Cardiac glycosides, toxic effects

The answer is b. (Hardman, pp 703-704J Low K stores due to the effects of thiazide diuretics such as hydrochlorothiazide increase susceptibility to cardiac glycoside toxicity... 

The electrocardiographic effects of cardiac glycoside toxicity in 688 patients have been reviewed in the context of three cases of digoxin toxicity (49). The three cases featured bidirectional tachycardia in a 50-year-old man with a plasma digoxin concentration of 3.7 ng/ml, junctional tachycardia in a 59-year-old man with a plasma digoxin concentration of 4.3 ng/ml, and complete heart block in a 90-year-old woman whose postmortem digoxin concentration was 5.0 ng/ml. 

They antagonize the positive inotropic and chronotropic effects of catecholamines. Cardiac arrhythmias associated with excessive adrenergic stimulus, released endogenous catecholamines or sensitization of the heart by anes-thetics or cardiac glycosides may effectively be treated by 6-blockade. Some B-blockers also possess membrane or local anesthetic action and are effective against arrhythmias due to ischemia or cardiac glycoside toxicity as well. This membrane action was shown to be independent of 6-blockade since resolved isomers of B-blockers possessed equal antiarrhythmic potency but unequal B-blocking action. 

Cardiac glycosides have a small ratio of toxic to therapeutic concentration. Possible adverse effects are nausea, vomiting, abdominal pain, diarrhoea, fatigue, headache, drowsiness, colour vision disturbances, sinus bradycardia, premature ventricular complexes, AV-block, bigeminy, atrial tachycardia with AV-Block, ventricular fibrillation. There are several mechanisms relevant for their toxic action (Table 2). 

Some insects can protect themselves against the toxins present in their food plants by storing them. One example is the monarch butterfly, the caterpillars of which store potentially toxic cardiac glycosides obtained from a food plant, the milkweed (see Harborne 1993). Subsequently, the stored glycosides have a deterrent effect upon blue jays that feed upon them. 

Cardiac glycosides affect all excitable tissues, including smooth muscle and the central nervous system. The gastrointestinal tract is the most common site of digitalis toxicity outside the heart. The effects include anorexia, nausea, vomiting, and diarrhea. This toxicity is caused in part by direct effects on the gastrointestinal tract and in part by central nervous system actions. 

Potassium and digitalis interact in two ways. First, they inhibit each other s binding to Na+,K+ ATPase therefore, hyperkalemia reduces the enzyme-inhibiting actions of cardiac glycosides, whereas hypokalemia facilitates these actions. Second, abnormal cardiac automaticity is inhibited by hyperkalemia (see Chapter 14). Moderately increased extracellular K+ therefore reduces the effects of digitalis, especially the toxic effects. 

Calcium ion facilitates the toxic actions of cardiac glycosides by accelerating the overloading of intracellular calcium stores that appears to be responsible for digitalis-induced abnormal automaticity. Hypercalcemia therefore increases the risk of a digitalis-induced arrhythmia. The effects of magnesium ion appear to be opposite to those of calcium. These interactions mandate careful evaluation of serum electrolytes in patients with digitalis-induced arrhythmias. 

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]. 

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