Drugs Used In Dysrhythmias

(A) is the correct answer. The digoxin dose needs to be halved.

This is because, similar to warfarin, there is a CYP interaction with digoxin and amiodarone. Since amiodarone will inhibit CYP enzymes and thus double the levels of digoxin in the blood, it is necessary to halve the digoxin dose.

This is clinically significant because digoxin has a low therapeutic index. It is a small target that you want to hit, and monitoring is crucial with this duo.

(D) is a false statement. And it is very false. This should be a take-home message. Amiodarone has a very LONG half-life (ranges from 35 to 110 days). That is over 3 months! This can be attributed to the fact that the volume of distribution is high (66 L/kg) and its high lipophilicity.

(A) is a true statement. Amiodarone can block sodium channels (1), block beta receptors (2), block potassium channels (3), and block calcium channels (4). You can imagine how adversely affected patients can be with amiodarone.

(B) is very true. Amiodarone is metabolized by 3A4, which is a hot-spot for many, many drugs. Examples include digoxin, warfarin, cyclosporinem and quinidine.

(C) is also very true. This is a major problem with amiodarone. It has "extra-cardiac effects". For instance, amiodarone has iodine in its structure and that can cause some thyroid issues, such as hypothyroidism. In the eyes, corneal microdeposits may occur, turning the cornea yellow. What makes this worse is that the half-life is so long (recall 35-110 days), meaning that the effects are long-lasting.

As you can imagine, monitoring with amiodarone is crucial. For instance, for the thyroid issue, you want to measure T4 and TSH at baseline and every 6 months. It isn't uncommon to see a patient on amiodarone and levothyroxine.

(D) is the false statement. Recall that beta-blockers will block the beta-receptors in the body. By doing so, the effects of norepinephrine are reduced, leading to a smaller increase in the heart rate during exercise, for example. At rest, the heart rate will be slower than normal because of the blockade of the receptors, leading to BRADYCARDIA.

(A) is a true statement because the idea is to actually slow the ventricular rate. This can be done by limiting the number of impulses that reach the AV node.

(B) is also true and is especially true for metoprolol. "Sudden death" is from ventricular abnormalities, which can be reduced in chance by blocking the proarrythmic effects of norepinephrine.

(C) is certainly true. Norepinephrine is released in the AV node to speed conduction. Beta-blockers will block the beta-1 receptors and interfere with the actions of norepinephrine. By doing so, less impulses get conducted through the AV node and help control the atrial arrythmias.

(B) is the correct answer. The warfarin dose needs to be halved.

This is because amiodarone inhibits CYP enzymes, thereby increasing the concentrations of warfarin. Therefore, it is recommended to halve these doses when co-administered.

This is a true statement.

Metoprolol, atenolol, and esmolol are indeed cardio-selective.

Propranolol and labetalol are non-selective. For instance, labetalol can block alpha-receptors.

(A) is the false statement. Recall that quinidine blocks voltage gated potassium channels, which prolongs the action potential (repolarization depends on this channel). Therefore, sodium channels stay in the inactivated state longer until the negativity of the membrane is reestablished. While this may be desired, the prolongation of the action potential means a prolongation of the QT interval, which can be deadly. A type of ventricular tachycardia, Torsades de Pointes, may terminate or lead to ventricular fibrillation, a condition where cardiac output is surely compromised.

(B) is a true statement. Procainamide is indicated for ventricular arrhythmias but the body can produce antibodies to the drug, giving rise to lupus erythematosis. This is an autoimmune syndrome where the immune system will attack healthy tissues. This is actually unique for this set of drugs.

(C) is also correct. Disopyramide can block muscarinic receptors, known as an "atropine-like" effect. Therefore, patients may feel the anticholinergic effects (faster heart rate, for example). This is a hallmark of disopyramide and quinidine.

(D) is also true. Potassium channel blockers will slow depolarization down and increase the QT interval on their own. This is disastrous with sodium channel blockers, which can also prolong the QT interval. Although the risks for both may not be 100%, the potential risk is higher when both types are co-administered. Thus, they should be avoided together.

(B) is the false statement here. Lidocaine is metabolized by the liver, and quite heavily. In fact, the maintenance dose for lidocaine must actually be reduced with hepatic dysfunction. Remember: L = lidocaine = liver.

(A) is a true statement. This is a class 1B sodium channel blocker. Another example of this is mexiletine. Mexiletine can actually be administered orally because it avoids first pass metabolism.

(C) is a true statement. Lidocaine and mexiletine are indicated for ventricular arrhythmias. In fact lidocaine is also indicated for ventricular fibrillation and pulseless ventricular tachycardia (discussed later).

(D) is a true statement. Lidocaine is lipohilic. In addition, neurons utilize electrically gated sodium channels for their own action potentials. It is in the realm of possibility that lidocaine can disrupt these channels and indeed, that is the case. These reactions include drowsiness, dizziness, and convulsions.

(A) is the false statement. Adenosine has a half-life of LESS than 10 seconds. This is necessary as adenosine would be used in an acute setting.

(B) is a true statement. SVT frequently uses the AV node as part of its reentrant pathway, which is dangerous. Adenosine can be used to help slow conduction down. This is known as "pharmacologic cardioversion".

