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64 Cards in this Set
- Front
- Back
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What are the Therapeutic effects of Digitalis mainly due to?
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Its VAGAL tone enhancement
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What are the TOXIC effects of Digitalis mainly due to?
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Its inhibition of Na/K ATPase - when excessive
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Why is increased vagal tone therapeutic, but over inhibiting Na/K ATPase is toxic?
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The former is Antiarrythmic
The latter is Proarrythmic |
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How is it that excess Digoxin leads to arrythmias?
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It increases the automaticity of spontaneous pacemaker sites in Purkinje fibers of the ventricle.
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What is the mechanism by which digoxin increases the automaticity?
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Overinhibition of Na/K ATPase leads to excess Ca in the cell and afterdepolarizations
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What are Afterdepolarizations?
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An extra release of Ca after the initial AP in a cardiac myocyte due to the extra storage when Na/K ATPase is inhibited.
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What do afterdepolarizations lead to if not corrected?
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Atrial or ventricular flutter and fibrillation
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What are the 3 good parasympathomimetic effects of Digoxin?
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-Decreased HR
-Decreased AV node conduction velocity -Increased ERP in the AV node |
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What is the main toxic parasympathomimetic effect that can result from toxic concentrations of Digoxin?
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Heart block
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What is the PR interval an index of?
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The rate of conduction from the SA node to the AV node.
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What is the QRS width?
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The rate of depolarization through the the ventricle
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What is the QT interval an index of?
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Depolarization and Repolarization of the ventricle
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What are 2 EKG changes that therapeutic levels of Digoxin can produce?
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-Prolonged PR interval dt vagal slowing of AV node conduction
-Inverted Twaves dt faster repolarization of the ventricle |
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What may begin to be seen on the EKG at toxic concentrations of Digoxin?
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Uncoupled P waves
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What can be seen at more severely toxic Digoxin concentrations?
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Bigeminy - ectopic foci in the ventricles.
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What % of patients on Digoxin can get arrythmias at toxic doses?
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50%
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What do the ectopic foci that produce bigeminy and trigeminy in the ventricles have the potential to accumulate into?
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Tachycardia and fibrillation
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So what is the main THERAPEUTIC electrophysiologic effect of digitalis?
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Increased vagal tone which decreases AV conduction
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What are the 2 TOXIC electrophysiologic effects of digitalis at toxic doses?
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-Overly increased vagal tone causing complete AV block
-Overly decreased Na/K ATPase causing ventricular and atrial arrythmia |
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And what are the 2 mechanisms by which overly blocking Na/K ATPase will lead to arrythmias?
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1. Increased automaticity
2. Sparks reentry AP's |
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What is the therapeutic index of all digitalis preparations?
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2
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Why is the TI of digitalis so narrow?
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It has many associated side effects.
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What side effect is seen in 75-100% of patients on Digitalis?
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GI Upset
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What will be seen in young adults that are at the toxic threshold?
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Nausea and vomiting
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What side effect is seen in 15-90% of patients on Digitalis?
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Visual effects - Blurred vision, photophobia, and Greenish-yellow discoloration.
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What side effects of Digitalis are seen in 30-90% of patients, particularly the older ones?
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Neurologic and neuromuscular effects
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What are some Neurologic and neuromuscular effects of Digitalis?
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-Fatigue
-Muscle weakness -Anxiety, nightmares, delirium |
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What is the most dangerous side effect of Digitalis and in what % of patients does it occur?
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Cardiac arrythmias - 30-40%
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What type of cardiac arrythmia can occur from Digitalis toxicity?
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Any kind - because you're both blocking AV node conduction via Vagal effects, and increasing Calcium by blocking Na/K ATPase
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What are the 3 cardiac manifestations that Digitalis can cause at toxic levels?
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-Arrythmias - both ventricular and supraventricular
-Blocks - SA and AV blocks -CHF exacerbation! |
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What are 6 Conditions which Enhance Digitalis toxicity?
