Term
| what is the basis for normal cardiac rhythm? |
|
Definition
1. conduction occurs over a predetermined path
2. refractory period permits orderly conduction of depolarizing impulses
3. single pacemaker discharging at the highest frequency dominates - usually SA node |
|
|
Term
| what are conditions that tend to be pro-arrhythmic? |
|
Definition
1. shortening of AP duration and refractory period
2. slowing conduction
3. marked dispersion in the recovery of the refractory period |
|
|
Term
| what defines resting potential? |
|
Definition
open K channels
Na channels are closed at rest |
|
|
Term
| anti-arrhythmic drugs function as? |
|
Definition
| ion transporters - Na, K, Ca |
|
|
Term
| what is the resting membrane potential of a normal cell? |
|
Definition
|
|
Term
| the resting membrane potential is established by? |
|
Definition
| Nernst equation - taking into consideration the channels that are open, namely the inward rectifier K |
|
|
Term
| what is the Nernst equation? |
|
Definition
|
|
Term
| what is threshold of an AP? |
|
Definition
voltage at which Na channels open
Na is rapidly influxed |
|
|
Term
| what is phase 0 of an AP? |
|
Definition
rapid influx of Na after threshold is reached
channels close rapidly |
|
|
Term
|
Definition
| rate at which the influx of Na occurs during phase 0 of the AP |
|
|
Term
| what are the 3 states a Na channel can be in? |
|
Definition
resting
activated
inactivated |
|
|
Term
| status of the Na channel at rest? |
|
Definition
| m subunits block channel and prevent Na from entering the cell |
|
|
Term
| what happens to Na channel upon activation? |
|
Definition
| threshold is reached --> m subunits change conformation --> rapid Na influx |
|
|
Term
| what is Vmax dependent on? |
|
Definition
| depends on amount of active Na channels - the more active channels, higher the Vmax |
|
|
Term
| how is Na channel inactivated? |
|
Definition
| h subunit blocks channel and Na can no longer enter the cell |
|
|
Term
| during what phase of the AP does recovery of Na channels occur? |
|
Definition
|
|
Term
| what is recovery of Na channels and what is it dependent on? |
|
Definition
when Na channel moves from inactivated to resting state
voltage gated phenomenon |
|
|
Term
| how is Vmax dependent on Na channels? |
|
Definition
| the more Na channels in resting state prior to stimulation (the more negative the voltage) = higher Vmax |
|
|
Term
| how do anti-arrhythmic drugs slow conduction? |
|
Definition
change % of Na channels in resting state
less Na channels to be activated = decreased conduction of AP |
|
|
Term
| what happens during phase 2 of AP? |
|
Definition
Ca influx through L-type channels
responsible for contraction |
|
|
Term
| what happens during phase 3 of the AP? |
|
Definition
K channels open - K is effluxed from the cell
Na channels shift from being inactive to resting |
|
|
Term
| what happens at the END of phase 3 of the AP? |
|
Definition
| Na is low in the cell, K is high outside - Na/K ATPase kicks in to remove Na in exchange for K |
|
|
Term
| what are the characteristics of a Purkinje fiber AP? |
|
Definition
very rapid upstroke
well defined plateau
distinct rate of diastolic depolarization |
|
|
Term
| what is characteristic about atrial cells AP? |
|
Definition
|
|
Term
| what is characteristic of the SA node AP? |
|
Definition
rapid rate of phase 4 depolarization
slow upstroke (phase 0) |
|
|
Term
| what is the ability of a cell to alter its resting potential to the excitation threshold without the influence of an external stimulus? |
|
Definition
|
|
Term
| why does lidocaine have no effect on atrial cells? |
|
Definition
they have a short AP
only works on cells that have long AP |
|
|
Term
| which cells have rapid upstroke (phase 0) in their AP? |
|
Definition
|
|
Term
| which cells have rapid phase 4 depolarization? |
|
Definition
SA node - move from resting to threshold fairly readily
basis of automaticity |
|
|
Term
| enhanced automaticity is a mechanism of what? |
|
Definition
|
|
Term
| QT prolongation on EKG is representative of what? |
|
Definition
| prolongation of AP of ventricles |
|
|
Term
| PR prolongation on EKG is representative of what? |
|
Definition
| prolongation of AP of atrium |
|
|
Term
| upstroke of the AP is driven by what? |
|
Definition
opening of Na channel
open for a short time then become inactive until reach a certain voltage |
|
|
Term
Na channels going from their inactive to resting conformation is dependent on what?
