L 31-32

Question 1

What are the general classes of anti-arrhythmic drugs?

Answer 1

Class I: Na channel blockers Class II: beta blockers Class III: K channel blockers Class IV: Ca channel blockers Miscellaneous

Question 2

Types of Myocardial fibers and location

Answer 2

Fast Response Fibers: Atria, Ventricles, Bundle of His, Purkinje cells Slow Response Fibers: S-A Node, A-V node

Question 3

Effective refractory period (ERP)

Answer 3

Shortest interval at which premature stimuli result in a propagated response.

Question 4

Action Potential Duration (APD)

Answer 4

Depolarization to repolarization

Question 5

Describe action potential in heart including phases and ion movement

Answer 5

Phase 0: rapid depolarization as fast acting Na channel open and Na enters cell. (In slow response fibers like S-A and A-V nodes this phase is Ca dependent.) Phase 1: Partial rapid repolarization from inactivation of fast sodium channels Phase 2: Plateau phase, Ca channels open allowing Ca movement into cell maintaining depolarization Phase 3: Repolarization, Ca channels close, K channels open allow K to leave the cell, Na channels still returning to resting state Phase 4: Resting membrane potential

Question 6

What is Vmax of action potential?

Answer 6

Vmax is the fastest RATE of depolarization in phase 0

Question 7

Relationship between Vmax and Vm for an action potential

Answer 7

Vmax (rate of depolarization) is dependent on the Vm (resting membrane potential when the signal comes through) Low (or depolarized) Vm causes a slower response (lower Vmax) to signals. Vmax is greatest when Vm is greatest (the most polarized) Anything that partially depolarizes the membrane will slow the conduction velocity!

Question 8

Basic causes of arrhythmias

Answer 8

1) Disorders in automaticity 2) Disorders in conduction velocity 3) Both

Question 9

Determinants of pacemaker rate that can be targeted to slow rate for arrhythmia therapy

Answer 9

1) More neg maximum diastolic potential 2) Reduce rate of diastolic depolarization 3) Raise threshold potential

Question 10

Subsets of the Class I antiarrhythmic agents

Answer 10

A: blocks open/activated Na channels and lengthens ERP B: blocks inactivated Na channels and shortens ERP C: blocks all Na channels and has no effect on ERP

Question 11

Quinidine mechanisms and cardiac effects

Answer 11

Prototype of class 1A Binds open Na channels=>decreased Vmax in Phase 0 and decreased Repolarization=> Increase APD and ERP Blocks K+ channels=>prolonged depolarization Blocks M receptors=>increased HR and A-V conduction Widens QRS and QT on EKG Can cause S-A and A-V block

Question 12

Quinidine other effects (besides on heart)

Answer 12

Blocks alpha receptors=>hypotension Causes G.I. irritation=>DIARRHEA, nausea, vomiting CINCHONISM=tinnitus, headache, vertigo, allergy Affects NMJ because it blocks Na channels=>enhanced NMJ blocking effects

Question 13

Quinidine pharmacokinetics

Answer 13

Oral administration I.V.=>hypotension, I.M.=>pain t1/2=6 hours 80% metabolized by liver, 20% kidney 70-80% plasma protein bound

Question 14

Quinidine toxicity

Answer 14

Low therapeutic index Cardiac toxicity most significant=blocks, EKG changes, reducing automaticity and membrane response, new arrhythmias and torsade Tachycardia Quinidine Syncope & Death (w/digitalis or prolonged QT) Torsade des pointes DIARRHEA Cinchonism

Question 15

Procainamide

Answer 15

Class 1A anti-arrhythmic Like Quinidine, except faster onset and faster metabolism Safe I.V. administration Acetylated in Liver: fast and slow acetylaters will have different levels in blood Prone to torsade des pointes like Quinidine Can cause Lupus