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122 Cards in this Set
- Front
- Back
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Where in the automatically firing system of cells in the heart is the depolarization most rapid?
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In the sinoatrial node.
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Which are the remaining parts of the heart which exhibit automaticity?
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Atrioventricular node, the bundle of His and the purkinje system.
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How are the arrhythmias characterized?
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According to their site of origin and type of disturbance.
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What are the causes of arrhythmias?
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Most arrhythmias arise as a result of abberrant impulse generation (impaired automaticity), or from a defect in conduction of the impulse.
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Give example of two important atrial arrhythmias.
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Atrial fibrillation and atrial flutter.
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Give examples of two important supraventricular arrhythmias.
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AV nodal reentry and acute supraventricular tachycardia
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Give examples of two important ventricular arrhythmias.
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Acute ventricula tarchycardia and ventricular fibrillation.
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What structure in the heart normally sets the pace of cardiac contraction?
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The SA node
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What are causes of abnormal automaticity?
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Abnormal automaticity may occur if myocardial cells are damaged, for example by hypoxia or hypokalemia.
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What is the effect of most antiarrhythmic agents?
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They suppress automaticity by blocking either sodium or calcium channels to reduce the ratio of these ions to potassium.
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What is reentry?
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A phenomenon which can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway.
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What is the most common cause of arrhythmias?
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Reentry
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Where do the reentries occur?
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Anyway along the cardiac conduction system.
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What effects do the antiarrhythmics have on conduction defects?
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They inhibit reentry by decreasing conduction velocity or increasing the refractory period, preventing reexitation.
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Are most antiarrhythmics useful clinically?
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No, only a few, like lidocaine for ventricular arrhythmias and adenosine or verapamil for supraventricular tachycardias.
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What is the danger with the antiarrhythmics?
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Many of the antiarrhythmics are known to have proarrhythmic properties.
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How many classes of antiarrhythmic drugs are there?
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4
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How many subclasses are there in the Class I antiarrhythmic group?
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3 subclasses, Class IA, IB and IC
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What is the mechanism of action of respective class of antiarrhythmics in the Class I?
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Class IA are sodium channel blockers
Class IB are sodium channel blockers Class IC are sodium channel blockers |
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What is the mechanism of action of the Class II antiarrhythmics?
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They are beta blockers
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What is the mechanism of action of the Class III antiarrhythmics?
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They are potassium channel blockers.
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What is the mechanism of action of the Class IV antiarrhythmics?
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They are calcium channel blockers.
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What is the effect of the class IA?
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They slow Phase 0 depolarization in ventricular muscle fibers.
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What is the effect of the class IB?
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They shorten phase 3 repolarization in ventricular muscle fibers
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What is the effect of the class IC?
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They markedly slow Phase 0 depolarization in ventricular muscle fibers.
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What is the effect of the class II?
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They inhibit Phase 4 depolarization in SA and AV node.
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What is the effect of class III?
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They prolong phase 3 repolarization in ventricular muscle fibers.
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What is the effect of the class IV?
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They inhibit action potentials in SA and AV nodes
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Why is classifying the antiarrhythmics into groups depending on their effect on the action potential not entirely clear-cut?
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Because many of them possess bridging mechanisms of action.
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Class I antiarrhythmics block Na channels in a mechanism identical to the...
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local anesthetics
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What are the different states of the voltage dependent sodium channel?
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Resting, active and inactivated
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To what state of the voltage dependent calcium channels do the class I antiarrhythmics show highest affinty?
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To the active and inactive states, not to the resting states.
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Why has the use of class I antiarrhythmics been declining?
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Because of their proarrhythmic effect.
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What does it mean that the class I antiarrhythmics are "use-dependent"?
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That they will only affect channels in the active or inactive state and not in the resting state.
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What does the use dependence translate to clinically?
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That the drugs will only affects rapidly depolarizing tissues such as tachycardic tissues, without interfering with the normally rhythmically depolarizing heart.
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What is the result of the prolonged phase 0 depolarization on the action potential?
