Term
| what is the idea behind all antiarrhythmic dugs? |
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Definition
| to decrease automaticity, decrease the phase IV slope, decrease the rate of firing, and make it more difficult to generate a new AP |
|
|
Term
| what happens during phase 0 of the cardiac AP? |
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Definition
|
|
Term
| what happens during phase 1-3 of the cardiac AP? |
|
Definition
|
|
Term
| what happens during phase 4 of the cardiac AP? how can ischemia affect this? the PNS? |
|
Definition
| automaticity, which ischemia can increase the slope of and the PNS decreases the slope of |
|
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Term
| what are the general phases of the cardiac action potential? |
|
Definition
| phase 4 (resting membrane potential subject to rapid spontaneous depolarization), phase 0 (rapid depolarization due to fast Na+ channel opening), phase 1 (inactivation of fast Na+ channels/notching due to start of K+ efflux), phase 2 (plateau due to Ca++ inward movement and K+ efflux), and phase 3 (Ca++ channels close, K+ efflux continues and finishes depolarization) |
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|
Term
| what is the pacemaker? the node of slowest conduction? area of most rapid conduction? |
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Definition
| pacemaker: SA node, slowest conduction: AV node, and fastest conduction: purkinje fibers |
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Term
| what is the effective refractory period? how do the sodium channel blockers affect this? |
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Definition
| the initial part of the AP, lasting to the end of phase 2, during which no more APs can fire. the Na+ channel blockers will increase this effective refractory period (but not the AP duration) |
|
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Term
| what is the ion gradient of the cell membrane maintained by? |
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Definition
| Na/K ATPase and Na/K exchanger (remember digitalis M/A) |
|
|
Term
| what is the key method that induces arrhythmias? |
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Definition
|
|
Term
| what is triggered automaticity? |
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Definition
| either early or late afterdepolarizations; can be due to some drugs (digitalis). they occur later on the plateau (early), and right after (late) |
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Term
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Definition
| re-entry arrhythmias/bypass tracts occur when an electrical impulse recurrently travels in a tight circle within the heart, rather than moving from one end of the heart to the other and then stopping (often due to conduction blocks due to ischemia) |
|
|
Term
| what is the cause of supraventriclar tachycardia? |
|
Definition
| ectopic foci in the atria |
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Term
| besides supraventricular tachycardia, what else can ectopic foci cause? |
|
Definition
| premature ventricular contractions |
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|
Term
| what can digitalis and come of the class 1a agents cause? |
|
Definition
| torsade de pointes - a type of ventricular tachycardia |
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Term
| what characterizes the class Ia Na+ channel blockers? |
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Definition
| class 1a, (which also have significant effect on blocking K+ channels, increasing the refractory period, making it more difficult to fire another AP - QT is enhanced) |
|
|
Term
| what characterizes the class Ib Na+ channel blockers? |
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Definition
| class Ib does not block K+ channels, and therefore do not increase the AP duration. they do however increase the effective refractory period (more difficult to fire an AP due to the binding of the Na+ channel) |
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Term
| what characterizes the class Ic Na+ channel blockers? |
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Definition
| class Ic are not used often. they are more similar to Ib in that they will not increase the QT interval, but they do block the K+ channel more than Ib (decrease the phase upstroke and the slope of phase 4) |
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Term
| how do beta blockers (class II) function as anti-arrhythmics? |
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Definition
| beta blockers bind to the beta adrenergic receptors antagonistically, activate cAMP which phosphorylates PKA, which phosphorylates Ca channels, keeping them open, and decreasing automaticity via decreasing the phase 4 slope |
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|
Term
| what do K+ channel blockers (class III ) do? |
|
Definition
| increase the action potential duration |
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|
Term
| what do the Ca+ channel blockers (class IV) do? |
|
Definition
| decrease the phase 4 slope |
|
|
Term
| what is the action of adenosine? |
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Definition
| adenosine increases the diastolic potential and opens K+ channels |
|
|
Term
