Download Transcripts/4_24 11-12 (Ku)

Neuro: 11:00 – 12:00
Friday, April 24, 2009
Dr. Ku
Abbreviated Terms:
I.
Principles of Cardiovascular Pharmacology
Scribe: Brittney Wise
Proof: Laura Adams
Page 1 of 8
Introduction [S1]: Drugs Used in the Treatment of Arrhythmias and Sudden Coronary Death
a. Notes on the board:
i. Heart Rate  Electrical Properties  either Bradycardia or Tachycardia  Tachycardia can be further
broken down into Supraventricular and Ventricular
II. [S2] Key Points
a. Arrhythmias are heart rate problems and/or electrical problems.
b. Our electrical system that drives the heart involves specialized conducting tissues.
i. You have SA Node (pacemaker), atrial fibers, AV Node, His bundles, left and right bundles, and then you
have the Purkinje fibers.
ii. These are specialized wiring and they tell the heart to contract all at the same time.
iii. You can’t have some of the heart or heart cells contracting while the others are not contracting.
c. When you have ventricular fibrillation, or any kind of fibrillation, and you look at the heart, you see something
like a bed of worms; the cells are all contracting on their own. In order to correct this you need a defibrillator to
stop all the extra movement/contractions and let the pacemaker take over and correct the heart rate.
d. Take Home Messages:
i. pacemaker cells
1. include the ones in the SA node
a. they have the fastest rhythms
b. they are the natural pacemaker cells
2. the AV node and the Purkinje fibers all have a so called primary and secondary pacemaker; they
have intrinsic activity for the ability to self depolarize themselves
3. the fastest ones dominate and that’s why we say that the SA node dominates
4. when we have a problem with the sick sinus syndromes (injury to the sinus node) what happens is
the other cells, Purkinje fibers or AV node or His bundle then take over as the secondary
pacemakers; sometimes he calls this mutiny; when the natural pacemaker is not doing too well the
other ones will then take over; this is when you start having arrhythmia problems
ii. non-pacemaker cells are the so called ventricular muscles
1. these are really for contraction
iii. the other thing you have to remember from previous lectures are the ionic basis of action potentials
1. know phases 0-4 (5 phases total) and what channels and/or conductance do they involve
iv. when a cell dies they are no longer able to maintain electrochemical gradients
1. normally potassium is very high inside and low outside
2. normally sodium is very high outside and low inside
3. so you want to maintain that sodium/potassium ATPase pump
4. if you poison the pump the cell is no longer able to maintain the sodium/potassium gradient, the cell
will then have water come in and the cell will swell up and die
5. you need energy to maintain electrochemical gradient
v. you also need to understand the relationship between action potentials and EKGs; you can stick a
1. action potentials are when you put an electrode into a single cell to determine
2. you are not going to stick a single cell into someone’s heart so you use the EKG; know the different
parts of the EKG (P, QRS, T) and their relation to depolarization and repolarization
III. [S3] Classification of Arrhythmias
a. There are two types of arrhythmias: tachycardia vs. bradycardia
i. Tachycardia – fast heart rate; this constitutes most of the diagnosis
ii. Bradycardia – low heart rate;
1. very hard to determine at what level of beats per minute is bradycardia, all we know is that it is a low
heart rate
2. a lot of time you don’t worry about a lower beat per minute until you start seeing people that are
dealing with syncopy (passing out) then you have problems
3. If you have a low heart rate and you are not passing out you shouldn’t worry about it
b. Normal heart rate is about 60 beats per minute
c. You can drop to about 50 beats per minute when you sleep
d. Athletes or people who meditate can control themselves and can drop their heart rate to about 30, 20, or 15
beats per minute
e. There are 2 major types of tachycardia:
