Antiarrhythmic Flashcards
1
Q
What are the various classes of anti-arrhythmics?
A
a. Class I: Fast Sodium Channel Blockers
b. Class II: Beta-Adrenergic Antagonists
c. Class III: Inhibitors of Repolarization
d. Class IV: Calcium Channel Blockers
e. Other: (adenosine, digitalis, etc.)
2
Q
Conduction system of the heart?
A
- Sinoatrial (SA) node
- Atria- pauses at AV node
- Atrioventricular (AV) node
- Bundle of His
- Bundle Branches
- Purkinje fibers
- Ventricles
3
Q
What is the action potential in cardiac myocytes?
A
-
Phase 0 rapid depolarization - (-60 is threshold with all or nothing depolarization)
- fast sodium channels open;
- fast inward flow of Na+;
- closing K+ channels )
-
Phase 1 begin repolarization
- sodium channels close
- K+ channels open
-
Phase 2 plateau (where class II antiarrhythmics work and Class Iv (CCB))
- slow calcium channels open
- slow inward flow of Ca2+
-
Phase 3 repolarization (Where Class III antiarrhtyhmics work)
- calcium channels close
- potassium channels open
- slow outward K+ current
-
Phase 4 pacemaker potential; return to resting membrane potentials
- combo increased inward current and decreased outward current
- occurs most rapidly in SA node, but all myocardial cells capable
- Refractory period (phases 1-3) (periods of repolarization)
4
Q
What occurs during NSR?
A
- Sinoatrial node is cardiac pacemaker
- Normal sinus rhythm 60-100 beats/min
- Depolarization triggers depolarization of atrial myocardium
- Conducts more slowly through AV node
- Conducts rapidly through His bundles and Purkinje fibers
5
Q
What occurs during SA/AV node action potential?
A
Phase 0- Ca is major ion causing depolarization at the nodes (Na in myocytes)- kinetics of Ca is slower than Na
- upstroke
- Critical firing threshold (-40mV)
- Slower and Ca2+ mediated
Phase 3
- Repolarization
- Inactivation of Ca2+ and Na+ channels
- Activation of K+ channels
Phase 4
- Gradual depolarization
- Slow inward Na+ (If funny current) and Ca2+ currents
6
Q
What is the effect of SNS and PSNS on SA node?
A
- SA Node rate controlled by autonomic nervous system
- Sympathetic system stimulation
- (ß1 receptors activated)
- Increases catecholamines
- Increased heart rate (positive chronotropic effect)
- Increased automaticity
- Facilitation of conduction of AV node
- Parasympathetic system predominates- at rest, vagal tone of PSNS
- (M2 muscarinic receptors)
- Decreases heart rate
- Inhibits AV conduction
- Reduced automacity
7
Q
How are arrhythmias classified?
A
- An arrhythmia is a disturbance in the electrical activity of the heart
- Classified according to:
- Site of origin of abnormality (atrial/ junctional / ventricular)
- Complexes on ECG (narrow/broad)
- Heart rhythm (regular/irregular)
- Heart rate is increased or decreased
8
Q
Mechanism of Arrhythmia Production?
A
-
Altered automaticity - latent pacemaker cells take over the SA node’s role; escape beats (ectopic)
-
caused by excessive SNS activity (ie epinephrine bolus)
- increase stage 4 depolarization in cells other than SA node
- ischemic cell can take over as pacemaker
-
caused by excessive SNS activity (ie epinephrine bolus)
-
Delayed after-depolarization - normal action potential of cardiac cell triggers a train of abnormal depolarizations
-
main cause is high calcium levels, triggering inward current and train abnormal AP
- Too much Ca, activated Na/Ca exchanger (1 Ca outward and 3 Na inward- net charge 1)–> reach threshold and inappropratie firing
- Also hypokalemia, and prolonged QT interval
-
main cause is high calcium levels, triggering inward current and train abnormal AP
-
Re-entry - refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit
- abnormal tissue, WPW,- abnormal conduciton pathway
- infarction- dead myocardial tissue that doesn’t conduct impulse and impulses have to travel around it
-
Conduction block – impulse fail to propagate in non-conducting tissue
- fibrosis, ischemic damage to conducting system
9
Q
Factors that can underlie cardiac arrhythmias?
