Exam 3: Anti-Arrhythmic Agents Flashcards
Phase 0:
Rapid depolarization; fast inward Na+ flow; upstroke of action potential graph
Phase 1:
Partial repolarization; Na+ channels close; ‘peak’ of AP graph
Phase 2:
Plateau; slow Ca2+ channels open; flat ‘pause’ on AP graph
Phase 3:
Repolarization; Ca2+ channels close; K+ channels open; downstroke on AP graph
Phase 4:
Pacemaker potential; slow upward stroke between APs
Which phases are refractory?
1-3
Normal SA rate:
60-100
Normal AV rate:
40-60
SA node resting potential:
-55 mV
Purkinje fiber firing rate:
15-30
Receptors in the atria that affect the SA node:
β1 and M2
Two types of defects in electrical activity:
Defect in formation of impulse
Defect in conduction of impulse
Define altered automaticity:
Latent pacemaker cells take over the SA node’s role; escape beats
Define delayed after-depolarization:
Normal AP of cardiac cell triggers train of abnormal depolarizations
Define re-entry:
Refractory tissue reactivates repeatedly/rapidly due to unidirectional block, which causes a circuit effect
Define conduction block:
Impulses that fail to propagate in non-conducting tissue (like MI-injured heart)
Causes of delayed after-depolarization:
Electrolyte abnormalities
Drug toxicities
Most common way arrhythmias are formed:
Re-entry
Arrythmias require tx when:
Cause cannot be corrected
Hemodynamic function compromised
Arrhythmia can cause more serious arrhythmias or comorbidities
Acute non-pharmacological tx of arrhythmias:
Vagal maneuvers
Cardioversion
Prophylactic non-pharmacological tx of arrhythmias:
Radiofrequency catheter ablation
Implantable defibrillator
Class I antiarrhythmic drugs:
Na+ channel blockers
Class II antiarrhythmic drugs:
β-blockers
Class III antiarrhythmic drugs:
K+ channel blockers
Class IV antiarrhythmic drugs:
Ca+ channel blockers
Class V antiarrhythmic drugs:
Unclassified
Class Ia agents are:
Intermediate Na+ channel blockers
Effects of class Ia agents:
↓ depolarization rate
↓ conduction velocity
Prolonged repolarization
↑ AP duration
Class Ia prototype and examples:
Quinidine*
Procainamide
Disopyramide
Moricizine
Indications for disopyramide:
Suppress atrial/ventricular tachyarrhythmia
S/E of disopyramide:
Myocardial depression
Can precipitate CHF/HoTN
Class Ib agents are:
Fast Na+ channel blocker
MoA of class Ib agents:
Blocks Na+ channels; doesn’t affect the rate of depolarization, but shortens AP duration and refractory
Prototype and examples of class Ib agents:
Lidocaine*
Mexiletine
Tocainide
Phenytoin
Indications for lidocaine:
Acute tx/prevention of ventricular dysrhythmias esp. immediately after MI
Lidocaine used after MI because:
Raises the vfib threshold
Dosing for lidocaine:
1 - 1.5 mg/kg IV
Infusion: 1-4 mg/min
Max dose: 3 mg/kg
PK of lidocaine:
50% protein bound
Hepatic metabolism with an active metabolite
10% renal elimination
Drugs/conditions that impair metabolism of lidocaine:
Cimetidine
Propranolol
CHF, MI, liver dysfunction, GA
Drugs that induce metabolism of lidocaine:
Barbiturates
Phenytoin
Rifampin
Half-time of lidocaine:
1.4 - 8 hrs
Therapeutic concentration of lidocaine:
1-5 mcg/ml
Indication for mexiletine:
Oral/chronic suppression of ventricular tachyarrhythmias
Class Ic agents are:
Slow Na+ channel blockers
MoA of class Ic agents:
Potent decrease of depolarization rate, decrease of conduction rate, increased AP
Prototype and examples of class Ic agents:
Flecainide*
Propafenone
Indications for flecainide or propafenone:
Ventricular PVCs, v-tach
Atrial tachyarrhythmias
WPW (flecainide)
S/E of flecainide:
Proarrhythmic
MoA of class II agents:
Depress spontaneous phase 4 depolarization, decreasing SA node discharge
↓ conduction through AV node
↓ contractility
Indications for class II agents:
SVT, atrial and ventricular arrhythmias
Ventricular dysrhythmias during MI/reperfusion
Tachyarrhythmias 2/2 digoxin toxicity
Prototype and examples of class II agents:
Propranolol*
Metoprolol
Esmolol
Labetalol
Indications for propranolol:
Prevent recurrence of tachyarrhythmias (both SVT and VT) from SNS stimulation
Dosing of propranolol:
1 mg/min (total 3-6 mg) IV
10-80 mg PO
Onset, peak, duration, half-time of propranolol:
Onset: 2-5 min
Peak: 10-15 min
Duration: 3-4 hrs
E1/2t: 2-4 hrs
Cardiac effects of propranolol:
↓ HR, contractility, CO
↑ PVR, coronary VR
PK of propranolol:
Highly protein-bound Hepatic metabolism (weak metabolite)
Therapeutic plasma level of propranolol:
10-30 ng/ml
S/E of propranolol:
Bradycardia Hypotension Myocardial depression Fatigue Bronchospasm Drug fever Rash Nausea Raynaud's Glucose interference
Precautions for propranolol:
Reactive airway disease
Hypovolemia
CHF
AV block
Dosing for metoprolol:
5mg IV over 5 min
Max dose 15 mg over 20 min
Onset, duration, half-life of metoprolol:
Onset: 2.5 min
E1/2t: 3-4 hrs
Metabolism of metoprolol:
Metabolized by liver
Dosing of esmolol:
0.5 mg/kg IV bolus
Infusion: 50-300 mcg/kg/min
Duration of esmolol:
< 15 min
Clinical effect of esmolol:
↓ HR without significantly ↓ BP at small doses
Metabolism of esmolol:
Plasma esterases (not the same as sux ones)
MoA of class III agents:
↓ conduction velocity and prolong refractory period/action potential
Indications for class III agents:
SV/V arrhythmias
Prophylaxis during cardiac surgery r/t a-fib
Preventative tx for patients w/ past cardiac death who cannot have AICD
Prototype and examples of class III agents:
Amiodarone*
Dronedarone
Sotalol
Amiodarine has properties of these classes:
III primarily
Also I, II, IV
MoA of amiodarone:
K+/Na+/Ca+ channel blocker
ɑ- and β-blocker
Indications for amiodarone:
Prophylaxis or acute tx of atrial and ventricular arrhythmias
Amiodarone is 1st line drug when:
Heart is resistant to electrical defibrillation
Dosing of amiodarone:
Bolus 150-300mg over 2-5 min (up to 5 mg/kg)
Infusion: 1mg/hr x 6hr, 0.5 mg/hr x 18hr
Half-time of amiodarone:
29 days!!