(C) is a true statement. Theophylline is an adenosine antagonist. When adenosine is administered, there are brief periods of aystole. Therefore, it may be necessary to reverse some of the effects of using adenosine and an adenosine antagonist such as theophylline will be used.

(B) is the false statement. Despite its pros, dronedarone has some major drug interactions. Because dronedarone is a moderate inhibitor of 3A4 and an inhibitor of 2D6, it is recommended to avoid inhibitors of the 3A system. This includes cyclosporine, ketoconazole, and ritonavir. Dronedarone can also prolong the QT interval, so it is best to avoid class 1 and 2 antiarrythmics as well as tricyclic antidepressants such as amitriptyline.

Dronedarone should also be cautioned with simvastatin, which is metabolized by 3A4. It is NOT a contraindication, but simvastatin does have a stipulation. The maximum dose of simvastatin in a patient taking dronedarone is 20 mg.

(A) is a true statement. Dronedarone has a half-life of about 24 hours, which is significantly less than that of amiodarone. Recall that amiodarone's half-life ranged frmo 35-110 days.

(C) is also a true statement. Dronedarone does not have any iodine in its structure, which is good to yield less organ system toxicities. However, GI adverse effects are more common with dronedarone. This can be mitigated with food.

One last thing: you want to avoid dronedarone in severe systolic heart failure. There is an increase in mortality in patients with heart failure. Interestingly, amiodarone can be used in that setting.

The Class 1C sodium channel blockers are flecainide and propafenone.

Sotalol is a potassium-channel blocker. Diltizem is a calcium channel blocker.

An interesting pnemonic is:

Vaughan Williams - Class 1 antiarrhythmics
1A = double (disopyramide) quarter (quinidine) pounder (procainamide)
1B = lettuce (lidocaine) mayo (mexilitine) pickles (phenytoin)
1C = fries (flecainide) please (propafenone)

***Received from a resident in Fall 2013

(A) is the false statement here. These fast fibers will have a more positive membrane potential. Therefore, more sodium channels stay in the inactivated state in the damaged area and conduction will be slowed in that region.

(B) is a true statement. Sodium channel blockers do not bind to the channel in the resting state. Cells stimulated at a fast rate will be more effective for the sodium channel blockers.

(C) is true. Sodium channel blockers will bind to the sodium channel and reduce the number of channels that are capable of opening. By doing so, it will take longer for the channel to go from the inactive state to the resting state, which increases the effective refractory period. We essentially want to keep the damaged cells from conducting, as they can become an ectopic site and control the heart.

(D) is true. As you will see soon, there are sub-classes of these sodium channel blockers.

The Class 1A sodium channel blockers are quinidine, procainamide, and disopyramide.

This is a false statement. Let's delve into magnesium more.

Magnesium acts as a calcium channel BLOCKER to slow the SA node impulse. The inside of the cell is more hyperpolarized and the conduction is slowed. This is used as the DRUG OF CHOICE for Torsades de Pointes. It can also be used if there is some sort of ventricular abnormality due to HYPOmagnesemia. It fortunately has an immediate onset, which is good for that emergency situation.

(C) is the true statement here. Calcium channels will help limit impulses into the AV node. The same is true for beta-blockers. But they do this in different mechanisms. Beta-blockers will block beta-1 receptors in the AV node where as CCBs will block the calcium channels. This a synergistic effect and will allow fewer impulses through the AV node.

(A) is a false statement. Recall that the AV node (and SA node, for that matter) rely on the opening and closing of calcium channels in their slow response fibers. By blocking these channels, there are less channels participating in the action potential, slowing conduction through the AV node.

(B) is false. By slowing conduction through the AV node, it will spend more time in the refractory state, which will manifest itself as a prolongation of the PR interval on the EKG.

Remember: the NON-dihydropyridines are used here. These include diltiazem and verapmil. These do NOT include nifedipine and amlodipine.

(C) is the correct answer. The take-home message is that dofetilide MUST be dosed based on creatinine clearance.

Calculating the creatinine clearance, you will get 49.5 ml/min (rounding may result in a different value, but it should be close).

Between 40-60 (inclusive on both ends), the dofetilide dose must be 250 mcg PO BID.

For your reference...
If > 60 --> 500 mcg PO BID
If 40-60 --> 250 mcg PO BID
If 20 - 125 mcg PO BID
If Contraindicated

(B) is the correct answer. Let's delve into sotalol a little more.

Sotalol is a class 3 drug. It does have some beta-blocking effects, and it is non-selective in that regard. It can prolong the action potential due its ability to block potassium channels. Therefore, it can prolong the QT interval.

The important thing to remember is that you need to look at two things with sotalol: 1. EKG; 2. CrCl

At the end of the day, the CrCl must be looked at because sotalol is not metabolized and is renally excreted. You MUST know the creatinine clearance to dose sotalol!

This is the correct set. Sodium channel blockers will block the sodium channels to reduce the number of channels that can open and ultimately become an ectopic site.

Class 1A sodium channel blockers include procainamide, quinidine, and disopyramide, and are notorious for prolonging repolarization and thus prolonging the action potential.

Class 1B sodium channel blockers include lidocaine, mexiletine, and phenytoin.

Class 1C sodium channel blockers include flecainide and propafenone.

The Class 1B sodium channel blockers are lidocaine, mexiletine, and phenytoin