i. Supraventricular arrhythmias – anything above the AV node
1. Ex// Atrial arrhythmias, paroxysmal atrial tachycardia (PAT), atrial flutter, atrial fibrillation, etc.
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 2 of 8
2. Most of the time we don’t worry about the atrial problems because as long as you maintain
ventricular rate you are ok because ventricular rate that determines your cardiac output
3. More often now people with atrial flutter and atrial fibrillation problems it’s not because of heart rate
problems, but because with atrial fibrillation for example, the blood is not moving; most of the time if
you look at the structure of your atria the right atria tends to be smoother and the left atria tends to
have more trabeculae where blood can get trapped and form a blood clot because the atria is not
contracting; all of a sudden if the atria move and loosen these clots they can shoot into the brain and
you can have a stroke
4. So atrial fibrillation and atrial arrhythmias are mainly complications because of blood clots not
because the cardiac output drops
ii. Ventricular arrhythmias – what we focus on the most
1. With this you see right away a drop in your blood pressure or cardiac output
IV. [S4] Pathogenesis of Cardiac Arrhythmias
a. What causes arrhythmias then? We have 2 basic mechanisms:
i. #1 is due to abnormal generations of impulses
ii. #2 is due to the disorder of impulse conductions
b. The 3 major parameters of electrical properties that you need to know are:
i. automaticity
ii. conduction velocity
iii. excitability
c. When you have problems with any of the above 3 you will have arrhythmic problems
d. Abnormal generation of impulses due to automaticity problems increase the rhythms of secondary pacemaker
cells such as the Purkinje fibers or the His bundles or you have trigger activities
V. [S5] Mechanisms for Altering the Automaticity of pacemaker cells (SAN and AVN)
a. There are different ways that you can alter the rate of firing. You can change the slope (how fast it is), the
impulse potential, and/or the threshold potential.
b. Class 2 and Class 4 antiarrhythmics drugs decrease the slope of phase 4 and phase 0.
i. This is the primary mechanism to decrease the heart rate.
VI. [S6] Factors Influencing Automaticity
a. Again, to summarize it he gave us a table.
b. You can run up a flight of stairs really fast and run your heart rate up and that’s sympathetic activation. This will
increase your rate of firing and increase the sympathetic tone. If you are really tired you just massage your
adrenal gland and it will release epinephrine and this will get you going again.
c. The parasympathetic will of course decrease heart rate. Right now as you are sitting in class the
parasympathetic representation is very high and the sympathetic is very low.
d. There are different ways that you can see different modulations with the autonomic system.
e. Metabolic: includes cases like acidosis and hypoxia
f. Mechanical: as it relates to stretch
g. Drugs: this lecture will be talking about these in reference to antiarrhythmia drugs
h. Electrolytes: includes things like calcium and potassium
i. So this table is basically a summary that you should be familiar with.
VII. [S7] Abnormal Generation of Impulses
a. Another mechanism is called triggered activities; you have DADs and EADs
i. DADs – secondary depolarization occurring early in diastole and this is after a full repolarization has been
achieved
1. DAD stands for Delayed Afterdepolarizations
2. The cells polarize, repolarize, depolarize, and then repolarize up and down in oscillations
3. At the end of this phase 4 period, when they hit the threshold they can generate an action potential;
this is a normal contraction
4. Too much calcium can cause DADs (calcium overload in the cell)
5. Drugs that cause this: catecholamines, cardiac glycosides, and digoxin
ii. EADs – stands for Early Afterdepolarizations
1. Occur early after depolarization, early before (he said a phase but I couldn’t understand him)
2. These are a secondary/slow inward Na current, most frequently related to Torsades de Pointes.
b. By clinical definition, if you have just one depolarization then that’s ok but when you get up to 6 per minute you
start classifying it as ventricular arrhythmias.
c. Eventually this can lead to spontaneous or ventricular tachycardia because you have too calcium. We need
calcium but too much is never good.
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 3 of 8
d. These cannot initiate by themselves. What is the difference between these and auto-rhymicity? The autorhythmic cells can initiate by themselves (ex// SA node).
e. These trigger activities cannot initiate by themselves; they always have to have something preceding them. But
they can sustain themselves once they have been activated.
