Na+ Channels Blockers and Beta Blockers Flashcards
What two classes of the antiarrhythmics can be used to deal with a reentry issue and why?
- Na+ channel blockers - because they can slow AP duration and thus slow ocnduction, making it a bidirectional block
- K+ channel blockers - because they prolong the effective refractory period, slowing conduction
How do the Na+ channel blockers slow conduction specifically?
they block Na+ entry into the cell, thus prolonging phase 0 and slowing conduction
How do the K+ channel blockers promote the refractory time of the cell specifically?
It slows the efflux of K+ during phase 3 so the cell doesn’t repolarize as quickly and sodium channels stay inactivated for longer - prolonging the refractory time of the cell
What is accommodation?
when heart tissue is damaged and can’t generate ATP, the Na/Ca and Na/K exchangers don’t work and you get depolarization of the RPM - hence the Na+ are inactivated and can’t take part in the depolarization
The depolarization then falls on Ca2+, which makes is resemble a slow-response AP - and develop automaticity
In general, how do you deal with accomodation?
you need to convert the permeability profile back to fast-response and allow Na+ permeability to dominate the depolarization
hence, you need to alter the Ca2+ permeability
Specifically what calcium channels are blocked by Ca2+ channel blockers?
They block the T-type channels, which are depolarized at relatively low membrane potentials - this slows the influx of Ca2+ and allows for Na+ channels to fully repolarize and excite the cell in a fast-response manner
Do the Na+ channel blockers bind to and block slow or fast Na+ channels
the fast ones - the ones responsible for the rapid depolarization
What do Na+ channel blockers do to alter the shape of the action potential curve?
if decreases the slop of phase 0, so depolarizaiton is slowed
the amplitude of the action potential is also decreased
Na+ channel blockers will decrease conduction velocity in what type of heart tissue, then? Why?
Na+ channel blockers will decrease conduction velocity in non-nodal tissue
they won’t have an effect on nodal tissue because the nodal APs are dependent on Ca2+
How are the Na+ channel blockers divided into subdivisions?
based on their differing effects on action potential duration and effective refractory period.
What are the Na+ channel blocker’s effects on effective refractory period actually due to?
not due to the Na+ blockade, but rather the non-specific secondary activity on efflux of K+ in phase 3
Rank the subclasses of Na+ channel blockers in terms of effectivness of Na+ blockade?
1c better than 1a better than 1b
Rank the Na+ channel blocker subclasses based on which increases the effective refractory period the most
1A more than 1C (actually not much at all) more than 1B (which actually decreases it!)
What are three class 1B drugs?
What are three class 1B drugs?
What are three class 1B drugs?
lidocaine
tocainide
mexiletine
lidocaine
tocainide
mexiletine
lidocaine
tocainide
mexiletine
lidocaine
tocainide
mexiletine
afib
atrial flutter
supraventriculae and ventricular tachyarrhythmias
What are the class 1Bs typically used to treat?
ventricular tachyarrhythmias
What are the class 1Cs typically used to treat?
surpaventricular tachyarrhythmias and ventricular tachyararhythmias
What are the effects of Beta-blockers?
They inhibit sympathetic activation of cardiac automaticity and conduction, so they slow the heart rate, decrease AV node conduction velocity,and increase AV node refractory period
What are the beta blockers used to treat?
supraventricular arrhythmias and to reduce ventricular ectopic depolarizations (as seen in MI)
What are the cardiac effects of procainamide?
class 1A antiarrhythmic - slows upstroke of AP, slows conduction, prolongs QRS on EKG and prolongs ERP by non-specific blockade of K+ channels
WHat are the extracardiac effect sof procainamide?
ganglion blocking properties leading to reduced peripheral vascular resistance and causing hypotention
What are the two important toxicities of procainamide?
Because of the excessive AP prolongation, you have QT interval prolongation with potential induction or torsades de pointes
Long term use can cause a syndrome resemble lupus erythematosus
How is procainamide metabolized?
the drug is metabolized to NAPA (has class 3 activity) in the liver.
