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29 Cards in this Set
- Front
- Back
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Describe Class II antiarrhythmic drugs
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-Beta-adrenergic blockers
-Have antiarrhythmic actions because they prevent the arrhythmia-inducing effects of the sympathetic nervous system (among these are the sympathetic induced increases in automaticity of the sinus node as well as ectopic pacemakers which are beta1 effects) |
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What is the protypical class II antiarrhythmic drug?
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Propranolol
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What does propranolol block?
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Beta1 and Beta2 receptors
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Describe the effects of propranolol on atrial arrhythmias
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-Effective against those atrial arrhythmias that result from sympathetic nervous system activation and that might occur during exercise or periods of emotion or stress
a) Inappropriate sinus tachycardia b) Paroxysmal atrial tachycardia (due to sympathetic activation) c) Paroxysmal atrial flutter and fibrillation (due to sympathetic activation) (rhythm control) d) Propranolol can reduce the ventricular rate during atrial fibrillation without affective the fibrillation (rate control). It does this by prolonging AV nodal refractory period |
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Describe the effects of propranolol on ventricular arrhythmias
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-Effective against ventricular arrhythmias that result from activation of the sympathetic nervous system (arrhythmias associated with exercise, anesthesia, pheochromocytoma, thyrotoxicosis)
-Propranolol ususally not effective in the treatment of arrhythmias associated with organic heart disease that are not caused by sympathetic activity -Some ventricular arrhythmias associated with acute myocardial infarction may be caused at least partly, by increased sympathetic activity -A beta blocking drug is used in this intensive care setting |
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Describe the use of Propranolol in the prevention of sudden cardiac death
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-Most often associated with ischemic heart disease and results from ventricular fibrillation
-Patient at high risk are those who have had and survived an acute myocardial infarction -Prophylactic therapy with beta-receptor blocking drugs following infarction, following discharge from the hospital, significantly reduces the incidence of sudden death (an exception to the rule that chronic antiarrhythmic drug therapy does not decrease sudden cardiac death) -Mechanism of action for this effect is not completely understood -May be due to suppression of potential life-threatening arrhythmias caused by catecholamines or by decreasing oxygen utilization |
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Describe the effect of propranolol on the ECG
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Sinus rate: Therapeutic concentrations slow sinus rate; toxic concentrations may cause severe sinus bradycardia
PR interval: Therapeutic concentrations prolong the PR interval by slowing conduction through the AV node; toxic concentrations may exaggerate this effect and cause heart block QRS duration - Usually no effect in therapeutic or toxic concentrations. Beta blockers do not cause ventricular arrhythmias by depressing conduction in the ventricles QT interval- No effect; ventricular arrhythmias are not produced |
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Describe the administration and elimination of Propranolol
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i. Propranolol can be administered orally or IV
ii. Propranolol metabolism and excretion. 70-100% of a dose is metabolized by the liver; less than 1% is excreted unmetabolized by kidney |
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Describe the toxic effects of propranolol
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Major undesirable effects are on the cardiovascular system and are attributable to sympathetic blockade
i. Depression of myocardial contractility, precipitation of congestive heart failure can sometimes occur ii. Effects of electrical activity of heart iii. Hypotension |
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What do Class IV antiarrhythmic drugs block?
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L-type Calcium Channels
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Describe Class IV antiarrhythmic drugs
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-L-type Ca channel blockers
-Drugs act by reducing Ca influx through the membranes of cardiac, smooth muscle and nerve cells -Site of action is the L-type voltage-gated Ca2+ channel -There are 9 Ca channel blocking drugs currently approved for use in the US |
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What are the important Class IV drugs?