VIII. [S8] Pathogenesis of Cardiac Arrhythmias
a. We are now going to move onto impulse conduction. We are moving onto excitability and conductivity issues.
b. Non-uniformities:
i. The problem is that the heart must have uniform conductivity just like wiring; you cannot have one area
overloaded; if you overload you can have one area that starts a fire (and that’s basically what happens in
the heart)
ii. When the heart is getting big and you are about to have a heart attack (where certain cardiac muscle cells
die) you can say the heart was non-uniform and that the current was no longer passing through the heart
attack area uniformly.
iii. This is what reentry arrhythmias are all about. They are due to 2 things (1) the non-uniformity of excitability
and (2) the non-uniformities of conductivity.
iv. When you increase the excitability what we are talking about is the ERP. ERP stands for effective
refractory period. During ERP basically the heart will not respond and you need a higher voltage to get the
heart excited and for the cells to fire. The longer this period you can say the less excitable this tissue is
because it takes it longer before you can get it excited. If the refractory period is getting narrower then it is
getting more excitable.
c. The yellow line on the graph shows you the less excitable graph where you stretch the action potential duration.
d. How do you increase action potential duration? How do you change the ERP? Very easily, you go back to the
ionic basis and inhibit sodium or potassium channels.
i. So again, you change the ERP by changing the potassium channels. If you activate potassium channels
they will repolarize very fast. If you block them they will change the excitability of your cell.
e. Phase 3: remember that during this phase the reason the cell repolarizes is due to potassium efflux is
happening; if you block this potassium channel then you will prolong the action potential duration so that they
are not repolarizing.
f. SQ: Is the ERP the same as the absolute refractory period?
g. Answer: During the absolute refractory period nothing can happen. Regarding the ERP, during this period the
cell will respond.
IX. [S9] Major Determinants of Conduction Velocity
a. How do we decide conduction velocity? By 2 things: (1) upstroke of velocity of phase 0, how fast is phase 0,
how fast does sodium rush into the cell, and (2) the amplitude of the upstroke.
b. If you start with -90 and then change to -95 the height is more and you can conduct faster. This is a basic
principle of conduction velocity.
c. If you look at this you can see Purkinje fibers and ventricular muscle. These can conduct very fast.
d. However, the AV node conducts very slowly. The upstroke and the amplitude are very slow.
e. There used to be a cable theory taught back in high school. So just like when you buy extension cords, you buy
good ones that are thick. The thicker they are the faster they conduct.
i. Purkinje fiber has a very thick cable that conducts very fast.
X. [S10] Graphs (please note that this slide was very hard to transcribe because he was very unclear with what
he was referring to on the slide)
a. If you put excitability and conductivity together you get reentry arrhythmias. This is top left graph is showing a
signal coming down from the SA node going through the atrial fibers, to the AV node, then to the His bundle,
and then branching into the Purkinje branches. The signal then comes into the muscle fiber, depolarizes the
cells and you get an action potential that shows up on the EKG.
b. What happens when you have a mini heart attack or areas of ischemia? One or more of the fibers is damaged
so it’s considered ½ dead. We need to define ischemia vs. infarcted.
i. Ischemia means that you have an imbalance between supply and demand. You can salvage these cells
and bring them back to normal.
ii. Infarction means that you have necrotic or dead cells that will form scar tissue and cannot regenerate.
c. With ischemic injury the cells are very sluggish and they don’t respond very well. This is what happens after a
mini heart attack. What happens is when a signal comes in the cells are just not ready and they don’t respond.
d. (If you can picture the graph as top, middle, and bottom I think it will help you follow what he says below.)
e. The top graph responds perfectly so they conduct very quickly.
f. The bottom graph depolarizes and then it figures out that there is another way for it to get back to the block. So
these cells are able to respond now that they have recycled back the current.
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 4 of 8
i. Basically what you see in the bottom 2 graphs is that the front door is locked but the back door is open, so
the current comes back through the back door forming a circuit. This is what allows for an extra stimulus or
extra contraction.
XI. [S11] Reentry Arrhythmia (with unidirectional block)
a. This is a cartoon illustration that is showing you a normal action potential with all the phases.
b. Ischemic cells (decrease oxygen supply/demand) have a low ATP. When you don’t have enough ATP what
happened to the sodium; potassium ATPase pumps? Answer: it becomes sluggish. When it becomes sluggish
they are not pumping sodium out and potassium in so you get a lot of accumulation of sodium and calcium in
the cell. What happens when you have positive charges inside the cell is that you become less negative. You
need to pump the sodium out because you need the cell to become more negative and ready for the next action
potential.
i. If you become sluggish you get a lot of positive inside the cell so the cells are basically partially
depolarized. They are not as good as normal cells so when a stimulus comes they will depolarize correctly
the 1st time but since they are slow it will slow down the conduction. So the whole process becomes very
slow. So, when the 2nd stimulus comes in, a normal cell will be able to fire, but the ischemic cell will not be
able to fire. They are blocked.
