Myocardial insufficiency leads to a decrease in stroke volume and venous congestion with formation of edema. Administration of (thiazide) diuretics (p. 62) offers a therapeutic approach of proven efficacy that is brought about by a decrease in circulating blood volume (decreased venous return) and peripheral resistance, i.e., afterload. A similar approach is intended with ACE-inhibitors, which act by preventing the synthesis of angiotensin II (| vasoconstriction) and reducing the secretion of al-dosterone (| fluid retention). In severe cases of myocardial insufficiency, cardiac glycosides may be added to augment cardiac force and to relieve the symptoms of insufficiency.
In more recent times p-blocker on a long term were found to improve cardiac performance — particularly in idiopathic dilating cardiomyopathy — probably by preventing sympathetic overdrive.
A. Pharmacokinetics of cardiac glycosides
The electrical impulse for contraction (propagated action potential; p. 136) originates in pacemaker cells of the si-noatrial node and spreads through the atria, atrioventricular (AV) node, and adjoining parts of the His-Purkinje fiber system to the ventricles (A). Irregularities of heart rhythm can interfere dangerously with cardiac pumping function.
noatrial and AV nodes. In some forms of arrhythmia, certain drugs can be used that are capable of selectively facilitating and inhibiting (green and red arrows, respectively) the pacemaker function of sinoatrial or atrioventricular cells.
Sinus bradycardia. An abnormally low sinoatrial impulse rate (<60/min) can be raised by parasympatholytics. The quaternary ipratropium is preferable to atropine, because it lacks CNS penetrability (p. 107). Sympathomimetics also exert a positive chronotropic action; they have the disadvantage of increasing myocardial excitability (and automaticity) and, thus, promoting ec-topic impulse generation (tendency to extrasystolic beats). In cardiac arrest epinephrine can be used to reinitiate heart beat.
Sinus tachycardia (resting rate >100 beats/min). p-Blockers eliminate sympathoexcitation and decrease cardiac rate.
Atrial flutter or fibrillation. An excessive ventricular rate can be decreased by verapamil (p. 122) or cardiac glycosides (p. 130). These drugs inhibit impulse propagation through the AV node, so that fewer impulses reach the ventricles.
II. Nonspecific drug actions on impulse generation and propagation.
Impulses originating at loci outside the sinus node are seen in supraventricular or ventricular extrasystoles, tachycardia, atrial or ventricular flutter, and fibrillation. In these forms of rhythm disorders, antiarrhythmics of the local anesthet ic, Na+-channel blocking type (B) are used for both prophylaxis and therapy. Local anesthetics inhibit electrical excitation of nociceptive nerve fibers (p. 204); concomitant cardiac inhibition (cardiodepression) is an unwanted effect. However, in certain types of arrhythmias (see above), this effect is useful. Local anesthetics are readily cleaved (arrows) and unsuitable for oral administration (procaine, lidocaine). Given judiciously, intravenous lidocaine is an effective antiarrhythmic. Procainamide and mexiletine, congeners endowed with greater metabolic stability, are examples of orally effective antiarrhyth-mics. The desired and undesired effects are inseparable. Thus, these antiar-rhythmics not only depress electrical excitability of cardiomyocytes (negative bathmotropism, membrane stabilization), but also lower sinoatrial rate (neg. chronotropism), AV conduction (neg. dromotropism), and force of contraction (neg. inotropism). Interference with normal electrical activity can, not too paradoxically, also induce cardiac arrhyth-mias-arrhythmogenic action.
Inhibition of CNS neurons is the underlying cause of neurological effects such as vertigo, confusion, sensory disturbances, and motor disturbances (tremor, giddiness, ataxia, convulsions).
Was this article helpful?