−1 in those on cadralazine and from 65 to 69 beats · min−1 on prazosin. Body weight was unchanged. Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability. Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily.
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  • 87
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    European journal of clinical pharmacology 17 (1980), S. 161-164 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; blood pressure ; heart rate ; plasma renin activity ; aldosterone ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the antihypertensive effect of nifedipine were studied in 7 cases of moderate essential hypertension. In a double-blind crossover study, nifedipine 10 mg or a placebo were administered sublingually 4 times a day for 2 days, and the results were compared. Each dose of nifedipine reduced systolic and diastolic blood pressure by 14% both in the supine and upright positions. The antihypertensive action lasted for about 3 h and it was not cumulative. The reduction in blood pressure was associated with a temporary increase in heart rate. Administration of nifedipine 10 mg did not significantly raise plasma renin activity or plasma aldosterone. The drug was well tolerated and no side effects were detected.
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  • 88
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    European journal of clinical pharmacology 17 (1980), S. 333-337 
    ISSN: 1432-1041
    Keywords: atenolol ; chlorthalidone ; hypertension ; chronic treatment ; co-administration ; plasma half-life ; urine half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7±1.1 and 6.3±0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p〈0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.
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  • 89
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    European journal of clinical pharmacology 24 (1983), S. 573-577 
    ISSN: 1432-1041
    Keywords: beta-blockers ; serum lipoproteins ; atenolol ; metoprolol ; hypertension ; VLDL ; HDL ; hypertriglyceridaemia ; hypercholesterolaemia ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several β-blockers increase VLDL-TG and decrease HDL-cholesterol concentrations. The underlying mechanism ist not yet clear. Some studies have suggested that the effect is less pronounced during treatment with selective β-blockers. The effects of 2 such drugs, metoprolol 200 mg/day and atenolol 50 mg/day, have been compared in 50 hypertensive patients (WHO Stage I–II), mean age 47 years. Serum lipoproteins were determined in 20 patients before treatment and after treatment with either drug for 3 months. Both drugs were equally effective in reducing blood pressure. After atenolol the initial VLDL-cholesterol concentration of 1.04 mmol/l had not changed, but it rose to 1.29 mmol/l after metoprolol (p〈0.05). The HDL-cholesterol concentration 1.42 mmol/l did not fall during atenolol treatment, but during metoprolol there was a small reduction to 1.31 mmol/l (p〈0.05). Hyperlipoproteinaemia is common in hypertensive patients, 40% of the present group had hypertriglyceridaemia and 25% had hypercholesterolaemia. Thus, atenolol 50 mg was found not to affect lipoproteins, whereas metoprolol 200 mg increased the VLDL concentration in 75% of the patients.
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  • 90
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    European journal of clinical pharmacology 24 (1983), S. 49-53 
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; cardiac failure ; haemodynamic effects ; non-invasive monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22–31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15±4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2±0.3 l/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33±5 ml and 23±3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23±3 ms) and an increase in the left ventricular ejection time (29±3 ms). The quotient PEP/LVET fell from 0.36±0.01 to 0.28±0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
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  • 91
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    European journal of clinical pharmacology 24 (1983), S. 191-197 
    ISSN: 1432-1041
    Keywords: hypertension ; beta-blocker ; diuretic ; screening ; naturalistic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A naturalistic study was set up to screen, identify and treat hypertensive patients aged 20–60 years in a rural general practice. 3,222 patients (92%) of a stable population of 3,489 were screened by 2 nurse research assistants and of these 455 patients (14%) were found to be hypertensive or borderline hypertensive. After careful assessment, 192 of these patients were found suitable for treatment and subsequently 138 entered the study. Two well recognised treatment regimes were used and no significant difference between patient response resulted. 84 patients (60.9%) completed the 2 year duration of the study discussed here. The cost of the study is not feasible in an average general practice, but day to day running of such a project, run along clearly defined treatment regimes was managed easily by 2 research assistants: this reduced, therefore, the work load on individual general practitoners.