NAPA excreted by kidneys
15-20% plasma protein binding
What are the cardiac effects of quinidine?
class 1A antiarrhythmic - slows upstroke of AP, slows conduction, prolongs QRS on EKG, prolongs effective refractory period by non-specific blockade of K+ channels, antimuscarinic effects
What are the extracardiac effects?
antimuscarinic effects = adverse GI with diarrhea, nausea, and vomiting
conchonism - headache, dizziness, tinnitus at toxic concentrations
What’s the major toxicity of quinidine?
excessive QT prolongation with induction of torsades de pointes, arrhtymia and syncope
Describe the pharmacokinetics of quinidine?
readily absorbed from GI tract, eliminated by hepatic metabolism and excreted via kidneys
Why is quinidine rarely used for arrhythmias?
because of the extracardiac adverse effects - other drugs are much better tolerated
What are the cardiac effects of disopyramide?
slows upstroke of AP slows conduciton prolongs QRS prolongs ERP antimuscarinic effects
What are the extracardiac effects of disopyramide?
atorpine-like activity, so urinary retention, dry mouth, blurred vision, constipation
What’s the main toxicity for disopyramide?
excessive QT prolongation and torsades depoints
may precipitate heart failure de novo or in patients with preexisting left ventricular dysfunction - so don’t use in patients with heart failure
What are the pharmacokinetics for disopyramide?
loading dose is NOT recommended because of risk of precipitating heart failure. hepatic metabolism, renal excretion. protein binding 50-60%
What is disopyramide used for in the US?
ventricular arrythmias only
WHat are the cardiac effects of lidocaine?
selective depression of conduction in depolarized cells. Little effect seen on EKG in normal sinus rhythm.
What are the toxicities of lidocaine?
it’s one of the least cardiotoxic class 1 antiarrhytmics! Most common effects are paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, convulsions. Most common in elderly.
What are the pharmacokinetics of lidocaine?
extensive first-pass hepatic metabolism, so only 3% of oral dose apears in plasma, thus you have to give parenterally
half life of only 1-2 hours
What are the main therapeutic uses for lidocaine?
it’s the agent of choice for termination of ventricular tachycardia and prevention of v fib after cardioversion in the setting of acute ischemia.
However, it’s NOT used prophylactically because it increases total mortality for some unknown reason
What are the cardiac effects of mexiletine? WHat is it actually?
It’s an orally active congener of lidocaine!!!
Selective depression of conduction in depolarized cells. Little effects seen on EKG in normal rhythm.
What are the extracardiac effects of mexiletine?
there’s significant efficacy in relieving chronic pain due to diabetic neuropathy and nerve injury!!!!
What are the common adverse effects of mexiletine?
tremor, blurred vision, lethargy, nausea
How is mexiletine metabolized/
hepatic metabolism
renal excretion
protein binding 50-60%
half life 8-20 hours (longer than lido)
What is tocainide?
another lidocaine analog
What are the pharmacokinetics of tocainide?
glucuronidation metabolism!
renal excretion
protien binding 10-20%
What is tocainide used for?
nothing - not sold in US anymore
What are the cardiac effects of flecainide?
slows upstroke of AP
slows conduction
potent blocker of Na+ and K+ channels with slow unblocking kinetics
Does NOT prolong the AP or QT interval
What are the toxicities of flecainide?
severe exacerbation of arrhythmia if given to someone with a preexisting ventricular tachyarrhythmias and those with previous MI and ventricular ectopy
What are the pharmacokinetics of flecainide?
metabolism and elimination both hepatic and renal. protein binding 40%
What are the cardiac effects of propafenone?
slows upstroke of AP
slows conduciton
!!Weak beta-blocking activity!!
spectrum of action similar to quinidine, but doesn’t prolong AP
What are the toxicities of propafenone?
metallic taste and constipation
arrhytmia exacerbations can also occur
What is the therapeutic use for propafenone?
supraventricular arrhythmias
What are the cardiac effects of moricizine?
slows upstroke of AP
slows conduction
does not prolong AP duration
What are the pharmacokinetics of moricizine?
extensive first pass hepatic metabolism
protein binding 95%!
What is moricizine used for?
nothing anymore - not sold in the US. Was used for ventricular arrhytmias
Who should you NOT give the 1Cs to?
people with pre-existing structural damage like an MI - they will make the arrhythmias way worse
What are 4 examples of beta blockers?
proporanalol
acebutolol
esmolol
sotalol
What are the major general toxicities of the beta blockers
can precipitate CHF, so don’t use in patients with CHF
can also inhibit bronchodilation and exacerbate asthma, so use with caution
What is the extra toxicity of sotalol among the beta blockers?
It can cause QT prolongation and torsades de pointes, so we only use it for severe arrhythmias
