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Spring Therapeutics Exam #4 - Electrophys & Arrhythmias
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71
Health Care
Graduate
05/13/2010

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Term
transmembrane potential
Definition
voltage difference between interior & exterior of cell; established by eletrochemical gradients of Na, K, Ca, & Cl ions
Term
resting membrane potential (RMP)
Definition
-80 to -90 mV
Term
depolarization
Definition
occurs when transmembrane potential changes and becomes LESS NEGATIVE
Term
repolarization
Definition
occurs when transmembrane potential RETURNS to negative RMP
Term
action potential
Definition
transient alteration of transmembrane potential & is the impulse responsible for cardiac conduction
Term
automaticity
Definition
ability of cardiac cells to spontaneously depolarize to generate action potentials
Term
refractory period
Definition
time during which a cell cannot be stimulated by another action potential
Term
Phase 0 of AP
Definition
rapid depolarization (upstroke) due to:
- rapid influx of Na;
- influx of Ca starts at -60 mV;
Term
Phase 1 of AP
Definition
initial repolarization due to:
- transient active eflux of K;
Term
Phase 2 of AP
Definition
plateau due to:
- K efflux (repolarization) balanced by Ca influx (depolarization)
Term
Phase 3 of AP
Definition
rapid repolarization due to:
- K efflux increases while Ca influx decreases;
Term
Phase 4 of AP
Definition
resting membrane potential (diastole) due to:
- established by active transporters (Na/K ATPase, Na/Ca exchanger);
Term
SA node
Definition
normal pacemaker, has the fastest inherent rate: 60-100 bpm
Term
Overdrive suppression
Definition
impulses from fastest pacemaker prevent spontaneous firing of slower, downstream pacemakers;
- failure/blockage of upstream pacemakers means downstream pacemakers take over & result in a HR that is in range of inherent rate of new pacemaker
Term
AV Junction
Definition
slower pacemaker;
40-60 bpm
Term
Ventricle
Definition
slowest pacemaker;
20-40 bpm;
Term
P wave
Definition
ECG component that represents atrial depolarization & contraction
Term
PR interval
Definition
ECG component that represents AV nodal conduction duration
Term
QRS complex
Definition
ECG component that represents ventricular depolarization & contraction
Term
T wave
Definition
ECG component that represents ventricular repolarization
Term
ST segment
Definition
ECG component that represents period when ventricles are depolarized
Term
QT interval
Definition
ECG component that represents ventricular action potential duration & represents beginning of QRS complex to end of T wave
Term
QT interval shortens
Definition
tachycardia causes this to occur to QT interval
Term
QT interval lengthens
Definition
this occurs to QT interval in bradycardia
Term
Bradyarrhythmias
Definition
MoA:
- failure of impulse initiation;
- decreased automaticity;
Term
Heart block
Definition
MoA:
- failure of impulse propagation from atrium to ventricles;
Term
tachyarrhythmias
Definition
MoA:
1) enhanced automaticity;
2) triggered automaticity;
3) re-entry
Term
Increased phase 4 slope
Definition
caused by increased rate, due to adrenergic stimulation, hypokalemia, mechanical stretch, ischemia
Term
decreased phase 4 slope, hyperpolarization
Definition
caused by decreased rate that can occur with ACh, or parasympathetic stimulation
Term
Delayed Afterdepolarizations (DADs)
Definition
follows a normal AP & is due to increased intracellular Ca (ischemia, adrenergic stress, digitalis, HF) & usually occurs with underlying rapid HRs
Term
Early Afterdepolarizations (EADs)
Definition
interrupts Phase 3 repolarization & is often due to hypokalemia, drugs that prolong AP, and usually occurs with underlying SLOW HRs
Term
Re-Entry
Definition
occurs when impulse re-enters & depolarizes an area more than once;
Requires:
- 2 pathways for conduction;
