Antiarrhythmics Flashcards
FAST Cardiac AP
Cardiomyocyte (cardiac cells) action potential
FAST Cardiac AP
Phase 0
Rapid depolarization
Na+ channel opens → Na+ inward flow
FAST Cardiac AP
Phase 1
Begin repolarization
Na+ channel closes
FAST Cardiac AP
Phase 2
Plateau
Slow Ca2+ channels open → Ca2+ flows inward
Ø net ion movement
FAST Cardiac AP
Phase 3
Repolarization
Ca2+ channel close
K+ channel open → slow outward K+ efflux
FAST Cardiac AP
Phase 4
Pacemaker potential
Return to resting membrane potential
Diastole -90mV
SLOW Cardiac AP
Pacemaker action potential
SA/AV node
SLOW Cardiac AP
Phase 4
No resting membrane potential
Gradual depolarization
Slow inward Na+ & Ca2+ currents
Funny channels
SLOW Cardiac AP
Phase 0
Slower depolarization
Ca2+ mediated
Upstroke
Threshold -40mV
SLOW Cardiac AP
Phase 3
VGCa2+ channels close rapidly
↓Na+ permeability
↑K+ permeability → repolarization
Cardiac Pacemaker
SA node
NSR
Normal sinus rhythm
60-100bpm (70-80)
AV Node Conduction Rate
40-60bpm
Purkinje Fibers Intrinsic Rate
15-40bpm
Arrhythmia
Disturbance in the heart electrical activity
Atrial, junctional, or ventricular
When to intervene & treat arrhythmias?
Arrhythmias → cardiac dysfunction
↑demand ↓CO → hemodynamic compromise
Arrhythmia Types
Altered Automaticity
Latent pacemaker cells take over the SA node role → ectopic beats
Arrhythmia Types
Delayed After-Depolarization
Normal cardiac cell AP triggers abnormal depolarizations
Repetitive discharge or arrhythmias
Arrhythmia Types
Re-Entry
Refractory tissues reactivated repeatedly & rapidly d/t unidirectional block → causes abnormal continuous circuit
Arrhythmia Types
Conduction Block
Impulse fail to propagate in non-conducting tissues d/t ischemia, scarring, fibrosis (damaged tissue)
Non-Pharmacological Arrhythmia Treatments
Acute: - Vagal maneuvers - Cardioversion Prophylactic: - Radiofrequency catheter ablation - Implantable defibrillator Pacing - external, temporary, or permanent
Class I Antiarrhythmics
Phase 0 Na+ channel blockers → decreases AP propagation (depolarization rate) & slows conduction velocity
Sub-classes IA/B/C
Used to treat SVT, Afib, & Wolfe-Parkinson White
Class IA
Disopyramide (Norpace), Procainamide (ACLS), & Quinidine
Slow conduction velocity & pacemaker rate
Intermediate Na+ channel blocker (dissociation) ↓depolarization rate
Direct depressant effect on SA/AV node
↑AP duration
Used to treat atrial & ventricular arrhythmias
Class IA Prototype
Quinidine
No longer manufactured
Disopyramide (Norpace)
Class IA
Suppresses atrial & ventricular tachyarrhythmias
PO route
Significant myocardial depression & potential to precipitate CHF & HoTN
Procainamide
Class IA
1° used to treat ventricular tachyarrhythmias (less effective w/ atrial)
ACLS
Procainamide PK
15% protein binding
Elimination 1/2 time 2hrs
Procainamide Dose
Load 100mg IV Q5min until rate controlled
Max 15mg/kg
Followed by 2-6mg/min infusion
Procainamide SE
Myocardial depression → HoTN
Syndrome that resembles lupus erythematous
Monitor blood levels*
Therapeutic Procainamide Levels
4-8mcg/mL
What drugs replaced IA drugs? Why?
