E1: Antiarrhythmic Drugs Flashcards
Compare and contrast cardiac action potentials (Conductile vs contractile)
Location
Pacemaker?
Depolarization
Plateu phase
Repolarization
Fast or slow
Conductile:
Location: SA and AV node
Pacemaker
Depolarization: Ca2+
Plateu phase: NONE
Repolarization: K+
Fast or slow: SLOW
Contractile:
Location: atrial and ventricular
NONpacemaker
Depolarization: Na+
Plateu phase: Ca2+
Repolarization: K+
Fast or slow: FAST
Class I
Class II
Class III
Class IV
Class V
Class I: Na+ channel blockers
Class II: beta-receptor blockers
Class III: K+ channel blockers
Class IV: Ca2+ channel blockers
Class V: Miscellaneous agents
Disopyrimide-Norpace
Class
MOA
Pharmacodynamics (which type of cells/phases and use dependence?)
ADR
Precaution/Warning
Class Ia Na+ channel blocker (Moderate)
MOA: ↓ Na+ influx into atrial and ventricular myocytes by moderate blockade of Na+ channels
Pharmacodynamics:
1. effects on action potential in contractile cells
a. ↓ the rate of phase 0 depolarization
-↓ Na+ conductance
b. prolongs phase 3 repolarization
-↑ effective refractory period (ERP)
-K+ channel blockade
2. Use dependence of Na+ blockers
agents bind to channels more when in an active state
a. The faster the rate, the more binding to the channels
ADR: Anticholinergic, hypotension, cardiac failure
Precaution/Warning:
1. 2nd/3rd degree heart block
2. Glaucoma
3. Proarrhythmic effect (QTc Prolongation
Lidocaine (Xylocaine)
Class:
MOA:
Pharmacodynamics:
ADR:
Precaution/Warning
Class: Ib Na+ channel blockade (MILD)
MOA: ↓Na+ influx into cell by mild blockade of Na+ channels
Pharmacodynamics
1. Only minor effect to the rate of phase 0 depolarization
2. ↓ effective refractory period (ERP) (Not advantageous )
3. binds to and dissociates from the channel receptor quickly
4. Anesthetic properties
ADR: paresthesias, tremor, slurred speech, agitation, anxiety; bradycardia, circulatory shock, coronary artery vasospasm, hypotension
Precaution/Warning:
1. 2nd/3rd degree heart block
Propafenone
Class:
MOA:
Pharmacodynamics:
ADR:
Precautions/Warning:
Class Ic: Na+ potent channel blockers
MOA: very potent Na+ channel blockade
Pharmacodynamics
1. ↓ the rate of phase 0 depolarization
2. ↓ influx of Na+ into virtually all cardiac cells (SA node and ventricles)
3. No effect on repolarization
4. Na+ channel blockade evident at normal heart rates (60-100 beats/min)
5. propafenone has beta-blocking actions
ADR: taste disturbances, dizziness,
-GI: N,V
Precautions/warning: pro-arrhythmic, ↑ risk of cardiac arrest/sudden death
Which Na Channel has the characteristic?
1. Moderate Na+ channel block and prolonged repolarization
2. Mild channel block and shortened repolarization
3. Marked Na+ channel block and no change in repolarization
- Class IA
- Class IB
- Class IC
What type of cells do Class I antiarrhythmics act on
Ventricular myocytes
Class II
3 examples
MOA
Pharmacodynamics
Acebutolol (Sectral)
Esmolol (Brevibloc)
Propranolol
MOA: inhibit overall sympathetic impulses going to the heart by blocking beta-1, beta-2 receptors in the SA and AV nodes
Pharmacodynamics:
1. slows ventricular rate by slowing SA and AV node conduction
2. ↓ phase 4 slope (↓ depolarization)
3. Block beta1 –> ↓ HR –> ↓ O2 consumption –> anti-ischemic effect
4. Membrane stabilizing effect
–Na+ channel blockade
–Class I effects
5. ↓ phase 4 slope of depolarization
—Prolongs time to depolarization
Esmolol
Pharmacodynamics
Kinetics
ADR
Precautions
Pharmacodynamics
beta-1 selective antagonist
Pharmacokinetics
IV only
Very short acting: T1/2 9 min
ADR
CV: asymptomatic hypotension (25%)
Precautions/Warnings/CI
hypotension
Propranolol
Use
Pharmacodynamics
DI
ADR
Precaution/Warning
General Information/Uses
Control supraventricular and ventricular arrhythmias
Pharmacodynamics
beta-1, beta-2 non-selective adrenergic antagonist