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It is prolonged.
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Do the Class IA antiarrhythmics show any other class activity?
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Yes they show class III potassium channel blockade activity.
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What is the effect of Class IB drugs on the action potential?
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They shorten the duration by decreasing the time of repolarization.
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What is the effect of class IC agents on the action potential?
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They significantly prolong it and thus cause a marked dcrease in conduction velocity.
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What is the effect on the action potential by the Class III drugs?
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They cause a longer action potential.
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What is the effect of the Class III drugs on the ECG?
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They cause a prolonged QT segment.
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What are such ECG changes associated with?
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Prolonged QT segments are associated with life-threatening ventricular tachyarrhythmias (torsades de pointes).
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What are drugs other than the Class III antiarrhythmics which may cause a prolongation of the QT segment?
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Cisapride, grepafloxacin, terfenadine and astemizole were all withdrawn from the market beecause of this. Additionally, Erythromycin, clarithromycin, pentamidine, moxifloxacin, levofloxacin, imipramine, desipramine, amitriptyline, doxepin, thioridazine, mesoridazine, haloperidol, risperidone, ziprasidone and qutiapine are some of the many drugs known to prolong the QT segment.
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Which is the prototype Class IA drug?
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Quinidine
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Quinidine also has concomitant Class ... activity.
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III
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What types of arrhythmias may quinidine cause?
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Polymorphic ventricular tachycardia (torsades de pointes) which may degenerate into ventricular fibrillation.
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Which drugs are replacing quinidine and why?
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The calcium antagonists, such as amiodarone and verapamil, because of toxic potential of quinidine.
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What are the therapeutic uses of Quinidine?
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Quinidine is used in a wide variety of arrhythmias, including atrial, AV-junctional, and ventricular tachyarrhythmias. Quinidine is used after cardioversion to maintain sinus rhythm.
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What are the adverse effects of Quinidine treatment?
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Severe arrhythmia
SA or AV block or asystole Hyperkalemia exacerbates cardiotoxic effects. Nausea, diarrhea and vomiting. Cinchonism Positive coombs test. |
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What is cinchonism?
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It is characterized by blurred vision, tinnitus, disorientation and psychosis.
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Which are the remaining two drugs of the Class IA agents?
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Procainamide and Disopyramide
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What are the actions of Procainamide?
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Similar to those of quinidine.
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What are the side effects of Procainamide?
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After chronic use of procainamide, there are many side effects, including reversible systemic lupus erythrematosus.Toxic concentrations may cause asystole or induction of ventricular tachyarrhythmias. Central nervous syystem side effects include depression, hallucination, and psychosis. GI intolerance is less frequent than with quinidine.
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What are the differences in the effects produced by quinidine and disopyramide?
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Disopyramide causes a greater inotropic effect and causes peripheral vasoconstriction.
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What are the side effects of Disopyramide?
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Disopyramide may cause anticholinergic effects such as dry mouth, urinary retention, constipation and blurred vision.
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Which is the prototype Class IB drug?
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Lidocaine
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Which are the Class IB drugs?
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Lidocaine, Mexiletine, Tocainamide
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What is the speed of association with the sodium channels?
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The Class 1B drugs show a rapid association with active or inactive sodium channels.
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In what type of arrhythmias are the Class IB drugs especially useful?
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In ventricular tachyarrhythmias
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Which drug was the drug of choice for emergency treatment of cardiac arrhythmias?
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Lidocaine
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What are the effects of lidocaine on the action potential?
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Lidocaine decreases the duration of the action potential due to a shortened phase 3 repolarization.
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What are the therapeutic uses of lidocaine?
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Lidocaine is useful in treating ventricular arrhythmias arising during myocardial ischemia, such as that experienced during a myocardial infarction.
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Why is lidocaine not useful for treating atrial or av junction arrhythmias?
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Because lidocaine doesnt slow conduction.
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How is lidocaine administered?
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Lidocaine is given I.V because of rapid metabolism by the liver.