Class IC
Toxicity potential to precipitate heart failure
Class IB
Lidocaine, Mexiletine, & Phenytoin
Fast Na+ channel blocker (dissociation) Inhibits Na+ ion influx Minimal effect on max velocity depolarization rate Shortens AP duration & refractory period ↓automaticity
Lidocaine
Class IB prototype
Used to treat ventricular arrhythmias; particularly effective to suppress re-entry rhythms (Vtach, fibrillation, PVCs)
Lidocaine PK
50% protein binding
Extensive 1st pass effect
Hepatic metabolism w/ active metabolite that prolong elimination 1/2 time
10% renal elimination
Lidocaine Dose
1-1.5mg/kg IV
Infusion 1-4mg/min
Max dose 3mg/kg
Lidocaine SE
Toxicity
HoTN, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheaded, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest, potential to augment pre-existing neuromuscular blockade
Mexiletine
Class IB
PO agent
Chronic ventricular tachyarrhythmias suppression
- Consider cardiac clearance prior to surgery
150-200mg Q8H
Amine group avoids hepatic 1st pass metabolism
Phenytoin (Dilantin)
Class IB
Used to suppress ventricular arrhythmias associated w/ dig toxicity, other ventricular tachycardias, or torsades de pointes
Phenytoin PK
IV mix in NS (precipitates in D5W) Pain or thrombosis when admin in peripheral IV Rapid infusion → HoTN Hepatic metabolism; renal excretion Elimination 1/2 time 24hrs
Phenytoin Dose
1.5mg/kg IV Q5min up to 10-15mg/kg
Phenytoin SE
CNS disturbances, partially inhibits insulin secretion, bone marrow suppression, nausea
Associated w/ Stevens-Johnson syndrome
Toxicity - CNS symptoms, vertigo, ataxia, slurred speech
Therapeutic Phenytoin Levels
10-18mcg/mL
Class IC
Flecainide & Propafenone
Slow Na+ channel blocker (dissociation)
Potent ↓depolarization rate (phase 0) & conduction rate ↑AP & shortens AP duration
Suppresses SA node w/ marked His-Purkinje conduction inhibition
Used to treat PVCs or Vtach & atrial Wolfe-Parkinson White
Class IC Prototype
Flecainide
PO agent
Used to suppress PVCs, ventricular tachycardia, atrial tachyarrhythmias, Wolf-Parkinson White syndrome
Pro-arrhythmic SEs
Propafenone
Class IC
PO agent
Suppresses ventricular & atrial tachyarrhythmias
Pro-arrhythmic SEs
Class II Antiarrhythmics
β adrenergic blockers (phase 4) ↓SA node discharge → slows HR ↓myocardial oxygen requirements
Slower conduction via atrial tissues & AV node → prolonged PRI interval ↑AP duration ↓automaticity
Used to treat SVT, atrial (fib or flutter) & ventricular arrhythmias, suppress & treat ventricular dysrhythmias during MI & reperfusion, tachyarrhythmias 2° dig toxicity
Propranolol, Esmolol, Metoprolol, & -olols
Class II Prototype
Propranolol
Non-selective β adrenergic antagonist
Used to prevent supra-/ventricular tachyarrhythmias reoccurrence precipitated by sympathetic stimulation
↑SA node conduction
Propranolol PK
Onset 2-5min
Peak 10-15min
DOA 3-4hrs
Elimination 1/2 time 2-4hrs
Propranolol SE
↓HR, contractility, CO ↑SVR & coronary vascular resistance Improved filling ↓MVO2 Bronchoconstriction
Metoprolol
Class II
Selective β1 antagonist
Metoprolol Dose
5mg IV over 5min
Max dose 15mg over 15min
Metoprolol PK
Onset 2.5min
DOA 3-4hrs
Hepatic metabolism
Okay in mild CHF
Esmolol
Class II
Selective β1 antagonist
Esmolol Dose
0.5mg/kg IV bolus over 1min
Infusion 50-300mcg/kg/min
Esmolol DOA
< 10min
Hydrolysis via plasma esterases
Esmolol SE
Effects HR w/o significantly ↓BP (in small doses)
Class III Antiarrhythmics
K+ channel blockers (phase 2/3)
Prolongs cardiac depolarization ↑AP duration & lengthens repolarization
Used to treat supra- & ventricular arrhythmias, prophylaxis in cardiac surgery patients w/ Afib, control rhythm in Afib, preventative therapy in patients not candidates to receive internal cardiac defibrillator
Amiodarone, Sotalol. Dofetilide, & Ibutilide
Class III Prototype
Amiodarone
Class I, II, & IV antiarrhythmic properties
K+/Na+/Ca2+ channel blocker
α & β adrenergic antagonist
Used in prophylaxis or treatment atrial & ventricular arrhythmias (refractory SVT/Vtach/Vfib or atrial fibrillation)
Amiodarone PK
Extensive protein binding 96% Lipophilic w/ large Vd Prolonged elimination 1/2 life 29 days Hepatic metabolism w/ active metabolite Biliary & intestinal excretion
Amiodarone Dose
Bolus 150-300mg IV over 2-5min up to 5mg/kg
Followed by 1mg/hr infusion x6hrs then 0.5mg/hr x18hrs
Amiodarone SE
Pulmonary toxicity/edema ARDS Photosensitivity rashes Grey/blue skin discoloration Thyroid abnormalities Corneal deposits CNS/GI disturbances Pro-arrhythmic effects (Torsades de pointes) Heart block HoTN Sleep disturbances Abnormal LFTs Inhibits hepatic P450
Therapeutic Amiodarone Level
1-3.5mcg/mL
What’s the 1st line Vtach or Vfib treatment when resistant to electrical defibrillation?
