Dysrythmias Flashcards
What is resting potential determined by?
Ion gradients and membrane permeability
What are the phases of AP?
Phase 0= Potential of membrane reaches 60-80mv opening fast Na channels Na in to cell potential will reach 20-30mV at this point Na channels deactivated (resting cardiomyocyte at 70-90mV because of maintenance with na/K atpase pump of high extracellular Na and low extracellular K)
Phase 1 = Repolarization K ions efflux
Phase 2= membrane potential balanced by influx of Ca and Na (via slow channels) in addition to efflux of K- Plateu
Phase 3 = Ventricular repolarization, efflux K greatly exceeds Ca and Na influx
Phase 4 = Na actively pumped from cell via Na/K ATPase resulting in restoration of ion concentrations
Dysfunction of pulse generation or conduction at any site can result in what?
Arrhythmia
- Heart may beat too slow (Bradycardia)
- Heart may beat too fast (sinus or vent. Tach, atrial or ventricular premature depolarization, atrial flutter)
- Heart may respond to impulses originating from sites other than the SA node
- Heart may respond to impulses traveling along accessory pathways that lead to deviant depolarizations (A-V reentry, Wolff-Parkinson White syndrome)
What are the groups of arrhythmia based on anatomic site?
Ventricular: tachycardia, fibrillation
Atrial: flutter & fibrillation
AV Junction: AV nodal reentry, acute SVT
Organized into subgroups depending of ECG findings
What does the P wave on ECG represent?
Atrial depolarization
What does QRS represent on ECG?
Ventricular depolarization
What does T represent on ECG?
Ventricular repolarization
What is QT interval a marker of?
Ventricular repolarization time
What does the PR interval mark?
Time of conduction from atria to ventricles through AV node.
What is abnormal automaticity?
SA node fastest rate of Phase 4 depolarization, therefore higher rate of discharge of pacemaker cellslatent pacemakers are depolarized by impulses from SA node
Other pacemaker cells with enhanced automaticity ->competing stimuli: damaged cells remain partially depolarized during diastole; reach firing threshold earlier than normal cells. Hypoxia, K+ imbalance
Drugs suppress automaticity by decreasing slope of Phase 4 depolarization and/or by raising threshold of discharge to less negative voltage: block Ca++ or Na+
What are the abnormalities in impulse conduction?
- Impulses from higher pacemaker centers conducted down pathways that bifurcate to activate entire ventricular surface
- Unidirectional block (injury or prolonged refractory period)->impulse travels in retrograde direction and reenters conduction pathway at point of bifurcation -> reexcitation of ventricle, causing premature contraction or sustained ventricular arrhythmia
- Drugs prevent reentry by slowing conduction and/or increasing refractory period required to convert unidirectional block into a bidirectional block
What are the classes and MOA of antiarrhythmics?
Class MOA
IA Na blocker slows Phase 0 depol
IB Na blocker shortens Phase 3 repol
IC Na blocker markedly slows Phase 0 depol
II B-blocker suppresses Phase 4 depol III K+-blocker prolongs Phase 3 repol IV Ca++-blocker shortens AP
What are the Class IA antiarrhythmic agents?
Quinidine
Procainamide
Disopyramide
Quinidine (prototype)- MOA
Class IA antiarrhythmic agent
BLOCK NA+ CHANNELS in their open (activated) or refractory (inactivated) state. It SLOWS PHASE 0 DEPOLARIZATION, thus slowing conduction, prolonging action potential and increase the ventricular effective refractory period. Suppresses arrhythmias caused by INCREASED NORMAL AUTOMATICITY. Inhibits ectopic arrhythmias and ventricular arrhythmias. Also, prevents reentry arrhythmias by producing bidirectional block.