- area of unidirectional block in one pathway;
- slowed conduction in unblocked pathway;
Term
Normal Sinus Rhythm (NSR)
Definition
regular rate & rhythm of healthy heart;
HR: 60-100 bpm, all ECG components are NORMAL;
Term
Sinus Bradycardia
Definition
sinus node fires slower than normal, at a rate of <60 bpm; rhythm is still regular w/ normal complex & intervals;
Causes: vagal stimulation, hypoxia, medications (beta-blockers)
Term
Sinus Tachycardia
Definition
sinus node fires faster than normal, HR >100 bpm; rhythm is still regular w/ normal complex & intervals;
Causes:
- fever, anxiety, pulmonary embolism, MI, drugs (atropine, anticholinergics), many other drugs
Term
Atrial Arrhythmias
Definition
due to 1 or more irritable foci in atrium;
- characterized by P wave changes
Term
Supraventricular Tachycardia (SVT)
Definition
originates above ventricles but exact origin is unknown;
HR >= 130 bpm, rhythm is regular, P waves are NOT discernable;
Causes: medications (stimulants), hypoxia, heart dx
Term
Atrial Fibrillation (Afib)
Definition
hundreds of atrial ectopic foci fire at once & atrium depolarizes in small sections & as a result of contraction of atria is impaired & AV node cannot conduct atrial impulses;
Atrial Rate: 350-700 bpm;
Rhythm: 'irregularly irregular';
NO P waves present; QRS complexes at irregular intervals;
Causes: MI, lung dx, valvular heart dx, stimulants, EtOH
Term
Atrial Flutter (AFL)
Definition
one atrial ectopic focus fires at a rapid rate but AV node conducts only some impulses;
Atrial Rate: 250-350 bpm;
"Sawtooth" flutter waves replace P waves, & 2 or more flutter waves to each QRS complex;
Causes: underlying heart dx, lung dx
Term
AV Blocks (heart block)
Definition
SA node fires normally but conduction of impulse is partially or completely interrupted in AV conduction pathway;
impairs or blocks transmission of impulse from atria to ventricles;
1) PR interval is prolonged (> 0.2 sec) OR
2) P waves not consistently followed by QRS complexes;
Causes: AV node ischemia, medications (digoxin, beta-blockers, CCBs), MI;
Term
1st degree AV block
Definition
impulse is delayed from SA node to ventricles & site of block is AV node;
PR interval prolonged > 0.2 sec;
1 P wave to each QRS complex;
Term
2nd degree AV block type 1
Definition
site of block is usually AV node but PR-interval is progressively prolonged until some P wave impulses are not conducted --> "dropped" QRS complexes;
Atrial Rate: 60-100 bpm;
Ventricular rate < atrial rate;
Rhythm is usually irregular
Term
2nd degree AV block type 2
Definition
site of block is His-Purkinje system;
Atrial Rate: 60-100 bpm;
Ventricular rate = 0.12 sec) indicate bundle branch block (BBB)
Term
3rd degree AV block
Definition
complete heart block;
Atrial Rate: 60-100 bpm;
Ventricular rate: 20-60 bpm (slow);
Rhythm is regular;
P waves are NOT associated with QRS complexes;
QRS complexes are widened if BBB
Term
Ventricular Arrhythmias
Definition
due to 1 or more irritable foci in ventricles taht cause retrograde depolarization of atria;
more dangerous form;
Term
Premature Ventricular Complexes (PVCs)
Definition
premature beat from irritated ventricular tissue that occur at any rate;
rhythm is regular but interruped;
Wide (>0.12 sec), shape is different from other QRS complexes NOT preceded by P wave;
Causes:
- heart dx, hypokalemia, hypoxia, hypomagnesemia, stimulants
Term
Ventricular Fibrillation (VF)
Definition
many irritable foci in ventricles fire rapidly;
no discernable P waves or QRS complexes, very irregular rhythm;
No cardiac output, pt functionally dead & requires IMMEDIATE defibrillation;
Causes:
- heart dx, hypokalemia, hypoxia, hypomagnesemia, stimulants, drowning, electrical shock, drug overdose
Term
Reducing automaticity in ectopic foci
Definition
alter discharge in spontaneous pacemakers by:
1) decrease phase 4 slope;
2) increase threshold potential;
3) increase max diastolic potential;
