Anti-Arrhythmetic Drugs

Question 1

What is the rationale or goal for Anti-Arrhythmetic drugs considering that there is no cure

Answer 1

• Normalize conduction velocity
• rectify altered exciteablity of cardiac cells
• Maintain normal sinus rhythm

Question 2

Torsade de Pointes, a persistant EAD tachyarrhythmia pathology can be induced by prolonged use of what drugs

Answer 2

Prolonged use of:
1) Antiarhythmic drugs
2) Tricyclic Antidepressants
3) antiviral drugs –> gene mutations

Question 3

How does prolonged use of Antiviral drugs lead to Torsade de Pointes
What are the 3 specifics

Answer 3

Antiviral drugs can lead to mutations in genes for ion channels:

A) KCNQ1 & HERG; –> K+ CHANNEL Mutation

B) SCN5A –> Na+ CHANNEL mutation

Question 4

An Inotropic HF drug known as _____ induces TdP
What is used to treat this drug induced TdP

(anatomy word)

Answer 4

Digitalis is the Inotropic HF drug which causes TdP

Treated by MgSO4 infusion/ bolus dose

Question 5

4 classes of drugs associated with QT prolongation (ventricular cycle long) and TdP
(all anti)

Answer 5

Antiarrhythmatics
Antimicrobials
Antidepressants
Antipsychotics

Question 6

Class 1A Antiarrhythmics - MOA, CI

Answer 6

MOA:
-Moderately blocks Na channels (preferentially open channels than inactive)
-Also, K channel blocking (increase ERP)
-Decrease phase 0 upstroke
-decreases myocardial conduction

CI: QT prolongation (can cause TDP)

Question 7

Quinidine

Answer 7

Class 1A
- Moderately Blocks Na Channels
- Strong Anticholinergic effect

CI: Atrial Flutter, b/c increases nodal conduction

DDI: Digoxin, b/c same CYP Digoxin toxicity
AE: -ocular toxicity

Question 8

Disopyramide

Answer 8

Class 1A
-Moderately blocks Na channels
-Severe Anticholinergic effects

CI: Uropathy, Glaucoma

AE: ocular toxicity

Question 9

Procainamide

Answer 9

Class 1A
-Moderately blocks Na channels
- less anticholinergic effect
-Acetylated to active form in the liver N-acetylprocainamide

DDI: Digoxin

Question 10

Class 1B Antiarrhythmics

Answer 10

MOA:
- Blocks Na channels, open and inactive, (prefer inactive) (weakest in class 1)
- Decreases ERP
- Decreases AP duration

AE: unwanted CNS effects, dizziness and seizure, b/c cross BBB

Question 11

Lidocaine

Answer 11

Class 1B
- blocks Na channels (weak)
-also local anesthetic for ocular and dental procedures

Question 12

Mexiletine

Answer 12

Class 1B
-blocks Na channels
(weak)
-Analog of Lidocaine
with negligible QT influence compared to Lidocaine, and less vagolytic effects

Question 13

Phenytoin

Answer 13

Class 1B
-blocks Na channels (weak)
-Also used as epileptic medication
-CYP3A4 inducer

Question 14

Class 1C Antiarrhythmics

Answer 14

MOA:
-Blocks Na channels (Most potent blocker) (mostly open/active state)
-Decrease phase 0 upstroke (ventricular cells)
No change in ERP

ONLY FOR LIFE THREATENING, like Paroxysmal Supraventricular Arrhythmia
b/c can worsen pre-existing arrhythmia

Question 15

Class 1C safety warning

Answer 15

Encainide or Flecainide tx for average 10 months developed cardiac arrest or mortality in CAST study

Propafenone also has mortality warning

Question 16

Class 1 comparisons

Answer 16

-1C is strongest Na channel blocker (mostly open channels)
-1B is weakest Na channel blocker (both open and inactive, but mostly inactive channels)
-1A is moderate Na channel blocker (open channels preferred)

ERP effect
-1A increase (b/c K channel blocking)
-1B decrease
-1C no change

Question 17

Class 2 Antiarrhythmic

Answer 17

Beta Blockers
MOA:
-act on both SA and AV nodes
- slows phase 4 in PM cells
- prolongs ERP, decreasing rate of automaticity

Question 18

-Propranalol
-Sotalol

Answer 18

Non-specific Beta blocker (beta 1 and 2)
-WARNING: life threatening proarrhythmia

AE:
-beta 1: bradycardia and block
-beta 2: bronchospasm

Question 19

-Atenolol
-Metaprolol

Answer 19

Beta 1 specific blocker
- Preferred B/c only acts on SA node

AE:
-beta 1: bradycardia and block

Question 20

-Labetalol
-Carvedilol

Answer 20

Beta and Alpha 1 blocker
- if also vascular complication and SA node 100+

Question 21

Class 3 Antiarrhythmic

Answer 21

K channel blockers
MOA:
-prevent K efflux, slows rate of outward flow
- Longer plateau phase
- ERP increased

Used when K efflux is high and phase 2,3,4 are too fast

AE: Prolonged plateau can cause EAD and lead to TDP

Question 22

Sotalol

Answer 22

mixed class 2 and class 3
- nonselective beta blocker and K channel blocker

Question 23

Amiodarone

Answer 23

K channel blocker
-DEA metabolite is active form, longer half life
AE:
- toxic to thyroid follicular cells
-37% iodine, affinity to thyroid gland
- causes hypothyroidism if long term
- inhibits 5-deiodonase activity and prevents T4 to T3 conversion
Ophthalmic toxicity: corneal deposits, keratopathy
- optic neuropathy
CI: Skin, eye, thyroid conditions

Question 24

• Dronedarone
• Ibutilide
• Dofetilide

Answer 24

Dronedarone:
Substitute for Amiodarone with reduced toxic effects, less iodine, and decreased half life

• Ibutilide
• Dofetilide
  also alternatives

Question 25

Class 4 Antiarrhythmics

Answer 25

Ca channel blockers - SA and AV nodal tissue predominant - slows AP - slows conduction of impulses -regulated AV node mediated re-entry phenomenon

Question 26

-Verapamil -Diltiazem

Answer 26

Ca channel blockers AE: AV nodal block (Rare) CI: beta blockers, b/c HF problems DDI: Digoxin, Digoxin toxicity

Question 27

Class 0

Answer 27

Ivabradine: Inhibits Na entry, inward funny current through HCN Used for Arrhythmias due to SA nodal origin: Sinus Tachycardia

Question 28

Digoxin

Answer 28

Misc. group -HF drug with antiarrhythmic property -Reduces PM firing frequency (SA node) - Effective in A-fib and Paroxysmal Supraventricular Tachycardia Stringent monitoring narrow therapeutic window

Question 29

Adenosine

Answer 29

Misc. group - stim purinergic receptor - Decrease SA and AV nodal conductance

Question 30

Atropine

Answer 30

Anti muscarinic agent - inhibits M2 receptors in SA and AV nodes, normalize sinus rhythm and reverse AV nodal block AE: Tachycardia urinary retention,constipation CI: glaucoma

Question 31

Potassium

Answer 31

irregularity in heartbeat results from K out of range(3.5-5 mM)

Question 32

Stroke

Answer 32

Multiple re-entries, blood not pumped from atrium, results in clot 1. anticoagulants (Dabigatran, Rivaroxaban, Apixaban) 2. HR control (B-Blocker: Atenolol; or Ca channel blocker: Diltiazem. 3. Rhythm control ( Na channel blocker: flecainide, or K channel blocker Amiodarone.