antiarrhythmics

Question 1

What factors affect the voltage change difference between cells

Answer 1

-the amplitude and rate of rise of the action potential
-the resting membrane potential
(AV node -60, purkinje -90)
larger voltage change –> action potential propogates faster

Question 2

factors that affect resistance in cell to cell conduction

Answer 2

• gap junctions

- myocyte anatomy (big cells have less resistance than small)

Question 3

Early afterdepolarizations

Answer 3

• abnormal AP triggered by previous AP before cell is repolarized
• usually due to prolonged AP (slow HR) bc reactivation of Ca channels
• can lead to run of spontaneous activity
• -freq cause of torsades

Question 4

congenital long QT syndrome

Answer 4

• K channel mutation
• -predisposed to EAD, arrhythmias, syncope, SCD
• many drugs have been called off the market due to their proarrhthmic effects (blockade of hERG)

Question 5

delayed afterdepolarizations

Answer 5

• abnormal AP triggered by previous AP after cell is repolarized
• -usually due to abnormal intracellular Ca handling
• occurs when cell is sick (ischemia, MI) or HR is fast
• Ca overload leads to spontaneous cyclic activation of RyR, etc. depols spontaneously

Question 6

3 requirements for re-entry arrythmia

Answer 6

1. geometry for conduction loop (can be anatomic or functional barrier)
2. unidirectional conduction block
3. slow conduction

Question 7

mechanisms to reduce automaticity

Answer 7

• B and Ca channel blockers reduce slope, reduced automaticity
• Na and Ca channel blockers – increased threshold
• adenosine (activates K leak channels, lows potential away from threshold [increased MDP])
• K channel blockers prolong AP

Question 8

mech to prevent or abolish re-entry

Answer 8

1. slow depressed conduction (Na or Ca channel block)

2. lengthen refractory period (Na or K channel block)

Question 9

state and use dependent block

Answer 9

• slows recovery of ion channel by blocking w drug
• drug comes off as channel goes back to “resting” state
• Na channel block

-problem: lidocaine remains bound in ischemia bc membrane potential is higher than normal, tachycardia also accumulates drug

Question 10

procainamide

Answer 10

-oral/IV
SE: lupus like effect, nausea
-vent arrythmias, recurrent atrial arrythmias
-slow phase 0 depol, slow conduction via Na channel block
-dissociate from channels w medium kinetics, prolong AP. K channel blocking effect

Question 11

quinidine

Answer 11

• oral/IV
• diarrhea
• vent arrythmias, recurrent atrial arrythmias
• slow phase 0 depol, slow conduction via Na channel block
• dissociate from channels w medium kinetics, prolong AP. K channel blocking effect

Question 12

disopyramide

Answer 12

oral

• SE: neg inotrope (avoid in HF)
• vent arrythmias, recurrent atrial arrythmias
• slow phase 0 depol, slow conduction via Na channel block
• dissociate from channels w medium kinetics, prolong AP. K channel blocking effect

Question 13

lidocaine

Answer 13

IV
-slow phase 0 depol, slow conduction via Na channel block
-dissociate from channels w fast kinetics, shortens AP
SE: CNS tox (cumulative effect)
-actue vent arrythmias

Question 14

mexiletine

Answer 14

oral
-slow phase 0 depol, slow conduction via Na channel block
-dissociate from channels w fast kinetics, shortens AP
SE: CNS tox (cumulative effect)
-chronic Vent arrythmias

Question 15

flecainide

Answer 15

oral

• slow phase 0 depol, slow conduction via Na channel block
• dissociate from channels with slow kinetics
• most selective of Na channel blockers
• suppress PVC, but cause arrythmmias
• arrythmmogenic
• used for recurrent atrial arrythmias
• avoid in patients with underlying structural heart diesease or post MI

Question 16

propafenone

Answer 16

oral

• slow phase 0 depol, slow conduction via Na channel block
• dissociate from channels with slow kinetics
• most selective of Na channel blockers
• suppress PVC, but cause arrythmmias
• arrythmmogenic
• used for recurrent atrial arrythmias
• avoid in patients with underlying structural heart diesease or post MI

Question 17

mechanism of B blockers

Answer 17

-improve Ca handling in sick myocyte

Question 18

amiodarone

Answer 18

-K channel blocker
-prolongs action potential and refractory period
-oral/IV
use: atrial and ventricular arrythmias
-less arrythmogenic in pt with HF or post MI
SE: bradycardia, B and Ca blocking effects
-accumulates in tissues, can cause dose related pulm, liver, thyroid, eye, skin toxicity

Question 19

sotalol

Answer 19

oral (start in hospital)
–K channel blocker
-prolongs action potential and refractory period
use: atrial and ventricular arrythmias
SE:bradycardail (B blocking effects of L isomer), marked QT prolongation (torsades)

Question 20

dofetilide

Answer 20

oral (start in hospital)
–K channel blocker
-prolongs action potential and refractory period
used for atrial arrythmias, relatively safe in HF
SE: marked QT prolongation (torsades)

Question 21

ibutelide

Answer 21

IV (start in hospital)
--K channel blocker
-prolongs action potential and refractory period
acute conversion of Afib/Flutter
SE:  marked QT prolongation (torsades)

Question 22

dronedarone

Answer 22

oral (start in hospital)
–K channel blocker
-prolongs action potential and refractory period
atrial and ventricular arrhythmias
SE: lacks thyroid and pulm toxcity of amiodarone, but also doesn’t work

Question 23

therapeutic use for Ca channel blockers

Answer 23

• re-entry SVT involving AV node
• slow AV node conduction
• not for use in HF

Question 24

adenosine

Answer 24

-IV (half life

Question 25

digoxin

Answer 25

• slows vent response in AFib/Flutter
• sensitizes parasympathetic efferents (inhibits Ica)
• arrythmogenic with toxic levels