ii. When the cells are blocked, if you wait for a few milliseconds when the current comes back in the cell will
be ready to depolarize and they will fire again. This is what we call reentry stimulus.
c. So 2 things, excitability ERP problems increase ERP and conduction problems. This is a reentry arrhythmia.
d. Once we understand this how do we treat this?
i. You can increase your ERP further. If do this even the reentry can’t come in and you won’t respond. This
is what we call creating a bi-directional block. Blocking front and back.
ii. Or you can eliminate a block and shift the ERP back to the left. This allows the cell to now respond.
XII. [S12] Conditions Required for Cardiac Reentry
a. So this is showing you that in order to have a reentry to occur you have to have 3 things:
i. You have to have a loop
ii. Unidirectional block
iii. Zone of slow conduction
b. The normal myocardium has a very small heart you have very fast/rapid conduction fibers, so you don’t have
this reentry problem.
c. But when you have a hypertrophied heart, the heart is getting bigger and you are trying to supply electricity to a
larger heart. Why do you have a hypertrophied heart? Answer: hypertension, congestive heart failure, any of
these things will cause it.
i. It is more likely for you to have arrhythmias with these conditions. They are all related in some way.
XIII. [S13] Reentry Sites of 3 Major Arrhythmias
a. This is just showing you the different types of arrhythmias that you can have. This is the ventricular tachycardia
that he talked about (Wolf-Parkinson-White). This is very clinical so don’t worry about it.
XIV.
[S14] Class IA, IC, III, and IB
a. One way we can do treatment it is through Class 1A, Class 1C, and Class 3 drugs.
i. Basically you are converting the decreased membrane responsiveness and decreased conduction velocity
to a bidirectional block. A block in the front and in the back. This shift the entire action potential even
wider. So you eliminate the circuit with this.
b. Class IB increases membrane responsiveness and conduction velocity to eliminate the block. Now you are not
able to conduct through.
c. Which is better? Answer: it depends on the side effects. We would like to eliminate the block. That is our top
priority because the best way to do it is to eliminate the block. But this depends on how bad it is. Sometimes
you can just knock out the block and its better but if the person is sick or dying these drugs can cause problems.
i. Sometime the Electro-physiologists (EP’s) downstairs figure out where the trouble makers are. They will
then kill the trouble makers off usually by thermal ablation (internet definition = A procedure using heat to
remove tissue or a part of the body, or destroy its function). They can map the heart and tell you where the
trouble zones are. (sorry ya’ll I’m not really sure what he means by “trouble makers”)
XV.
[S15] Management of Arrhythmias
a. In term of management, he is going to try and give us the big picture.
i. Non-pharmacological
1. decrease emotional stress (this was the main point but he did say some other stuff I couldn’t
understand)
2. if you can’t manage the arrhythmias this way then you will need to move onto drugs
ii. Pharmacological
1. Primary antiarrhythmic drugs
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 5 of 8
2. Secondary antiarrhythmic drugs
3. Almost all antiarrhythmic drugs are basically poisons. They all have a lot of side effects.
iii. Surgically
1. Ex// surgical ablation, catheter ablation (where you use high frequency radiowaves, microwaves,
ultrasound)
2. Now more and more people are using pacemakers and defibrillators.
XVI.
[S16] Secondary Antiarrhythmic Agents: (Unclassified, Class V, or other)
a. There are some that we classify as class V, unclassified or other.
b. There are all different types of drugs: ex//s include cardiac glycosides, adenosines, or supraventricular
arrhythmias, magnesium sulfates (these are very useful), torsades do pointes, atropine, or even alpha receptor
agonists.
c. When your heart is pumping really fast what you need to do is just put some cold water on your face or stick
your hands in some cold water. By doing this you will vasoconstrict yourself. Your barroreceptors will sense
constriction and then send a signal to the brain. The brain will deactivate your sympathetic and increase your
parasympathetic to slow down your heart rate.
