Cardiac glycosides toxicity

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 prevalence of digitalis intoxication is from 16% to 20%. Color vision disturbances are especially common and may occur before, simultaneously with, or after the onset of cardiac toxicity. Although color vision disturbances are associated with cardiac glycoside toxicity decreased visual acuity without the accompanying classic symptom of xanthopsia is also common. 

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. 

Dilantin reversal of cardiac glycoside toxicity was well documented. Woodbury has shown that dilantin augments the active transport of Na and K" " in the brain, skeletal and cardiac muscle. Its ability to reverse digitalis toxicity has been attributed to a direct action on Na,K-ATPase . 

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. 

Digoxin (cardiac glycoside) and trihexyphenidyl (antimuscarinic drug) must be used with caution in elderly patients. Low doses are recommended in elderly patients to avoid toxicity. Lactulose may be safely administered to elderly patients with constipation. 

At overwintering sites of the monarch butterfly [Danaus plexippus) in Mexico, only one of the three local mouse species, Peromyscus melanotis, actually feeds on the butterflies. The monarchs contain cardiac glycosides (CG) and pyrrolizidine alkaloids (PA). All three species of mice have similarly low avoidance thresholds to PA (specifically, monocrotaline). But P. melanotis is less sensitive to CG (specifically, digitoxin) than the other two, Reithrodontomys sumichrasti and Peromyscus aztecus. Laboratory tests indicate that PA is toxic to young mice. 

Cardiac glycosides are medicinally important steroids. Cardenolides are used in heart therapy, as emetics, diuretics, and purgatives. They affect the Na+/K+-ATPase and are very toxic at high doses. 

Cardiac Glycosides Therapeutic and Toxic Plasma Digoxin Levels... 

Decreases in biliary excretion have been demonstrated at both ends of the age continuum. For example, ouabain, an unmetabolized cardiac glycoside that is secreted into the bile, is particularly toxic in the newborn. This is largely due to a reduced ability of biliary secretion to remove ouabain from the plasma. 

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