Module 42

Question 1

From the structure of digoxin would you expect that it would be well absorbed from the intestine?

Answer 1

• At first glance it looks like a sugar, which suggests that oral bioavailability would be low. However, there is only 1 hydroxy group on two of the sugars, and overall it is a lipophilic molecule. Its absorption is limited, not so much by its physical properties as by the fact that it is a good substrate for p-glycoprotein, and it is pumped back into the gut lumen. Even so, although variable, bioavailability is about 70%.

Question 2

Digoxin can be responsible for a variety of cardiac arrhythmias. What is the major risk factor for the development digoxin-related arrhythmias?

Answer 2

• The major risk factor is electrolyte imbalances, especially hypokalemia and hypomagnesemia. Therefore, diuretics, which are commonly prescribed along with digoxin, increase the risk of arrhythmias. Care must be taken to make sure that patients do not develop hypokalemia.
  High concentrations of digoxin are also a risk factor, and blood levels should be monitored because the therapeutic index is low, and there are several drug interactions that can lead to increased digoxin levels. These interactions include antibiotics that kill a bacteria that can metabolize digoxin and other agents that can compete with digoxin for clearance by p-glycoprotein. Adrenergic agents can also increase the risk of arrhythmias.

Question 3

How effective is digoxin in the treatment of heart failure? What condition is digoxin most effective in treating? Are any positive inotropic agents effective for the treatment of heart failure? What agents are most effective at treating chronic heart failure?

Answer 3

digoxin was almost the only treatment for heart failure, but its efficacy is very limited. One effect is significant: digoxin decreases the ventricular rate in atrial fibrillation, and that can be of significant benefit. If the ventricular rate is too fast it does not allow time for ventricular filling.
- In general, agents that increase the force of heart contraction (inotropic agents) appear to increase mortality. ACE inhibitors and other agents that decrease afterload (the resistance against which the heart has to pump) have proven to be more effective.