Digitalis cardiovascular effects

Digitalis has multiple direct and indirect cardiovascular effects, with both therapeutic and toxic consequences. In addition, it has undesirable effects on the central nervous system and gut. 

Gilhs RA, Quest JA (1980) The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 31 19-97... 

Borage and foxglove (Digitalis purpurea) have botanically similar leaves. Adverse cardiovascular effects due to foxglove consumption have been reported in persons that... 

We have long been Interested in the possibility that the cardiovascular effects of carboxylic lonophores could be harnessed to provide new drugs for the treatment of disease states such as heart failure and shock. There may, however, be subpopulations of man for whom lonophores may be particularly toxic. For example, a toxic Interaction between monensln and digitalis on the dog heart has been reported (37). Our oral absorption data do Indicate that If a useful human therapeutic application can be established, lonophores could be administered as drugs orally. 

Cardiovascular manifestations include hypertension and cardiac arrhythmias (e.g., heart block, atrial flutter, paroxysmal atrial tachycardia, ventricular fibrillation, and digitalis-induced arrhythmias). In severe hypokalemia (serum concentration <2.5 mEq/L), ECG effects include ST-segment depression or flattening, T-wave inversion, and U-wave elevation. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Edema and specific drugs for its treatment have long been problems of the physician and of the chemist interested in medicinal products. Digitalis and the many related cardiac glycosides were the first effective agents for the treatment of dropsy associated with congestive heart failure. However, it was soon recognized that the mobilization of the excess tissue fluid associated with this condition was due to a primary action on the heart with improved cardiovascular hemodynamics and only secondarily to an action upon the kidney. 

To better understand certain aspects of the mechanism of digitalis drugs, it would be useful to outline briefly their cardiovascular properties. The increased force of myocardial contraction produced by these glycosides is by far their most dramatic pharmacodynamic property. This positive inotropic (increased contractile force) action translates into increased cardiac output and effects on cardiac size and blood volume through diuresis (i.e., the relief of the edema that accompanies CHF). The rate of tension development is apparently affected, not the length of time during which contraction is maintained by the muscle fiber. Digitalis exerts its effect even in the presence of p-blockers or reserpine. 

Epinephrine usually Is administered slowly by Intravenous (IV) Injection to relieve acute asthmatic attacks not controlled by other treatments. Intravenous Injection produces an Immediate response. Use of EPI with drugs that enhance cardiac arrhythmias (digitalis or quinidine) Is not recommended. Tricyclic antidepressants and MAO Inhibitors will potentiate the effects of EPI on the heart. Epinephrine should be used with caution In Individuals suffering from hyperthyroidism, cardiovascular disease, hypertension, or diabetes. Adverse effects Include palpitations, tachycardia, sweating, nausea and vomiting, respiratory difficulty, dizziness, tremor, apprehension, and anxiety. 

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