Antiarrhythmics

Question 1

what is the definition of bradycardia? tachycardia?

Answer 1

Definition: any heart rhythm other than normal sinus
Bradycardia: < 60 bpm
Tachycardia: >100 bpm
< 30: pacemaker (atropine while waiting)
> 150 + unstable: DC cardioversion

Question 2

what is the basic science review of ion movement? (don’t focus on this)

Answer 2

Fast ENTRY/INFLUX of Na+ (Phase 0) is followed by Na+ channel inactivation & K+ EFFLUX (Phase 1) that leads to Ca2+ INFLUX via L-TCC influx ((Phase 2). This is followed by K+ efflux (Phase 3) and Na+ pump activation (Phase 3) to set the ionic equilibrium to normal. Next impulse generation depolarizes (Phase 4) to prepare the cell for the next ionic event of fast entry of Na+ (Phase 0). Note: Na+ Pump (Na+ extrusion for K+influx) and Ca2+ induced Ca2+ Release events are not shown here.

Question 3

look at the phases of the depolarization diagram and repolarization (but don’t focus on it)

Answer 3

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Question 4

hi how are you?

Answer 4

good

Question 5

what are class 1a drugs?

Answer 5

sodium channel (potassium channel)
decrease conduction velocity and increase QT (refr)
Quinidine

Question 6

what are class Ib drugs?

Answer 6

sodium channel (inactive only)
decrease conduction velocity
decrease QT
LIDOCAINE
mexilletine
phenytoin

Question 7

what are class Ic drugs?

Answer 7

sodium channel
decrease conduction velocity
keep QT the same or increase the QT
FLECANIDE

Question 8

What are class II drugs?

Answer 8

calcium channel (indirect through BB)
decrease conduction velocity and sinus, AV node
METOPROLOL

Question 9

what are class III drugs?

Answer 9

potassium channel
increase the QT
SOTALOL
AMIODARONE

Question 10

what are class 4 drugs?

Answer 10

they’re calcium channel (direct), they decrease conduction velocity and sinus, AV node
VERAPAMIL
DILTIAZEM

Question 11

what types of arrhythmias are there? (don’t focus on this)

Answer 11

generation - pacemaker cells, too fast, (too slow)

give class 2, 4 agents
Quiten Pacemaker Activity
SVT, A Flutter, A. Fibrillation

Condition (re-entry) - within or between chambers
Class 1,2,3,4 are useful
SVT, Afib, AFlttr, VFlttr, VFib

Question 12

what do supraventricular tachycardia, atrial flutter, and atrial Fib. do? What is the treatment?

Answer 12

Increase Rate from ATRIUM, Ectopic, Automaticity Increased pulses from atrium going thro A-V node
Bring to Sinus Rhythm by mechanical manipulation Direct Current Cardioversion, Ablation, Pacemaker.
Effective Antiarrhythmic Drugs: Class II – b Blockers (metoprolol,Bisprolol), Class IV - CCBs (Verapamil, Diltiazem) cut down the rate, b Block-  Ca2+ influx
If Persists after Ablation: Give Amiodarone or Sotalol
Digoxin is helpful if SVT/AFlttr, AFib, PAT– Its long
term use in CHF is Limited because of toxicity.
If untreated, it leads to stroke and heart failure.

Question 13

what do verntricular arrhythmias, and ventricular fibrillation do?

Answer 13

Life Threatening, Occurs Generally Following MI
Uncoordianated Ventricular beats – Re-entry block
Give CPR, Chest Compression, Defibrillation
Antiarrhythmics: Amiodarone (acts as a Class III + least proarrhythmic and other classes), Another useful agent is: Lidocaine (Class IB).
Lidocaine is a local Anesthetic, membrane stabilizer, it binds to Na+ channel avidly when it remains in the inactivated state. Most infarcted region of the ventricular myocardium remains in the inactivated state so Lidocaine selectively acts in these regions to inhibit re-entry circuit to rever to sinus Rhythm.

Question 14

what is the proarrhythmic effect? (don’t focus on this)

Answer 14

Most antiarrhythmics cause Torsades de pointes (Tdp) - Vent. Arrhythmia
Tdp is characterized by prolonged QT interval (Long QT Syndrome – LQTS).
Rx for drug-induced TdP: Magnesium, HCO3, Isoproterenol

Question 15

what is long QT syndrome AKA? what is the treatment?