this happens in what phase of the AP? |
|
Definition
|
|
Term
|
Definition
| by changing conduction of Na |
|
|
Term
| slow response cells are driven by what ion? |
|
Definition
|
|
Term
slow response cells are located where in the heart?
their activation is dependent on what rather than voltage? |
|
Definition
|
|
Term
| what 2 effects do Na channel blockers have that allow them to work as anti-arrhythmic drugs? |
|
Definition
1. raises threshold
2. decrease Vmax - less Na channels are in resting state |
|
|
Term
how do Na channel blockers increase threshold?
a. shift the time dependence of the refractory period
b. bind to the active site of Na channel and completely prevent Na channel from opening
c. shift the voltage at which the Na channels become active
d. increase Vmax
e. reduce resting potential |
|
Definition
c. shift the voltage at which the Na channels become active
Na channel blockers effect the number of active Na channels and decrease Vmax
resting membrane potential - determined by K |
|
|
Term
| phase 0 is driven by sodium in what cells? |
|
Definition
|
|
Term
| why is phase 3 (repolarization phase) of fast responders important? |
|
Definition
| because Na channels are activated during this phase |
|
|
Term
| what is the basis behind Na channel blockers anti-arrhythmic action? |
|
Definition
| they change the voltage at which Na channels recover --> increase threshold and reduce Vmax |
|
|
Term
| slow responders are more dependent on ___ for depolarization and their recovery from inactivation is dependent on ____. |
|
Definition
Ca
time rather than voltage |
|
|
Term
| what accounts for Ca channel blockers actions as anti-arrhythmic agents? |
|
Definition
they prolong refractory period and slow conduction
also accounts for their side effects |
|
|
Term
| how does sympathetic stimulation increase HR? |
|
Definition
| increases phase 4 depolarization in SA node |
|
|
Term
| how does parasympathetic stimulation decrease HR? |
|
Definition
affects K channels --> lowers resting membrane potential --> voltage has to increase farther to reach threshold
doesn't change phase 4 |
|
|
Term
| what are the 3 mechanisms of arrhythmias? |
|
Definition
1. abnormal impulse generation - abnormal automaticity or triggered activity
2. abnormal impulse conduction - slowing or block; unidirectional block
3. abnormal rate |
|
|
Term
| what are 3 ways automaticity can be altered to induce arrhythmia? |
|
Definition
1. change resting potential - move farther to reach threshold
2. change threshold potential - higher (slower rate)
3. change phase 4 depolarization - increase rate because reach threshold sooner |
|
|
Term
| how are B-adrenergic blockers used to reduce enhanced automaticity? |
|
Definition
| block SNS increases in phase 4 depolarization |
|
|
Term
| how are Na channel blockers used to reduce enhanced automaticity? |
|
Definition
| decreases active Na channels --> increases threshold --> blocks ectopic beat |
|
|
Term
| how are vagal effects used to reduce enhanced automaticity? |
|
Definition
|
|
Term
| how are K channel blockers used to reduce enhanced automaticity? |
|
Definition
| prolong refractory period (phase 3) - prolong AP effect |
|
|
Term
| what are 4 ways to reduce enhanced automaticity? |
|
Definition
1. decrease phase 4 slope - B blocker
2. increase threshold - Na channel blocker
3. increase maximum diastolic potential - vagal effector
4. increase AP duration - K channel blocker |
|
|
Term
which drugs are capable of blocking ectopic beats?
a. Na channel blockers
b. K channel blockers
c. B-adrenergic receptor antagonists
d. all of the above are correct
e. none of the above are correct |
|
Definition
| d. all of the above are correct |
|
|
Term
| what is the term for when a normal AP is interrupted by an abnormal depolarization? |
|
Definition
| after-depolarization - can be delayed or early |
|
|
Term
| what is an abnormal depolarization that occurs during phase 4 of the AP? |
|
Definition
delayed after-depolarization
caused by digoxin, enhanced SNS activity, ischemia - all involve Ca |
|
|
Term
| what drug can lead to a delayed after-depolarization as a side effect? |
|
Definition
|
|
Term
| what drugs are used to treat DAD? |
|
Definition
|
|
Term
| what is a depolarization that occurs during phase 3 of a normal AP? |
|
Definition
early after-depolarization
caused by hypokalemia, torsades de pointes - involves activation of Na channels |
|
|
Term
| what drugs are used to treat EAD? |
|
Definition
|
|
Term
which drugs are capable of blocking early after-depolarizations?
