Antiarrhythmic Drugs

Question 1

What are the two targets of mechanisms of antiarrythmics

Answer 1

§Abnormal automaticity (pacemaker activity)

§Abnormal propagation of electricity through the myocardium

Question 2

Mechanisms of AAD

Answer 2

Decrease excitability of cardiac tissue (CALM down)

Decrease pacemaker activity (SLOW down)

Inhibit conduction (BLOCK)

Question 3

AADs classifications (and pneumonic)

Answer 3

“Some Block Potassium Channels”

Vaughn-Williams Classification:

I –Na blocker (Sodium)

II – Beta blocker, blocks catecholamines (Beta blocker)

III –K channel blocker, prolong AP and repolarization, (Potassium)

IV – block L-type calcium channels (Calcium)

Question 4

Effect of Class 1 drugs

Answer 4

Decrease the slope of phase 0

Increase Effective Refractory Period (ERP)

Slow conduction of the action potential –Increasing QRS duration

Question 5

Differences between class 1 types

Answer 5

Question 6

Class 1 mechanism

Answer 6

Block re-entry by increasing ERP

Convert uni-directional block to bi-directional block

Question 7

Class 1a drugs and treatment

Answer 7

Quinidine, Procainamide

Can by used to treat atrial or ventricular arrhythmias

Question 8

Quinidine target, adverse effects, contraindication

Answer 8

Blocks Na+ current, but also Ikr, Iks, IKATP, and Ito

Prolongs PR, QRS, and QTc

Contraindicated if ischemic heart disease

Adverse Effects:

GI (most common): Nausea, anorexia, diarrhea

Tinnitus, hearing loss, visual disturbance, confusion (cinchonism)

Thrombocytopenia, hemolytic anemia (in G6PD deficiency), anaphylaxis

Anti-cholinergic effects

Question 9

Procainamide target, adverse effects, contraindication

Answer 9

Use: Drug of choice for atrial fibrillation in WPW (preexcited afib). Blocks accessory pathway muscle conduction and His-Purkinje system.

Contraindicated if ischemic heart disease

Adverse Effects:

GI side effects

Vasculitis, Raynaud’s phenomenon

Agranulocytosis

Hypotension, bradycardia, QT prolongation, torsades de pointes (Idiosyncratic)§Anti-cholinergic effects

Drug-induced lupus ~ 30% (+ ANA in 80%)

Question 10

Class 1b drugs and treatment

Answer 10

Lidocaine, Mexelitine

Shortens action potential duration, thus, no torsades risk

Used for ventricular tachycardia, especially if caused by ischemia

Question 11

Lidocaine special use, metabolism, and side effects

Answer 11

Lidocaine causes voltage dependent Na+ channel block (­ bigger effect in ischemic tissue)

Metabolism depends on hepatic blood flow

Side effects: Neurological (delerium, seizures, tremors)

Question 12

Why do 1Bs work well in ischemic tissue

Answer 12

Question 13

Class 1c drugs and treatment

Answer 13

Flecainide, propafenone

Used to maintain or restore sinus rhythm in atrial fibrillation

Question 14

Class 1c mechanisms and causes

Answer 14

Most potent Na+ channel blockers and greatest use-dependence

Increases QRS duration (decrease slope phase 0)

No change in QTc

Question 15

Flecainide contraindication and adverse effects

Answer 15

CONTRAINDICATED if structural heart disease (↓EF) or recent MI/ischemic heart disease

§Adverse effects: Dizziness, visual disturbance, marked negative inotropic effects – worsen HF

Question 16

How can 1c drugs cause arrythmia

Answer 16

Question 17

Class 1 effects on QTc, PR, QRS

Answer 17

Increase PR and QRS

• IA drugs prolong QTc
• IB drugs shorten QTc
• IC drugs primarily decrease slope phase 0 (increases QRS)

Question 18

Class III mechanism of action

Answer 18

K Channel blocker

blocks re-entry by increasing ERP duration so it is longer than conduction time

Question 19

Class III drug and treatment

Answer 19

Amiodarone (multiple class effects), Ibutilide,Dofetilide, Sotalol

Can be used for atrial and ventricular arrhythmias (dirty job, dirty drug)