4) increase AP duration
Term
Modify conduction of refractoriness in reentry circuits
Definition
Way to increase refractoriness:
1) increase voltage dependence of channel recovery, reducing available unblocked channels;
OR
2) prolong AP, also extending point at which channels recover from inactivation
Term
Class IA Antiarrhythmics
Definition
quinidine, procainamide, disopyramide;
- blockade of Na & K --> slows conduction velocity, prolongs refractory period, decreases automaticity by increasing threshold potential;
broad-spectrum agents used for supraventricular (SVCs) arrhythmias & ventricular arrhythmias
Term
quinidine
Definition
Class IA anti-arrhythmic
MoA: vagolytic & alpha adrenergic blocking properties;
Forms: PO, IV, IM;
PK: hepatic metabolism & elimination;
- CYP3A4 > CYP2C0; Strong inhibitor of CYP2D6, CYP3A4;
ADRs:
- prolonged QTc & TdP, VT, HF exacerbation, diarrhea, cinchonism, thrombocytopenia, hemolytic anemia, hepatitis;
Term
procainamide
Definition
Class IA anti-arrhythmic;
Forms: IV, IM, PO;
PK: hepatic metabolism, renal elimination;
- forms NAPA (Class III anti-arrhythmic activity, accumulates in renal failure);
ADRs:
- hypotension, prolonged QTc & TdP, diarrhea, drug-induced lupus, rare agranulocytosis;
Term
disopyramide
Definition
Class IA anti-arrhythmic;
Similar to quinidine but w/ greater anticholinergic activity;
Forms: PO only;
PK: hepatic metabolism (CYP3A4), renal elimination;
ADRs:
- anticholinergic: dry mouth, urinary retention, blurred vision, constipation; HF exacerbation, nausea, anorexia, prolonged QTc & TdP
Term
Class IB Anti-arrhythmics
Definition
lidocaine, mexilitene;
MoA: fast on-off Na channel antagonism --> depressed conduction in ischemic (depolarized) tissue; AP is either unaffected or shortened --> decreased automaticity;
Uses: only for ventricular arrhythmias
Term
lidocaine
Definition
Class IB anti-arrhythmic;
also used as local anesthetic;
Effective for post-MI arrhythmias;
Forms: IV only;
PK: hepatic metabolism;
ADRs: seizures, tremor, dizziness, sedation, paresthesias, nausea, slurred speech, hearing disturbances, Rare: sinus arrest, impaired conduction, ventricular arrhythmias;
Term
mexilitene
Definition
Class IB anti-arrhythmic;
Forms: PO only;
PK: hepatic metabolism, inhibits CYP1A2;
ADRs: tremor, dizziness, sedation, seizures, nausea, paresthesias, slurred speech, hearing disturbances;
Term
Class IC Anti-arrhythmics
Definition
flecainide, propafenone;
MoA:
- potent, slow-off Na channel blockers --> profound slowing of conduction, leaves refractory period unaltered; leads to decreased automaticity;
Uses:
- effective in both supraventricular AND ventricular arrhythmias BUT pro-arrhythmic effects limit use for ventricular arrhythmias;
Term
flecainide
Definition
Class IC anti-arrhythmic;
Only used in pts w/o structural heart dx;
Forms: PO only;
PK: hepatic metabolism, renal elimination, inhibits CYP2D6;
ADRs:
- pro-arrhythmic, HF exacerbation, blurred vision, dizziness, HA, tremor, nausea;
Term
propafenone
Definition
Class IC anti-arrhythmic;
similar to propanolol & has weak beta-adrenergic antagonism;
Forms: PO only;
PK: hepatic metabolism, 1st pass --> 5-hydroxypropafenone --> active as Na channel blocker, less beta effects; Inhibitor of CYP2D6;
ADRs:
- pro-arrhythmic, HF exacerbation, bradycardia, bronchospasm, fatigue, dizziness, metallic taste;
Term
Class II Anti-arrhythmics
Definition
Beta-blockers: esmolol, metoprolol, atenolol;
Acts in SA & AV nodes --> decrease conduction velocity, prolong refractory period, decrease automaticity;
Most useful for:
- tachycardias involving abnormal nodal automaticities or part of re-entry circuit;
- decreasing ventricular response in atrial tachycardias;
- controlling arrhythmias due to high sympathetic activity;
Use caution or AVOID if:
- sinus or AV node dysfunction (blocks);
- acute decompensated HF;
- asthma;
- peripheral vascular dx;
- poorly controlled DM;
Term
