Anti-Arrhythmic Drugs 1 Flashcards
Phase 4 involves
Na/K ATPase
SA Node
Pacemaker of the heart
- Do not need external stimulaus
- They have a constant Na and Ca leakage which is what leads to the beginning of the AP through slow Na channels opening
Delay in spread?
Yes, because you need the atria to contract before the ventricles contract
AV and Purkinje Fibers and AP?
They can but they don’t because the have lower BPM than the SA node
Effective Refractory Period
Cardiac muscles is refractory to re-stimulation during the AP
A normal cardiac impulse cannot re-excite an already excited area during this time
Atria ERP vs Ventricle ERP
Atria ERP is half the time that the ventricles is
Anti-arrhythmic drugs may alter the rhythmicity of the heart by:
1) Decreasing the slop of phase 4 (depolarization) - so it takes the heart longer to recover (beta blockers)
2) Elevating the threshold potential (Na and Ca channel blockers)
3) Increasing the maximum diastolic potential - so it delays the next AP (adenosine)
4) Increasing the duration of the AP (K channel blockers)
Through all mechanisms of anti-arrhythmic drugs, there will be ___?
Lesser number of AP at a given period of time
Class 1 Anti-Arrhythmics
Na Channel Blockers
Reduces slop of phase 0 and increase threshold
Class 2 Anti-Arrhythmics
Beta-blockers
blocks sympathetic and decreases the slop of phase 4
Class 3 Anti-Arrhythmics
K-channel blockers
Delays repolarization and increases AP time and EPR
Class 4 Anti-Arrhythmics
Ca-channel blockers
Blocks L type calcium channels which elevates threshold and affects phase 2
Advantages of Vaughan classification system
Convenient way of classifying by primary MOA Useful short hand Within a class they have similar adverse effects Good starting point
Disadvantages of Vaughan classification system
Drugs within a class do not necessarily have same effects
Almost all drugs are dirty drugs
Metabolites contribute to many actions and AE
Sodium Channel Blockers MOA
Bind the channels at the open or closed but not resting state
They release at phase 4 to allow the channel to recover
Class Ib
Fast recovery
Shows effects on fast heart rate
(Weak drugs)
- Lidocaine, mexiletine
Class Ic
Slow recovery
Shows effects at all heart rates
(Strong drugs)
- Flecainide, propafenone
Class Ia
Intermediate
Effects depend on the rate
- Disopyramide (quinidine, procainamide)
Flecainide (Tambocor)
Class Ic Slow Recovery
Potent Na channel blocker
Blocks some delayed rectifier K and Ltype Ca channels
Flecainide Na channel blockade results in:
Slowing of conduction in all part of the heart esp His-Purkinje
Inhibition of abnormal automaticity
Delayed AP in faster HR
Acts at normal HR and prolongs QRS
Flecainide Elimination and Metabolism
H/R
CYP2D6 and 1A2
Flecainide AE
Pro-arrhythmic and heart block
Blurred vision
Exacerbation of HF
Flecainide Caution
Patients with severe liver and renal impairment**, HF and electrolyte imbalance
Flecainide Contraindications
2nd and 3rd degree AV block or right bundle branch block
Cardiogenic shock
CAD
Propafenon (Rythmol)
Clasic 1c
Potent Na channel blocker with slow recovery
Most efficient in maintaining the sinus rhythm and modest with ventricular arrhythmias
Propafenone Elimination and Metabolism
hepatic
CYP2D6
Propafenone AE
Proarrhythmic effects
Exacerbation of HF
Bradycardia and bronchospasms
Propafenone Caution
Patients with severe liver impairment and heart failure
Propafenone Contraindications
Severe HF Prolongs PR and QRS intervals SA, AV and ventricular disorders Bradycardia Marked hypotension Electrolyte imbalance
Disopyramide (Norpace)
Class Ia Na blocker (increase threshold potential and decrease automaticity) with intermediate recovery Blocks K channels (prolongation of AP) and L type Ca-channels Vagal inhibition (anti-cholinergic effects)
Disopyramide (norpace) Elimination and Metabolism
H/R
CYP3A4
Disopyramide AE
Proarrhythmic effects Exacerbation of HF Heart block Dry mouth Constipation Urinary retention Precipitation of glaucoma
Disopyramide Caution
Patients with severe liver and renal
Impairment and HF
Disopyramide Contraindications
Cardiogenic shock
QT prolongation
2nd and 3rd degree AV block
Lidocaine (Xylocaine)
Class Ib
Na blocker with fast recovery (weak)
Automaticitiy is decreased by increasing the threshold potential and reducing the slop of phase 4
Lidocaine is not useful for the treatment of:
Arrhythmias
Lidocaine Elimination and Metabolism
H/R
CYP3A4
Lidocaine AE
Seizures when a large dose
Tremor, dysarthria
Nystagmus
Mexiletine (Mexitil)
Class Ib Weak Na channel blocker Analog of lidocaine suitable Chronic oral therapy NOT USEFUL FOR ATRIAL ARRHYTHMIAS
Mexiletine Elimination and Metabolism
H/R
CYP2D6 and CYP1A2
Mexiletine AE
Proarhythmic effect Exacerbation of HF Upper GI distress Lightheadedness Coordination difficulties
