Flashcards in Antiarrythmics Deck (60):
Explain the phases (0-4) of the action potential in cardiac cells. What channels are opening/closing? Which phases are the refractory period?
Phase 0: rapid depolarization (upstroke), Na fast in
Phase 1: partial repolarization, Na channels close
Phase 2: plateau, Ca slowly in
Phase 3: repolarization, Ca channels close, K slow out
Phase 4: pacemaker potential, return to resting potential
Refractory period is phases 1-3 (another signal can't be generated)
What is the intrinsic rate of SA node? AV node? Purkinje fibers?
SA has a higher resting potential of -55 (compared to -90 of most cells) so it fires more easily
How is the SA node controlled by SNS and PSNS?
SNS: B1 receptors activated, increases catecholamines (NE, epi), HR, automaticity, facilitates conduction of AV node
PSNS: M2 receptors activated, Decreases HR, inhibits AV conduction (ACh, vagal response)
What is altered automaticity?
Latent pacemaker cells take over SA node's role, escape beats
Ex: pain or stress can cause sinus tachycardia
What is delayed after-depolarization?
Normal action potential of cardiac cell triggers a train of abnormal depolarizations
Ex: this can be caused by drug or electrolyte imbalance
What is conduction block?
Impulse fails to propagate in non-conducting tissue
This can be due to damaged cardiac areas or because it is in its refractory period
What is re-entry?
Most common way arrhythmia is formed (most anti-arrhythmic drugs work on this)
Refractory tissue reactivated repeatedly and rapidly due to unidirectional block (due to ischemia or refractory period) which causes abnormal continuous circuit
How do the classes of antiarrhythmic drugs relate to the phases of cardiac conduction?
Class I: sodium channel blockers, phase 0
Class II: beta adrenergic blockers, phase 4
Class III: potassium channel blockers, phase 1-2
Class IV: calcium channel blockers, phase 2
Class V: unclassified
What are Class I agents? How do they work?
Block sodium channels which depress phase 0
This decreases depolarization rate and slows conduction velocity
What are class IA agents? Name a few.
Intermediate Na channel blockers
Decreased depolarization rate
Slows conduction velocity
Quinidine (this is the prototype, not used often), procainamide, disopyramide- most common, oral agent, moricizine- oral agent
What are class IB agents? Name a few
FAST Na channel blockers
Little effect on velocity of depolarization, but shortens action potential duration and shortens refractory period
Lidocaine (the prototype), mexiletine (oral agent for tachyarrhythmias), phenytoin
What is lidocaine used for?
FAST sodium channel blocker
Used in acute treatment/prevention of ventricular dysrhythmias, especially right after an MI
Vtach, Vfib, PVCs
1-1.5 mg/kg IV, infusion 1-4 mg/min (max dose 3 mg/kg)
Is lidocaine protein bound, what is the metabolism like? E1/2t?
50% protein binding
Active metabolite which prolongs E1/2t
E1/2t = 1.4-8 hours
Therapeutic plasma concentration 1-5 mcg/mL
10% renal elimination
What IMPAIRS metabolsm of lidocaine? What INDUCES it?
IMPAIRED by drugs such as cimetidine and propanolol or conditions like CHF, acute MI, liver dysfunction, GA
INDUCED by drugs like barbiturates, phenytoin, or rifampin
Adverse effects of lidocaine?
Hypotension, bradycardia, seizures, CNS depression, drowsy, dizzy, lightheaded, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment preexisting neuromuscular blockade
(Like with LA toxicity, CNS first, then myocardial depression to respiratory depression)
What are Class IC agents? Name some.
SLOW Na channel blockers
Potent decrease of depolarization rate (phase 0) and decreased conduction rate with increased action potential
Inhibit conduction through His-Purkinje system
Flecainide (the prototype), propafenone
What is Flecainide used for? (This is the same for propafenone)
Effective in treatment of suppressing ventricular PVCs and Vtach, also atrial tachyarrthmias, WPW syndrome (re-entry rhythm)
Has proarrhythmic side effects
What are Class II agents? What are they used for?
