Antiarrhythmic Drug Pharmacology Flashcards
Ionic conductances in heart cells
- where two gradients are important
- what ions are important
- what is the electrical charge of a cell like
Gradients
- electrical
- concentration
Na+ and K+
- Na outside
- K inside
Cells are more negative inside
**understand how all of these points tie together
What interval on ECG is used as the time it takes the myocardium to repolarize?
QT interval
Important features of pacemaker cells
They are specialized non-contractile cells
They are physiological depolarized - meaning they normally sit at a depolarized resting membrane potential compared to myocytes
They have high automaticity - the ability to generate AP regardless of input from outside the cell (although influences can change this automaticity)
They have Ca2+ dependent spikes
Important features of ventricular myocytes
They are contractile cells
They are hyper polarized
They exhibit less automaticity than pacemaker cells
They have Na+ dependent spikes
What currents are important for pacemaker cell APs?
Ica - carries AP upstroke (0)
Ik - repolarizing K+ current (3)
If - diastolic pacemaker current (4)
Ik(ACh) - K+ current activated by vagus (4)
Where are most automaticity mechanisms found for pacemaker cells?
In phase 4 - diastolic pacemaker current - If
This is mediated by HCN channels
What currents are important for mycocyte APs?
INa - carries AP upstroke (0)
Ikto - “transient outward” repolarizing K+ current (1)
IcaL - plateau Ca2+ current critical for mm contraction (2)
Ik - repolarizing K+ current (3)
If - pacemaker curent (4, very minimal)
The later and later you move in the relative refractory period, a stimulus of the same strength results in
stronger and stronger depolarizing
What causes the refractory period in electrically excitable cells?
The behavior of voltage gated sodium channels
-“h” gate closure inactivates the channel and during this period, it cannot open to depolarization — this is the absolute refractory period
What has a strong influences upon the recovery of cells from inactivation?
the membrane potential of the cell
–a hyperpolarized membrane potential promotes recovery from inactivation
What is an arrhythmia?
A depolarization of the heart deviating from normal with respect to one or more of the following:
- rate or regularity (altered automaticity)
- site of origin (ectopic pacemaker)
- conduction pathway (direction of conduction)
What are the mechanisms of arrhythmia?
- Enhanced automaticity - abnormal pacemaker rate or location
- Triggered activity - abnormal secondary depolarization triggered by a sinus AP
- Re-entry - abnormal conduction pathway
When is there enhanced automaticity?
Where there is strong sympathetic drive to SA node
When AV node depolarized faster than SA and assumes control of its pacing
When myocytes have increased expression of HCN channels - these channels are important for controlling automaticity
What are the two main examples of triggered activity?
EAD - early after depolarization
DAD - delayed after depolarization
What are the key features of EAD?
Caused by prolonged AP
Arises from a depolarized Vm
–before cell has a chance to return to its normal resting membrane potential
Caused by
- slowed HR
- hypokalemia
- long QT syndrome
What are the key features of DAD?
Caused by Ca2+ overload
- -Increased Na/Ca exchanger current
- -leading to increased depolarizing sodium current
Arises from normal Vm
Often seen with rapid HR or conditions that lead to rapid HR like:
- myocardial ischemia
- adrenergic stress
- digoxin intoxication
How does a re-entry circuit cause an arrhythmia?
by creating an ectopic pacemaker
There are three key features that must be met for a reentrant circuit to be established. What are they?
- There must be multiple (2+) parallel pathways
- There must be some kind of obstacle to conduction that creates a unidirectional block
- The timing of the circus waveform is such that the conduction time around the circuit must be slower (take longer time) than the effective refractory period of tissue
Class I anti-arrhythmics
Na+ channel blockers
Class II anti-arrhythmics
Beta adrenergic antagonists
Class III anti-arrhythmics
Agents that prolong refractory period (K+ channel blockers)
Class IV anti-arrhythmics
Ca2+ channel blockers
Which classes of anti-arrhythmics are mainly concerned with the action of the pacemaker cells?
Classes II and IV
Which classes of anti-arrhythmics are mainly concerned with the action of myocytes?
Classes I and III
What currents are modulated by B-adrenergic activity?
the two key currents of pacemaker APs
- L-type Ca+ for upstroke (0)
- “funny” currents (4) that spontaneously depolarize
these are important for setting HR
