Cardiac Arrhythmia Drugs Flashcards
What are arrhythmias?
Heart condition where disturbances in:
- Pacemaker impulse formation
- Contraction impulse conduction
- Combination of the two
Results in rate and/or timing of contraction of heart muscle that may be insufficient to maintain normal cardiac output.
What creates the resting potential?
Unequal distribution of ions (interior of the cell is negative with respect to the outside).
Na+ higher outside than inside the cell
Ca2+ much higher outside than inside
K+ higher inside than outside.
It is maintained by ion selective channels, active pumps ad exchangers
Explain the ventricular cardiac action potential
Phase 0 - Opening of voltage gated Na channels
Phase 1 - Transient outward K+ current
Phase 2 - Opening of voltage gated Ca2+ channels (some K+ channels also open).
Phase 3 - Ca2+ channels inactivate, voltage gated K+ channels open.
Phase 4 - resting.
What effect do class 1 drugs have?
Block Na channels which slow the conduction in tissue (phase 0). It has a minor effect on action potential duration.
What effects do class 2 drugs have?
Beta blockers which bloke sympathetic action (act on B1 adrenoreceptors in the heart) so, decrease the slope of the pacemaker potential in the SA node and slow conduction at AV node.
What effects do class 3 drugs have?
Block K+ channels so prolong plateau phase and increase AP duration.
This prolongs the refractory period.
What effects do class 4 drugs have?
Ca2+ channel blockers which decrease inward Ca2+ currents resulting in a decrease of phase 4 spontaneous depolarisation.
They decrease slope of AP at SA node, decrease AV nodal conduction, decrease force of contraction (negative isotropy)
Where is slow cardiac action potential?
SA and AV node
Explain the slow cardiac action potential
Pacemaker potential / Funny current (If)- Na+ in via HCN channels.
Opening of voltage gated Ca2+ channels.
Then opening of voltage gated K+ channels so K+out
How do Ca2+ channel blockers affect slow Cardiac AP?
Reduce conduction velocity
Decrease AV nodal conduction
Decrease slope of AP at SA node.
Decrease force of contraction
What drugs affect automaticity?
Catecholamines (B agonist)- increase phase 4
Muscarinic agonist and adenosine - slow down phase 4
What are some mechanisms of arrhythmias?
Abnormal impulse generation - Automatic rhythms (enhanced normal automaticity and exotic focus), triggered rhythms (delayed and early afterdepolarisations)
Abnormal conduction - conduction block (1st, 2nd, 3rd), reentry loops (circus movements, reflection)
Where can reentry occur?
WPW - ventricles to atrium and visa versa (AV node, bundles, pathway and renter atrium)
AV node - split into slow and fast pathway
If abnormal rhythm generation how could drugs work?
Decrease of phase 4 slope in pacemaker cells
Raise the threshold
In the case of abnormal conduction, how could drugs work?
Decrease conduction velocity
Increase (ERP) effective refractory period (so the cell won’t be reexcited again)
What are antiarrhythmic drugs used for?
They aim to restore normal sinus rhythm and conduction to prevent more serious and possibly lethal arrhythmias from occurring.
They are used to:
Decrease conduction velocity
Change duration of ERP
Suppress abnormal automaticity
Give examples of class 1A agents
Procainamide, quinidine, disopyramide.
What effects do class 1A agents have on cardiac activity?
Decrease conduction
Increase refractory period
Decrease automaticity
Increase threshold
What are class 1A drugs used for?
Wide spectrum
Quinidine: Maintain sinus rhythm in Atrial fibrillation and atrial flutter and to precent recurrence, brugada syndrome.
Procainamide: acute IV treatment of SV and Ventricular arrhythmias.
ADRs of 1A?
Hypotension, reduced CO, Proarrythmias, DIzziness, confusion, insomnia, seizures, GI effects, Lupus-like syndrome.
Give examples of class IB agents?
Lidocaine( IV), mexiletine (oral)
How do 1B agents affect cardiac activity?
Increase threshold
Decrease phase 0 conduction in fast beating or ischaemic tissue.
APD slightly decreased
When do you use 1B agents?
Ventricular tachycardia
Side effects of iB?
Less side effects than 1A
GI upset
Dizziness, drowsiness
IC example?
Flecainide and propafenone
1C effect on cardiac activity?
Very slow binding offset kinetics
Substantially decrease phase 0 in normal
Decrease automaticity (increase threshold)
Increase APD and refractory period especially in rapidly depolarising tissue.
What are 1C used for?
SV arrhythmias (fibrilation and flutter)
Premature ventricular contractions
WPW syndrome