Inotropic cardiac glycosides

Inhibition of the Na+/K+-ATPase leads to a loss of potassium and an increase of sodium within the cell. Secondary intracellular calcium is increased via the Na VCa -exchanger. This results in a positive inotropic effect in the myocardium, with an increase of peak force and a decrease in time to peak tension. Besides this, cardiac glycosides increase vagal activity by effects on the central vagal nuclei, the nodose ganglion and increase in sensitivity of the sinus node to acetylcholine. 

There is reason to beheve that cardiac glycosides, like other inotropic substances, act on the contractibility of the heart by affecting the process of calcium ion transfer through the membrane of myocardiocytes. The effect of cellular membranes in electric conductivity is mediated by transport of sodium, calcium, and potassium ions, which is a result of indirect inhibitor action on the (Na+-K+) ATPase of cell membranes. 

Cardiac glycosides display positive inotropic activity by a direct effect on the myocardial cells, trig-... 

Digoxin, prototype of the cardiac glycosides, is frequently used postoperatively for the management of atrial fibrillation. This effect is based on the impairment of AV conduction and unrelated to digoxin s positive inotropic activity. In the treatment of post-operative atrial fibrillation digoxin may be... 

Uses Acute CHF, ischemic cardiomyopathy Action Inotrope w/ vasodilator Dose IV bolus 0.75 mg/kg over 2-3 min maint 5-10 mcg/kg/min, 10 mg/kg/d max i if CrCl <10 mL/min Caution [C, ] Contra Bisulfite allergy Disp Inj SE Monitor fluid, electrolyte, renal changes Interactions Diuretics cause significant hypovolemia T effects OF cardiac glycosides EMS Avoid diuretic use, can cause profound hypovolemia incompatible w/ dextrose solns monitor ECG for hypokalemia (flattened T waves) OD May cause profound hypotension use IV fluids w/ caution d/t fluid buildup in lungs, pressors may be used... 

Cardiac glycosides cause a positive inotropic effect which means an increase of the cardiac beat volume by enhanced contraction ability. The reason for this is supposed to be aligned with the direct inhibition of the transport enzyme sodium/ potassium-ATPase. The decrease of sodium ions enhances the calcium ion concentration, which activates the myofibrillic enzyme and inactivates proteins like tropo-myocine and tropomine. Till present, a final proof for this hypothesis is lacking, the toxicity, however, is definitely aligned with these effects [97]. 

The positive benefits of extracts of two species of Digitalis purpurea (foxglove and lanata) were recognized long before the active constituents were isolated and structurally characterized. The cardiac glycosides, which include digoxin, digitoxin, and deslanoside, exert a powerful and selective positive inotropic action on the cardiac muscle (see Chapter 35). 

The relationship of intracellular sodium to intracellular calcium is such that a very small increase in sodium in terms of percentage increase leads to a disproportionately large increase in calcium. Therefore, a direct effect on the sodium/potassium-ATPase to inhibit sodium pump activity is the primary mechanism of the positive inotropic effect of the cardiac glycosides, while secondary elevation of intracellular calcium provides the ionic punch to increase contractility. A diagram of the relationship between sodium/potassium-ATPase and calcium is shown in Figure 12.6. 

TIZANIDINE CARDIAC GLYCOSIDES -DIGOXIN Risk of bradycardia when tizanidine is given with digoxin Tizanidine has a negative inotropic effect Monitor PR closely... 

Crataegus species (hawthorn, maybush, whitethorn) contain a variety of flavonoids, including rhamnosides, schaf-tosides, and spiraeosides. They have a positive inotropic effect on the heart by a mechanism different from that of cardiac glycosides, catecholamines, and the phosphodiesterase type III inhibitors (1) and are effective in mild heart failure (2). 

MOA Digoxin (cardiac glycoside) is a positive inotropic agent that inhibits the Na+/K+ ATPase pump. Inhibition of the pump causes an increase in intracellular sodium that allows the Na+/Ca exchanger to increase intracellular calcium. The heart is then able to use the increased intracellular calcium to increase contractility. 

Digoxin, the most commonly used cardiac glycoside, is indicated for the treatment of CHF and for the treatment of supraventricular tachyarrhythmias. It possesses positive inotropic and electro-physiological effects resulting from the inhibition of Na, K -ATPase, which increases intracellular sodium ion concentrations. This increase in intracellular sodium ions slows down calcium extrusion from the cell, resulting in an increase in intracyto-plasmic calcium and, thereby, an increase in the contractile force. 

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