Beta-adrenergic antagonists. Depress phase 4 depolarization in SA node causing slowed HR, decrease in myocardial oxygen requirement (good for CAD pt), slows speed of conduction, prolongs P-R interval, decrease contractility/automaticity
Treats SVT, atrial and ventricular arrhythmias, during MI and reperfusion, treat tachyarrhythmias secondary to dig toxicity
Name some Class II agents.
Labetolol (off-label use because it blocks alpha and beta)
What is propranolol used for?
It is a nonselective beta-adrenergic antagonist
Used to prevent reoccurrence of tachyarrhythmias, both supraventricular and ventricular precipitated by sympathetic stimulation
Decreases phase 4, decreases automaticity and rate
Propranolol dose? Onset? Peak effect? Duration? E1/2t?
1 mg/min (total 3-6 mg) IV or 10-80 mg po
Onset 2-5 min
Peak effect 10-15 min, duration 3-4 hours
E1/2t 2-4 hours
Cardiac effects of propranolol?
Decreased HR, contractility, CO
Increased PVR, coronary vascular resistance
Decreased oxygen demand
Pharmacokinetics of propranolol? Therapeutic plasma level?
90-95% protein bound
Hepatic metabolism, weak metabolite
Therapeutic plasma level 10-30 mcg/mL
Propranolol side effects and cautions?
SE: bradycardia, hypotension, myocardial depression, fatigue, worsening bronchospasm, fever, rash, nausea, worsening Raynauds, interferency with glucose metabolism
Caution with reactive airway disease, hypovolemia, CHF, AV block
Metoprolol: what is it? Dose? Onset? E1/2t?
Selective B1 blocker
5 mg IV over 5 min; max dose 15 mg over 20 min
Onset 2.5 min
E1/2t 3-4 hours
Metabolized by liver
Can be used in mild CHF (because of selectivity)
What is esmolol? Dose? Duration? Effects?
Selective B1 blocker
Dose: 0.5 mg/kg IV over 1 min, then 50-300 mcg/kg/min
Duration: less than 15 min
Effects HR without decreasing BP significantly in small doses
Rapidly hydrolyzed by plasma esterases (not the same esterases as sux, no effect on sux metabolism)
What do class III agents do? Name some.
Block potassium ion channels resulting in prolonged depolarization and action potential duration, lengthened repolarization, prolong QT interval, increase automaticity (good for rate control)
Treat SVT, ventricular arrhythmias, control Afib
Amiodorone (the prototype), dronedarone, sotalol
What is Amiodarone?
Class III antiarrhythmic (also has class I, II, IV properties)
K/Na/Ca channel blocker, alpha and beta adrenergic antagonist
Prophylaxis or acute treatment of atrial and ventricular arrhythmias (refractory SVT, refractory VT/VF/AF)
First line drug of Vtach and Vfib resistant to defibrillation
What is the only rhythm that amiodarone is CONTRAINDICATED in?
Torsades de points because amiodarone prolongs QT, it can CAUSE torsades and does not treat this rhythm
Amiodarone dose? E1/2t?
Dose: bolus 150-300 mg IV over 2-5 min, up to 5 mg/kg, then 1 mg/hr x 6 hours, then 0.5 mg/hr x 18 hours
Prolonged E1/2t of 29 days!
Amiodarone metabolism/excretion/protein binding?
Hepatic metabolism, active metabolite
Therapeutic plasma level 1-3.5 mcg/mL
Extensive protein binding 96%
Adverse effects of amiodarone?
Pulmonary toxicity, photosensive rashes, grey/blue skin, thyroid abnormalities, corneal deposits, CNS/GI disturbance, pro-arrhythmic effects (torsades, prolongs QT interval), heart block, hypotension, decreases contractility, nightmares, abnormal LFT, inhibits P-450 (so reduces clearance of digoxin, warfarin)
What are class IV agents? Name some.
