Lecture 4 - Antiarrhythmics Flashcards
In what type of patients is arrhythmia a frequent problem?
- 25% of patients with digitalis (heart failure)
- 50% of anesthetized patients
- 80% of patients with MI
T or F: anti-arrhythmic drugs can produce arrhythmia
true
What is the normal pacemaker?
SA node
What are the conduction fibres??
AV node, bundle of His, Purkinje fibres
What is included in the term “healthy myocardium”?
atria and ventricles
Super briefly describe how atria and ventricles contract using SA and AV nodes
- SA node causes atria to contract
- AV node allows for a pause for ventricles to fill
- Then ventricles contract
Normal cardiac rhythm = ?
sinus rhythm
Define arrhythmia
any rhythm that is not a normal sinus rhythm with normal AV conduction
What is the main pacemaker and initiator of heart beat?
SA node
SA node = ____bpm
60-100
AV node spontaneously discharges at ____ bpm (normally overridden)
40-60
What is the function of conduction fibres?
to excite the ventricular mass as near simultaneously as possible
Purkinje fibres spontaneously discharge at ___bpm (overridden)
20-40
P wave
atrial depolarization
QRS complex
ventricular depolarization
T wave
ventricular repolarization
PR interval
conduction time atria to ventricles
QRS interval
time for all ventricular cells to be activated
QT interval
duration of ventricular action potential
Most anti arrhythmic drugs act on ___ _____
ion channels
Class 1 Antiarrhythmic drugs block __ channels
Na
Class 2 Antiarrhythmic drugs block _______
B-receptors
**class 2 antiarrhythmics are B-blockers lol
Class 3 Antiarrhythmic drugs block __ channels
K
Class 4 Antiarrhythmic drugs block ___ channels
Ca
Class __ Antiarrhythmic drugs have other mechanisms
5
List some Class 1 Antiarrhythmic drugs
procainamide, lidocaine, flecanide
List some Class 2 Antiarrhythmic drugs
propranolol, metoprolol, esmolol (B blocker)
List some Class 3 Antiarrhythmic drugs
amiodarone, sotalol
List some Class 4 Antiarrhythmic drugs
Verapamil
List some Class 5 Antiarrhythmic drugs
magnesium, adenosine, digoxin
Class 2 and 4 antiarrhythmic drugs act on _____ cells
pacemaking
Class 1, 3, and 5 antiarrhythmic drugs act on _____ cells
non-pacemaking
Na is higher _____
extracellular
K is higher ______
intracellular
Cl is higher ______
extracellular
Ca is higher _____
extracellular
The only ion higher intracellular is __
K+
What causes depolarization?
positive charge in cell (Na+ and Ca2+ entering)
What causes repolarization?
negative charge in cell (K+ leaving)
What are the pacemaker cells?
SA node
AV node
What are the non-pacemaker cells?
atria
ventricles
purkinje fibres
Describe the electrophysiology of non-pacemaker cells:
Phase 0
Phase 0 - Depolarization:
- voltage gated Na channels open
- rapid depolarization
- Na channels
Describe the electrophysiology of non-pacemaker cells:
Phase 1
Phase 1 - Slight Repolarization:
- Distinctive to non-pacemaker cells
- Cl channels open briefly and chloride enters cell
Describe the electrophysiology of non-pacemaker cells:
Phase 2
Phase 2 - Plateau:
- Distinctive to non-pacemaker cells
- Opening of Ca channels
- Ca enters cell
- Causes further release of Ca from SR
- Ca dependent contraction
Describe the electrophysiology of non-pacemaker cells:
Phase 3
Phase 3 - Repolarization:
- K channels open
- movement of K out of the cell repolarizes the membrane
- returns to resting membrane potential
- Ca is removed from the cytoplasm and tissue relaxes
Describe the electrophysiology of non-pacemaker cells:
Phase 4
Phase 4 - Diastolic (resting) potential:
- no time-dependent currents during phase 4
- as a result, resting potential, is substantially more negative (-80mV) than SA/AV nodes
Describe the electrophysiology of non-pacemaker cells:
Absolute/Relative Refractory Period
Phase 3:
- Na channels recover from inactive to resting state
- Repolarization switches sodium channels from inactive to resting
- If the Na channels are in the inactive state the myocyte cannot be depolarized = absolute refractory period
- If only a portion of the Na channels are in the inactive state the myocyte may depolarize but a less rapid depolarization = relative refractory period
What does Depolarization of the resting membrane potential in non-pacemaker (fast) cells cause?
- decreases the number of sodium channels available
- decreases the rate of depolarization
- decreases the strength and speed of the impulse
*slow depolarization of the resting membrane potential caused by hyperkalemia, schema, drugs blocking sodium channels will decrease the upstroke of eliminate it all together
So, need completely ____ membrane and “resting” sodium channels
repolarized
Describe the sodium channel gates in resting conformation
- m gate closed
- h gate open
Describe the sodium channel gates in activated conformation
- m gate open
- h gate open
Describe the sodium channel gates in inactivated conformation
- m gate closed
- h gate closed
*absolute refractory period
How do Class 1 Antiarrhythmics alter the appearance of the action potential in non-pacemaking (fast) cells?
Class 1 are the Na channel blockers
- so they would prevent the rising phase of depolarization (phase 0)
- only affects non-pacemaking cells
How do Class 3 Antiarrhythmics alter the appearance of the action potential in non-pacemaking (fast) cells?
Class 3 are K channel blockers
-so they would prevent K+ efflux and delay repolarization
Describe the electrophysiology of pacemaker cells:
Phase 0
- threshold reached - Ca channels open
- rapid depolarization
- then Ca channels close
Describe the electrophysiology of pacemaker cells:
Phase 3
-voltage gated K channels open and membrane repolarizes
Describe the electrophysiology of pacemaker cells:
Phase 4
- spontaneous depolarization
- pacemaker current - I f (funny current) = increased Na+ influx
- increased Ca influx
- decreased K efflux
- intrinsic firing rate: SA > AV > bundle of his > purkinje fibres
- *note: bundle of his and purkinje fibres are “fast” cells but have very slow Phase 4 depolarization
How do Class 4 Antiarrhythmics alter the appearance of the action potential in pacemaking (slow) cells?
Class 4 block Ca channels
-so this would prevent Ca influx and slow the depolarization phase
How do Class 2 Antiarrhythmics alter the appearance of the action potential in pacemaking (slow) cells?
Class 2 are Beta blockers
- prevent increased Na+ influx (If)
- prevent increased Ca2+ influx (ICa)
**don’t really understand this right now…look into it
Non-pacemaker (fast) cells:
RMP = ?
-80 to -95 mV
Non-pacemaker (fast) cells:
Phase 0 current = ?
sodium
Non-pacemaker (fast) cells:
Phase 0 kinetics = ?
fast
Non-pacemaker (fast) cells:
Conduction velocity = ?
0.5 - 5 m/sec
Non-pacemaker (fast) cells:
Automaticity = ?
yes ??
Pacemaker (slow) cells:
RMP = ?
-40 to -65 mV
Pacemaker (slow) cells:
Phase 0 current = ?
calcium
Pacemaker (slow) cells:
Phase 0 kinetics = ?
slow
Pacemaker (slow) cells:
Conduction velocity = ?
0.01 to 0.1 m/sec
Pacemaker (slow) cells:
Automaticity = ?
yes