Pharmacology Afib Flashcards
Which phase should you focus on if you wanna change HR (2)
Phase 0
Phase 4
Where in the heart are most depolarization mediated by Ca in?
Slower/faster
SA and AV nodes
- slower (less steep on ECG)
- But depolarization in the SA node is faster than the AV node (making it the heart’s pacemaker)
Where in the heart are most depolarization mediated by Na in? Slower/faster
Atrium
- Faster (more steep on ECG)
Define automaticity. How are pacemaker channels activated
In the SA node: the pacemaker channels are the HCN (hyperpolarization-activated, cyclic nucleotide-gated)
- (or “funny” sodium channels)
What does hyperpolarization activated mean
refers to cells that conduct MORE current as the cell becomes more repolarized (in phase 3/4)
- This means that after an AP -> cell repolarizes -> channels become active again and begin depolarization -> start of another heartbeat
What is the state of the sodium channel at rest
closed/open/inactivated
What triggers it?
Closed
- depolarization to the threshold voltage opens it (becomes activated)
What happens to Na channels as the membrane potential reaches +70mV?
Sodium channels close and enter inactivated state
How do Na channel blockers work?
bind the Na channel in the inactivated state -> prolong the length of time spent in the inactivated state (delayed return to resting state)
What is the difference between calcium and sodium channel conformations (2)
Which phase?
Ca transitions between states is SLOWER and occurs at MORE POSITIVE potentials
* This can be seen in the plateau phase (2) of the AP (when Na current is off and the Ca current continues to rise then slowly fall)
Define refractory period
the time between phase 0 and sufficient recovery of Na/Ca channels (return to resting state)
- When no new APs can be propagated
What are the drugs, kinetics (slow/fast/int), effect on ECG, type of arrhythmia used (atrial/ventricular) of the following class
1a
1b
1c
1a: quinidine, disopyramide
- INT kinetics
- Inc QRS interval + inc QT interval
- broad spectrum
1b: lidocaine
- FAST kinetics
- Decrease QT interval
- used for ventricular arrhythmias
1c: Flecainide, propafenone
- SLOW kinetics
- decrease SLOPE of QRS (most inc in QRS)
- atrial (supraventricular) arrhythmias
What is the aim of anti-arrhythmic drugs regardless of their MOA (3)
Reduce ectopic pacemaker activity (i.e suppress abnormal automaticity more than SA node)
OR
reduce conduction
OR
inc refractory period in depolarized tissue
Why don’t anti-arrhythmic drugs affect the whole heart?
Know this
Channel-blocking drugs bind poorly to the closed channels, but bind WELL to the activated and inactivated channels.
* Thus, better blockage of activity where there is lots of action (fast tachycardia, etc.). This is known as “use-dependent” or “state-dependent” drug activity.
i.e
- they are good at blocking activity during tachycardia (when more channels are active/inactive at the same time)
OR
- block activity when there is loss of membrane potential
What do class 1 anti-arrhythmic drugs block
Sodium channel blockers
What are the extent of Na channels blocking dependent on? (2) Why?
- heart rate
- resting membrane potential
Since drugs bind active/inactive state and not closed/rest state
What is the overall effect of class 1 anti-arrhythmics?
- Threshold for excitability is increased (to require a more negative potential (more depolarization) to reset the inactive channel)
- increase refractoriness (more negative potential must be reached)
i.e
to require a more negative potential to reset the inactive channel AND require a greater membrane depolarization to evoke an action potential.
What are class II anti-arrhythmic drugs
MOA? (4)
Beta-blockers
- Decrease magnitude of Ca current
- Decrease pacemaker activity
- Decrease Ca stored in the SR
- Decrease early/delayed afterpolarizations
What are the overall effects of Class II drugs?
- Slowed HR
- Dec AV conduction (through increase AV node refractory period)
- Propanolol can block Na channels
Minimal effects on ventricular conduction
What are beta blockers useful in? (2)
- re-entrant arrythmias that involve the AV node
- Controlling ventricular response to Afib/Aflutter
What are Class III anti-arrhythmic drugs
MOA
Block potassium channels to
- prolong the action potential
- increase refractory period to maintain or restore sinus rhythm
Risk of class III drugs? (2)
- Prolong QT interval and increase risk of torsade de pointes
Amiodarone MOA
Overall effect? (2)
- Direct blocking of POTASSIUM channel -> prolonged ref. period + QT interval
(Amiodarone is not associated with TdP) - Blocks Na + Ca channels
- Non-competitive B-blocker
- Changing expression of other proteins (via thyroid receptor interaction)
(Amiodarone is a structural analog to thyroid hormone)
Overall effect:
- Slow HR
- slowed AV conduction
ADRs of amiodarone
- photosensitivity (deposit in cornea)
- thyroid dysfunction (hypo + hyper)
- hepatitis
- optic and peripheral neuropathy
Dronedarone safety and efficacy compareed to amiodarone
Efficacy
- possibly less effective
Safety
- less toxic since there is no thyroid effects
What are class 4 anti-arrhythmics drugs
MOA
effects
Drugs:
- NDHP calcium channel blockers (cardio-selective)
MOA
- Block calcium channels (L-type) to slow HR, slow AV conduction, and increase AV refractory period.
effects
- slow HR
- slow AV conduction (seen in donal tissues)
- inc AV refractory period
Adenosine
MOA
effect (3)
Use
MOA
- activates adenosine receptors -> decreased Ca2+ current + increase K+ current
Effect
- shortened AP in the atrium
- hyperpolarization of nodal cells -> slowed AV conduction
Use
- diagnostic tool to differentiate atrial vs ventricular arrhythmias
