Nordgren: Na +- Channel Blockers Flashcards
What does a Na channel blockade do?
Alters the AP duration and kinetics of Na channel blockade
Which class is the largest and oldest group of antiarrhythmic drugs?
Class I- Na channel blockers
What do Na channel blockers do?
Bind to and block FAST Na channels.
What are FAST Na channels responsible for?
Rapid depolarization (phase 0) of fast response cardiac APs.
What affect does a Na channel blocker have on an AP?
- Decreased slope of phase 0 and amplitude of the AP.
2. Reduces the rate and magnitude of depolarization and leads to a decrease in conduction velocity in non-nodal tissue.
Do Na channel blockers have an effect on nodal tissue?
NO because those AP are dependent on Ca to depolarize.
Why are there subdivisions of class I drugs?
Because they have differing effects on AP duration and effective refractory period.
- subclasses differ in eff
How do the subdivisions of class I differ?
Some effect ERP adue to non-specific secondary activity of drugs on efflux of K in phase 3.
Some subclasses also differ in efficiency for reducing the slope of phase 0.
How do the three class I Na channel blockers differ in terms of increasing the ERP (effective refractory period)?
IA- Increase ERP
IB- Decreases ERP
IC- maintains ERP
IA>IC>IB
Class IB drug?
lidocaine
How does the rate of association of the Na blocker drug with the channel differ?
IA- immediate rate of association
IB- rapid rate of association
IC- slow rate of association
What is the effect of a IA drug?
- Slows the rate of rise (phase 0) of AP.
2. Prolongs AP (increases the ERP)
What is the effect of drug IB?
Shortens the refractory period (phase 3 repolarization) and decreases duration of the AP.
What is hte effect of drug IC?
Markedly slow phase 0 depolarization and has no effect on the refractory period.
What drugs are used to treat atrial fibrillation, flutter; supraventricular and ventricular tachyarrhythmias?
Class IA
What are the three class IA drugs? How do these drugs differ in terms of anticholinergic activity?
QPD
quinidine
procainamide
disopyramide
All three are anticholinergic but D>Q>P.
What are the SE of qunidine?
Cinchonism (blurred vision, tinnitus, HA, psychosis)
Cramping and nausea
Enhances digitalis toxicity
What is the SE of procainamide?
lupus like syndrome in 25-30% of pts
What is the SE of disopyramide?
Negative inotropic effect
What drug class treats ventricular tachyarrhythmias?
Class IB
What are the three drugs in class IB?
Lidocaine- IV only; VT and PVCs
tocainide
mexiletine
Which class IB drugs are orally active lidocaine analogs?
tocainide
mexiletine
Which class IB drugs have good efficacy in ischemic myocardium?
Lidocaine
Mexiletine
Which class IB drug can cause pulmonary fibrosis?
Tocainide
What drug class is used for life-threatening supraventricular tachyarrhythmias and ventricular tachyarrhythmias?
Class IC
What are the three class IC drugs? What type of arrhythmia do they treat?
flecainide- SVT
Propafenone-SVT adn VT
moricizine- VT; IB activity
Which class IC drug can induce life-threatening VT?
flecainide (usually used to treat SVT)
Which Class IC drug causes beta blocking and Ca channel blocking activity that can worsen heart failure?
propafenone
What are class II Na blockers?
Beta adrenoceptor blockers
What are class II drugs used for?
To prevent and treat supraventricular arrhythmias and to reduce ventricular ectopic depolarizations and sudden death in pts w/ MI.
Why do Beta blockers have antiarrhythmic effects?
Because of their ability to INHIBIT sympathetic activation of cardiac automaticity and conduction.
What do Beta blockers do?
- Slow the heart rate
- Decrease the AV node conduction velocity
- Increase the AV node refractory period
- Have little to no effect on ventricular conduction and repolarization
Cardiac effects: Procainamide (IA)
Slow upstroke of AP, slows conduction, prolongs QRS on ECG, prolongs ADP by non-specific blockade of K channels
**NO antimuscarinic effects
Extracardiac effects: Procainamide (IA)
Ganglion blocking properties> reduce peripheral vascular resistance and can cause hypertension.
Toxicity: Procainamide (IA)
Excessive AP prolongation, QT interval prolongation, induction of TORSADAS DE POINTES arrhythmia and syncope, excessive slowing of conduction. Long term can cause SYNDROME RESEMBLING LUPUS.
Pharmacokinetics: Procainamide
Drug metabolism
T1/2
PPB
Drug metabolite (NAPA) Hepatic metabolism to NAPA, NAPA via renal elimination.
T1/2 of NAPA is longer than procainamide.
Plasma protein binding 15-50%
TU: procainamide
Atrial and ventricular arrhythmias
2nd or 3rd choice drug for sustained ventricular arrhythmias associated w/ acute MI.
Why do you want to avoid long term therapy with procainamide?
It can lead to frequent dosing and lupus related events.
CE: Quinidine (IA)
Slows upstroke of AP slows conduction prolongs QRS on ECG prolongs ADP by nonspecific blockade of K channels Antimuscarinic effects
ECE: Quinidine (IA)
GI effects of diarrhea, nausea and vomiting obeseved in 1/3-1/2 of pts. Cinchonism observed at toxic conc.