Quinidine- Indications
atrial and ventricular tachyarrhythmias, used to maintain sinus rhythm post cardioversion
Quinidine- contraindications
Heart block SA node dysfunction Cardiogenic shock Severe uncompensated heart failure SLE w/procainamide also shizophrenia
Quinidine- ADRs
- Arrhythmias (SA or AV block or asystole; toxic levelsVentricular Tachy (with toxic levels not therapeutic levels) exacerbated by hyper-K+)
- N/V/D
- Cinchonism (blurred vision, tinnitus, HA, disorientation, psychosis)
- Metabolism inhibited by cimetidine; induced by phenytoin, rifampin, barbituates
- Displaces digoxin on binding protein; decreased digoxin clearance
Procainamide- MOA
Class IA antiarrhythmic agent
Derivative of local anesthetic procaine
Actions similar to quinidine
Metabolized to N-acetylprocainamide (NAPA) which prolongs duration of AP (Class III properties)
Porcainamide- ADRs
- hypotension with IV route thus give PO
- 25-30% reversible lupus erythematosus-like syndrome with chronic use
- Aystole or ventricular arrhythmias at toxic conc
- Depression, hallucinations, psychosis
Disopyramide- MOA
Class IA antiarrhythmic agent
Actions similar to quinidine
Produces negative inotropic effectclinically important decrease in contractility in LV dysfunction
Disopyramide- uses
Used to tx ventricular arrhythmias
Alternative to procainamide or quinidine
Disopyramide- contraindications
Contraindicated in heart failure
Causes peripheral vasoconstriction- worsens this
Disopyramide- ADRs
Anticholinergic= urinary retention, blurred vision, dry mouth, constipation
proarrhythmic
What are the class IB antiatthythmic agents?
Lidocaine
Mexiletine
Tacainide
Lidocaine- Indications
Class IB antiarrhythmic agent
Indications: ventricular arrhythmias post MI or arising from myocardial ischemia.
Lidocaine- pharmacokinetics
IV because of extensive 1st pass metabolism
Dose adjustment in liver failure
Lidocaine- Contraindications and ADRs
Contraindications
SA disorders
AV block
ADRs
Confusion, slurred speech, drowsiness, parasthesias, agitation, cardiac arrhythmias
Mexiletine and Tocainide
Class IB antiarrhythmic agents
Actions similar to lidocaine
Mexiletine->chronic ventricular arrhythmias associated with previous MI
Tocainide->tx ventricular tachyarrhythmias
Pulmonary toxicityfibrosis
What are the class IC antiarrhythmic agents?
Flecainide
Propafenone
Flecainide (prototype)- MOA and ROA
Class IC- questionable safety
blocks Na+ channels. Slows phase 0 depolarization->slowing conduction; minor effect on duration of AP and refractoriness.
ROA: oral or IV
Flecainide- indications
Refractory ventricular arrhythmias (PVCs)
Flecainide- contraindications
CHF (negative inotropic effect)
Flecainide- ADRs
Dizziness, blurred vision, HA, nausea
Can aggravate pre-existing arrhythmias or induce life threatening ventricular tachycardia that is resistant to treatment
Propafenone
Similar action to flecainide
What are the class II antiarrhythmic agents?
Propranalol
Metoprolol
Esmolol
Propranalol, Metoprolol, Esmolol (class II)-MOA
DIMINISH PHASE 4 DEPOLARIZATION thus depressing automaticity, prolonging AV conduction and decreasing heart rate and contractility.
Propranalol, Metoprolol, Esmolol (class II)- indications
- Post MI prevent ventricular arrhythmias (also thought to prevent cardiac rupture)
- Tachyarrhythmias caused by increase sympathetic activity (NE and epi)
- Atrial flutter and fibrillation
- AV nodal reentrant tachycardia
What are the class III antiarrhythmic agents?
Sotolol (Betapase)-oral,
amiodarone (Cordarone,Pacerone)-oral & IV, dofetilide
Sotolol (Betapase), amiodarone (Cordarone, Pacerone), dofetilide (Class III)- MOA
Blocks potassium channels -> prolonging both repolarization and duration of AP thus lengthening effective refractory period.
Sotolol (Betapase), amiodarone (Cordarone, Pacerone), dofetilide (Class III)- Indications
ventricular and supraventricular arrhythmias.
Sotalol-MOA
Class III antiarrhythmic agent with potent beta-blocker activity
Effective in preventing arrhythmia recurrence and decreasing mortality in pts. with sustained VTACH
Sotalol- ADRs
torsade de pointes 3-4%
Really bad rhythm
Dofetilide
Class III
Persistant Afib and heart failure or CAD with impaired LVF
Initiated in hospital; restricted to MDs who have completed manufacturer’s training session ->proarrhythmic
Not something we could be prescribing
Amiodarone- MOA
Class III
- Contains iodine and is structurally related to thyroxine
- Class I, II, III, and IV actions
- Dominant effect is prolongation of AP duration and refractory period
- Antianginal (used in patients with angina) and antiarrhythmic activity
Amiodarone- Indication
refractory SVT and ventricular tachyarrythmias
**Does not reduce incidence of sudden death or prolong survival in pt. with CHF
Amiodarone- Long term use ADRs
PULMONARY FIBROSIS GI intolerance Tremor Ataxia HYPER- OR HYPOTHYROIDISM Neuropathy, muscle weakness BLUE SKIN DISCOLORATION ->accumulation of iodine in skin
What are the class IV antiarrhythmic agents?