a. Na channel blockers
b. Ca channel blockers
c. B-adrenergic receptor blockers
d. all of the above
e. none of the above |
|
Definition
|
|
Term
| when are B-adrenergic blockers used to reduce DADs? |
|
Definition
| adrenergic stress-induced DAD |
|
|
Term
| besides Na channel blockers, what else is also effective against EADs? |
|
Definition
|
|
Term
| what is considered the leading cause of atrial fibrillation? |
|
Definition
|
|
Term
| what 3 things are necessary for re-entry to occur? |
|
Definition
1. conduction system must permit the establishment of a circuit in which the impulse can re-enter a given region
2. unidirectional block must occur at some point in the circuit
3. conduction time must be long enough so that impulse does not reach refractory tissue upon re-entry |
|
|
Term
| what are the mechanisms to counter re-entry? |
|
Definition
1. prolong refractoriness - increase chance that when reach tissue it is refractory
2. cause bidirectional block |
|
|
Term
| what are 3 ways to prolong refractory period to counter re-entry? |
|
Definition
1. Na channel blockers - delay recovery of Na channels; increase threshold
2. K channel blockers - prolong AP
3. Ca channel blockers - prolong AP in SA/AV node |
|
|
Term
| how do you cause bidirectional block to counter re-entry? |
|
Definition
| Na channel blocker - slow conduction; Vmax effect |
|
|
Term
which drugs are capable of blocking re-entry?
a. Na channel blockers
b. K channel blockers
c. Ca channel blockers
d. all of the above
e. none of the above |
|
Definition
d. all of the above
Ca channel blockers used in the AV/SA node |
|
|
Term
| what are the properties of class I anti-arrhythmic agents? |
|
Definition
1. elevate threshold - block re-entry, suppress enhanced automaticity, disrupt EAD
2. slow conduction - reduce Vmax, block re-entry (bidirectional block)
3. all are Na channel blockers |
|
|
Term
| why is the rate of recovery from Na blockade important? |
|
Definition
drugs that recover quickly are not active in cells with short AP (like atrium)
drugs with slower recovery from blockade are active against AP that are short |
|
|
Term
| what is the importance of altered membrane potential on Na blockade by lidocaine? |
|
Definition
the more positive the membrane potential of ventricle, the better lidocaine is at terminated the AP (blocking Na channels)
not effective in atrium or normal ventricles (ischemia increases membrane potential) |
|
|
Term
| what are the class 1A anti-arrhythmic agents? |
|
Definition
|
|
Term
| what are the 4 pharmacological actions of quinidine? |
|
Definition
1. Na channel blocker - increases threshold and slows conduction
2. K channel blocker - prolongs AP duration
3. a-adrenergic receptor blocker
4. vagal inhibitor |
|
|
Term
| what 2 actions of quinidine cause its side effects? |
|
Definition
1. a-adrenergic receptor blocker
2. vagal inhibitor |
|
|
Term
| what are the therapeutic uses of quinidine? |
|
Definition
1. broad spectrum anti-arrhythmic - NOT drug of choice due to toxicity
2. supraventricular tachycardia
3. can be used to suppress ventricular arrhythmia |
|
|
Term
| side effects of quinidine? |
|
Definition
1. torsade de pointes - 2-8%; tachycardia, QRS widening and QT prolongation
2. anti-muscarinic actions increase AV nodal automaticity and conduction velocity - cause ventricular tachycardia
*3. GI problems - 30-50%
*4. chronic exposure - cinchonism (blurred vision, ringing in ears)
5. thrombocytopenia |
|
|
Term
| what is the mechanism of torsade de pointes as a side effect of quinidine? |
|
Definition
K inhibition - QT prolongation
Na channel blocker slows conduction; decrease Vmax - QRS widening |
|
|
Term
| what are the pharmacological actions of procainamide? |
|
Definition
1. similar actions to quinidine - effect Na, K channels
*2. lacks quinidine's vagolytic and a-adrenergic blocking activity |
|
|
Term
| therapeutic uses of procainamide? |
|
Definition
1. broad spectrum anti-arrhythmic
2. treat Wolff-Parkinson-White Syndrome
3. treat wide QRS tachycardia of undetermined etiology |
|
|
Term
| how does procainamide treat WPW syndrome? |
|
Definition
| slows conduction over accessory pathways and can terminate arrhythmia |
|
|
Term
| how is procainamine administered? |
|
Definition
|
|
Term
| how is procainamide eliminated? |