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  • 92
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    European journal of clinical pharmacology 40 (1991), S. 67-70 
    ISSN: 1432-1041
    Keywords: Dilevalol ; oxprenolol ; hypertension ; emotional stress ; haemodynamic changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single dose of 200 mg dilevalol, β-adrenoceptor blocker with additional vasodilating properties, and 200 mg oxprenolol on haemodynamic changes induced by emotional stress have been compared in 12 male young Caucasian patients with newly diagnosed labile hypertension. No difference was noted in the stress-induced increase of total peripheral resistance (TPR) following administration of the two substances (11% versus 6%). However, dilevalol revealed a vasodilating action by decreasing TPR at rest (from 1004 to 951 dyn·s·cm−5) and diastolic blood pressure (BP) (from 87 to 75 mm Hg) whereas TPR at rest remained unchanged after the intake of oxprenolol.
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  • 93
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    European journal of clinical pharmacology 40 (1991), S. 453-460 
    ISSN: 1432-1041
    Keywords: Diltiazem ; metoprolol ; quality of life ; hypertension ; multicentre study ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary General well-being, adverse effects and antihypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120–240–360 mg/day or metoprolol 50–100–200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mm Hg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mm Hg (SBP/DBP). Target pressures (DBP ≤ 90 mm Hg and/or a reduction in DBP of ≥ 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120–360 mg and 50–200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.
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  • 94
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    Molecular and cellular biochemistry 104 (1991), S. 45-50 
    ISSN: 1573-4919
    Keywords: hypertension ; Dahl rats ; angiotensin converting enzyme ; cardiac hypertrophy ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Angiotensin II has previously been reported to have in vivo and in vitro cardiac hypertrophic effects. We used the salt-sensitive Dahl rat genetic strain to separate mechanical (pressure overload) vs. hormonal (renin-angiotensin system) input in cardiac hypertrophy. Blood pressure was significantly increased and left ventricular hypertrophy, as indexed by LV/BW ratios, was present at 7 and 15 days in rats receiving 4% and 8% NaCl compared to the 1% controls. There was no effect of the angiotensin converting enzyme inhibitor, enalapril maleate, on lowering the blood pressure in 8% NaCl-treated animals, however, there was a significant reduction in LV/BW ratio in 8% NaCl-treated animals that received this drug. Left ventricular angiotensinogen mRNA activity was significantly reduced in rats receiving 4% and 8% NaCl. In this model of hypertension the cardiac hypertrophy which develops is largely dependent on mechanical forces though there remains a significant contribution to this process from either circulating or localized angiotensin II production. Regulation of angiotensinogen gene expression in the hypertrophied left ventricle suggests that volume and electrolyte control of angiotensinogen gene expression in the heart and/or hereditary factors are predominant in the control of regulation of this gene in the left ventricle of Dahl rats.
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  • 95
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    Bulletin of experimental biology and medicine 95 (1983), S. 412-414 
    ISSN: 1573-8221
    Keywords: brain ; blood-brain barrier ; hypertension ; angiotensin ; noradrenalin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 96
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    Bulletin of experimental biology and medicine 96 (1983), S. 1631-1633 
    ISSN: 1573-8221
    Keywords: smooth muscles ; calcium ; intracellular vesicles ; hypertension
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    Topics: Biology , Medicine
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  • 97
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    Bulletin of experimental biology and medicine 90 (1980), S. 1082-1085 
    ISSN: 1573-8221
    Keywords: hypertension ; adrenalectomy ; fat cells ; isoproterenol
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  • 98
    ISSN: 1573-904X
    Keywords: hypertension ; rat ; dihydropyridine ; nanocapsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We have addressed two problems associated with the use of dihydropyridine calcium entry blockers in antihypertensive therapy, namely, potent vasodilation and short half-lives, by incorporating the representative blocker, darodipine, into a nanocapsular vehicle. In awake, renovascular hypertensive rats, darodipine nanocapsules lowered blood pressure when given orally or intramuscularly, and the initial fall in blood pressure was less marked than that observed with the same dose of darodipine dissolved in polyethylene glycol 400 (PEG). Intramuscular administration of the nanocapsular form of darodipine had an antihypertensive effect which lasted for at least 24 hr.
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  • 99
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    Bulletin of experimental biology and medicine 111 (1991), S. 598-602 
    ISSN: 1573-8221
    Keywords: electric field of the heart ; portal vein ; smooth muscle cells ; hypertension ; spontaneously hypertensive rats
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  • 100
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    Bulletin of experimental biology and medicine 90 (1980), S. 1510-1513 
    ISSN: 1573-8221
    Keywords: adaptation ; hemorrhage ; hypotension ; hypertension ; reinfusion
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