membrane stabilizing activity (MSA)
Drug Interactions
Non-DHP CCB: bradycardia, HF
Propranolol IR serum levels may be increased if taken with food
ADR
CV: hypotension , bradycardia , 1st degree heart block
CNS: dizziness , fatigue , depression
Precautions/Warnings/CI
1. Bradycardia/AV block
2. use cautiously in bronchospastic disease ie Asthma
3. Cardiac ischemia after abrupt discontinuation (Inderal LA, Inderal XL)
–should not be withdrawn abruptly
–Gradually taper over 1-2 weeks to avoid acute tachycardia
Class III Agents: ______ Channel blockers
K+ channel blockers
- Amiodarone (Pacerone)
- Dronedarone-Multaq
- Ibutilide-Covert
- Sotalol: Betapace
- Amiodarone (Pacerone)
- Dronedarone-Multaq
- Ibutilide-Covert
- Sotalol: Betapace
All same class
MOA
Pharmacodynamics
MOA: blocking K+ channels
Pharmacodynamics
↓ K+ efflux out of cell in Phase 3 of action potential
Prolong phase 3 repolarization
↑ ERP
Amiodarone
Class
General information/use
Pharmacodynamics
DI
ADR
Required Testing/Monitoring
Precaution/Warning
Class III: K+ Channel Blocker
General Information/Uses
Most common antiarrhythmic
“Wide spectrum” antiarrhythmic
Supraventricular and ventricular arrhythmias
heart failure
Pharmacodynamics
Mainly acts as Class III agent at therapeutic doses used (low)
Prolongs repolarization Lengthens refractory period
amiodarone also
blocks Na+ channels
α and β adrenergic antag effects
blocks Ca++ channels
Drug Interactions
CYP450 substrate 3A4,2C8 (major)
Amiodarone inhibits CYP 2C9 and interferes w/ metabolism of warfarin thru CYP 2C9
Need to ↓ warfarin doses by 30-50%
Amiodarone ↑ digoxin conc 50% so need to ↓ dig doses by 50%
Contains iodine in structure
ADR:
1. optic neuropathy, corneal microdeposits, vortex keratopathy
2. GI: Nausea
3. Pulmonary toxicity
4. Derm: skin photosensivity (10%)
- skin deposits of the drug can result in a photodermatitis that cause a gray-blue tint of the skin when exposed to sunlight
5. Endocrine: hypothyroidism (1-10%)
hepatotoxicity (5%)
Required Testing:
1. LFT
2. PFT
3. TTF
4. Annual eye exam
Precautions/Warnings/CI
Life-threatening arrhythmias
QT interval prolongation –> Torsades de Pointes (class effect)
Pulmonary toxicity (pneumonitis/fibrosis)
Hepatotoxicity
Dronedarone
Class
General information
Pharmacodynamics
ADR
Precaution
Class III: K+ Channel Blocker
General Information
1. Originally derived from amiodarone
—less lipophyllic
—-structure has been modified through the addition of a methylsulfonyl group and the removal of iodine
–less toxicities
2. Used in most forms of A.Fib
Pharmacodynamics
Class I,II,III,IV properties
ADR
CV: QTc prolongation (28% vs 19% placebo), bradycardia (3%)
GI: diarrhea (9%), nausea (5%), abd pain (4%) (Neuromuscular weakness (7%)’
Precautions/Warnings/CI
New onset HF has been observed, CI in Class IV HF
Hepatotoxicity including acute liver failure has been reported
Pulmonary disease (pulmonary fibrosis, pneumonitis)
Life-threatening arrhythmias
QTc interval prolongation –> Torsades de Pointes (class effect)
Strong CYP inhibitors
Pregnancy cat: X
Sotalol (Betapace)
Class
Pharmacodynamics
DI
ADR
Precaution/Warning
Class III: K+ Channel blocker
Pharmacodynamics
1. Mixed class II (Beta receptor blockade) class III (K+ channel blockade) properties
Non-selective Beta-1 Beta-2 blocker
2. Block beta1 –> ↓ HR –> ↓ O2 consumption –> anti-ischemic effect
NOTE: No Membrane stabilizing effect (activity)
3. ↓ phase 4 slope of depolarization
4. Sotalol only adds
A. ↑ phase 3 repolarization (K+ blockade)
B.↑ Action Potential duration
C. Class III effect
Drug Interactions
Non-DHP CCB: bradycardia, HF
ADR
CV: bradycardia, hypotension
Precautions/Warnings/CI
1. Bradycardia/ 2nd/3rd degree AV heart block
2. use cautiously in bronchospastic disease ie Asthma
A. Should not be withdrawn abruptly
Gradually taper over 1-2 weeks to avoid acute tachycardia