XVII. [S17] Classification of Antiarrhythmic Agents
a. These are the different classifications: Class 1-4. Most of the time he won’t ask us to memorize these individual
drugs but it is important for us to realize that we need to know the differences between the different classes. At
the least understand the different classes. (He just said he probably won’t ask us to memorize the drugs but
then he said that he might give us a list of drugs and ask us to pick out the Class 1 drug or the Class 2 drug.)
b. Class 1 – within class one you have class 1A, 1B, and 1C
c. Class 2 – within class 2 (beta blockers) you have a non-selective beta blocker and a cardiac selective beta
blockers
d. Class 3 – you can have mixed ones or pure class 3 drugs
e. Class 4 – these are the calcium channel blockers
f. Basically all antiarrhythmic drugs they all have different actions or excitability and conductivity. The only thing
they share in common is that they will decrease automaticities.
XVIII. [S18] V. - W. Classification of Antiarrhythmic Drugs
a. Class 1 – sodium channel blockers
i. these are the ones that we were referring to when we were talking about action potentials; they block the
phase 0 or upstroke velocity of sodium
b. Class 2 – are the beta blockers
i. remember the pacemaker cells that spontaneously hyperpolarize and depolarize themselves because of
the catecholamines, cAMP, and the beta receptors
ii. beta blockers are good for atria type arrhythmias by blocking the pacemaker cells of the SA and AV nodes
iii. they block catecholamines
c. Class 3 – block the phase 3 of the action potential
i. these are potassium channel blockers
ii. these are primarily working on the ERP, the repolarization phase
d. Class 4 – include the calcium channel blockers
i. phase two is also due to calcium channels
ii. these are very good for atria arrhythmias of the SA node or AV node
XIX.
[S19] Class IA
a. The prototype of Class 1A is Quinidine. This is the very first antiarrhythmic drug that came out. Just remember
this one. All the new drugs are always compared to Quinidine (is one new drug or the other better than
Quinidine).
b. The primary mechanism of action is to block the fast sodium channel, decrease conduction. They cause sort of
a depression because they block the sodium channels. Remember phase 0 determines how fast they conduct.
When you block the sodium channel the conduction is slower.
c. So, you would decrease the dV/dt upstroke velocity of phase 0, you would increase action potential duration,
increase QRS, and you would increase your QT. QT prolongation is a big deal.
d. Remember that he wanted us to know the relationship between action potential and EKG.
e. They also block potassium channels which prolongs repolarization. Just because they do this does not mean
that they are classified with the Class 3 drugs. They primarily block the sodium channels but they have
additional effects. They also block the potassium channel which prolongs repolarization.
XX. [S20] Torsades de pointes
a. Most of the time scientists and electrophysiologists are control freaks and want to know exactly what is going on
in a situation. The only time they really throw their hands up is with torsades de pointes.
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 6 of 8
b. Torsades de pointes is a polymorphic ventricular tachycardia. When you have an arrhythmia like this you have
no idea where they come from. This really baffles scientists.
c. These patients can come in and you will be able to look at their EKG and say that they have a prolonged QT but
you can’t tell them why so it’s very hard to treat them.
d. Because of the polymorphism there is basically a 2 channel problem:
i. Inward sodium channel problem
ii. Outward potassium channel problem
e. Genetic mutations are present with this. Some patients are more vulnerable to torsades de pointes. In these
patients there is a mutation associated with these 2 channels.
f. They have also found out that a lot of different drugs and antibiotics can cause a prolonged QT interval causing
torsades do pointes.
g. So today when drugs go through their screenings, not just cardiovascular drugs this can be any drug, they have
to go through cardiovascular toxicity screenings. They screen for QT prolongations. If the drug causes
prolongation of the QT cycle the drug will be dead and will never get through the FDA.
h. Class 1 antiarrhythmic drugs can also trigger torsades de pointes because they prolong the QT. This is a major
complication with the Class 1 drugs.
XXI.