A
- Arterial hypoxemia
- Electrolyte imbalance
- Acid-base abnormalities
- Myocardial ischemia
- Altered sympathetic nervous system activity
- Bradycardia
- Administration of certain drugs
- Enlargement of a failing ventricle
10
Q
When do we treat arrhythmias?
A
- They cannot be corrected by the removing the precipitating cause
- Hemodynamic function is compromised
- The disturbance predisposes to more serious cardiac arrhythmias or co-morbidities
11
Q
Management of arrhythmias?
A
- Acute management (clinical assessment of patient and diagnosis)
- Chronic treatment
- Prophylaxis treatment
- Non-pharmacological (vagal maneuver, cardioversion, reentry- RFCA of pathway, defibrillators)
- Pharmacological (some antiarrhythmic drugs are also proarrhythmic)
12
Q
Non pharmacologicla treatment of arrhythmias?
A
- Acute
- Vagal maneuvers
- Cardioversion
- Prophylaxis
- Radiofrequency catheter ablation
- Implantable defibrillator
- Pacing (external, temporary, permanent)
13
Q
What are the Vaughan Williams Classification of Antiarrhythmic drugs?
A
- Class I: Sodium channel blockers
- Ia- ex disopyramide - Na-channel block intermediate dissociation
- Ib- lidocaine- Na channel block fast dissociation
- Ic- Flecainide- sodium channel block slow dissociation
- Class II: Beta adrenergic blockers
- Class III: Potassium channel blockers
- Class IV: Calcium channel blockers
- Class V: Unclassified drugs
14
Q
What are some drugs unclassified in Vuaghan Williams system?
A
- Atropine
- Adrenaline (epinephrine)
- isoprenaline (isoproteronol)
- digoxin
- adenosine
- Calcium cholorid
- Magnesium chloride
15
Q
What is MOA of Class I antiarrhythmic agents?
A
- Block sodium channels
- Blocks inward sodium ion flow during depolarization which will slow conduction rate and result in suppression of the maximum upstroke velocity (V max) of the cardiac action potential
- bind alpha subunit on sodium channel
- bind more strongly in open, inactivated state
- lidocaine binds preferentially inactivated state
- do not bind readily in rested state
- “use dependent block”
- Slows conduction
- Depresses Phase 0
16
Q
MOA Class IA agents? Examples?
A
- Intermediate Na+ channel blocker (intermediate dissociation)
- Decrease depolarization rate (phase 0)
- Slows conduction velocity
- Increase refractory period (prolonged repolarization)
- Increase AP duration
- Decreased automaticity
- Examples:(more historical)
- Quinidine –Not currently available in US
- Procainamide
- Disopyramide
17
Q
What is procainamide use? dose? s/e?
A
- Class IA
- Used in the treatment of ventricular tachyarrhythmias (less effective with atrial)
- Dose: Loading 100 mg every 5 minutes until rate controlled (max 15 mg/kg); then infusion 2-6 mg/min
- Side effects:
- Myocardial depression leading to hypotension
- Sydrome that resembles lupus erythematosus
18
Q
What is disopyramide? uses? s/e?
A
- Class Ia
- Used in the treatment of both atrial and ventricular tachyarrhythmias
- Oral agent
- Side effects:
- Significant myocardial depressant effects
- Anticholinergic effects, which result in blurred vision, dry mouth, constipation, and urinary retention
- off target effect, independent Na chanel
19
Q
What are class IB agents? their effects? examples?