Class III Anti-arrhythmics
Definition
amiodarone, dofetilide, ibutilide, sotalol;
MoA:
- K channel blockers --> prolongs AP & refractory period, NO effect on conduction velocity or automaticity;
Amiodarone, sotalol effective for both supraventricular & ventricular arrhythmias;
Ibutilide, dofetilide ONLY used for supraventricular arrhythmias;
Term
amiodarone
Definition
Class III anti-arrhythmic & other anti-arrhythmic properties;
analog of thyroid hormone;
Broad-spectrum, widely used;
Forms: PO & IV;
PK: variable bioavailability, very large VD, hepatic metabolism & elimination (CYP3A4, CYP2C9), very long elimination T1/2 (15-100 days), give loading doses;
ADRs:
- IV: hypotension, phlebitis; prolonged QTc & TdP, hyper/hypothyroidism, photosensitivity, corneal microdeposits, optic neuropathy/neuritis, increased LFTs (hepatitis), pulmonary fibrosis, neurotoxicity;
Term
Monitoring Parameters for Amiodarone
Definition
Pulmonary fibrosis: CXRY baseline then q12 months unless symptomatic;
Thyroid dysfunction: thyroid fcn tests baseline then q6 months;
Optic neuritis: ophthalmologic exam baseline then q12 months;
Hepatitis: LFTs baseline then q6 months;
Bradycardia/heart block: ECG baseline then q3-6 months
Term
dronedarone
Definition
Class III anti-arrhythmic;
New agent, structural analog to amiodarone;
Shorter T1/2: 24 hrs;
1st drug to demonstrate reduction in mortality & hospitalizations for pts w/ Afib
Term
dofetilide
Definition
Class III anti-arrhythmic;
Potent, pure blockade of K channels in heart;
Forms: PO only;
PK: 80-95% bioavailability, C/I if CrCL <20 ml/min;
ADRs:
- prolonged QTc & TdP (C/I if QTc >440 msec), HA, dizziness;
Drug Interactions:
- C/I: cimetidine, verapamil, trimethoprim, ketoconazole, prochlorperazine, megesterol, HCTZ, other QTc-prolonging drugs;
- other anti-arrhythmics should be stopped or held for at least 3 half-lives;
use caution if given w/ CYP3A4 inhibitors;
Term
sotalol
Definition
Class II & III anti-arrhythmic;
- inhibits K channels AND is a non-selective beta-antagonist;
Forms: PO only;
PK: no hepatic metabolism, renally eliminated;
ADRs:
- prolonged QTc & TdP, dizziness, weakness, fatigue, bradycardia, bronchospasm, HF exacerbation;
Term
ibutilide
Definition
Class III anti-arrhythmic;
Prolongs AP by inhibiting K channels, activates slow inward Na current;
ONLY used for conversion of Afib/flutter;
Forms: IV only;
PK: extensive 1st pass metabolism orally, undergoes rapid hepatic metabolism;
ADRs: prolonged QTc & TdP, HA, hypotension;
Term
Class IV Anti-arrhythmics
Definition
diltiazem, verapamil;
MoA:
- L-type Ca channel blocker --> works in SA/AV nodes to slow conduction, prolong refractoriness, decrease automaticity;
Decreases ventricular response to supraventricular arrhythmias;
Effective for exercise-induced or triggered-automaticity arrhythmias;
Use caution or avoid if:
- sinus or AV node dysfunction (blocks);
- HF;
- Wolff-Parkinson-White Syndrome;
Term
Digoxin
Definition
MoA: increases intracellular Ca --> positive inotropic effect, increased automaticity;
vagotonic effects --> indirect electrophysiological effects --> hyperpolarization --> shortens atrial APs, increased AV node refractoriness;
Used to control ventricular response to Afib/flutter;
Narrow therapeutic index, complex PK;
Term
adenosine
Definition
naturally-occurring nucleoside --> activated ACh-sensitive K channels in sinus, AV nodes --> shortens AP --> hyperpolarizes myocardium --> decreases automaticity;
Eliminated in seconds by uptake into almost any cell type --> requires rapid bolus dose;
ADRs: dyspnea, chest fullness (short-lived);
causes characteristic pause of short flatline on ECG (lasts 5 sec);
Term
magnesium (Mg)
Definition
administered acutely for termination /prevention of recurrence of TdP;
- effective even if serum blood level is normal;
- dose NOT shorten QTc interval but is still effective;
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