Calcium channel blockers
Verapamil
Diltiazem
Verapamil, diltiazem (class IV)- MOA
Calcium channel blockers
slowed phase 4 spontaneous depolarization and slowed conduction in tissues dependent on Ca++ currents such as the AV node.
Verapamil, diltiazem (class IV)- indications
Atrial arrhythmias Reentrant supraventricular tachycardia Reducing ventricular rate in atrial flutter and fibrillation HTN Angina
Verapamil, diltiazem (class IV)- ADRs
Hypotension due to peripheral vasodilation
Contraindicated in pts. With preexisting depressed cardiac function due to negative inotropic properties
What are the proarrhythmic effects of antiarrhyhmic drugs?
CAST trial -> encainide and flecainide (class IC) successfully prevented ventricular ectopic beats in pts. with MI->2-3 fold increase in cardiac deaths due to arrhythmias Also increased mortality with moricizine
What reduced mortality in dysrythmias?
Beta-blockers
What may reduce mortality but there is insuffiecient data?
Amiodarone, disopyramide, mexiletine, procainamide, propafenone, quinidine, tocainide, sotalol
Adenosine- MOA
Endogenous nucleoside that acts at tissues in the lungs, afferent nerves, and platelets.
MOA: high doses decreases conduction velocity, prolongs the refractory period and decreases automaticity in the AV node.
Pharmacokinetics:
Adenosine- contraindications
2nd and 3rd degree heart block, sick sinus syndrome
Adenosine- indications
DOC fro abolishing supraventricular tachycardia
Adenosine- ADRs
transient facial flushing, chest pain, dyspnea, bronchospasm.
Digoxin- MOA
shortens refractory period in atrial/ventricular cells while prolonging effective refractory period and decreasing conduction velocity in Purkinje fibers.
Digoxin- Indications
Control ventricular rate in AFib and Aflutter
Digoxin- ADRs
ectopic ventricular beats-> VTACH/VFIB (usually treated with lidocaine)
What is atrial fibrillation?
Extremely rapid (atrial rate 400-600 beats/min), disorganized atrial activation
Variable conduction to the ventricles (irregular pulse); AV node “filters out” most atrial impulses reaching the ventricle, causing ventricular rate to be less than the atrial rate (usually 120-180 bpm
What is the average age for atrial fibrillation?
75 y/o
What are the common etiologies of atrial fibrillation?
- myocardial ischemia/infarction
- hypertensive heart disease
- valvular disorders
- congenital abnormalities
- cardiomyopathy
- chronic lung disease
- rheumatic heart disease
What is the predominant mechanism of atrial fibrillation?
Predominant mechanism is multiple wavelets of depolarization moving around the atria chaotically, rarely completing a reentrant circuit
What are the less severe symptoms of atrial fibrillation?
Some patients may be asymptomatic
palpitations
irregular pulse
dizziness
dyspnea
What are the sever sx of atrial fibrillation
acute heart failure
unstable angina pectoris
hypotension
What is the self terminating type of atrial fibrillation?
Paroxysmal
What is the type of atrial fibrillation that does not terminate on its own?
Persistent
Does acute treatment differ b/w paroxysmal and persistent? What about chronic tx?
Acute treatment does not differ between the two types
Chronic treatment is given to almost all patients with persistent atrial fibrillation, but is typically only given to patients with paroxysmal atrial fibrillation that is recurrent
Treatment principles are the same for both paroxysmal and persistent atrial fibrillation
When should immediate DIRECT-CURRENT CARDIOVERSION (DCC) be considered?
Immediate direct-current cardioversion (DCC) should be considered in all patients who are severely symptomatic or hemodynamically unstable
What might be all that is needed to alleviate sx if tachycardia is believed to be responsible?
Rapid control of ventricular rate
What do all patients need with a fib?
Anticoagulation
Ventricular rate control
Goal resting heart rate < 110 or lower if known to alleviate symptoms
Restoration and/or maintenance of normal sinus rhythm
Pharmacological therapy to maintain sinus rhythm is indicated in patients who have troublesome symptoms related to AF and who can tolerate antiarrhythmic drugs
Patients in normal sinus rhythm do NOT have lower mortality than patients in atrial fibrillation
Trials of normal sinus rhythm does not decrease chance of death, it should not be your first priority unless its leading to other sx.