A
Fast Na+ channel blocker (fast dissociation)
- Decreases AP duration
- Decreases effective refractory period
- Produces little effect on maximum velocity depolarization rate
- because fast dissociation
- Decreases automaticity (particularly in ectopic ischemic cells)
- useful for ischemic myocytes
- preferentially block cells ifring rapidly and leave normal sinus rhythm intact
- bind selectively to inactivated channels and associate/dissociate very quickly
- Examples:
- Lidocaine - Class IB Prototype
- Mexiletine
- Tocainide
- Phenytoin
20
Q
Lidocaine class? Use?
A
- Class IB antiarrhythmic
- Used in the treatment of ventricular arrhythmias
- Used in acute treatment of ventricular dysrhythmias in immediate aftermath of MI (Rang & Dale, 7th ed. p 256)
- Is no longer recommended for preventing ventricular fibrillation after acute MI (Stoelting, 8th ed. P. 523)
- Particularly effective in suppression reentry rhythms: ventricular tachycardia, fibrillation, PVCs
21
Q
Lidocaine dose, max dose? metabolism?
A
- Dose: 2 mg/kg IV, infusion 1-4 mg/min
- (max dose 3 mg/kg)
- Therapeutic plasma concentration 1-5 ug/mL
- Hepatic metabolism
- Active metabolite with antiarrhythmic activity
- Metabolism may be impaired by drugs such as cimetidine and propanolol, or physiologic altering conditions such CHF, acute MI, liver dysfunctioin, GA; or can be induced by drugs like barbiturates, phenytoin, or rifampin
- dependent on hepatic blood flow for metabolism
22
Q
Lidocaine adverse effects
A
- hypotension
- bradycardia
- seizures- inhibiting the inhibitors
- CNS depression
- drowsiness, dizziness
- lightheadedness
- tinnitus
- confusion
- apnea,
- myocardial depression,
- sinus arrest, heart block
- ventilatory depression
- cardiac arrest
- can augment preexisting neuromuscular blockade
23
Q
What is Mexilitetine?
A
- Class IB antiarrhtyhmic
- Orally effective amine analogue of lidocaine
- Used in treatment of chronic ventricular tachyarrhythmias
- 150-200 mg Q 8hrs
- Used in chronic pain treatment also
24
Q
Phenytoin class, use?
A
- Class IB
- Used in treatment of ventricular arrhythmias associated with digitalis toxicity
- Maybe torsades de pointes and ventricular tachycardias with prolonged QTc interval
25
Q
Phenytoin dose, therpeutic levels, adverse effects?
A
- Dose: 100 mg (1.5 mg/kg IV) every 5 min., up to 10-15 mg/kg (max dose 1,000 mg)
- Can precipitate in D5W; mix in NS
- Pain or thrombosis when given in small peripheral IV
- Therapeutic blood levels 10-18 mcg/mL
- Adverse effects:
- CNS disturbances
- partially inhibits insulin secretion (leads to increased blood glucsose)
- bone marrow depression
- nausea
26
Q
Class IC agents effects? examples?
A
- Slow Na+ channel blocker
- (slow dissociation)
- Potent decrease of depolarization rate (phase 0)
- Potent slowing conduction velocity
- No effect AP
- No effect refractory period
- Decreased automaticity
- Examples:
- Flecainide - Class IC Prototype
- Propafenone
27
Q
Flecainide use?
A
- Used in the treatment of recurrent tachyarrhythmias associated with abnormal conducting pathways (ie. Wolff-Parkinson-White syndrome (reentry rhythm)
- Used in the treatment of atrial tachyarrhythmias
- Lots of proarrhythmic side effects
- supresses conduction through cardiac cycle
- Long acting
- Should not be used post-MI (sudden death)
28
Q
What is propafenone use?
A
- Used in treatment of ventricular and atrial tachyarrhythmias
- Has weak beta-blocking and calcium-channel blocking properties
- cross over between class I, II, IV
- Oral agent
- Has proarrhythmic side effects
- because slow to dissociate
29
Q
What are Class II agents MOA? Use? Examples?