Amiodarone
Sotalol
Class II/III
Non-selective β adrenergic antagonist & K+ channel blocker
*Caution in patients w/ asthma
Used to treat severe sustained ventricular tachycardia & Vfib, prevent tachyarrhythmias reoccurrence, especially atrial fib & flutter
Renal excretion
Sotalol SE
Prolonged QT interval Bradycardia Myocardial depression Fatigue Dyspnea AV block
Dofetilide & Ibutilide
Class III
Used to convert atrial fib or flutter to NSR & maintenance NSR after conversion
Pro-arrhythmic prolongs QT interval
Class IV Antiarrhythmics
Calcium channel blockers (phase 2) block slow Ca2+ channels
Used to treat vascular (angina, HTN, pulm HTN, cerebral artery spasm, Raynaud, migraine) & non-vascular conditions (asthma, esophageal spasm, dysmenorrhea, premature labor)
Verapamil, Diltiazem, & Nifidipine
Ca2+ Ion Channels
Locations
- Skeletal muscle cell membranes
- Vascular smooth muscle
- Cardiac muscle
- Mesenteric muscle
- Neurons
- Glandular cells
Ca2+ Channel Blockers
MOA
Bind to the receptor on VGCa2+ ions to maintain the channels in an inactive or closed state
Block slow Ca2+ channels → decreases conduction through the AV node and shortens phase 2 (ventricular myocytes AP plateau)
Interfere with inward Ca2+ ion movement across myocardial & vascular smooth muscle cells
- Primary site at AV node
↓heart contractility
Ca2+ Channel Blockers
Subtypes
L, T, N, & P channels
L-type Ca2+ channel determines ______
Vascular tone & cardiac contractility
↓Ca2+ keeps intracellular Ca2+ levels low
Ca2+ Channel Blockers
CV Effects
↓contractility/inotropy
↓HR
↓SA node activity
↓conduction rate & impulses via AV node
→ vascular smooth muscle relaxation ↓SVR & BP (arterial > venous)
Ca2+ channel blockers are used to treat:
- SVT & ventricular rate control in A fib & A flutter
- Used to prevent SVT reoccurrence
NOT used to treat ventricular arrhythmias
Class IV Prototype
Verapamil
- Synthetic papaverine derivative
- Less vasodilation
Verapamil 1° Action Site
AV node
- Depresses the AV node
- Negative chronotropic effect on SA node
- Negative inotropic effect on myocardial muscle
- Moderate vasodilation on coronary as well as systemic arteries
Verapamil Clinical Usages
SVT, vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal & fetal dysrhythmias, premature labor onset
Verapamil PK
Highly protein bound
PO absorption w/ extensive hepatic 1st pass
Active metabolite - Norverapamil
Renal & bile excretion (urine almost unchanged)
Oral peak 30-45min
IV peak 15min
Elim 1/2 time 6-12 hours
Verapamil SE
Myocardial depression, HoTN (treatment = 1G Ca2+ gluconate), bradycardia, constipation, nausea, potentiates NMB effects
LA activity or toxicity w/ regional
Verapamil Dose
2.5-10mg IV over 1-3min (max dose 20mg)
Continuous infusion 5mcg/kg/min
Do NOT administer Verapamil IV w/ ______
β blocker
Verapamil Drug Interactions
Verapamil & β-blockers → heart block
Verapamil ↑LA toxicity risk
Verapamil & Dantrolene → hypokalemia d/t slowing inward K+ ions movement → CV collapse
Diltiazem
Class IV
Benzothiazepine derivative
Principle action site = AV node
Intermediate potency b/w Verapamil & Nifedipine
Minimal CV depressant effects
Used to treat SVTs & HTN
Diltiazem Clinical Usages
SVT, vasospastic angina pectoris, HTN, hypertrophic cardiomyopathy, maternal & fetal tachydysrhythmias
1st line SVT treatment
DILTIAZEM
Diltiazem PK
PO onset 15min Peak in 30min 70-80% protein bound Excreted via bile & urine (inactive metabolite) Elim 1/2 time 4-6 hours
↑dose w/ hepatic disease
Mixed cardiac & vascular effects - myocardial depression, HoTN, bradycardia, & constipation
Nifedipine
Class IV
Dihydropyridine derivative