Block slow calcium channels, primarily at AV node
Works at phase 2 (plateau)
Decreases contractility (neg iontropic), vasodilation, hypotension
Used for ventricular rate control in Afib/Aflutter
NOT used for ventricular arrythmias!
Verapamil (the prototype), diltiazem
Dose 2.5-10 mg IV over 1-3 min (max dose 20 mg)
Continuous infusion 5mcg/kg/min
What is the big contraindication for verapamil?
B-blockers. Will cause heart block
Metabolism/excretion pharmacokinetics of verapamil? E1/2t?
Highly protein bound
Hepatic metabolism, with active metabolite
Excreted in urine and bile
E1/2t 6-8 hours
Side effects of Verapamil?
Myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs neuromuscular blockers
Anesthetic considerations of verapamil?
Myoardial depression and vasodilation with inhalational agents
Potentiate neuromuscular blockers
Increase LA toxicity risk
With dantrolene can cause hyperkalemia
Decreases clearance of digoxin
Diltiazem is a class IV antiarrhythmic, ca channel blocker
5-20 mg IV (0.25-0.35 mg/kg) over 2 min
Continuous infusion 10 mg/hr
Diltiazem pharmacokinetics? E1/2t?
E1/2t 4-6 hours
Highly protein bound
Excreted in urine
Diltiazem side effects?
Less myocardial depression compared to verapamil
Myocardial depression, hypotension, constipation, bradycardia, nausea, prolonged effect of NM blockers
List some class V agents
What is Adenosine? What is it used for?
Bines to A1 purine nucleotide receptors which activate adenosine receptors to open K channels and increase K currents. This slows SA and AV node conduction
Used for acute reasons only, to terminate SVT or diagnose Vtach
Not for Afib/Aflutter
6 mg IV, rapid bolus
Repeat if necessary after 3 min, 6-12 mg IV
Less than 10 sec!!
Eliminated by plasma and vascular endothelial cell enzymes
Adenosine side effects? Contraindications?
SE: excessive AV or SA node inhibition, facial flushing, headache, dyspnea, chest discomfort, nausea, bronchospasm
Contraindicated in asthma or heart block
What is digoxin, what is it used for?
Cardiac glycoside steroid, increase ca which increases inotropy,
Decreases HR, preload, and afterload
Increases vagal activity
Slows AV conduction by increasing refractory period
Treats CHF, used for Afib or Aflutter (controls ventricular rate)
Digoxin dose? Onset?
0.5-1 mg in divided doses over 12-24 hours
Onset of action 30-60 min
Digoxin e1/2t, therapeutic levels, pharmacokinetics?
E1/2t 36 hours
Narrow therapeutic index, 0.5-1.2 mcg/mL
Weak protein binding
90% excreted by kidneys
Reduce dose in elderly/ renal impairment
Digoxin adverse effects?
Arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
Potentiated by hypokalemia and hypomagnesemia
Toxicity can happen easily due to the small range of the therapeutic index
Digoxin toxicity treatment?
Phenytoin for ventricular arrhythmias
Antidote: digoxin immune Fab
Class IA agent, resembles effects of lidocaine
Not used often anymore except to treat torsades de points
Also can be used to suppress ventricular arrhythmias associated with digitalis toxicity or be used to treat ventricular tachycardias
Phenytoin dose? Therapeutic blood levels?
Dose: 1.5 mg/kg IV every 5 min up to 10-15 mg/kg
Therapeutic blood levels 10-18 mcg/mL
Phenytoin pharmacodynamics? E1/2t?
Metabolized by liver
Excreted by urine
E1/2t 24 hours
Phenytoin adverse effects?
Partially inhibits insulin secretion
Bone marrow depression
What is atropine? What is it used for?
Muscarinic receptor antagonist
Used to treat unstable bradyarrhythmias
Also used for asystole and PEA
Atropine dose? Onset? Duration?
0.4-1 mg IV, repeat as necessary
Onset less than 1 min
Duration 30-60 sec
Metabolized by liver