Mostly used for converting Afib to NSR or maintaining NSR after cardioversion

Question 20

Class III effect on EKG

Answer 20

Increase action potential duration (QTc)

Prolong repolarization - ­ refractory period

No change in QRS (phase 0 not affected)

May not increase risk of Torsades

Question 21

Amiodarone dosing and metabolism

Answer 21

P450 inhibitor – can increase many drug levels

Large volume of distribution; lipid soluble; >10 gms needed to saturate fat stores; Half-life 13-103 days

Question 22

Amioderone side effects

Answer 22

Also has class I, II, and IV effects (dirty job, dirty drug) – but most side effects are due to accumulation outside heart!

Hyperthyroidism: Need to stop drug

Hypothyroidism: Most common! Supplement T4; usually don’t need to stop

Pulmonary: Appears like pulmonary edema on CXR

Photosensitivity, gray/blue skin discoloration

Question 23

What to monitor on amioderone

Answer 23

annual eye exams, liver function tests, thyroid studies, pulmonary function tests (LFT, TFT, PFT)

Question 24

Class II drugs MOA

Answer 24

Question 25

Class II effects on EKG

Answer 25

↓HR ↑PR interval Decreased ventricular rate in Afib No change in QRS or QTc

Question 26

Beta Blockers common use

Answer 26

Use: Most **tachyarrhythmias (atrial and ventricular)** Only anti-arrhythmics shown to **reduce arrhythmic mortality post-MI** (okay for ischemic or structural heart disease)

Question 27

Beta blockers side effects

Answer 27

Caution in **systolic heart failure** due to negative inotropy (especially with IV) Possible bronchospasm with nonselective Can cause heart block, bradycardia

Question 28

Class II drugs

Answer 28

Question 29

Class IV mechanisms

Answer 29

Block activated and inactivated L-type calcium channels **Prolongs phase 4 of nodal AP**, much like beta blockers, decreasing pacemaker activity **increases AV node refractory period** duration (blocks AV node reentry) **reduces Ca2+ entry** preventing Ca2+ overload (prevents DADs)

Question 30

Class IV effect on EKG

Answer 30

Decrease HR and increase PR interval

Question 31

Class IV drugs and treatment

Answer 31

**Diltiazem**, Verapamil Used for rate control of **atrial fibrillation**

Question 32

Class IV adverse effects

Answer 32

bradycardia, hypotension, heart block, **worsen heart failure due to negative inotropy**

Question 33

Potency of class 1 drugs

Answer 33

Intensity of sodium channel blockade: **IC\>IA\>IB**

Question 34

Digitalis (Digoxin) MOA

Answer 34

Question 35

Digoxin use

Answer 35

Anti-arrhythmic use: ONLY for r**ate control of Afib** when all else fails or is contraindicated (systolic heart failure) Narrow therapeutic window

Question 36

Digoxin toxicities and what to give

Answer 36

Competes for binding site with K – **toxicity aggravated by hypokalemia** **Toxicity: nausea, vomiting, bradycardia, ECG changes** Pro-arrhythmic effects due to high intracellular Na (higher resting potential): Increased automaticity, Ventricular Tachycardia, AV block, ST segment abnormalities **Treat with Digibind (Ab)**

Question 37

Digoxin toxicity on EKG

Answer 37

Question 38

Adenosine use and MOA

Answer 38

Drug of choice for **termination of SVTs that depend on AV node** Activates K channels à K out à takes cell longer to depolarize Blocks Ca influx Inhibits AV node reentry = **BLOCKS AV node conduction** **Half life is second** -- transient

Question 39

Adenosine side effects and contraindication

Answer 39

Side effects: flushing via endothelial-dependent relaxation of smooth muscle, av block, nausea, shortness of breath Caution: Can trigger Afib by changing atrial refractoriness. **Contraindicated for pre-excited Afib(WPW)**