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CHAIDA
-Catecholamines -Hypothyroidism -Antiarrythmics - Quinidine -Ischemia -Diuretics - K loss -Amiodarone |
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What does Amiodarone do?
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Decreases renal excretion
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How do Catecholamines enhance Digitalis Toxicity?
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By increasing the upstroke of the action potential, increasing HR, etc.
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How does K loss lead to Digitalis toxicity?
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By enhancing its ability to bind to the alpha subunit of Na/K ATPase
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How does Ischemia enhance Digitalis Toxicity?
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By depolarizing tissue which makes it easier to inhibit the Na/K ATPase
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How do both Quinidine and Amiodarone enhance Digitalis toxicity?
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By reducing the renal excretion of Digitalis which leads to more of it in the system for a longer time.
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What is the first step in treating Digitalis toxicity?
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Use a lower dose or stop it.
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What can be given to compete with Digitalis for binding to the Na/K ATPase?
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Potassium salts
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What is a good antiarrythmic that doesn't effect the AV node so won't lead to anymore AV blockade in Digitalis toxicity?
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Lidocaine
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What can increase the excretion of Digitalis in the stools?
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Steroid binding resins - Cholestyramine
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What is the best way to get rid of toxic effects of Digitalis?
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Specific antibodies - Digibind
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What is the last resort treatment for digitalis toxicity?
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The paddles - DC Countershock
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What are the 2 main digitalis glycosides used clinically?
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-Digoxin
-Digitoxin |
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How are Digoxin and Digitoxin NOT different?
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In their therapeutic indexes
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Which glycoside is used more often? Why?
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Digoxin - because its half life is much shorter than that of Digitoxin
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What is the main structure of the cardiac glycosides?
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A steroid linked to a bunch of sugar residues
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What are the 2 main differences between Digoxin and digitoxin?
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1. Digoxin has a much lower oil:water partition coefficient and is absorbed less completely
2. Digitoxin has a much longer half life. |
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What is Digoxin aka?
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12-hydroxydigitoxin
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What is the predominant way that Digoxin is excreted?
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By the kidney via glomerular filtration and tubular secetion - unchanged.
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How much Digoxin is excreted by the kidney per day?
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37%
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What is the halflife of
-Digoxin -Digitoxin |
Digoxin = 1.6 days
Digitoxin = 5-7 days |
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So what do you have to do if kidney function is reduced and you want to give Digoxin?
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Lower the dose
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How much is Digitoxin absorbed from the GI tract? Digoxin?
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Digitoxin = 100%
Digoxin = 60-85% |
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What is Digitoxin subject to?
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Liver-enterophepatic recycling
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So how much Digitoxin is lost by the GI tract per day?
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10%
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How is Digitoxin excreted?
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As inactive metabolites
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Considering the long half life of Digitoxin, how would you need to start a patient on it?
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By giving a loading dose to get them up to Css, then give maintainence doses.
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What is the structural difference between Digoxin and digitoxin?
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Digoxin = polar
Digitoxin = nonpolar |
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So what are the 3 Major uses of Digitalis Glycosides?
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1. Systolic left heart failure
2. Certain cardiac arrythmias 3. Previous relief of symptoms |
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Why is Digitalis used to treat previous relief of symptoms?
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When taken OFF digitalis, patients tend to do worse than if they had never been on it - so once you start, DON'T STOP.
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Where Digitalis has good effects of improving sympoms by increasing Ejection Fraction, what doesn't it do?
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Does not reduce mortality.
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What are 3 types of cardiac arrythmias the digitalis glycosides are used to treat?
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-Atrial fibrillation
-Atrial flutter -Paroxysmal supraventricular tachycardia |
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How does Digitalis treat atrial fibrillation and flutter?
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By blocking the AV node which slows the ventricular rate.
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What WON'T Digitalis do for the ventricular rate?
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Convert back to a NORMAL rate - have to use another drug in addition, or else shock it back into normal rythm.
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