What is the most common mechanism by which impulse formation in pacemaker cells is either quickened or slowed?
Increasing or decreasing the slope of phase 4 of the action potential (the inward sodium “funny current”) will increase or decrease the rate of discharge, respectively.
Name the two basic categories of causes of arrhythmia.
1. Disturbance of impulse formation (in the pacemaker cells)
2. Disturbance of impulse conduction
In the Vaughan-Williams classification, what defines Class I drugs? What effect is made on the duration of the action potential (and thus, the refractory period) by Class IA, Class IB, and Class IC drugs, respectively?
Class I antiarrhythmics block sodium channels. Class IA prolong the action potential. Class IB shorten the action potential. Class IC have no effect on the action potential.
Give one example (or two if you can) for each of these antiarrhythmics: Class IA, Class IB, Class IC.
Class IA: Quinidine, Procainamide. Class IB: Lidocaine (Lignocaine). Class IC: Flecainide.
In the Vaughan-Williams classification, what defines Class II drugs?
Class II antiarrhythmics are β-adrenoceptor antagonists.
In the Vaughan-Williams classification, what defines Class III drugs? Give two examples of Class III drugs.
Class III antiarrhythmics are K+ channel blockers, they prolong the action potential (and thus the refractory period). e.g. amiodarone, sotalol.
In the Vaughan-Williams classification, what defines Class IV drugs? Give two examples of Class IV drugs.
Class IV antiarrhythmics are calcium channel blockers, thereby reducing automaticity and slowing conduction. e.g. Verapamil, Diltiazem.
Briefly explain the cardiac effects of amiodarone.
It is a Class III antiarrhythmic, useful in treating serious ventricular arrhythmias. It blocks K+ channels, which prolongs the action potential, slowing the heart rate, and prolonging the QT-interval.
Briefly explain some of the adverse effects of chronic amiodarone use.
The drug accumulates in many tissues, which can produce pulmonary fibrosis, reduced liver function, skin discolouration from skin deposits. Amiodarone molecules contain iodine, and can thereby affect thyroid hormone production.
What are two adverse effects that can be produced by amiodarone in patients with pre-existing SA-node or AV-node disease?
Bradycardia and heart block.
Briefly discuss the drug interactions of amiodarone.
Amiodarone is a potent inhibitor of several cytochrome p450 enzymes, which means that its administration can postpone the elimination of statins, digoxin and warfarin.
Which type of calcium channels does verapamil block?
L-type (both activated and inactivated)
What is the oral bioavailability of verapamil?
What are the cardiac effects of verapamil?
Verapamil blocks Ca2+ channels, thereby prolonging the action potentials of pacemaker cells in the SA-node and AV-node, and slowing conduction.
Name one extracardiac effect of verapamil.
Name one supraventricular arrhythmia that verapamil can convert to sinus rhythm, and name two other arrhythmias that it is much less useful in converting to sinus rhythm.
Useful: Supraventricular tachycardia. Much less useful: Atrial fibrillation, Atrial flutter.
Why is adenosine less effective in patients who have had a lot of caffeine, or theophylline?
Because caffeine and theophylline are adenosine receptor blockers.
Which parts of the heart does adenosine act on? What are the molecular effects of adenosine in cardiac tissue, which cause its therapeutic effect?
Adenosine acts on the SA-node and AV-node. Adenosine opens K+ channels, allowing the cell membrane to hyperpolarize, prolonging the action potential. Adenosine also reduces Ca2+ influx, suppressing the ability of pacemaker cells to depolarize.
What can you say about diltiazem?
Its mechanism of action and clinical applications are essentially equivalent to those of verapamil.
What is another name for lidocaine?
What effect do class IV antiarrhythmics have on myocardial contractility?
Verapamil and Diltiazem are NEGATIVE inotropes.