Used to treat angina pectoris
1° action site = peripheral arterioles
Nifedipine PK
IV, PO, or sublingual PO effects in 20min Peaks in 60-90min 90% protein bound Hepatic metabolism Renal excretion Elim 1/2 time 3-7 hours
Nifedipine SE
Coronary & peripheral vasodilation (properties > Verapamil)
Little to no effect on the SA or AV node
↓SVR & BP
Reflex tachycardia
→ myocardial depression in patients w/ LV dysfunction or on β-blockers
Ca2+ Channel Blockers SE
Cancer w/ prolonged administration
Cardiac problems → hear block
Bleeding d/t platelet dysfunction
GI constipation
Vertigo, HE, flushing, HoTN, paresthesias, & muscle weakness
Induce renal dysfunction
Coronary vasospasm w/ abrupt discontinuation (slow wean to discontinue)
Ca2+ Channel Blockers
Drug Interactions
Myocardial depression & vasodilation w/ inhalational agents
Potentiate NMBs
Interact w/ Ca2+ mediated platelet dysfunction
↑plasma Digoxin concentration via ↓plasma clearance
H2 antagonists (Ranitidine & Cimetidine) alter hepatic enzyme activity → potential to ↑Ca2+ channel blockers plasma levels
Ca2+ Channel Blockers Toxicity
↑chronotropy
Reverse w/ IV Ca2+ or Dopamine administration
What Ca2+ channel blocker has the greatest impact on coronary artery dilation?
Nicardipine
Table 18-2
Ca2+ channel blocker pharmacologic effects (Verapamil, Nifedipine, Nicardipine, & Diltiazem)
Clevidipine
Class IV
Dihydropyridine
Blocks 1° L-type channels
POTENT vasodilator
Metabolism via plasma esterases → reflex tachycardia & rebound HTN when d/c
Clevidipine Dose
Bolus 1mg
1-2mg/hr double every 90sec
MAX 20mg/hr (up to 32mg/hr short duration)
Clevidipine Onset
< 30 seconds
Clevidipine DOA
< 1 min
Class V Antiarrhythmics
Other (unclassified drugs)
Different MOA - not on ion channels or unknown
Adenosine, Digoxin, Phenytoin (Dilantin), Atropine, & Magnesium
Adenosine
Class V
Acute treatment ONLY
Used to treat SVT or diagnose V tach
Adenosine MOA
Binds to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels & ↑K+ currents) shortens AP
Slows AV node conduction
↓excitability (hyperpolarization)
Adenosine PK
Elim 1/2 time < 10 seconds
Metabolism via plasma & vascular endothelial cell enzymes
Adenosine Dose
6mg IV rapid bolus 1st dose 60% effective
Repeat after 3min 6-12mg 2nd dose 90%
20mL rapid flush via large bore PIV or central line
Access closest to the heart
Adenosine SE
Facial flushing, headache, dyspnea, chest discomfort, bronchospasm, excessive AV or SA nodal inhibition, & nausea
Contraindicated in asthma or heart block (slows AV node conduction)
Digoxin
Class V
Cardiac glycoside
Used to treat A fib or A flutter (controls ventricular rate) especially w/ impaired heart function
Digoxin MOA
↑vagal activity ↓SA node activity & prolongs conduction impulses via AV node
↓HR, preload, & afterload
Slows AV conduction via ↑AV node refractory period
Positive inotropy used to treat CHF
Digoxin PK
Onset 30-60min Elim 1/2 time 36 hours Narrow therapeutic index Weak protein binding 90% renal excretion
Reduce dose in elderly or renal impaired patients
Digoxin Dose
0.5-1mg in doses divided over 12-24 hours
Therapeutic Digoxin Level
0.5-1.2ng/mL
Digoxin SE
Arrhythmias, heart block, agitation, anorexia, nausea, diarrhea, confusion
- Potentiated by hypokalemia & hypomagnesemia
Digoxin Toxicity Treatment
Phenytoin (ventricular arrhythmias)
Pacing
Atropine
Maintain normal electrolyte levels
Magnesium
Class V
MOA at Na+, K+, & Ca2+ channels
Used to treat Torsades de pointes
Magnesium Dose
1 gram IV over 20min
Antiarrhythmic Agents
Used to prevent, suppress, or treat a disturbance in cardiac rhythm
- A fib, A flutter, SVT, V tach, V fib, brady arrhythmias, heart block
