Cardiac responses to drug at the extremes of age

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Abstract

Although current knowledge concerning drug responsiveness in the human heart is still deficient at both extremes of age, i.e. in the fetus and the elderly, new information is beginning to emerge. Pharmacodynamic studies have provided a fairly comprehensive picture of the appearance and maturation of the automatic receptors, and also of the emergence and development of sympathetic-adrenergic and parasympathetic-cholinergic mechanisms in the prenatal human heart. A timetable can now be drawn up for the earliest detection of intrinsic responsiveness to numerous adrenergic and cholinergic agonists and antagonists, and to inotropic and antiarrhythmic drugs in the human embryonic and fetal heart. Information on the antenatal cardiac pharmacodynamics of antiarrhythmics and inotropic drugs is mostly confined to some of the classical remedies, so that a systematic study of the effects of the various newer drugs is warranted. As legal abortions yield prenatal hearts only in very limited numbers, human embryonic and fetal cardiac tissue and cell cultures could also be used for such research under both physiological and pathological conditions, such as hypoxia or simulated ischemia. Since the sporadic data available on the transplacental efficacy of maternally administered cardioactive agents are encouraging, extensive clinical investigation into the pharmacological control of intrauterine cardiac arrythmias and heart failure, based on new, high-resolution fetal echocardiographic techniques to monitor the success of drug therapy at the various stages of prenatal development, is also a stimulating challenge. In the elderly human heart, pharmacodynamically-based alterations in responsiveness to drugs have so far been conclusively proven for adrenergic agents. There is a decrease in intrinsic cardiac reactivity to β-adrenergic agonists and, to some extent, to antagonists. It appears that if β1-adrenoceptor-mediated cardiac responses are reduced by old age, the β2-adrenoceptor-effector system is not. Virtually nothing is known of the intrinsic responsiveness of the aged human heart to inotropic drugs and antiarrhythmic agents. The use of tissue or cell cultures originating from apparently healthy parts of biopsy samples obtained from elderly human heart during surgery would allow large-scale pharmacodynamic studies to be performed with all kinds of cardio-active drugs. As concerns the diminished β1 -adrenergic responsiveness, the aged heart might be regarded as the mirror image of the prenatal heart, although the nature and direction of the underlying processes are obviously different.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalTherapie
Volume46
Issue number4
Publication statusPublished - Jan 1 1991

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Keywords

  • extremes of age
  • human heart
  • intrinsic drug responsiveness
  • pharmacodynamics

ASJC Scopus subject areas

  • Pharmacology (medical)

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