|
Definition
| rapidly undergoes acetylation to N-Ac-procainamide --> acts as a class III agent to prolong AP |
|
|
Term
| side effects of procainamide? |
|
Definition
less pronounced than quinidine (including GI problems)
rapid admin - can cause hypotension and cardiac toxicity
**chronic exposure - can lead to lupus erythematosis-like syndrome; reversible and will disappear upon withdrawal |
|
|
Term
| what is the class 1B anti-arrhythmic agent? |
|
Definition
|
|
Term
| where is lidocaine effective in the heart? |
|
Definition
| only in ventricular tissue (ischemic with elevated resting potential) - little effect on normal tissue |
|
|
Term
| what are the pharmacological actions of lidocaine? |
|
Definition
1. dominant effect - reduction in phase 4 depolarization --> suppresses enhanced automaticity
2. reduces phase 0 slope (depresses Vmax) - effect is small in normal tissue; can suppress re-entry by bidirectional block
3. actually shortens AP duration - unlike quinidine |
|
|
Term
| therapeutic uses of lidocaine? |
|
Definition
suppress ventricular arrhythmia
not used routinely for all arrhythmia after MI because might increase mortality |
|
|
Term
|
Definition
| IV due to first pass hepatic metabolism |
|
|
Term
| lidocaine toxicity/side effects? |
|
Definition
can exacerbate heart block and heart failure
least toxic of class I anti-arrhythmic
most common are CNS - convulsions, respiratory arrest, paresthesia |
|
|
Term
| what are congeners of lidocaine that resist first pass hepatic metabolism? |
|
Definition
|
|
Term
| mexilitene/tocainide administration? |
|
Definition
| oral - avoid hepatic first pass metabolism |
|
|
Term
| mexilitene/tocainide actions? |
|
Definition
|
|
Term
| mexilitene/tocainide side effects? |
|
Definition
major - CNS
tocainide - can cause potentially fatal bone marrow aplasia; not widely used |
|
|
Term
| what are the class IC anti-arrhythmic agents? |
|
Definition
|
|
Term
| pharmacological actions of flecainide? |
|
Definition
1. blocks Na channels - slow off rate so effective in atria
2. dominant effect- slowing conduction; phase 0 depression (effect Vmax)
3. mixed effect on AP duration - prolongs in ventricles, shortens in purkinje |
|
|
Term
| therapeutic uses of flecainide? |
|
Definition
1. effective in suppressing supraventricular and ventricular arrhythmia
2. primarily used in treating atrial arrhythmia - toxicity in patients with ventricular arrhythmia; provokes or exacerbates ventricular arrhythmia due to conduction slowing; can also depress contractility |
|
|
Term
| pharmacological actions of propafenone? |
|
Definition
1. Na channel blocker - relatively slow rate of recovery
*2. major effect - slow conduction in fast response tissue (Vmax effect)
*3. prolongs PR and QRS |
|
|
Term
| therapeutic uses of propafenone? |
|
Definition
1. used chronically to maintain sinus rhythm in patients with supraventricular tachycardia
2. can terminate atrial fibrillation
better at converting atrial fibrillation than maintaining normal rhythm |
|
|
Term
| metabolism of propafenone? |
|
Definition
by CYP2D6 - absent in ~7% of caucasians and african americans
first pass metabolism - extensive if have enzyme; significantly reduced in those without |
|
|
Term
|
Definition
1. prolonged treatment - exacerbate ventricular arrhythmia caused by atrial flutter and re-entry tachycardia
2. can exacerbate heart failure
3. exerts some B-adrenergic blocking activity |
|
|
Term
| what are the class 2 anti-arrhythmic agents? |
|
Definition
propranolol
carvedilol
atenolol
metoprolol |
|
|
Term
| what are the pharmacological actions of class II anti-arrhythmic? |
|
Definition
block sympathetic activity:
1. reduce AV conduction and prolong AV refractoriness --> block re-entry involved AV node
2. decrease automaticity - ectopic beats
3. block DAD
4. can cause bradycardia
exhibit quinidine-like effects |
|
|
Term
| therapeutic uses of class II agents? |
|
Definition
1. treat supraventricular arrhythmia
2. controls arrhythmia cause by catecholamines, ischemia, exercise, cardiac surgery, and pheochromocytomas
*3. reduces mortality following MI |
|
|
Term
| what drug type should be used routinely following MI? |
|
Definition
|
|
Term
| side effects of class II agents? |
|
Definition
1. hypotension
2. left ventricular failure
