Cardiac glycosides, congestive heart failure

The outcome of this is to couple ATP hydrolysis with the vectorial transport of Na+ and K+ across the plasma membrane. The inhibition of the (Na+-K+)-ATPase by cardiac glycosides such as digitalis (an extract of foxglove leaves), which blocks the dephosphorylation of the E2-P form of the enzyme, is the basis for a number of steroid drags which are commonly prescribed for the treatment of congestive heart failure. 

Cardiac glycosides are drags used in the treatment of congestive heart failure or cardiac arrhythmia, by inhibiting the Na+/K+ pump. This inhibition increases the amount of Ca + ions available for contraction and improves cardiac output and reduces distention of the heart. Cardiac glycosides are extracted from plant material. 

In summary, cardiac glycosides increase contractile force and reduce heart rate and AV conduction. In addition, cardiac glycosides suppress the sympathetic hyperactivity which occurs in advanced stages of congestive heart failure via a complex mechanism involving the central nervous system. 

Myocardial cell membrane ATPase, the enzyme present in heart muscle, is the site of action of the cardiac steroid glycosides, which have a specific action on the heart muscle. These drugs increase the force of contraction of the muscle (positive inotropic effect) as well as its conductivity and automaticity. They are also valuable in treating congestive heart failure, in which the circulatory needs of organs are no longer satisfied, and heart arrhythmias, in which the rhythm of the cardiac contractions is upset. The effect of the drug is that the force of contraction increases and the heart rate is slowed (chronotropic effect). Consequently, the cardiac output is elevated while the size of the heart decreases. 

Crude leaf preparations of Digitalis have been in medical use since 1785. Pure cardiac glycosides are now available. These preparations in injectable tinctures or powdered leaf tablets are used extensively for the treatment of congestive heart failure. They increase the force of the heart muscle and the power of systolic contraction, apparently by inhibiting the active transport of K and Na ions through cell membranes. 

Glycosides of the gitoxigenin series are less active than the corresponding members of the digitoxigenin-derived series. Digitoxin is the only compound routinely used as a drug, and it is employed in congestive heart failure and treatment of cardiac arrhythmias, particularly atrial fibrillation. 

Foxglove, Cardiac Glycosides, and Congestive Heart Failure... 

The most important and common drugs in the treatment of congestive heart failure are the cardiac glycosides, which may occur naturally in the body. 

Blood pressure remains unchanged following the administration of cardiac glycosides. In congestive heart failure, the cardiac output is reduced but the total peripheral resistance is increased, and these effects are reversed by cardiac glycosides. 

Cardiac glycosides bring about diuresis by increasing both cardiac output and renal blood flow the latter in turn reverses the renal compensatory mechanism activated in congestive heart failure. Consequently, the production of aldosterone is reduced, sodium retention is reversed, and the excretion of edematous fluid is enhanced (Figure 35.5). 

Adverse effects Thiazide diuretics induce hypokalemia and hyperuricemia in 70% of patients, and hyperglycemia in 10% of patients. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular hypertrophy, ischemic heart disease, or chronic congestive heart failure) and who are concurrently being treated with both thiazide diuretics and digitalis glycosides (see p. 160). Diuretics should be avoided in the treatment of hypertensive diabetics or patients with hyperlipidemia. 

Biochemical evidence and transfection studies suggest that a and p isoforms can assemble in different combinations and potentially form functional pumps. The sodium pump is specifically inhibited by a series of naturally occurring steroids, such as ouabain (Hansen 1984). Based on their clinical use, these substances are also referred to as cardiac glycosides or cardioactive steroids. Cardiac glycoside sensitivity is conferred by the a subunit of the Na-K-ATPase, and this class of drags is used to treat congestive heart failure (Scheiner-Bobis and Schneider 1997). 

Drug interactions with cardiac glycosides can be subdivided into six types, according to mechanism. Interactions with digoxin have been reviewed (SEDA-6, 173) (196-198). Drug interactions with digitoxin have been briefly reviewed in the context of its use in the treatment of congestive heart failure (199). 

CARDIAC GLYCOSIDES have a pronounced effect on the failing heart, increasing the force of contraction, so they were formerly widely used to Increase the force in congestive heart failure treatment (e.g. digitoxin, digoxin). 

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