| what is the resting state of Na+ channels? open/activated? inactivated channel? |
|
Definition
| resting: no ion movement, open/activated: Na+ in, inactivated channel: no ion conduction |
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|
Term
| how does HR affect the level of drug block (use dependent blockade)? |
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Definition
| the more the channel is activated, the greater the drug block - therefore antiarrhythmic effects are increased with increased HR |
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|
Term
| what do antiarrhythmics have a high/low affinity for respectively? |
|
Definition
| antiarrhythmics have a high affinity for activated/inactivated channels and little affinity for resting/closed channels |
|
|
Term
| what is the progression of Na+ channel activation throughout the AP? |
|
Definition
| resting -> activated -> inactivated |
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|
Term
| what state of Na+ channels do class Ia drugs such as quinidine prefer? |
|
Definition
|
|
Term
| what state of Na+ channels do class Ib drugs such as lidocaine prefer? |
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Definition
|
|
Term
| what state of Na+ channels do class Ic drugs such as flecainide prefer? |
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Definition
|
|
Term
| what is the effect of Na+ channel blockers on the cardiac AP? |
|
Definition
| decreased phase 4 slope and increased threshold (for firing) |
|
|
Term
| what are the class Ia Na+ channel blockers that we need to know? |
|
Definition
| quinidine, procainamide, and disopyramide |
|
|
Term
| what is the effect of quinidine, procainamide, and disopyramide administration? |
|
Definition
| the class Ia drugs block Na+ channels mostly in phase 0 (open state) *prolong the refractory period AND block K+ channels. there is decreased excitation, conduction, automaticity, and increased repolarization |
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|
Term
| what may increase the toxicity of class Ia Na+ blockers? |
|
Definition
| hyperkalemia may increase toxicity - if with much extracellular K+, it may keep the drug around longer (counteracts effects) |
|
|
Term
| how do class Ia Na+ blockers affect EKGs? |
|
Definition
| the QRS and QT will be increased. the class Ia Na+ blockers, mostly disopyramide, can have anticholinergic effects on the vagal control of the heart - leading to an initial increase in HR |
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|
Term
| what are the class Ia Na+ blockers used for? |
|
Definition
| supraventricular (AV node and above) and ventricular arrhythmias |
|
|
Term
| what is quinidine used for? does it have any adrenergic effects? |
|
Definition
| supraventricular and ventricular arrhythmias. quinidine does have some alpha blocking activity, and can cause hypotensive effects, esp with IV admin |
|
|
Term
| what are ADRs associated with quinidine? |
|
Definition
| **hearing effects (cinchonism), torsade de pointes (can be induced due to prolonged QT), dizziness/fainting at higher doses, thrombocytopenia, hepatitis, and **decreased digoxin clearance** (competes in the kidney), GI disturbances |
|
|
Term
| how does procainamide compare to quinidine? what is unique about its metabolites? |
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Definition
| similar cardiovascular effects, but less of a hypotensive effect due to a lack of an alpha blocking component. it's metabolite, NAPA is a class III antiarrhythmic (blocks K+ channels), which adds to the inherent class Ia K+ blocking characteristic |
|
|
Term
| what are ADRs associated with procainamide? |
|
Definition
| it can induce a **lupus-like blood disorder (rash/fever/hep/arthralgia), cardiac and CNS depression, and can be proarrhythmic |
|
|
Term
| when is disopyramide used? |
|
Definition
| as a second line drug, as it has the highest anticholinergic effect - caution in use w/elderly (particularly those with glaucoma) |
|
|
Term
| what are ADRs associated with disopyramide? |
|
Definition
| cardiac depression, prolonged QRS/QT intervals, proarhythmia, and high anticholinergic effects |
|
|
Term
| what is the main effect of class Ib/lidocaine administration? |
|
Definition
| a decrease in excitability, phase 4 automaticity and afterpotentials. it has a preference for inactivated Na+ channels, particularly ischemic and rapidly driven cells and minimal K+ blocking effects. |
|
|
Term
| what parts of the AP/EKG are affected by class Ib/lidocaine? |
|
Definition
| automaticity, QT and AP duration are decreased, ***ERP is increased |
|
|
Term
| what are class Ib/lidocaine used for? |
|
Definition
| paraenterally (high 1st pass metabolism) for ventricular arrhythmias due to MI or ischemia |
|
|
Term
| what are ADRs associated with lidocaine? |
|
Definition
| cardiac depression (will temporarily flatline the heart), bradycardia/asystole with high doses. CNS stimulant at high doses |
|
|
Term
| what are oral versions of lidocaine? |
|
Definition
|
|
Term
| what are the class Ic/flecainide Na+ channel blockers used for? |
|
Definition
| flecainide is used in a limited fashion, only for serious supreventricular and life-threatening ventricular arrhythmias/paraoxysmal a fib. flecainide has a marked depolarization decreasing effect, esp w/His-pj sys > AV node |
|
|
Term
| what is the effect of class Ic/flecainide administration? ADRs? |
|
Definition