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Does lidocaine have a very narrow theraputic index?
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No, it shows a rather wide toxic to therapeutic index.
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Does lidocaine impair left ventricular function or have any negative inotropic effects?
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No
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What are the side effects of lidocaine?
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CNS effects such as drowsiness, slurred speech, paresthesias, agitation, confusion and convulsions. Cardiac arrhythmias may also occur as a consequence of lidocaine.
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What are the actions of Mexiletine and tocainamide?
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They show actions similar to lidocaine.
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What is the indication for mexiletine?
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Mexiletine is used for the chronic treatment of ventricular arrhythmias associated with previous MI.
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What are the indications for Tocainamide treatment?
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Ventricular tachyarrhythmias
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What class of drugs does Flecainide belong to?
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Class IC
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Which are the class IC antiarrhythmics?
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Flecainide and Propafenone
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What are their rate of dissociation from resting sodium channels?
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They show a slow dissociation from resting sodium channels.
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What implications does this have?
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The slow dissociation from the resting sodium channels causes profound effects also on the normally beating heart.
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What are the indications for the class IC antiarrhythmics? (Flecainide and Propafenone)
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They are approved for use in refractory ventricular arrhythmias and for the prevention of paroxysmal atrial fibrillation associated with disabling symptoms and paroxysmal supraventricular tachycardia.
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What is the meaning of paroxysmal?
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Spastic (a sudden appearance of something)
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Are the class IC drugs considered safe?
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No, not at all
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What are the effects of the class IC drugs on the action potential?
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Due to substantially decreased speed of phase 0 ddepolarization they prolong the action potential. This causes marked slowing of conduction in all heart tissues.
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How is flecainide administered?
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Orally
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What are the adverse effects of Flecainide?
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Dizziness, blurred vision, headache, nausea. Aggravation of preexisting arrhythmias. Induction of life threatening ventricular arrhythmias that are resistant to treatment.
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What are the actions of Propafenone?
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They are very similar to those of Flecainide.
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In what type of arrhythmias may the Class II agents be useful?
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In the trachyarrhythmias caused by increased sympathetic activity. They are also used in atrial fibrillation and flutter and for AV nodal reentrant tachycardia.
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What effects does Propranolol have on the heart rhythm of a patient who just underwent a MI?
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Propranolol reduces the incidence of sudden arrhythmic death after MI which is normally the most common cause of death in this group of patients.
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Which is the beta blocker most often used in arrhythmias?
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Metoprolol
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Which is the beta blocker we might use in acute arrhythmias?
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Esmolol intravenously
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What are the effects of the Class III antiarrhythmics on the action potential?
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They prolong the duration of the action potential by inhibiting repolarization of cells. (the refractory period)
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Which are the class III antiarrhythmics?
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Amiodarone, Sotalol and Dofetilide
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To what compound is Amiodarone structurally related and what does amiodarone contain?
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Amiodarone is structurally related to thyroxine and contains iodine.
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What are the effects of amiodarone?
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It has complex effects, showing class I, II, III and IV activity. The dominant effect however is prolongation of the action potential duration and the refractory period.
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What are the therapeutic uses of amiodarone?
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Amiodarone is effective in the treatment of severe refractory supraventricular and ventricular tachyarrhythmias.
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Which is the most commonly employed antiarrhythmic?
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Amiodarone
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Why is it strange that amiodarone is the most commonly employed antiarrhythmic?
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Because of its side effect profile.
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How is amiodarone administered?
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Orally, however absorption is incomplete.
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What is the half-life of amiodarone?
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Several weeks!
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When do full clinical effects of amiodarone treatment take effect?
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Full clinical effects may not be achieved until 6 weeks after initiation of therapy.
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What are the adverse effects of amiodarone?
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After long term use, more than half of the patients on amiodarone have so severe side effects that the drug needs to be discontinued.
