QUESTIONS

1. Explain the mechanism of Digoxin's positive inotropic effect.
    
2. What is Digoxin's effect on the autonomic nervous system & why is it a good thing?
    
3. What effect does Digoxin have on baroreceptors?
    
4. Should you give Digoxin with food?
    
5. When might you want to give parenteral Digoxin?
    
6. Digoxin is eliminated chiefly by the liver/kidneys (Choose one).
   
   Digitoxin is eliminated chiefly by the liver/kidneys. (Choose one).
    
7. Which has a longer half life in the dog: digoxin or digitoxin?  How about in the cat?
    
8. When should one run a digoxin level?
    
9. Lasix usage may lead to potassium depletion in our patient.  What effect would this have on digoxin metabolism?
    
10. What in the hell is a Fab Fragment?
     
11. What might be an indication that you need to add a beta blocker to digoxin therapy?
     
12. Describe the basic molecular structure of digoxin.
    
    
    
    
     

ANSWERS

1. Digoxin is a Na+/K+/ATPase poisoner.  This means that the pump craps out & the myocardial cell is stuck w/a whole bunch of  sodium inside. Fortunately, there is a sodium/Calcium exchange mechanism that can come into use in this situation.  Cool. Now we have a bunch of calcium inside the myocardial cell.  "I'll take that, thank you," says Mr. Sarcoplasmic reticulum.  More calcium in the sarcoplasmic reticulum leads to stronger contractility.
   
   (Note: if the myocardial cell is not healthy, the sarcoplasmic reticulum may not be able to take up calcium & in this case, digoxin will not be a + inotrope to speak of.)
   
   
   
   
    
2. Digoxin increases vagal tone which leads to slowed conduction through the AV node. It is this event that helps with supraventricular arrhythmias.  As a negative chronotrope, digoxin also helps the coronary circulation supply the heart w/blood.  (Am I correct in believing that the heart doesn't get any blood supply circulated to it in systole?)
   
   
   
   
    
3. Many people are starting to digitalize sooner rather than later because of this effect.  In CHF, baroreceptors become "hypersensitive" meaning that they are quicker to turn on sympathetic tone than in a normal patient.  Digoxin resets these baroreceptors to normal (less tendency to excite the symp. N.S.)
   
   
   
   
    
4. Do not give digoxin with food.  You will get a 50% less reduction in serum concentration.  Give it between meals.
   
   
   
   
    
5. Well, one indication would be if you are doing research on parenteral dig.  But seriously folks, there really aren't a lot  of indications for parenteral Dig.  You would use it for some reason the animal cannot take it PO.  You might try it for supraventricular arrhythmias but at best it takes 1.5-3 days to get a signif. blood level.
   
   It must be given IV as SQ or IM dosing is very painful.  You want to give it as a slow infusion to avoid acute vasoconstriction.
   
   
   
   
    
6. Digoxin is eliminated chiefly by the liver/kidneys
   
   Digitoxin is eliminated chiefly by the liver/kidneys.
   
   (Paul, I recall from school that kidney disease would be good indication for choosing digitoxin over digoxin.  I haven't heard a word on digitoxin since I left school. Why is ithis?)
   
   
   
   
    
7. Digoxin has a longer half life in the dog (20-30 hours vs. 6-14 hours)
   
   Digitoxin has a longer half life in  the cat (>100 hours vs. 10-79 hours)
   
   Because of the long half life in the cat, digitoxin should never be considered in the cat.
   
   (Paul, did I read "79" hours correctly?!)
   
   Paul, our freshman pharm. teacher told us:  The Mixed function oxidases add -0H to digitoxin thus converting it into digoxin.  Both digitoxin & digoxin  are conjugated & dumped into the GI tract, de-conjugated & reabsorbed. This give digitoxin another chance to work on the heart.  At the time I understood it to explain why digitoxin had a longer half life than digoxin but this isn't the case. What was our teacher really trying to explain to us?)
   
   
   
   
    
8. There are 3 situations when one should run a digoxin level:
   
   *  4-7 days after first starting digoxin (or changing the dose)
   
   *   If an animal on digoxin suddenly decompensates (it may be because he developed a toxic arrhthmia)
   
   *  If an animal on digoxin suddenly becomes anorectic or nauseated.
   
   Run your level 8-10 hours after the last dose.  A good level would be 1-2.5 ng/dl
   
   
   
   
    
9. Hypokalemia will increase digoxin's binding to the sodium/potassium pump plus decreases renal clearance of digoxin.  All this potentiates digoxin's effects & increases the chance of toxicity (right?)
   
   
   
   
    
10. Does it have something to do with the 5th Beatle?  No.  These are Digoxin antibodies that you can use in the event of an acute life-threatening Dig. toxicity.
    
    
    
    
     
11. Say you have a good therapeutic level of digoxin but the heart rate of  the patient is still >150.  If you are treating a supraventricular arrhythmia, add a beta blocker about now to get the heart rate lower. 
    
    
    
    
     
12. Digitalis glycosides consist of a steroid nucleus, an unsaturated lactone ring & a sugar stuck on to the lactone ring.  The sugar determines solubility, half life etc.  Digoxin has an extra -0H making it more polar (less GI absorption, reduced protein binding & increased urinary excretion relative to digitoxin.