What are the general classes of anti-arrhythmic drugs?
Class I: Na channel blockers Class II: beta blockers Class III: K channel blockers Class IV: Ca channel blockers Miscellaneous
Types of Myocardial fibers and location
Fast Response Fibers: Atria, Ventricles, Bundle of His, Purkinje cells Slow Response Fibers: S-A Node, A-V node
Effective refractory period (ERP)
Shortest interval at which premature stimuli result in a propagated response.
Action Potential Duration (APD)
Depolarization to repolarization
Describe action potential in heart including phases and ion movement
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
What is Vmax of action potential?
Vmax is the fastest RATE of depolarization in phase 0
Relationship between Vmax and Vm for an action potential
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!
Basic causes of arrhythmias
1) Disorders in automaticity 2) Disorders in conduction velocity 3) Both
Determinants of pacemaker rate that can be targeted to slow rate for arrhythmia therapy
1) More neg maximum diastolic potential 2) Reduce rate of diastolic depolarization 3) Raise threshold potential
Subsets of the Class I antiarrhythmic agents
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
Quinidine mechanisms and cardiac effects
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
Quinidine other effects (besides on heart)
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
Oral administration I.V.=>hypotension, I.M.=>pain t1/2=6 hours 80% metabolized by liver, 20% kidney 70-80% plasma protein bound
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
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