What is the DOC for a fib?
DCC (direct-current cardioversion)
Anticoagulation- acute atrial fibrillation treatment
- Initially in an institutional setting with parenteral medications, i.e. UNFRACTIONATED HEPARIN OR LOW-MOLECULAR-WEIGHT-HEPARIN
- Transition to an oral antithrombotic agent (WARFARIN, ASPIRIN, OR DABIGATRAN) as soon as possible, where appropriate
Ventricular rate control- acute atrial fibrillation
- Medications are given intravenously
- DIGOXIN may be used, but may take 24-48 hrs. for full clinical effect; reasonable choice if patient has underlying heart failure; not effective in restoring NSR
- β-BLOCKERS, DILTIAZEM OR VERAPAMIL have quicker onsets of action and are better choices for acute control of ventricular rate
- AMIODARONE is typically used: 1) when other drugs have failed or cannot otherwise be given due to its delayed onset of action; 2) when chemical cardioversion is desired in addition to rate control
How do you restore normal sinus rhythm?
- Electrical cardioversion
Direct-current cardioversion (DCC), a.k.a. shock
Most rapid and effective method of restoring NSR in an unstable patient
Requires conscious sedation and specialized personnel and equipment - Chemical cardioversion
Generally less effective than DCC
Allows for determination of an effective agent if long-term therapy is required
May be attempted for several days; if this fails, DCC may be attempted
Do you need to cardiovert a patient that is not having sx?
NOPE
What are the characteristics favoring long-term pharmacologic rate control (no cardioversion)?
- no deterioration in symptoms with atrial fibrillation when heart rate controlled
- normal or near normal LV function
- left atrial size > 50 mm (low probability of maintaining NSR)
- duration of atrial fibrillation > 1 year (low probability of maintaining NSR)
- failure to maintain NSR despite cardioversion and adequate antiarrhythmic drug therapy
What are the characteristics favoring an attempt at cardioversion?
- symptomatic when NSR not present
- LVH or markedly decreased LV function (AFib usually associated with more symptoms)
- left atrial size < 50 mm
- duration of atrial fibrillation < 1 yr
- younger, more active patients
When is cardioversion contraindicated?
contraindication to chronic anticoagulation: alcohol abuse erratic diet Medication non adherence Unable to have INR monitored
What is the anticoagulation for chronic atrial fibrillation therapy?
- No risk factors for stroke or unable to tolerate anticoagulation= aspirin or clopidrogel plus aspirin
- 1 moderate risk factor for stroke aspirin or oral anticoagulant
- 2 or more risk factors for stroke oral anticoagulant plus aspirin
What is the oral anticoagulation for chronic atrial fibrillation therapy?
Warfarin or Dabigatran (direct thrombin inhibitor)
What is the dabigatran therapy for chronic atrial fibrillation therapy?
Dabigatran-Potent, reversible direct thrombin inhibitor
FDA approved October 2010 for patients with atrial fibrillation
Half-life 12-17 hrs; ~80% renally excreted
What is the ventricular rate control for chronic atrial fibrillation therapy?
Ventricular Rate Control- continue from acute therapy with oral agent or agents
What is the maintenance of sinus control for chronic atrial fibrillation therapy?
Most cases of atrial fibrillation recur due to underlying cardiac disease
Patients with symptomatic recurrences of atrial fibrillation should be considered candidates for long-term antiarrhythmic prophylaxis or catheter ablation in an effort to maintain normal sinus rhythm and reduce symptoms
Antiarrythmics- QUINIDINE
while somewhat effective in maintaining NSR at 1 year, may increase mortality (proarrhythmic?) and is no longer widely used
Antiarrythmics- FLECAINIDE AND PROPAFENONE
Flecainide and propafenone are effective, but fear o proarrhythmia (esp. in patients with ischemic heart disease) has limited their use to patients without CAD or heart failure
Antiarrythmics- AMIODARONE, SOTALOL, AND DRONEDARONE
Amiodarone, sotalol, and dronedarone have β-blocking properties and may be helpful for ventricular rate control should atrial fibrillation recur
Antiarrythmics- DOFETILIDE
Dofetilide has reasonable efficacy, but may prolong the QT interval in a dose-related manner and may therefore predispose to torsades de pointes (0.8% incidence). Consequently, it is plagued by a very laborious titration procedure and is therefore not used much.
What are the drugs used to maintain NRS (Normal sinus rhythm?
Amiodarone Dofetilide Dronedarone Felcainide Propafenone Sotalol