Interstitial pulmonary fibrosis, Gastrointestinal tract intolerance, tremor, ataxia, dizziness, hyper- or hypothryoidism, liver toxicity, photosensitivity, neuropathy, muscle weakness, and blue skin discoloration caused by iodine accumulation in the skin. |
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What has recent clinical studies on amiodarone shown?
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That amiodarone doesn't decrese the incidence of sudden death or prolong survival in patients with CHF.
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What is special about Sotalol?
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Even though Sotalol is a Class III antiarrhythmic, it shows potent beta blocker activity. (Class II activity)
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What are the actions of Sotalol on the action potential?
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Sotalol blocks the potassium flow in the outward rectifier, which prrolongs both repolarization and the duration of the action potential.
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What are the therapeutic uses of Sotalol?
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Sotalol and other beta blockers are used for long-term therapy to reduce the rate of sudden death following a MI.
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What is positive about the side effects of Sotalol?
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Sotalol has the lowest rate of acute or longterm adverse effects of the antiarrhythmics. A serious side effect however, is torsades de pointes arrhythmias due to QT interval prolongation.
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When is Dofetilide used?
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Dofetilide can be used as a first line antiarrhythmic in patients with persistent atrial firbrillation and heart failure or in those with coronary artery disease with imparied left ventricular function.
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Can all physicians prescribe Dofetilide?
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No, only physicians who underwent the manufacturer's training session may prescribe Dofetilide.
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Which are the drugs which are recommended by experts for the treatment of atrial fibrillation in a wide range of patients?
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Dofetilide, beta blockers and amiodarone.
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What is the half life of Dofetilide?
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10 h
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Where is Dofetilide excreted?
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80% unchanged and 20% metabolites in the urine.
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What type of compounds are the Class IV antiarrhythmics?
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Calcium channel blockers
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Which are the calcium channel blockers used for arrhythmias?
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Verapamil and diltiazem
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What is the effect of the Class IV antiarrhythmics on the action potential and conduction velocity?
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They reduce the calcium current and therefore slow Phase 4 spontaneous depolarization and they also slow conduction in tissues that are dependent on calcium currents, such as the AV node.
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What is the difference between Verapamil, diltiazem and Nifedipine?
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Verapamil shows the greatest inhibition of heart calcium channels whilst Nifedipine has a greater action of the calcium channels of the smooth muscles. Diltiazem has an intermediate action on the heart and smooth muscle of the vessels.
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What type of calcium channels do these drugs preferentially bind to?
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The voltage gated calcium channels and not the ligand gated ones which are also present in the heart.
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In what state of the voltage gated calcium channels do the Class IV antiarrhythmics bind?
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In the open state.
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So the Class IV antiarrhythmics are....
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use dependent.
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What are the therapeutic uses of the Class IV antiarrhythmics?
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They are more effective against atrial than ventricular arrhythmias. They are useful in treating supraventricular tachycardias and in reducing the ventricular rate in atrial flutter and fibrillation. In addition these drugs are used to treat hypertension and angina.
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How are Verapamil and diltiazem administered?
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Per oral
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What are the adverse effects of the Class IV antiarrhythmics?
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They have negative inotropism and are therefore contraindicated in patients with preexisting depressed cardiac function (heart failure). Both drugs may produce hypotension.
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What are the other two antiarrhythmics which are not grouped in any of the four groups?
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Digoxin and Adenosine
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What is the antiarrhythmic action of digoxin?
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It shortens the refractory period in atrial and ventricular myocardial cells while prolonging the effective refractory period and diminishing conduction velocity in the AC node.
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When may we use digoxin in treating arrhythmia?
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Digoxin is used to control the ventricular response rate in atrial fibrillation and flutter.
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What are the effects of Adenosine on the hearth rhythm?
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In high doses, adenosine decreases conduction velocity, prolongs the refractory period and decreases automaticity in the AV node.
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When do we use adenosine to treat arrhythmia?
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Intravenous Adenosine is the drug of choice for abolishing acute supraventricular tachycardia.
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What are the toxicities of adenosine?
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It has rather low toxicity with flushing, chest pain and hypotension.
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