Anti-Arrhythmic Drugs Flashcards
What is an arrhythmia?
- Disturbance of normal cardiac rhythm
- Site: atrial, junctional, ventricular
- Rate: tachycardia or bradycardia
What are the four basic mechanisms for arrhythmias?
- Delayed after depolarisation- raised intracellular ion levels
- Ectopic pacemakers- encouraged by SNS activity
- Re-entry- diseases myocardium
- Heart block- disease in conducting system (AVN)
How do drugs correct arrhythmias?
- Anti-Arrhythmics act by
- Suppressing abnormal impulses
- Altering re-entry circuit- slowing it by disturbing rhythm
- If rhythm removed that is self-amplifying, breaks amplification
Why do arrhythmias occur?
- Abnormal impulse generation (automaticity), e.g. ectopic pacemakers
- Abnormal impulse conduction (e.g. re-entry)
How does an impulse conduct through the heart?
- Slow depolarisation at SA node- reaching threshold triggers AP
- Pacemaker potential
- Extended plateau in Purkinje fibres and ventricles-sustained contractions due to Ca influx extending duration of AP
What happens at phase 0 of cardiac action potential and what drugs can be used?
- Rapid depolarisation
- Fast sodium influx
- Drugs: sodium channel blockers- class 1
What happens at phase 1 of cardiac action potential?
- Partial repolarisation
What happens at phase 2 of cardiac action potential and what drugs can be used?
- Plateau (calcium influx)
- Sustaining action potential
Drugs: - Class 2- β blockers, β receptors linked to Ca influx
- Class 4- calcium channel blockers
What happens at phase 3 of cardiac action potential and what drugs can be used?
- Repolarisation (potassium efflux)
- Hyperpolarisation
Drugs: - Class 3- potassium channel blockers
What happens at phase 4 of cardiac action potential and what drugs can be used?
- Pacemaker depolarisation (slow sodium and calcium influx in SA and AV nodes)
- Baseline
- Pacemaker tissue- potential that slowly depolarises there and triggers the next action potential
Drugs - Class 2 β blockers also work here due to calcium influx
What miscellaneous drug can be used to alter ion current in cardiac AP?
- Digoxin (glycoside)
- Inhibits primary pump–>inhibit secondary pump
- Na/K ATPase- primary exchanger for ion balance
- Ca/Na passive exchanger- uses primary gradient
- Blocks sodium re-entry so more calcium in cell
- Alter rhythm- calcium determines heart rhythm
What is the pacemaker current?
- If (funny) current in SAN and AVN carries Na+ ions in at resting voltage- slow depolarisation
- Pacemaker depolarisation- largely Ca influx
- Slow L-type Ca channels also important in AVN
- Target of class 4 drugs
How does sympathetic nervous system affect the heart?
- Circulating Adr/NA acting on β-1 adrenoceptors
- Increases funny current in pacemaker tissues
- Increases slope of pacemaker depolarisation in phase 4
- Reaches threshold sooner
- Next heart beat occurs sooner, increases heart rate
- β-1 blockers (class 2 anti-arrhythmics)
How does parasympathetic nervous system affect the heart?
- Vagus nerve receiving ACh, acting on M2 muscarinic receptor
- Opens specific K channels (K-ACh channels)- influx
- Causes SAN hyperpolarisation- less active
- Pacemaker slow depolarisation reduced
- Longer to reach threshold
- Next beat slower, AP delayed, slower HR
- Atropine blocks Msc receptors- used in bradycardia to increase heart rate
List the classes of anti-arrhythmic drugs
- Class 1-Na channel blockers
- Class 2- β-adrenoceptor blockers
- Class 3- K+ channel blockers
- Class 4- Ca channel blocker
- Miscellaneous group (or class 5): adenosine, glycosides, atropine
Describe Class 1- sodium channel blockers
- Like local anaesthetics
- Blocking fast Na channels in phase 0
- Blocks AP on peripheral nerve- prevents pain and other sensations
How can slope be measured?
- Using upstroke velocity- Vmax
What is the effect of class 1A on Vmax?
- Disopyramide
- Reduce Vmac and prolong action potential
What is the effect of class 1B on Vmax?
- Lidocaine
- Slightly reduce Vmax and shorten action potential
What is the effect of class 1C on Vmax?
- Flecainade
- Greatly reduce Vmax but have no effect on AP duration
Give examples of class 2 β-adrenoceptor blockers
- E.g. atenolol, metoprolol, propranolol
What do class 2 β-adrenoceptor blockers do?
- Block action of Adr/NA on β-1 adrenoceptors on heart muscles/conducting tissue
- Reduce inward Na+ (If) current in SA nodes, slowing pacemaker depolarisation in phase 4
- Indirectly reduce Ca influx in phase 2- plateau of AP, phase 4- depolarisations
- Suppress abnormal pacemakers- e.g. ectopic
- Strongly reduce AV conduction (increased refractory period) slowing heart rate
What do class 3 potassium channel blockers do and give 2 examples?
- Block K+ efflux and repolarisation (phase 3)
- Extend duration of action potential
- Class 3- Amiodarone
- Other actions (Blocks Na and β channels)
- Long half life
- Sotalol
- Class 3 + β blocker (class 2)
Give examples of class 4 calcium channel blockers
- E.g. Verapamil (Non-dihydropyridine)
- Dihydropyridine
