Ch 14: Anti- Arrhythmic's

Question 1

Anti-Arrhythmics

Answer 1

• atria and ventricles MUST work in a coordinated fashion to EFFECTIVELY pump blood to body cells
• any arrhythmic event could potentially be damaging, OR DEADLY

** NORMAL CYCLE: SA node depolarization, spreads over atria, atrial contraction, slow conduction through AV node, to bundle of His, bundle branches, Purkinje fibers, then ventricle depolarization

Question 2

AP in slow response tissue

Answer 2

• SA node and AV nodal tissue

- have a net positive charge influx at 4 phase due to Na+ entry

Question 3

Effective refractory period

Answer 3

Na+ channels become unable to open again until they reach -60 mv

Question 4

Relative refractory period

Answer 4

between -60 and -90, may be able to activate some Na+ channels if intense AP occur

Question 5

SA nodal action potential

Answer 5

” Funny Channels” (HCN)
- SLOW Na+ = Na+ influx & “pacemaker potential” –> 4 phase

To depolarize:
T-type Ca++ channels (transient) & L-type Ca+ channels (long lasting) –> 0 phase

Repolarization through K+ efflux –> 3 phase

Question 6

How do we impact HR speed?

Answer 6

Your heart rate is lower when you are at rest. When you exercise, you heart speeds up and pumps more blood, which allows oxygen-rich blood to flow easily and reach your muscles.

Question 7

Fast Response Tissue Action Potential

Answer 7

• Including atria, ventricles, bundle of His, Purkinje fibers

a) 0 phase: 
from resting (-90) to -60 opens Na+ (fast inward) channels >> +20mv

b) 1 phase:
Na+ channels inactivate, K+ efflux (slow transient K+ ch) brings back 0mv

c) 2 phase:
slow L-type Ca++ channels open to allow plateau

d) 3 phase:
Ca++ inactivates, delayed rectifier K+ opens to efflux

e) 4 phase:
stable potential at baseline (K+ ch open)

Question 8

If channels don’t work?

Answer 8

1) Loss of function
result in the gene product having less or no function (being partially or wholly inactivated).

2) Gain of function
A mutation that confers new or enhanced activity on a protein.

Question 9

Arrhythmias are caused by:

Answer 9

• Disease state, scarring
• Acidosis or Alkalosis
• Electrolyte imbalance
• Drug toxicity
• too many catecholamines
• Ischemia/hypoxia

Question 10

Mechanisms of Arrhythmia

Answer 10

1) disturbances of impulse formation
2) disturbances of impulse conduction
3) Both above

Question 11

Disturbances in impulse formation

Answer 11

• Abnormal action potentials “triggered” by a preceding AP
• Early afterdepolarization (EAD; phase 3)
• • from an abnormally long QT interval. Could be from genetic defect or drugs that prolong QT (potassium-ch blockers)
• Delayed afterdepolarizations (DAD; phase 4)
• • often w/ high intracellular Ca++

Question 12

Afterdepolarizations

Answer 12

abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart. Afterdepolarizations may lead to cardiac arrhythmias.

Early (EAD): interrupt phase 3 of the myocardial action potential

Delayed (DAD): Interrupt phase 4 of AP

Question 13

Early Afterdeopolarizations

Answer 13

Lead to Tachyarrhythmias

treat w/ drugs that reduce action potential duration

Question 14

Types of Arrhythmias

Answer 14

1) Enhanced automaticity
2) Triggered beats
3) Reentry

Question 15

Enhanced automaticity

Answer 15

Increased phase 4 slope increases rate of AP’s (DAD)

• Can lead to flutter or fibrillation if in multiple sites
• Due to increased B stimulation, hypokalemia, hypercalcemia

Question 16

Triggered beats

Answer 16

Linked to prior AP if slow phase 3 (EAD).. (membrane stays above -30 to -50, another AP can begin
- due to high catechizes, hypoxia/ischemia, CO2

• EAD (triggered beats) or DAD(enhanced automaticity) are issues w/ impulse propagation

Question 17

Reentry

Answer 17

Due to pathology (Ischemia, etc), conduction velocity in an area is impaired

• due to a block, by time the depolarization can emerge the tissue is no longer refractory and sets off a new AP
• due to impulse conduction

Question 18

Drugs to Treat Arrhythmia

Answer 18

Class I anti- arrhythmics

• • Are Na+ channel blockers
• • Reduce conduction velocity and reduce triggered beats

I-A Drugs: slow phase 0 and AP propagation
- Quinidine, Procainamide

I-B Drugs: slow rate of rise of 0 phase only in impaired tissue
(lidocaine, mexilitine)

I-C Drugs: slow 0 phase and propagation (propafenone, flecainide)

side effect: arrhythmias, dizziness, nausea

Question 19

Class I anti- arrhythmic’s

Answer 19

• reduce Na+ influx, and thus conduction velocity
• tendency to reduce abnormal pacemakers
• since arrhythmic tissue spends more time in “open state” (Na+ channels), will tend to block faster than non- arrhythmic tissue

Question 20

Class II anti- arrhythmic’s

Answer 20

• Beta Blockers (esmolol, propanolol)
• block B-1 receptors
• decrease phase 4 slope and prolong effective refractory period

Side effects: reduced CO, arrhythmia (rare)

Question 21

Class III anti- arrhythmic’s

Answer 21

• Repolarization prolongers (amiodarone, sotalol, dofetilide)
• block K+ channels (Increase QT interval)
• Lengthen AP duration/ effective refractory period

Question 22

• side effects for amiodarone:

Answer 22

pulmonary toxicity, liver damage, etc

Question 23

Sotalol: main side effect

Answer 23

• Torsade de pointes arrhythmias
• Polymorphous ventricular tachycardia
• can be disastrous to use a Class Ia

Question 24

Class IV anti- arrhythmic’s

Answer 24

• Ca++ channel blockers
• Reduce slow calcium current in SA and AV nodes (phase 4), slows rise of 0 phase
• Increased PR interval
• Diltiazem, verapamil (most effective)

Side effects:
slow HR, peripheral vasodilation
leads to dizziness, headache

Question 25

All anti-arrhythmic’s can cause

Answer 25

dizziness
arrhythmia
hypotension

Question 26

OTHER DRUGS

Answer 26

• Adenosine at High Concentrations
  (hyperpolarizes tissue)
• Digitalis Glycosides
  (block Na-K-ATPase)
  can increase parasympathetic activity
• K+ can either improve or worsen, but perhaps can help
• Mg++ can have an effect similar to K+
• Ablation
  (radio waves through intracardiac catheter)
• Defibrillators, pacemakers