[S21] Key Facts Associated with Class IA
a. They cause cardiac depression.
b. Quinidines
i. These are orally effective and cause a marked cardiac depression
ii. You never give these in an IV (intravenous) form because you will kill the patient. If you need to give these
in an emergency situation give an IM (intramuscular) injection.
iii. They also can have anticholinergic reactions. They can cause tachycardia problems. These are side
effects.
iv. Hyperkalemia enhances action (when the patient has hypokalemia the drug is not as good)
v. Cinchonism – you always associate this as a side effect with Quinidines
1. the quinidines come from quinine which is an anti-malarial drug which is extracted from cinchona
tree bark
2. Side effects include: tinnitus, vertigo, and others are all associated with cinchonism
c. Procainamide
i. Has less anticholinergic actions so less constipation problems (anticholinergics cause a slowing of the GI
tract therefore they have a potential for constipation)
ii. They will cause tachycardia issues
iii. The metabolites will remain active longer because they have longer ½ lives
iv. Side effects include: systemic lupus and agranulocytosis (he said these were easy test questions for him to
ask)
XXII. [S22] Class IB
a. The prototype is lidocaine and local anesthetics. If you give in IV form it can be a potent antiarrhythmic drug.
b. Phenytonin is an anti-convulsant drug.
c. Tocainide is orally effective.
d. Mexiletine is also a Class 1B drug.
e. The primary mechanism of action people this is that these block the fast sodium channels but this is not actually
true. They only have moderate effects on the fast sodium channels. Most likely they decrease action potential
duration aka decrease the ERP. They also decrease the QT interval.
f. These are the least cardiac depressive. These are the ones that will not cause torsades de pointes.
XXIII. [S23] Key Facts Associated with Class IB
a. Lidocaine is the least cardiac toxic of all antiarrhythmic drugs of choice, or post MI or heart surgery.
b. They are least useful against atrial arrhythmias. They are mostly for ventricular arrhythmias.
c. Lidocaine is very limited. Quinidine on the other hand is a very broad spectrum drug and is good for
supraventricular and ventricular arrhythmias.
d. The plasma ½ life of lidocaine is about 10 minutes, but the chemical ½ life is about 2 hours. This is important
because most of the time when you use lidocaine for antiarrhythmic action you give bolus injection. You give a
bolus in the form of IV drips. You do this because they clear very fast. They also act very fast to clear
antiarrhythmic actions within minutes of administration.
i. However, if you drip over night you are giving too much lidocaine. Why? Because the tissues are taking
up lidocaine. The chemical ½ life is about 2 hours. The plasma ½ life clears very fast because it is taken
up. You have to be very careful. It might be the least cardiac toxic but you can’t just keep the patients on a
drip IV. You will get in trouble if you drip over a long time or overnight.
ii. Adverse side effects: mostly CNS related (such as seizures and twitching)
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
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e. Tocanide is the same as lidocaine except it is orally effective.
XXIV. [S24] Class IC
a. The prototype is Flecainide.
b. You will also hear about Propafenone and Moricizine. These are very limited drugs and they are very toxic.
c. Their primary action is to block the sodium channels; they block the heck out of these and can cause severe
depression.
d. They really slow conduction. When they slow conductions you create other problems. The increase the QRS
but there is no change in the QT.
e. They do not cause torsades de pointes but they may cause a reentry somewhere else.
XXV. [S25] Indications
a. These are primarily for chronic stable ventricular arrhythmias, especially those that do not respond to
conventional antiarrhythmics. These are not the front line of drugs. Class 1C is like the 2nd or 3rd line and is
used when patients don’t respond to front line drugs.
b. These are very toxic. Numerous drug interactions can precipitate congestive heart failure and proarrhythmias
(they can cause arrhythmias themselves because they are decreasing conduction velocity). Remember for
reentry to occur you have to have a circuit, a unidirectional block, and decreased conduction velocities.
c. Class 1C can eliminate the block on one side and basically shut it down, but because it decreases conduction
velocity somewhere else they are causing another circuit to fall. They shut down one area and cause
arrhythmias somewhere else. That’s why they are called proarrhythmic. The clinical trials are what showed that
these were causing people to die so they stopped them. Why does this drug stick around because they are very
effective for certain patients that don’t respond to other drugs.
XXVI. [S26] Class II Antiarrhythmic Agents
a. These are the beta blockers that are primarily block phase 4 (spontaneous depolarization of the pacemaker cell)
b. Beta-adrenergic receptors blockers.
c. Examples include:
i. Propranolol (non-selective)
ii. Metoprolol (cardiac selective)
iii. Sotalol and Atenolol
iv. Esmolol – very short ½ life of like 8-10 minutes; people say why do you even bother to have this drug; this
is used in patients in the coronary care unit with arrhythmias; this is used for very rapid acute management
d. You don’t want these hanging around too long because beta blockers ultimately inhibit the sympathetic
stimulation and can cause bradycardia. You can decrease cardiac contractility and heart rate. You especially
don’t want to use these when the heart has already failed and has problems. You don’t want to depress the
heart further.
e. You don’t’ want to use these long term.
f. They decrease AVN transmission causing (couldn’t understand this word) issues.
