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The cardiac glycosides were originally isolated from the Digitalis purpurea plant; a fact that is reflected in their names—digitalis, digoxin, and digitoxin. The term digitalis is a general one that is usually used when referring to the drug digoxin.
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The cardiac glycosides (DIGOXIN and DIGITOXIN) improve myocardial contractility. They inhibit Na+–K+–ATPase.
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These drugs inhibit sodium–potassium–ATPase and enhance release of intracellular calcium from the sarcoplasmic reticulum. This increase in intracellular calcium causes an increase in the force of contraction of the myocytes throughout the heart. In addition to their use in chronic heart failure, both digoxin and digitoxin will slow the ventricular rate in atrial flutter or fibrillation by increasing the sensitivity of the atrioventricular (AV) node to vagal stimulation. This makes them antiarrhythmic drugs as well (see Chapter 13).
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Digoxin has a shorter half-life, no (the ultimate fewer) metabolites, is less completely absorbed from the GI tract, and is less protein bound than digitoxin.
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The cardiac glycosides have a low therapeutic index.
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As noted in Chapter 2, the therapeutic index is the LD50 divided by the ED50. A low therapeutic index means that the plasma concentration that causes serious toxicity (that is, may be fatal) is only slightly higher than the therapeutic dose. The therapeutic index is between 1.6 and 2.5 for the cardiac glycosides. Toxicity of the cardiac glycosides is more common in patients with low serum potassium levels. This is quite important, because many patients with heart failure are taking “dig. and diuretics” (shorthand for digoxin and a diuretic).
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Toxicity resulting from cardiac glycosides can be manifested by:
Arrhythmias
Anorexia, nausea, and diarrhea
Drowsiness and fatigue
Visual disturbances
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Among these toxic effects, it is the arrhythmias that can be life threatening.
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These drugs were covered earlier in the autonomic nervous system section (see Chapter 9). Here is a quick review.
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DOBUTAMINE is a β1 agonist. At moderate doses, it increases contractility of the heart without changing blood pressure or heart rate.
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Dobutamine is used to increase cardiac output in heart failure and can be used in the treatment of shock. Dobutamine has some α1 and β2 agonist effects that play a role in maintaining peripheral vascular resistance. It is only given intravenously, so its use is limited.
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DOPAMINE has dopamine receptor agonist activity and, like dobutamine, is used in the treatment of acute heart failure.
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In patients with impaired renal function, the use of dopamine (instead of dobutamine) may preserve renal blood flow and, as a result, renal function. Administration of dopamine is also limited to the IV route.
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PHOSPHODIESTERASE INHIBITORS
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Inamrinone (formerly amrinone) and milrinone inhibit the cyclic adenosine monophosphate (cAMP) phosphodiesterase in cardiac and vascular muscle. This results in a positive inotropic action as well as a vasodilatory effect. There is little increase in heart rate.