A
MOA
- Beta-adrenergic antagonists.
- Decrease rate of spontaneous phase 4 depolarization resulting in decreased SA node discharge and decreased autonomic nervous system activity
- Decreased conduction velocity
- Decreased automaticity
-
Example:
- Propanolol – Prototype
- Metoprolol
- Esmolol
- Labetolol (off-label use)
USE:
- Used in treatment of SVT, atrial and ventricular arrhythmias
- Used in treatment ventricular dysrhythmias during MI and reperfusion
- Prevents catecholamine binding to beta receptors
- Slows of heart rate
- Decreases myocardial oxygen requirements
30
Q
Propranolol class, use?
A
- Class II Antiarrhythmic Drug- Prototype
- Beta-adrenergic antagonist (nonselective)
- Used to prevent reoccurrence of tachyarrhythmias, both supraventricular and ventricular precipitated by sympathetic stimulation
31
Q
Propranolol dose, pharmacokinetics?
A
-
Dose: 1 mg/min (total dose of 3-6 mg) IV or 10-80 mg po
- huge first pass effect
- Onset: 2-5 minutes (IV)
- Peak effect 10-15 minutes, duration 3-4 hours
- Elimination half-time 2-4 hours
- not forgiving. once you give it, stuck with it
- Highly protein bound 90-95%
- Hepatic metabolism, with weak metabolite
- Therapeutic plasma level 10-30 ng/mL
32
Q
Propranolol s/e?
A
- Cardiac effects: bradycardia, myocardial depression
- Side effects: hypotension, fatigue, bronchospasm, drug fever, rash, nausea, worsening Raynauds, interference with glucose metabolism
- cross BBB–> fatigue, depression
- Caution with reactive airway disease, hypovolemia, CHF, AV block
- not selective–> b2–> asthma, bronchospasm, worsen raynauds and interfere with glucose metabolism
33
Q
Metoprolol class, dose? pharmacokinetics? (onset, duration, metabolized…)
A
- Class II Antiarrhythmic Drug
- Beta-adrenergic antagonist (selective B1)
- Dose: Dose 5 mg IV over 5 minutes; max dose 15 mg over 20 min.
- Onset: 2.5 min.
- Duration: Half-life 3-4 hours
- Metabolized by liver
- crosses BBB
- Can be used in mild CHF
34
Q
Esmolol class, dose, duration?
Metabolism?
A
- Class II Antiarrhythmic Drug
- Beta-adrenergic antagonist (selective B1)
- if pt has serious asthma, probably wouldn’t use it still
- Dose: 0.5 mg/kg IV bolus over 1 min, then 50-300 mcg/kg/min
- Duration <15 mins
- Effects HR without decreasing BP significantly in small doses
Metabolism:
- Rapidly hydrolyzed by plasma esterases
- Not the same esterases as cholinesterases responsible for metabolism of sux, therefore no effect on sux metabolism
35
Q
Class III agents?
A
- Block potassium ion channels (impact on phase 3 of AP)
- Results in prolongation of cardiac repolarization by increasing the duration of the cardiac action potential and the effective refractory period, which results in prolongation of the QTc interval on ECG
- can promote polymorphic VT and torsades, especially when combines with other QT prolongaters
36
Q
Class III agent use?
A
- Highly effective at suppressing supraventricular and ventricular arrhythmias
- Prophylaxis in cardiac surgery patients r/t high incidence of Afib
- Preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
- Control rhythm in Afib
EXAMPLES:
- Amiodarone – Class III Prototype
- Dronedarone
- Sotalol
37
Q
Amiodarone class, use,
A
- Class III Antiarrhythmic Drug - Prototype
- also has Class I, II, and IV antiarrhythmic properties
- Potassium/ sodium/ calcium channel blocker, alpha and beta adrenergic antagonist
- Used for prophylaxis or acute treatment in the treatment of atrial and ventricular arrhythmias (refractory SVT, refractory VT/ VF, AF)
- 2nd line drug VT/ VF when resistant to electrical defibrillation
38
Q
Dose amiodarone? pharmacokinetics (metabolism, therapetuci level, pb?)
