cardiac glycosides and normal ventricular and pacemaker APs

Question 1

What is the main cardiac glycoside? bioavailibility? protein bound? half life? excretion

Answer 1

digoxin. 75% bioavailable, 20-40% protein bound, half life of 40 hrs; urinary excretion
half life is important- long time to reach a steady state.

Question 2

digoxin mechanism

Answer 2

inhibits the Na/K/ATPase, which establishes the Na and K gradient. there is more Na in the cell than normal. This slows the Na/Ca exchanger, which usually brings Na in and pumps Ca out (using Na’s gradient). this increases Ca concentration in the cardiac cells and increases contractility. There is also vagal stimulation of the heart.

Question 3

clinical use for digoxin

Answer 3

CHF (dig increases contractility), and afib: slows conduction through the AV node and depresses the SA node.

Question 4

clinical features of digoxin toxicity

Answer 4

mostly cholinergics: nausea, vomiting, diarrhea, blurry yellow vision.

Question 5

ECG findings for digoxin toxicity

Answer 5

incr. PR interval, decr. QT, ST scooping, T-wave inverstion, arrhythmia, AV block

Question 6

What factors predispose a patient to digoxin toxicity?

Answer 6

renal failure, hypokalemia (permissive for dig binding at the K binding site of Na/K ATPase), verapamil, amiodarone, and quinidine: decr. dig clearince and displaces dig from tissue binding sites

Question 7

Digoxin antidote

Answer 7

anti-digoxin Fab. if not available, try to slowly normalize K, cardiac pacer, Mg

Question 8

What happens in the different phases of a ventricular action potential?

Answer 8

phase 0: rapid depolarization due to opening of voltage-gated Na channels (Na comes in)
phase 1: slight initial repolarization due to opening of the fast voltage-gated K channels (K goes out)
phase 2: plateau as the outward K channel current is matched by the inward Ca current. Intake of calcium releases more calcium from the sarcoplasmic reticulum, which causes muscle contraction
phase 3: repolarization as slow inward voltage gated K channels open and voltage gated Ca channels close
phase 4: resting potential maintained by leaky K channels. Note that we also have Na-K-ATPase pmus and Na-Ca exchangers.

Question 9

How are ventricular APs different from skeletal muscle? (3 major differences)

Answer 9

1. Heart muscle has a plateau phase d/t matched Ca influx and K efflux
2. Heart depolarizes itself d/t “funny channels” (If channels) in the AV and SA nodes. this happens during diastole.
3. Heart muscles are electrically connected to each other via gap juctions

Question 10

Describe the pacemaker action potential and contrast it with the ventricular AP

Answer 10

phase 0: relatively slow upstroke because it is mediated by slower voltage-mediated Ca influx cells rather than the fast Na channels in ventricular AP (there are no fast Na channels in pacemaker cells).  this helps slow down conduction through the AV node.
no phase 1 or 2.
Phase 3 (repolarization) occurs as Ca channels are inactivated and K channels are activated (K efflux)
Phase 4: slow diastolic depolarization mediated by Na "funny channels."  these channels account for heart automaticity.  slope of channel opening determines HR

Question 11

How do adenosine and ACh affect pacemaker AP? QWhat about catecholamines?

Answer 11

ACh/adenosine decr. the rate of diastolic deplolarization.
catecholamines incr. the rate of depolarization and incr. HR.
sympathetic stim incr. the chance that If channels are open.

Question 12

Adenosine: mechanism and use

Answer 12

increases K out of cells. this hyperpolarizes the cell (inside even more negative) and decreases the intracellular Ca. it is the DRUG OF CHOICE for diagnosing/abolishing supraventricular tachycardia. it is very short acting

Question 13

adenosine adverse effects and special considerations

Answer 13

flushing, hypotension, chest pain. blocked by theophylline and caffeine.