Metabolism of amiodarone:
Hepatic metabolism
Biliary/intestinal excretion
Therapeutic level of amiodarone:
1.0 - 3.5 mcg/ml
Protein binding/Vd of amiodarone:
96% protein bound Huge Vd (extensively taken into tissues)
Administration consideration with amiodarone:
Can cause phlebitis - give in a large vein
Pulmonary S/E and considerations of amiodarine:
Pneumonitis, fibrosis, edema, ARDS (all related to ROS) - high FiO2 can exacerbate so keep it low
MoA of class IV agents:
Block slow calcium channels, primarily in the AV node
Shortens phase 2 in myocytes to ↓ contractility
Indications for class IV agents:
SVT and rate control in afib/aflutter
NOT used for vent arrhythmias
Prototype and examples of class IV agents:
Verapamil*
Diltiazem
Dosing for verapamil:
2.5 - 10mg IV over 1-3 mins (max 20mg)
Infusion: 5 mcg/kg/min
Contraindicated drug with verapamil:
β-blockers
PK of verapamil:
Highly protein bound
Hepatic metabolism - active metabolite
Excreted in urine/bile
Half-time of verapamil:
6-8 hrs
S/E of verapamil:
Myocardial depression Hypotension Bradycardia Nausea Prolongation of NMBs
Dosing of diltiazem:
5-20 mg IV over 2 min
Infusion: 10 mg/hr
Diltiazem vs. verapamil:
Diltiazem has less myocardial depression and less interaction with β blockers
PK of diltiazem:
E1/2t: 4-6 hrs
Highly protein bound
Hepatic metabolism
Excreted in urine
S/E of diltiazem:
Myocardial depression Hypotension Constipation Bradycardia Nausea Prolongation of NMBs
Examples of class V agents:
Adenosine
Digoxin
Phenytoin
Atropine
MoA of adenosine:
Binds to A1 purine nucleotide receptors; activates adenosine receptors to open K+ channels/increase K+ current)
End result: slows SA and AV node conduction
Indications for adenosine:
Termination of SVT or diagnose VT
Dosing for adenosine:
6mg IV, rapid bolus followed by flush
Repeat if needed at 3 minutes, another 6-12mg IV
Half-time of adenosine:
< 10 seconds
Metabolism of adenosine:
Plasma/vascular endothelial cell enzymes
S/E of adenosine:
Excessive SA/AV node inhibition Flushing Headache Dyspnea Chest discomfort Nausea Bronchospasm
Contraindications for adenosine:
Asthma
Heart block
MoA of digoxin:
Increases vagal activity, thus ↓ activity of SA node/prolongs AV conduction
↓ HR, preload, afterload
Also positive inotrope
Dosing of digoxin:
0.5 - 1mg, divided doses over 12-24 hrs
Onset, half-time of digoxin:
Onset: 30-60 min
E1/2t: 36 hrs
Therapeutic level of digoxin:
0.5 - 1.2 ng/dl
PK of digoxin:
Weak protein binding
90% excreted by kidneys
S/E of digoxin:
Arrythymias, heart block, anorexia, nausea, diarrhea, confusion, agitation
Digoxin S/E potentiated by:
Hypokalemia, hypomagnesemia
Tx for digoxin toxicity:
Vent. arrhythmias: phenytoin
Pacing
Atropine
Antidote: digoxin immune Fab
Indications for phenytoin:
Suppression of vent. arrhythmias from digoxin toxicity
Refractory torsades de pointes
Dosage of phenytoin:
1.5 mg/kg IV every 5 min, up to 10-15 mg/kg
Can be painful IV!
Therapeutic levels of phenytoin:
10-18 mcg/ml
Indications for atropine:
Unstable bradyarrhythmias
Option for asystolic/PEA
Dosage for atropine:
0.4 to 1.0 mg IV, repeat as necessary
Onset/duration for atropine:
Onset: 1 min
Duration: 30-60 min
Metabolism of atropine:
Hepatic
Precaution with atropine dosing:
Less than 0.4mg can have paradoxical response
Penetrates BBB; has CNS effects
Drugs for afib during arthoscopy:
Good heart function: amiodarone
Poor heart function: digoxin
Drugs for SVT during a laparoscopy:
Normal heart function: CCB (diltiazem), β-blocker
Impaired heart function: no cardioversion; digoxin or amiodarone
Drugs for V-tach during AAA:
Defib first if unstable!
Amiodarone, lidocaine, procainamide
