antiarrhythmics Flashcards
Phase 0 modulators
- Local anesthetics/Na channel blockers
- Slows Na influx, depolarization, and conduction
- Divided into class 1 a, b, and c
- Widens the QRS primarily and the QT somewhat
SE of Quinidine
prorrhythmic, prolongs QT which can lead to torsades
SE of Procainamide
Proarrhythmic, can have poor compliance, lupus like syndrome
Class 1A
Quinidine and Procainamide
- Blocks primarily Na channels and some K
- Has moderate effect on phase 0
- MOA: slows conduction velocity in ventricle and increases action potential duration
- Broad spectrum (flutter, afib, VT)
Class 1B
Lidocaine (IV) and Mexelitine (PO)
- Blocks ONLY Na channels
- Has no effect on phase 0 and somehow shortens duration of AP without decreasing refractory period.
- Use: Only works in Ventricular arrhythmias when heart too fast. NOT for AV or atrial.
Class 1C
Flecainide and Propafenone
- MOA: Blocks Na and K for a longer period of time so much longer QRS. Both tonic and rate dependent block.
- Use: Afib and flutter primarily. Also WPW
- SE: Proarrhythmic
Class 3: Classic drugs
Drugs that prolong repolarizaiton
Amiodarone, Sotalol, Dronedarone
Class 2: Beta adrenergic blockers
Propanolol, atenolol, timolol (PO) and Esmolol (IV)
- MOA: Depending on drug block beta 1 and/or beta 2 to slow AV conduction (beta receptors are on the Ca channels in pacemaker cells. phase 4)
- Use: AV re-entry rhythms and sinus tachycardias (sympathetic)
- Use caution with other drugs that lengthen AV conduction (CCB, digitalis), asthmatics, and diabetics
- can protect the V from the A in flutter and SVT.
- can break junctional rhythms
Amiodarone
Class 3
- MOA: Blocks Na, K, Ca, and beta.
- Widely used. Can also be used for SVT, post-MI arrhythmia, and in HEART FAILURE
- 3 month HL
- Signs of toxicity include corneal cholesterol deposits, blue skin tone, and thyroid, liver, and lung toxicity
Sotalol
Class 3
- Blocks K channels and beta receptors
- Used for a fib, flutter, and VT
Dronedarone
- Class 3 that is similar to amiodarone but has less thyroid toxicity and a short HL (24hrs)
- Used to prevent recurrence of afib/flutter rather than conversion
- SE: bradycardia, Torsades(QT prolonged), is metabolized by same enzyme that affects antifungals and ABX
- CONTRAINDICATED in HF
Class 3: New drugs
Dofetilide
- genetically engineered (cardiac selective/Ikr)
- MOA: blocks K channels only in the heart to prolong action potential duration
- Used primarily for afib and is ok for long term use in MI or HF pts
- first two doses usually given in hospital and monitored
- Risk of torsades (1-6%)
Class 4: Ca channel blockers
Verapamil and Diltiazem
- blocks Ca channels which have effects much like a beta blocker when treating arrhythmia (slows conduction in AV, increases AV refractory period, prolongs repolarization phase in AV
- Use caution with other drugs that slow AV conduction. can cause hypotension
Atropine in arrhythmia
treatment for vagal bradycardia
Adenosine
- stops AV conduction to terminate re-entry SV arrhythmias
- has a 10 second HL
Magnesium
TOC for Torsades
Digitalis
slows AV conduction
Used to treat afib flutter for HF
DC Cardioversion
TOC for unstable and life-threatening arrhythmias
Frequency dependent antiarrhythmics
have larger effects in arrhythmias with a high HR because they affect phase 0
tonic antiarrhythmics
have equal antiarrhythmic effects regardless of HR
Effect of K channel blocking on AP
Slows the outflow of K in phases 2 and 3 which increases the refractory period
Effects of Na channel blocking on AP
- Na channel blockers slow the influx of Na into the cell to decrease the slope of phase 0 (depolarization).
- Also, increases the threshold needed to open the Na channels and lengthens the refractory period.
Effects of Blocking Ca channels on AP
Ca movement makes the muscle contract. By slowing Ca influx, we decrease contraction strength, prolong the actual contraction, and increase refractory period
Phase 4 of AP
- This is the resting state of cardiac myocytes.
- K is within the cell and Na, Cl outside.
- The heart is in diastole
Phase 0 of AP
- Begins when pacing cells spread the AP to other cells (remember, cardiac myocytes are so closely linked that they begin depolarizing if an adjacent cell does so.
- -Na rushes into the cells very rapidly making the cell positively charged
Phase 1 of AP
- Na channels close
- -K starts leaking out.
Phase 2 of AP
- K continues to leave the cell while Ca travels inward.
- Ca entering the cell causes contraction
- this exchange is designed to be slow in cardiac myocytes so that you have sustained contraction (the plateau)
Phase 3 of AP
- Ca channels close (contraction stops)
- K continues to leave the cell (repolarizing)
Na/K ATPase
- The exchanging pump that restores the myocyte to the normal concentration of Na outside and K inside
- Note: there are other exchangers that work to move Ca back out of the cell so that the heart can contract again.
Pacemaker AP
- note that the pacemaker cells in the SA and AV nodes have their own distinct AP
- in phase 4 of pacemaker cells Na and Ca slowly leak into the cell until a voltage gated CA opens which is the phase 0 of pacers (this is why pacer cells have automaticity)
- -pacer cells lack phase 1 and 2 because they only need to depolarize to activate the myocytes
- please see Varner’s slide to see how antiarrythmics can affect the AP of pacemaker cells.
Refractory period
-the portion of the AP in which another impulse CANNOT be generated. typically beginning of phase 0 to mid point of phase 3
Ibutilide ( new drug)
-ONLY given IV in small boluses once or twice
-GIVEN in EP lab
-MOA- similar to dofetilde
-CONVERT Afib/Aflutter
-Not for continous use
6% or > incidence of Torsades
Antiarrythmics okay for HF
Amiodarone, Dofetilide, Digoxin
Antiarrythmics contraindicated for HF
Dronedarone!