A
- Dose: Bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg, then 1 mg/min x 6 hrs, then 0.5 mg/min x 18 hrs
- Prolonged elimination half-life (10-100 days)
- Hepatic metabolism, active metabolite
- Biliary/ intestinal excretion
- Therapeutic plasma level 1.0-3.5 ug/mL
- Extensive protein binding 96%
- Large volume of distribution
39
Q
Amiodarone adverse effects?
A
- Pulmonary toxicity / pulmonary fibrosis- low threshold for PFT
- Pulmonary edema
- ARDS
- Photosensitive rashes
- Grey/blue discolouration of skin
- Pro-arrhythmic effects (torsades de pointes)- from prolongation of QT, monitor potassium!
- Heart block
- Hypotension
- Inhibits hepatic P450
- Has Iodine
- can cause hypo/hyperthyroidism
- vision changes
- hepatitis
- phlebitis
40
Q
What is sotalol? class? use? s/e? caution?
A
- Class II and Class III Antiarrhythmic Drug
- only beta blocker that is placed in class III
- Beta-adrenergic antagonist (nonselective) and potassium channel blocker
- racemic- levo isomer= beta adrenergic antagnoist. levo and dextro= class III activity
- only BB that prolongs cardiac AP and QT interval by delaying slow outward K current (class III agent)
- Used to treat severe sustained ventricular tachycardia and ventricular fibrillation; to prevent reoccurrence of tachyarrhythmias, especially Aflutter and AF
- Side effects: prolonged QT interval (monitor K!), bradycardia, myocardial depression, fatigue, dyspnea, AV block
- Caution in patients with asthma
- Excreted in urine
41
Q
What is ibutilide?
A
- “Pure” Class III Antiarrhythmic
- Used for conversion of Afib or Aflutter to NSR
- Used to control rate in Afib or Aflutter
- Prolongs AP duration and increases refractory period
- by slowing repolarization through K
42
Q
Ibutilide dose, pharmacokinetics (onset, duration, metabolism)
A
- Dose: 1mg over 10 min, may repeat
- Onset within 10 min
- Duration 2-12 hrs
- Hepatic metabolism with weak metabolites
- Minimal effects on BP and HR
- High incidence of ventricular arrhythmias, so need to continuously monitor for atleast 4-6 hours post administration
43
Q
What is dofetilide?
A
- Class III antiarrhythmic
- Oral dosing
- Used for the maintenance of sinus rhythm after Afib or conversion of Afib to sinus
- Proarrhythmic
- Seems to be ok in post-MI patients
44
Q
MOA Class IV agents? Examples?
A
-
Block slow calcium channels
- cardiac selective ones like verapamil are mostly used here
- *primary site AV node- helps to slow heart rate
- Blocks slow calcium channels, which decreases conduction through AV node (block sponatenous phase 4 depolarization and decrease rate of rise in phase 0 in AV node) and shortens Phase 2 (the plateau) of the action potential in ventricular myocytes
- Contractility of the heart decreases
Examples:
- Verapamil – Class IV Prototype
- Diltiazem *
45
Q
Use of class IV agents?
A
- Used in the treatment of SVT and ventricular rate control in Afib and Aflutter
- Used to prevent reoccurrence of SVT
- Not used in ventricular arrhythmias
46
Q
Verapamil dose IV, continuous?
DO NOT use verapil with _____
, pharmacokinetics (1/2 life, PB, metabolism, excretion?