3. bronchospasms
4. in combo with verapamil - can cause heart failure and AV block |
|
|
Term
| what are the class 3 anti-arrhythmic agents? |
|
Definition
amiodarone
sotalol
dofetilide
ibutilide |
|
|
Term
| pharmacological action of class III anti-arrhythmic agents |
|
Definition
| prolong duration of AP without altering phase 0 depolarization or resting potential |
|
|
Term
| pharmacological actions of amiodarone? |
|
Definition
1. prolongs refractory period by blocking K channels
2. depresses conduction through SA and AV nodes
3. blocks automaticity by blocking Na channels
4. lowers Ca levels |
|
|
Term
| therapeutic uses of amiodarone? |
|
Definition
1. effective against a wide variety of supraventricular and ventricular arrhythmia
2. reduction in mortality |
|
|
Term
| what drug is the best at maintaining conversion of atrial fibrillation to sinus rhythm? |
|
Definition
|
|
Term
| what is the effect of amiodarone on mortality and sudden death? |
|
Definition
|
|
Term
| pharmacokinetics of amiodarone? |
|
Definition
1. low bioavailability
2. stored in adipose tissue
3. half life is extremely prolonged (~53 days) |
|
|
Term
| how does storing amiodarone in adipose tissue effect its pharmacokinetics? |
|
Definition
decreases bioavailability
increases half life |
|
|
Term
|
Definition
*1. hypotension - vasodilation and suppression of myocardial function
*2. hyperthyroidism (8%) - 2% are hypothyroid; inhibits T4 to T3 conversion
*3. peripheral neuropathy and myopathy
*4. most serious - pulmonary fibrosis
*5. can cause torsades de pointes |
|
|
Term
| pharmacological actions of dofetilide? |
|
Definition
1.pure K blocker - few extracardiac effects
2. terminates atrial fibrillation and maintains normal sinus rhythm |
|
|
Term
| why does dofetilide have few extracardiac effects? |
|
Definition
|
|
Term
| what is the affect of dofetilide on mortality in patients with heart failure or following MI? |
|
Definition
|
|
Term
| side effects of dofetilide? |
|
Definition
| can cause torsade de pointes - a K channel blocker --> prolong AP |
|
|
Term
| pharmacological actions of ibutilide? |
|
Definition
1. inhibits Ikr current
2. prolongs refractoriness
3. converts recent onset atrial fibrillation of flutter to normal sinus rhythm |
|
|
Term
| what is the toxicity of ibutilide? |
|
Definition
| most adverse reaction - torsade de pointes |
|
|
Term
| what are the class IV anti-arrhythmic agents? |
|
Definition
|
|
Term
class IV anti-arrhythmic agents block what type of channels?
do they target heart or vasculature? |
|
Definition
Ca channel blockers
HEART over vasculature |
|
|
Term
| what are the pharmacological actions of class IV agents? |
|
Definition
1. AV nodal conduction is slowed, AV nodal refractoriness is prolonged - prevents re-entry
2. effective against supraventricular arrhythmia
3. suppresses DAD |
|
|
Term
| what are the therapeutic uses of class IV agents? |
|
Definition
1. most valuable - managing atrial tachyarrhythmias
2. effective against idiopathic left ventricle tachycardia |
|
|
Term
| pharmacokinetics of class IV agents? |
|
Definition
1. IV or oral admin
2. narrow window of effectiveness
3. low bioavailability because of first pass metabolism |
|
|
Term
| side effects of class IV agents? |
|
Definition
1. hypotension
2. heart failure
3. sinus bradycardia or AV block
4. GI complaints - constipation, gastric distress
non-cardiac side effects are mainly GI |
|
|
Term
| what is a special anti-arrhythmic agent used mainly in the ER? |
|
Definition
|
|
Term
| what are the pharmacological actions of adenosine? |
|
Definition
1. slows automaticitiy and AV nodal conduction velocity - slows phase 4 depolarization
2. reduces cAMP --> lowers Ca current --> increases AV nodal refractoriness --> effective against re-entry
3. blocks DAD
4. blocks ectopic beats related to sympathetic activity
reverses effect of SNS |
|
|
Term
| therapeutic uses of adenosine? |
|
Definition
primarily - terminate re-entrant supraventricular arrhythmias
not useful in prophylactic management of atrial fibrillation because of transient duration of action |
|
|
Term
| administration of adenosine? |
|
Definition
| bolus to avoid rapid metabolism |
|
|
Term
| side effect of adenosine? |
|
Definition
| might feel dyspnea from vasodilation of vessels |
|
|