Toxicity: Quinidine
Excessive QT interval prolongation, induction of TORSADAS DE POINTES arrhythmias and syncope
Pharmacokinetics: Quinidine (IA)
Readily absorbed from GI tract and eliminated by hepatic metabolism and renal excretion.
TU: Quinidine (IA)
RARELY used b/c of cardiac and extracardiac adverse effects and the availability of better tolerated drugs.
CE: Disopyramide (IA)
Slows upstroke of AP slows conduction prolongs QRS on ECG prolongs ADP by nonspecific blockade of K channels Antimuscarinic effects (Same as Quinidine)
ECE: Disopyramide (IA)
Atropine-like activity–> urinary retention, dry mouth, blurred vision, constipation
Toxicity: Disopyramide (IA)
Same as quinidine. May precipitate heart failure de novo or in pts w/ pre-existing depression of left ventricular function. Not to be used as a first line drug in USA or in pts w/ heart failure.
Pharmakokinetics: Disopyramide (IA)
LOADING DOSES NOT RECOMMENDED b/c of risk of precipitating heart failure.
Hepatic metabolism, renal excretion.
Protein binding 50-65%
TU: Disopyramide (IA)
Effective for many supraventricular arrhythmias, but only used for ventricular arrhythmias in US.
CE: Lidocaine (IB)
Selective depression of conduction in depolarized cells.
Little effect seen on ECG in normal sinus rhythm.
Toxicity: Lidocaine (IB)
One of the least cardiotoxic Class I drugs.
Most common adverse effects: paresthesias, termor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, convulsions.
These effects occur most commonly in elderly or vulnerable patients.
Pharmacokinetics: Lidocaine (IB)
Extensive first pass hepatic metabolism> only 3% of orally administered appears in plasma.
Must give parenterally.
T1/2 1-2 hrs.
TU: Lidocaine (IB)
Good for termination of ventricular tachycardia and prevention of ventricular fibrillation after cardioversion in the setting of acute ishemia.
PROPHYLATIC USE MAY ACTUALLY INCREASE TOTAL MORTALITY > NOT ADVISED!
CE: Mexiletine (IB)
Selective depression of conduction in depolarized cells. Little effect seen on ECG in normal sinus rhythm.
Extracardiac effects: Mexiletine (IB)
SIGNIFICANT EFFICACY IN RELIEVING CHRONIC PAIN, ESPECIALLY D/T DIABETIC NEUROPATHY AND NERVE INJURY.
Toxicity: Mexiletine (IB)
Tremor, blurred vision, lethargy, nausea.
Pharmacokinetics: Mexiletine (IB)
Hepatic metabolism, renal excretion.
Protein binding 50-60%. T1/2 8-20 hrs.
TU: Mexiletine (IB)
Ventricular arrhythmias
CE: Tocainide (IB)
Selective depression of conduction in depolarized cells. Little effect seen on ECG in normal sinus rhythm.
Toxicity: Tocainide (IB)
Lidocaine analog.
Pharmacokinetics: Tocainide (IB)
GLUCORONIDATION METABOLISM, renal excretion (30-50% unchanged). Protein binding 10-20%.
TU: Tocainide (IB)
No longer sold in the US.
CE: Flecainide (IC)
Slows upstroke of AP, slows conduciton. Potent blocker of Na and K channels w/ SLOW UNBLOCKING KINETICS (but doesn’t prolong AP or QT interval)
Toxicity: Flecainide (IC)
Severe exacerbation of arrhythmia even when normal doses adminsitered to patients with preexisting ventricular tachyarrhythmias and those w/ previous MI and ventricular ectopy.
Pharmacokinetics: Flecainide (IC)
Metabolism and elimination both hepatic and renal.
Protein binding 40%.
TU: Flecainide (IC)
Supraventricular arrhythmias. Very effective in suppressing premature ventricular contractions.
CE: Propafenone (IC)
Slos upstroke of AP, slows conduciton. WEAK BETA BLOCKIGN ACTIVITY. Spectrum of action similar to quinidine, but does not prolong AP.
Toxicity: Flecainide (IC)
Metallic taste and constipation. Arrhythmia and exacerbation can also occur.
Pharmacokinetics: Flecainide (IC)
Hepatic metabolism, renal excretion. Protein binding 97%.
TU: Flecainide (IC)
Supraventricular arrhythmias.
CE: Moricizine (IC)
Slows upstroke of AP, slows conduction. Does not prolong AP duration.
Pharmacokinetics: Moricizine (IC)
Extensive first pass hepatic metabolism
Protein binding 95%
TU: Moricizine (IC)
Ventricular arrhythmias. Phenothiazine derivative. NO longer sold in US.
What are some examples of class II beta adrenoceptor blockers?
PASE
Propanolol
acebutolol
sotalol
esmolol
What are the adverse affects of propanolol?
Bronchospasm, bradycardia, fatigue.
It also has some class I activity.
In what pts is acebutolol good for?
Acebutolol is a cardioselective beta-blocking drug so it’s good for pts w/ asthma (avoid adverse effects like bronchospasm).
What is sotalol good for?
It is a nonselective beta blocking drug that prolongs the action potential (delays the slow outward current of K)
What do we use esmolol for?
It’s a short acting blocker used for intraoperative and acute arrhythmias.
