Term
Sing Vaughan Willliams
Classification
of
Antiarrhythmic Drugs
Class I |
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Definition
Na Channel Blockers
Effective in fast-response cells,
but not in SA or AV nodal cells
threshold for excitation
¯ responsiveness
¯ conduction velocity |
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Term
Williams
Classificiation
of
Antiarrhythmic
Class IA
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Definition
Prolong repolarization
medium-affinity block of Na and K channels
(Class III effects)
↑QRS & QT |
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Term
Williams
Classificiation
of
Antiarrhythmic
Class IB |
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Definition
Shorten repolarization
Na channel blockade
low-affinity block
use-dependent block
↓QT |
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Term
Williams
Classificiation
of
Antiarrhythmic
Class IC |
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Definition
Small effect on repolarization
Na channel blockade
high-affinity block
↑ QRS
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Term
Williams
Classificiation
of
Antiarrhythmic
Class II |
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Definition
Beta Blockers
blocks sympathetic stimulation
¯ AV conduction,
¯ HR,
¯ Ca overload,
¯ triggering by DAD
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Term
Williams
Classificiation
of
Antiarrhythmic
Class III |
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Definition
Prolong repolarization
K channel blockade
slows repolarization,
AP duration,
refractoriness
↑QT |
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Term
Williams
Classificiation
of
Antiarrhythmic
Class IV |
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Definition
Ca channel blockade
Effective in slow-response cells—SA and AV nodes.
¯ responsiveness.
¯ AV conduction, ¯ DAD.
refractoriness
uncouple ventricular rhythm
from atrial arrhythmia |
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IA
Quinidine |
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Definition
a-block, vagolytic ( AV conduction),
high risk of torsades de pointes
GI disturbances--diarrhea
Cinchonism
(tinnitus, headache, nausea, dizziness)
hypersensitivity reactions |
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IA
Procainamide |
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Definition
Ganglionic block—vasodilation
Lupus-like syndrome
CNS, GI disturbance |
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IA
Disopyramide |
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Definition
Antimuscarinic, decreases contractility
Greater anti-muscarinic action than quinidine
(very dry mouth) |
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IB
Lidocaine |
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Definition
I-V only,
rapidly distributed/metabolized,
strong use-dependent block,
may increase mortality after MI
Neurologic effects same as local anesthetics,
both CNS depression and stimulation |
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IB
Mexiletine |
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Definition
ongener of lidocaine with less first-pass metabolism
—can be given orally
CNS effects,
GI disturbance
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IC
Propafenone |
|
Definition
derivative of propanolol
7% of caucasians and African Americans
do not have the P450 2D6 enzyme
required for metabolism |
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class III
Amiodarone
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Definition
pulmonary fibrosis (can be fatal); phospholipidosis
affects metabolism of many other drugs
thyroid, hepatic dysfunction
CNS disturbance
Photosensitive reactions
C/I
Sinus or AV node dysfunction
lung disease
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
MISC
Digitalis |
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Definition
increases phase 4 slope and automaticity; “vagotonic” actions: hyperpolarization, shortened atrial action potentials, increased AV node refractoriness; no risk of AV block; produces DADs
hyperkalemia
GI disturbance
C/I
Sinus or AV node dysfunction
WPW (with atrial fibrillation)
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class III
Dronedarone |
|
Definition
Derivative of amiodarone,
but lacks iodine moieties,
is less lipophilic,
and is eliminated more rapidly
|
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class III
Dofetilide |
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Definition
very selective for K channels,
risk of torsades
prolonged QT interval |
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class III
Ibutilide |
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Definition
prolonged QT interval
not used orally,
high risk of torsades de pointes |
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IV
Verapamil |
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Definition
helps suppress DADs.
Negative inotropy limits use in the diseased heart,
hypotension
C/I
Sinus or AV node dysfunction
constipation
WPW (with atrial fibrillation) |
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class IV
Diltiazem |
|
Definition
helps suppress DADs.
Negative inotropy limits use in the diseased heart,
hypotension
C/I
Sinus or AV node dysfunction
WPW (with atrial fibrillation) |
|
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Term
Mechanisms & Specificity
Extra-Cardiac effects and toxicity
Antiarrhythmic Drugs
Class misc
Adenosine |
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Definition
naturally-occurring nucleoside that binds to a G-protein coupled receptor (P1);
half-life of <10 seconds; given as a large bolus I-V;
opens the same K channel opened by muscarinic M2 receptors;
directly inhibits AV nodal conduction ;
blocked by caffeine |
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Term
Disorders of
Impulse
generation |
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Definition
Sick sinus syndrome—alternating periods of bradycardia and tachycardia that are unaffected by high doses of atropine.
Ectopic pacemakers—impulses initiated at locations other than the SA node, usually occurring in diseased tissue. Can include the A-V node, Purkinje fibers or contractile fibers. SA node is normally the pacemaker because it has the highest rate of spontaneous depolarization, but other loci can become faster and assume the pacemaker role.
increased automaticity at ectopic locations can take over from normal SA rhythm.
normal automaticity at ectopic locations can take over from pathologically-slowed SA rhythm |
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Term
Disorders of
Impulse
Conduction |
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Definition
Reentrant signals
Signals that reenter a recently excited region of tissue, creating autonomous loops of excitation
Anatomically defined: Accessory pathways (Wolff-Parkinson-White)
Functionally defined: loops created by a combination of (1) uni-directional block of conduction; and (2) slowed conduction.
Triggered signals
Early afterdepolarization (EAD) is a spontaneous depolarization that occurs during the latter part of the repolarization. EADs become more frequent when the duration of the action potential (QT interval) is lengthened. A frequent cause of torsades de pointes.
Delayed afterdepolarization (DAD)
is a spontaneous depolarization that occurs after an action potential is complete. Probably caused by Ca overload and activation of Na/Ca exchanger.
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