Answer 15

Long QT Syndrome (Torsade de Pointes -TdP) XXX
Polymorphic Ventricular Tachyarrhythmia, Life Threatening
Either Congenital or Iatrogeinc (Drug-induced)
Methadone (opioid addiction), Classical/Typical Antipsychotics (haloperidol), Several Antiarrhythmics such as Quinidine, Procainamide (Class I), & all Class III agents precipitate Prolonged QT syndrome – TdP –
Both Hypokalemia, Hypomagenesemia aggravate TdP
Treatment: a) Withdraw the use of QT prolonging drug,
b) put on defibrillator – cardioversion
Pharmacological: c) i.v. infusion of Mg2+ 2g.
d) Isoprenaline (for drug-induced TdP)
e) Bicarbonate drip (HCO3)
Give: Amiodarone least proarrhythmic acts thro’ multiple
Classes although it is placed as Class 3 K+ channel blocker.

Question 16

what is amiodarone?

Answer 16

Class 3, 2, 4 activity- no better antiarrhythmic
Good for AFib, Aflutter, VT, VF (Universal)
Little Proarrhythmic effect
Weird PK: Vd= 66L/kg; t ½ = 25-100 days.
i.v and oral loading doses (10 gr,1-3 weeks)
Lots of AE (75% after 2 years; dose related (Thyroid, lung, liver, eye, skin, etc! - see next page)
Dronedarone is a newer agent just introduced has lesser AEs- Efficacy lower?

Question 17

what’s a good nutshell for antiarrhythmics?

Answer 17

√ Class I antiarrhythmic drugs act primarily as sodium channel blockers and they have greater access or higher affinity for cells in the activated or inactivated state than for cells in the resting state.
√ Cells in an ischemic area spend a larger proportion of time in the activated and inactivated states than in the resting state. It follows that the sodium channel blockers exert a greater effect in ischemic tissue than in normal tissue (eg. Use of Lidocaine in Ventricular Arrhythmia).
√ By further depressing conduction in the areas with depressed conduction (e.g. ischemic area), sodium channel blockers often produce bidirectional block. By this means they abort “re-entry” mechanisms to overcome arrhythmias.

Question 18

what is more of a nutshell?

Answer 18

√ Beta- blockers are most effective in conditions associated with high sympathetic activity. Increased cardiac rate, rate controller.
These are effective in overcoming SVT.
√ Calcium channel blockers are the drugs of choice in supraventricular tachycardia. Note that VERAPAMIL and Diltiazem have proportionally greater effect on cardiac tissue than vascular tissue compared to dihydropyridines (amlodipine or nifedipine), They are the drugs of choice.
√ While verapamil is effective - because of constipating effect cardiologists prefer using diltiazem. Nifedipine/Amlodipine are not used because of their preferential peripheral vascular selectivity – they cause reflex tachycardia. They are reserved and used for the management of essential hypertension.

Question 19

what a good summary?

Answer 19

There are 4 classes of antiarrhythmic effect. Drugs may act by more than 1 mech. (sotalol= 2+3)
“Proarrhythmic” effects are common with Class III agents, especially - TdP
TdP caused by prolonged QT (repolarization phase)
Dronedarone efficacy is yet to be established.
Amiodarone (acting via - 2,3, 4 Class) despite its adverse effects on prolonged use is the NUCLEAR WEAPON - Yes, it comes with problems!

Question 20

generally what are class I drugs?

Answer 20

Class I: Na+ Channel Blockers:
Lidocaine, Flecainide, Encainide
Block Conduction - Affects Phase 0 of AP.

Question 21

generally what are class II drugs?

Answer 21

Class II: ß- Blockers: Decease Ca2+ Influx

(METOPROLOL, Sotalol) SA Node Automaticity Conduction Velocity in A-V Node.

Question 22

what are class III drugs?

Answer 22

Class III: K+ Channel AMIODARONE, SOTALOL

Prolongs Action Pot. Duration & QT Interval,

Question 23

what are class IV drugs generally?

Answer 23

Class IV: CCBs: (VERAPAMIL, Diltiazem)

Slows Conduction Velocity in AV Node

Question 24

?what is the treatment for TdP

Answer 24

Treatment of TdP: Mg2+, Isoprenaline, HCO3_

Question 25

what are some side effects of amiodarone (AE)?

Answer 25

increase or decrease thyroid

liver: ALT, AST X2 cirrhosis
lung: fibrosis
eye: corneal deposits
skin: Photosensitive blue (smurf)