| increased PR, QRS - no effect on QT. negative inotropic, possibly can cause CHF and lethal arrhythmias. also blurred vision, dizziness, headache, CHF, bradycardia, and neutropenia. chronic flecainide administration has been linked to increased risk of mortality |
|
|
Term
| what are other versions of flecanimide? |
|
Definition
| other class Ic drugs are profenone and moricizine |
|
|
Term
| when used as an antiarrhythmic, lidocaine typically ___________? |
|
Definition
| reduces abnormal automaticity |
|
|
Term
| what is a risk with drugs that prolong the QT interval? |
|
Definition
| they can expose you to other possible arrhythmias |
|
|
Term
| what is the effect of the beta blockers? |
|
Definition
| they decrease the automaticity/phase 4 slope by decreasing Ca++ influx - slows conduction |
|
|
Term
| what are the selectivities of the 4 antiarrhythmic beta blockers? |
|
Definition
| propanolol - beta 1&2, esmolol, acebutolol, and metoprolol - beta 1 |
|
|
Term
| what is one of the main indications for using beta blockers? |
|
Definition
| to prevent recurrent MIs/sudden death in pts recovering from acute MIs |
|
|
Term
| what is esmolol used for? |
|
Definition
| emergency IV tx of atrial flutter/fib/sinus tach, to decrease ventricular rate - short half life |
|
|
Term
| what is the effect of class III/K+ channel blockers on the cardiac AP? |
|
Definition
| keeping the cell from releasing K+ keeps it positive longer, and thus unable to repolarize as quickly, ultimately lengthening the AP *increasing the QT interval* (thus inherent arrhythmic risk) |
|
|
Term
| what are the class III/K+ blocker drugs? |
|
Definition
| sotalol, bretylium, ibutilide, and dofetilide |
|
|
Term
| what is sotalol? what is its main indication? |
|
Definition
| a nonselective beta blocker w/class III properties (increased refractory period). it is indicated for ventricular arrhythmias, and is usually well tolerated even w/its risk of arrhythmia (can be used as maintenance) |
|
|
Term
| what is bretylium? what is it indicated for? |
|
Definition
| a class III drug that also depletes neuronal release of catecholamines, increasing refractory period and AP - used IV for emergency V fib tx |
|
|
Term
| what is ibutilide? what is it indicated for? |
|
Definition
| a class III drug used IV for A fib/flutter (not used for maintenance) |
|
|
Term
| what is dofetilide? what is it indicated for? |
|
Definition
| class III drug used PO for sinus rhythm maintenance of A fib (used inpatient due to proarrhythmic risk) |
|
|
Term
| what is amiodarone? what is it indicated for? |
|
Definition
| a class III drug that contains iodide and is a structural analog of thyroxine (can mess with thyroid). it has a marked effect to increase the refractory period, increase the effective refractory period, and AP duration (increase PR, QRS, and QT) - has class I, II, and IV effects. its main indication is superventricular arrhythmias, but it does have wider usage |
|
|
Term
| what is the onset of amiodarone? ADRs? |
|
Definition
| amiodarone has slow onset and long half life. it deposits in the eyes/skin as blue discoloration, can cause **pulm fibrosis (irreversible)**, GI/liver disturbances, neurologic, thyroid dysfunction, cardiac problems (brady/CHF/hypotension). it inhibits DMMS and increases conc/tox of most antiarrhythmic drugs, digoxin, and warfarin |
|
|
Term
| what are the class IV agents? |
|
Definition
| the Ca++ channel blockers, which have a very similar effect to the beta blockers - as they decrease automaticity |
|
|
Term
| what are the class IV drugs used as antiarrhythmics? what is their main indication? M/A? |
|
Definition
| Ca++ blockers verapamil and diltiazem are indicated for superventricular arrhythmias and slow the sinus rate, AV conduction and increase the PR interval for **A fib/flutter |
|
|
Term
| what is the effect of class IV agent administration? |
|
Definition
| decreased myocardial contractility with increased dose and decreased phase 2 plateau |
|
|
Term
| what are ADRs associated with class IV agents? |
|
Definition
| GI (constipation with verapamil), hypotension, decreased HR rate, *AV block, and CHF potential |
|
|
Term
| what is a caution for use of Ca++ blockers and beta blockers at the same time? |
|
Definition
|
|
Term
| when is adenosine used as a antiarrhythmic? what does it do? |
|
Definition
| emergency situations; adenosine makes the resting potential more negative and increases maximum diastolic potential - which slows the development of APs |
|
|
Term
| what is the primary mechanism associated with adenosine? |
|
Definition
| adenosine stimulates the P-1 purigenic receptor to open K channels = **hyperpolarization of the membrane, decreased Ca++ influx. this results in decreased automaticity/conduction through the *AV node* |
|
|
Term
| what are some ADRs associated with adenosine? |
|
Definition
| vasodilator, may cause some flushing/hypotension, brief bronchospasm |
|
|
Term
| when is magnesium used as an antiarrhythmic? |
|
Definition
| it is adm IV for torsades de pointes and digitalis-induced ventricular arrhythmias (as well as arrythmias associated with Mg deficiency) |
|
|
Term
| what is a good acute anti-AV node arrhythmic? |
|
Definition
|
|
Term
| what is a specific ADR associated with verapamil? |
|
Definition
|
|
Term
| does lidocaine block K+ channels? |
|
Definition
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