Anti-Arrhythmics Flashcards
What is the resting membrane potential?
-70mV
What ions are responsible for maintaining the resting membrane potential? Do they have a higher intracellular or extracellular concentration?
K+: high intracellular
Na+, Ca2+, Cl-: high extracellular
How many action potential phases are in the normal sinus rhythm?
Phase 0 to phase 4
What happens in each action potential phase?
Phase 0: Upstroke
- Na+ channel opens, Na+ enters cell
- RMP becomes more positive
Phase 1: Early-fast repolarisation
- Transient outward K+ channel, K+ exits cell
- RMP becomes a bit more negative
Phase 2: Plateau
- Ca2+ channel opens, Ca2+ enters cell
- RMP prevented from being more negative (exiting K+) by entry of Ca2+
Phase 3: Repolarisation
- Inward rectifying K+ channels open, K+ continues to moves out of cell
- RMP becomes more negative
Phase 4: Diastole
- Cell undercomes complete relaxation
What is the effective refractory period (ERF)? It lasts throughout which action potential phases?
Phase 0 to Phase 3 (just before Phase 4)
What is the importance of the ERF?
Important to prepare muscles for depolarisation. Another action potential cannot be generated during this time
What is the action potential duration (APD)? It lasts throughout which action potential phases?
Phase 0 to Phase 4
What is the importance of the APD? What is the difference in duration btwn ERP and APD?
Theoretically, don’t have to wait for Phase 4 to have another action potential, it can occur immediately after ERP but this is abnormal.
Physiologically, APD is longer than ERP
What does the P wave in an ECG represent?
Atrial depolarisation
What does the PR internal in an ECG represent?
The time between the onset of atrial depolarisation and ventricular depolarisation
What does the QRS complex represent in an ECG?
Ventricular depolarisation
What does the QT interval in an ECG represent? What is the significance of this?
Ventricular depolarisation and repolarisation
It is a rough estimate of the duration of an ventricular action potential from Phase 0 to Phase 4
What is excitability?
The cell can change its internal electrical balance to reach threshold.
Mechanism for depolarisation to occur.
What is automaticity?
The cell can generate an electrical impulse without being stimulated (automatic).
Mechanism for basal depolarisation until threshold is reached
What is conductivity?
The cell can transfer an electrical impulse to the next cell.
Mechanism for spread of depolarisation.
What are the classes of anti-arrhythmic drugs?
Class 1A, 1B, 1C: Na+ channel blockers
Class II: ß-blocker
Class III: K+ channel blocker
Class IV: Ca2+ channel blocker
What is an example of a Class 1A Na+ channel blocker?
Procainamide
What is the MOA of procainamide?
- Reduce rate of Phase 0 depolarisation
- Prolong Phase 3 repolarisation
- Reduce conductivity and automaticity
- Increase ERP and APD
What is an example of a Class 1B Na+ channel blocker?
Lidocaine
What is the MOA of lidocaine?
- Reduce rate of Phase 0 depolarisation
- Shorten Phase 3 repolarisation
- Reduce automaticity (little effect on conductivity)
- Reduce APD
- APD becomes shorter than ERP (usually APD longer than ERP) - No change in ERP
What is an example of a Class 1C Na+ channel blocker?
Flecainide
What is the MOA of flecainide?
- Reduce rate of Phase 0 depolarisation
- Shorten Phase 3 repolarisation (but not as much as Class 1b)
- Reduce conductivity and automaticity
- No/little effect on APD/ERP
What is the clinical use of flecainide?
(not a 1st line drug)
Refractory ventricular tachycardias that tend to progress to VF
What is an adverse effect of flecainide?
Can lead to sudden death if there is existing ischaemia
What are the Class II ß-blockers?
Metoprolol, Propranolol
What is the MOA of Class II ß-blockers?
- Reduce/suppress phase 4 depolarisation (slope)
- Reduce automaticity
- Prolong AV conduction
- Reduce HR and contractility (indirect effects on Ca2+ channels)
- Blocks ß1 receptors in cardiac myocytes reduces CICR - No change to APD & ERP
What are the clinical uses of Class II ß-blockers?
- Tachycardia caused by sympathetic activation
- Atrial fibrillation
- AV nodal re-entrant tachycardia
- Reduces sudden arrhythmic death (*only med that does this!)
- Protective
- Reduces long-term mortality
What are the Class III K+ channel blockers?
Amiodarone
What is the MOA of amiodarone? What other actions does it have?
- Prolongs Phase 3 repolarisation (no Phase 0 effect)
- Increases ERP and APD
Actions w properties of all 4 classes:
1. Block inward rectifying K+ channels Ikr and Iks – Class III (main)
- Block Na+ channels (although no Phase 0 effect) – Class I
- Block adrenergic receptor – Class II
- Block Ca2+ channels – Class IV
What is the bioavailability of amiodarone?
35-65%
How is amiodarone metabolised? Is it metabolised to an active or inactive form?
Hepatic metabolism to desethylamiodarone (bioactive)
How is amiodarone eliminated? What is the 1/2 life?
Eliminated by liver, H½:
- 3-10d (first 50%)
- Several weeks (second 50%)
After discontinuation, the effects of amiodarone are maintained for how long?
1-3 months
What are the clinical uses of amiodarone?
- Maintaining normal sinus rhythm in patients with atrial fibrillation
- Prevent re-entrant ventricular tachycardia
What are the adverse effects of admiodarone?
- Symptomatic bradycardia
2. Heart block
What are the Class IV non-DHP Ca2+ channel blockers?
Verapamil, Diltiazem
What is the MOA of Class IV non-DHP Ca2+ channel blockers?
- Prolong Phase 4 depolarisation (direct Ca2+ channel effect)
- Reduce conductivity on AV node
- Increase ERP and APD
What are the clinical uses of verapamil?
- Supraventricular tachycardia
- Hypertension
- Angina
What is an adverse effect of verapamil?
Hypotension
What is the contraindication of verapamil?
Pts w pre-existing depressed cardiac function (cardiac failure)
What other drug is used as an anti-arrhythmic but is not formally classified as a class?
Adenosine
What is the MOA of adenosine? When is it used?
- Suppress atrioventricular nodal conduction (used in emergency)
- Increase AV nodal refractory period
- Stimulates cardiac K+ channel (KACh)
- Inhibits Ca2+ current
What is the half life of adenosine in blood (infusion)?
<10s
What is a clinical use of adenosine?
Supraventricular tachycardia
What are the adverse effects of adenosine?
- Flushing
- SOB, chest burning
- Induction of AV block or AF
- Headache
- Hypotension