A
- Class IV Antiarrhythmic Drug - Prototype
- Calcium channel blocker
- Dose 2.5-10 mg IV over 1-3 minutes (max dose 20 mg)
- Continuous infusion 5 ug/kg/minute
-
Do not use IV verapamil with ß- blocker (heart block)
- overlapping effects and cause AV block
- Plasma1/2-life 6-8 hours
- Highly protein bound
- Hepatic metabolism, with active metabolite
- Excreted in the urine, and bile
47
Q
S/E and caution of verapamil?
A
- Side effects: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular blockers
- Caution:
- Myocardial depression and vasodilation with inhalational agents
- Can potentiate neuromuscular blockers
- Can increase risk of local anesthetic toxicity- because LA blocks Na and we’re already blocking Ca channel
- Together with Dantrolene can cause hyperkalemia
- Causes decreased clearance of Digoxin
- Contraindicated in WPW syndrome- will make things worse!
- Caution with use w/ beta blockers
48
Q
Diltiazem class, dose, pharmacokinetics
A
- Class IV Antiarrhythmic Drug
- Calcium channel blocker
- Dose: 5-20 mg IV (0.25-0.35mg/kg) over 2 min.
- Continuous infusion 10 mg/hour
- Plasma 1/2 life 4-6 hours
- Highly protein bound
- Hepatic metabolism
- Excreted in the urine
- Side effects: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular blockers
49
Q
What are some class V agnets?
A
- Adenosine
- Digoxin
- Atropine
50
Q
What is adenosine?
A
- Not in Vaughan Williams class
- Binds to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels and increase K+ currents)
- temporarily hyperpolarizes membrane
- Slows AV nodal conduction
- Used for acute Rx only
- Used for termination of SVT/ diagnosis of VT
-
adenosine is ubiquitous in normal physio. mediator of heart, vascular smooth muscle, vagus nerve.
- admin as drug to hyperpolarize
- works through same K channel as Ach?
51
Q
Adenosine dose? metabolism? s/e?
A
- Dose 6mg IV, rapid bolus
- Repeated if necessary after 3 minutes, 6-12 mg IV
- Duration 20-30 seconds
- causes major pause (one screen worth) from hyperpolarization allowing SA node ot take back over
- Eliminated by vascular endothelial cell enzymes
- Side effects: excessive AV or SA nodal inhibition, facial flushing, headache, dizziness, SOB, chest discomfort/pain, nausea, bronchospasm
- Contraindicated in asthma, heart block
52
Q
What is digoxin MOA?
A
- Not in Vaughan Williams class
- Cardiac glycoside
- inhibit Na/K atpase pump on cell membrane
- leads to increase intracellular Ca
- Increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses thru the AV node
- Slows AV conduction by increasing AV node refractory period
- Decreases HR, preload and afterload
- Positive inotrope- used to treat CHF
53
Q
Digoxin use in antiarrhythmic? dose? onet? metabolism?
A
- Used for the management of atrial fibrillation or flutter (controls ventricular rate), especially with impaired heart function
- Dose: 0.5-1 mg in divided doses over 12-24 hrs
- Onset of action 30-60 minutes
- T1/2 36 hours
- Narrow therapeutic index
- Therapeutic levels 0.5-1.2 ng/mL
- Weak protein binding
- 90% Excreted by kidneys
- Reduce dose in elderly/renal impairment
54
Q
Digoxin s/e?
A
- Arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
- potentiated by hypokalemia and hypomagnesaemia
- Toxicity treatment
- Phenytoin for ventricular arrhythmias
- Pacing
- Atropine
- Antidote: digoxin immune Fab
55
Q
Atropine? use? dose? onset? metabolized? caution?
A
- Muscarinic receptor antagonist
- Used to treat unstable bradyarrhythmias
- 0.4 to 1.0 mg IV and repeat as necessary (kids 0.02 mg/kg)
- Onset less 1 min; duration 30-60 minutes
- Metabolized by liver
- Caution dosing less than 0.4 mg
- Potential to evoking a paradoxical response
- Penetrates the BBB, CNS effects