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Verapamil - a phenylalkylamine derivative of papaverine
Diltiazem - a benzothiazepine |
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What are the 3 major classes of class IV drugs
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Phenylalkylamines
Dihydropyridines Benzythiazines |
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Describe the differences in Class IV drugs
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-Drugs differ in their pKa's and thus their extent of protonation
-At physiological pH, verapramil is almost completely protonated (+ charged), diltiazem is partly charged, while nifedipine is neutral -Differences in charge affect the ease with which the three drugs cross cell membranes and bind to ion channels -All drugs cause vasodilation because of their action of smooth muscle, and are used to decrease peripheral resistance -Only verapamil and diltiazem have antiarrhythmic effects |
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Describe use dependence of Class IV drugs
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-Related to drug protonation (charge)
-Charged drug cannot get to receptor site on the IC aspect of the channel unless the channel is opened -With each action potential (depolarization of the channel) the drug enters the channel and block accumulates -Uncharged (neutral drugs) can enter the cell by diffusing through the lipid membrane to the receptor on the inside of the channel and do not require the channel to open repetitively (little or no use dependence) -This property is called "tonic block" -Verapramil has greater use dependent effects than nifedipine and nifedipine has greater tonic block than verapamil |
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Describe the binding of calcium channel blocking drugs to the calcium channel
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-All calcium channel blocking drugs bind preferentially to calcium channel in the inactive state
-Preferential block of the inactivated Ca channel slows its recovery from inactivation -This has the greatest effect in the AV node of the heart where refractory period is prolonged -In working ventricular or atrial muscle, refractory period is not importantly affected |
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Describe tonic block and use-dependent block of verapamil
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-Shows little tonic block (because it is protonated)
-Prominent, use-dependent block -The occurrence of use-dependence block plays an important role in its antiarrhythmic properties |
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Describe tonic block and use-dependent block of nifedipine
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-Large component of tonic block (because it is not ionized)
-It shows use-dependent block only at high frequencies -There is a relative lack of use-dependent properties is one reason why it does not have efficacy as an antiarrhythmic drug -Tonic block is strongest at depolarized levels of membrane potential -Therefore, nifedipine's tonic block is more prominent in smooth muscle than in working ventricular or atrial muscle |
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Describe the characteristics of Diltiazem
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-Has characteristics intermediate between these extremes with some tonic and some use-dependent block
-Since it does have use dependent properties, it can be an effective antiarrhythmic drug |
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Describe the charge, use-dependent block, tonic-block, and tissue of verapamil
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Charge: +++
UDB: +++ TB: - Tissue: Heart S.M. |
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Describe the charge, use-dependent block, tonic-block, and tissue of diltiazem
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Charge: +
UDB: ++ TB: + Tissue: Heart S.M. |
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Describe the effects of Class IV drugs on the sinus node and sinus tachycardia
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-Not effective since they have only modest direct effect on sinus node cells in therapeutic concentrations to slow the rate of sinus node impulse initiation
-The sinus node has a depolarization phase dependent on L-type calcium current -Calcium channel blockers have little effect on sinus node in therapeutic concentrations because the molecular composition of sinus node calcium channels is different than in AV node or ventricular -In situ the direct effects on the sinus node are partly overcome by the baroreceptor reflex; enhanced sympathetic activation to the sinus node as a result of peripheral vasodilation |
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Describe the effects of Class IV drugs on the AV node and supraventricular (AV nodal reentrant) tachycardia
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-Verapamil and diltiazem are effective for the treatment of supraventricular tachycardia that is caused by AV nodal reentry
-Verapamil and diltiazem in therapeutic concentrations, slow conduction in AV node and prolong the PR interval by reducing the rapidity of depolarization and the amplitude of the action potential -Also increase the duration of the AV nodal effective refractory by prolonging the time required for the L-type Ca channel to recover (removal of inactivation) after an action potential -Can transiently block conduction in the AV nodal segment of the reentrant pathway, terminating the persistent reentry that causes this arrhythmia -Transient block in the AV node at rapid rates is a result of drug use-dependent blocking effects on AV node -When the arrhythmia stops and normal heart rate is reestablished, block of the Ca channels diminish and normal AV nodal conduction is restored -Nifedipine and other dihydropyridines do not have significant effects on the AV node -Although they weakly block the Ca current, the baroreceptor reflex completely overcomes this and therefore, they are not effective against this arrhythmia |
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Describe the effect of Class IV drugs on atrial flutter and fibrillation
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-Verapamil and diltiazem (but nifedipine and other dihydropyridines) slow the ventricular response during atrial flutter or fibrillation by causing increased conduction block of atrial impulses in the AV node without converting the atrial arrhythmia to sinus rhythm.
-Used to control the ventricular rate (rate control) |
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Describe the effect of Class IV drugs on ventricular arrhythmia
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-Calcium channel blockers are not effective in the treatment of ventricular arrhythmias
-Drugs decrease L-type Ca current during the plateau phase of the ventricular muscle action potential which decreases its positivity and which decreases muscle contractile force -Action potential duration and refractory period are not significantly changed |
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Describe the effects of Class IV drugs on the ECG
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Sinus rate - Verapamil and diltiazem slow sinus rate slightly in therapeutic doses. Direct slowing effect partly overcome by baroreceptor reflex from vasodilation
AV node- Verapamil and diltiazem prolong PR interval and prolong AV nodal refractory period QRS and QT - Verapamil and diltiazem do not significantly affect conduction and repolarization in ventricular muscle |
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Describe the toxic effects of Class IV drugs
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Effects on the heart include sinus bradycardia, AV block, weakened ventricular contraction (heart failure)
Vasodilation and hypotension |
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Describe the absorption, fate, and excretion of verapamil
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1. Peak effect in 10-15 minutes on IV injection or 1-2 hours on oral administration
2. 20% bioavailability of oral drug 3. Extensively metabolized by liver |
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Describe the absorption, fate, and excretion of diltiazem
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i. IV and oral preparations (50% bioavailability)
ii. Metabolized in liver |