XXVII. [S27] Principal Usefulness
a. Used for supraventricular arrhythmias or ventricular arrhythmias that are associated with excessive
catecholamines.
b. They decrease incidences of sudden deaths after AMI.
c. Toxicities you can read yourself.
XXVIII. [S28] Class III Antiarrhythmic Drugs
a. These primarily work on the phase 3. They are mostly potassium channel modulators. They inhibit potassium
channels and prolong the ERP creating a bi-directional block.
b. The problems are the long QT syndromes causing torsades de pointes.
XXIX. [S29] Class III Antiarrhythmic Drugs (Amiodarone and Dronedarone)
a. Amiodarone is a drug of choice. It was one of the 1st drugs that came out as a class 3.
i. This is considered a very dirty drug from a pharmacological point. It not only inhibits the ERP it also has
blocks the sodium channels like class 1 and blocks the beta receptor and blocks the calcium channels.
ii. It blocks anything and this is the reason it works.
iii. Scientists like to have singe target receptors for a drug to block. When you have one thing controlled,
something else with up-regulates or compensate. The body will always play games with us. They are
finding out more and more that you need multi-target drugs like this one.
iv. This drug will knock out all types of arrhythmias: atrial or ventricular.
v. The problem is that this has a very long ½ life and lasts about a month.
vi. Because of its drug interactions it has a lot of iodine and can cause a lot of thyroid problems.
b. Dronedarone is a newer drug and is an amiodarone-like compound without the iodine (so you are not affecting
the thyroid function)
i. The ½ life is a lot more manageable.
Neuro: 11:00 – 12:00
Scribe: Brittney Wise
Friday, April 24, 2009
Proof: Laura Adams
Dr. Ku
Principles of Cardiovascular Pharmacology
Page 8 of 8
ii. They also prevent EADs associated with ERPs.
XXX. [S30] Class III Antiarrhythmic Drugs (Sotalol, Dofetilide, and Ibutilide)
a. Sotalol is a beta blocker but because it also has class 3 actions we classify it as a Class 3 antiarrhythmic drug.
It has mixed action.
b. Dofetilide and Ibutilide are the pure Class 3 potassium channel blockers. But they have very limited
interactions. When you have the pure blockers they turn out not as good. Mixed ones are more effective.
XXXI. [S31] Class IV Antiarrhythmic Drugs
a. Again, Class 4 calcium channel blockers block the phase 2 here, but predominantly because of the so-called
spontaneous depolarization cells they are very good for atrial arrhythmias (SA node and pacemaker cells).
b. These are cardiac selective ones. These are primarily used for antiarrhythmia drugs.
XXXII. [S32] Class 1 (Phenylalkylamines), Class II (Benzothiazepines), and Class III (1,4-Dihydropyridines)
a. Calcium channel blockers you will hear of Verapamil and Diltiazem. You do not see people using Nifedipine for
those arrhythmias; you will see mostly cardiac selective calcium channel blockers.
XXXIII. [S33] Principal Usefulness
a. These are good for ventricular arrhythmias or arrhythmias that are associated with acute myocardial ischemia.
b. Toxicities are all here. Constipation, heart block, heart failure, and hypotension.
XXXIV. [S34] Treatment of Torsades de Pointes
a. Torsades de Pointe: which antiarrhythmic drug will you use?
i. You cannot use Class 1 drugs because they cause Torsades de Pointes.
ii. You cannot use Class 3 drugs because they cause Torsades de Pointes.
iii. When you have these kind of problems right away you check electrolyte problems. We correct
hypokalemia and hypomagnesemia because these are the usual underlying problems.
iv. You discontinue the drugs that prolong the QT interval.
v. You can do electrical pacing or use drugs to shorten the QT interval.
vi. Not many drugs can be used to treat Torsades de Pointes.
[end 46:13min]