Anti-Arrhythmics

Question 1

Role of Na Channels

Answer 1

Determine speed of membrane depolarization during AP: related to conduction velocity

Na channel blockers reduce conduction velocity - helps abolish tachyarrhythmias caused by re-entry circuits

Ca myocytes ONLY - does not help PM cells

Question 2

Refractory Period

Answer 2

Directly related to AP duration => tied to K outflow

Increased AP, prolongs refractory period - delays repolarization of APs (phase 3)

Question 3

Pacemaker Potentials

Answer 3

Drugs that slow/block inward Ca channels by slowing rate of rise of depolarizing PM potentials: decrease rate of phase 4, phase 0 in PM

Reduce conduction velocity at AVN

Question 4

Na Channel Blockers - general MOA

Answer 4

Decrease upstroke/phase 0 of atrial/ventricular myocytes = decreased amplitude of AP

Decreased conduction velocity of non-nodal tissue

Question 5

Class IA - Na Channel Blockers

Answer 5

Moderate Na channel blockade: increased slope 0
Increased APD/ERP DT K channel blockade

Tx: Afib/aflutter, SVT, VT

Bad for TdP (afterdepolarizations)

Question 6

Class IB - Na Channel Blockers

Answer 6

Weak Na channel blockade: mildly decreased slope of phase 0 - least of Na channel blockers

Decrease APD/ERP DT blockade of both inactivated, activated Na channels

Tx: Ventricular arrhythmias

Question 7

Class IC - Na Channel Blockers

Answer 7

Strong Na channel blockade, no effect on APD/ERP

Most increase in slope of phase 0

Tx: life threatening VT, SVT

Example: flecainide, propanfenone

Question 8

SE Na Channel Blockers

Answer 8

Vagolytic Activity: increase SA rate, AVN conduction

Suppress abN automaticity - MOA unknown

Question 9

Beta Blockers

Answer 9

Sympatholytics: block of B1 R inhibits activation of L type Ca channels via Gs - no Ca influx

Question 10

Intrinsic Activity of Beta Blockers

Answer 10

Partially activate receptor but block NE from binding to R = partial agonist, baseline sympathetic activity

Question 11

Beta Blockers: hypertension

Answer 11

Reduced renin secretion by kidneys DT blockade of B1 on JXC cells

Decreased angiotensin II, aldosterone secretion

Question 12

Use of Beta Blockers as Anti-Arrhythmics

Answer 12

Slows time to reach threshold potential so decreases rate

Increases slope of phases IV, 0

Blockers extra SNS stimulation, does not directly block Ca channels

Question 13

MOA Class III

Answer 13

Prolong AP = prolong ERP via blockade of K channels, primarily phase III

Prolong QT interval

Prolongation of ERP = suppression of reentry tachycardias

Question 14

Amiodarone

Answer 14

Class III - used for tach, fib, AF/afib

Decreases phase 4 slope and conduction velocity

Can potentially precipitate TdP if prolonged QT, bradycardia, AV blockade

Question 15

Sotalol

Answer 15

Class III - ventricular tachycardia, atrial fibrillation, atrial flutter

Inhibits opening of repolarizing K channels, increases ERP

Also has Class II activity, slowing of sinus rate

Question 16

CCB: arrhythmias

Answer 16

Block L type Ca channels

Decrease phase 4 in PM cells, decrease phase 0 in PM cells

Decrease in cardiac contractility

Question 17

Dihydropyridines

Answer 17

High vascular selectivity: reduce SVR, tx hypertension

end in “pine” - include amlodipine, nicardipine

Question 18

Non-dihydropyridines

Answer 18

Verapamil, diltiazem

Question 19

use of Ca Channel Blockers

Answer 19

Primarily atrial/supraventricular arrhythmia

Question 20

Adenosine - Cardiac Tissue

Answer 20

A1R: Gi/o, inhibits L type Ca channels in PM cells - inhibits If, decreases slope of phase 4 and decreases firing rate/decreased conduction velocity at AVN

Blocks release of NE at presynaptic nerve terminals

Question 21

Adenosine - VD Effects

Answer 21

A2R: Gs –> increase in cAMP, important for matching coronary BF = MVO2

Hyperpolarizing via activation of Katp channels/inhibition of MLC-K

Question 22

Use of Adenosine as Anti-Arrhythmic

Answer 22

SVT - AV nodal reentry

Not effective for flutter, fibrillation

Risk of coronary steal

Question 23

Digitalis

Answer 23

Blocks Na-K ATPase responsable for maintaining normal intracellular K/extracellular Na

Blockade of this pump affects activity of Na-Ca exchanger (3Na per 1 Ca): more accumulation of Na decreases pump activity so more Ca stays inside cell (less drive to pump Na out)

More Ca uptake by SR, more available to bind to troponin C = increased contractility

Question 24

Digitalis Toxicity

Answer 24

NSAIDS, Ca channel blockers, beta blockers, amiodarone, diuretics

Hypokalemia, hypercalcemia, hypomagnesemia: increased effect

Question 25

Use of Digitalis for AF/A fluter

Answer 25

Parasympathomimetic effects - reduced conduction of electrical impulses within AV node, some impulses blocked - ventricular rate falls