Antiarrhythmic Agents Flashcards
P wave
atria contraction
QRS wave
ventricular contraction
T wave
ventricular repolarization
PR interval
starts beginning of atrial depolarization to beginning of ventricular depolarization
ST segment
all cells depolarized
Phase 0 in Fast AP
rapid depolarization (fast Na+ channels open, influx of Na+)
Phase 1 in Fast AP
begin repolarization (K+ channels open, Na+ channels close)
Phase 2 in Fast AP
plateau phase (slow Ca++ channels open)
Phase 3 in Fast AP
repolarization (Ca++ channels close, K+ efflux)
Phase 4 in Fast AP
pacemaker potential, return to RMP
Refractory period
cannot generate another action potential, Na+ channels not in ready confirmation
Definition of arrhythmia
disturbance in the electrical activity of the heart
How are arrhythmias classified?
site of origin (atrial, junctional, vascular), complexes on ECG (narrow, broad), heart rhythm (regular, irregular), heart rate (increased, decreased)
Altered automaticity
latent pacemaker cells take over the SA node’s role, escape beats
ex. sinus bradycardia, tachycardia
Delayed after depolarization
normal action potential of cardiac cell triggers a train of abnormal depolarizations, leads to triggered arrhythmia
ex. Ca++ levels, R on T phenomena
Re-entry
refractory tissue reactivated repeatedly and rapidly d/t unidirectional block = abnormal continuous circuit
ex. WPW
Conduction block
impulse fail to propagate in non-conducting tissue
ex. heart blocks from tissue damage, fibrosis
Factors underlying cardiac arrhythmias
arterial hypoxemia, electrolyte imbalance, acid base abnormalities, myocardial ischemia, altered SNS activity, bradycardia, certain drugs, enlargement of a failing ventricle
Acute non-pharmacological treatment
vagal maneuvers, cardioversion, carotid massage
Prophylaxis non-pharmacological treatment
radiofrequency catheter ablation, implantable defibrillator
What non-pharmacological treatment can be external, temporary, or permanent?
pacing
Antiarrhythmic agents are used to..
prevent, suppress, or treat a disturbance in cardiac rhythm
Class I antiarrhythmic
sodium channel blockers - work at phase 0
Class II antiarrhythmic
beta adrenergic blockers - work at phase 4
Class III antiarrhythmic
potassium channel blockers - works at phase 2/3
Class IV antiarrhythmic
calcium channel blockers - works at phase 2
Class IA effect and drug examples
moderate depression and prolonged repolarization
ex. quinidine, procainamide, disopyramide
Class IB effect and drug examples
weak depression and shortened repolarization
ex. lidocaine, mexiletine, phenytoin, tocainide
Class IC effect and drug examples
strong depression with little effect on repolarization
ex. flecainide, propafenone, moricizine
Class II examples
esmolol, propranolol, metoprolol, timolol, pindolol, atenolol, acebutolol, nadolol, carvedilol
Class III examples
amiodarone, bretylium, sotalol, ibutilide, dofetilide
Class IV examples
verapamil, diltiazem
What rhythms are class I agents used to treat?
SVT, afib, WPW
How are Class IA agents eliminated?
hepatic metabolism
Disopyramide - Class IA Agent
suppresses atrial and ventricular tachyarrhythmias
taken orally
significant myocardial depressant effects so can cause CHF and hypotension
Why are Class IA agents not used commonly?
They cause toxicity that can lead to heart failure
Procainamide - Class IA Agent
Use, Dose, Side Effects
Use: treatment of ventricular tachyarrhythmias
Dose: loading 100mg IV q 5 mins until rate controlled (max 15 mg/kg), 2-6 mg/min infusion
Elimination half time: 2 hours
Therapeutic level: 4 - 8 mcg/mL
S/E: myocardial depression, hypotension, syndrome resembling lupus erythematous
Flecainide - Class IC Agent
treats ventricular PVCs, ventricular tachycardia, atrial tachyarrhythmias, WPW
oral agent
pro-arrhythmic side effects
Propafenone - Class IC Agent
treats ventricular and atrial tachyarrhythmias
oral agent
pro-arrhythmic side effects (Torsades)
Lidocaine - Class IB Agent
Pharmacokinetics
treats ventricular arrhythmias: ventricular tachycardia, fibrillation, PVCs (NOT SVT)
50% protein bound
hepatic metabolism - active metabolite
What impairs Lidocaine’s metabolism?
Cimetidine, Propranolol, CHF, acute MI, liver dysfunction, GA
What induces Lidocaine’s metabolism?
Barbiturates, Phenytoin, Rifampin
Lidocaine
Dose, Side Effects
Not pro-arrhythmic!
Dose: 1-1.5 mg/kg IV, 1-4 mg/min infusion (max 3 mg/kg)
A/E: hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, cardiac arrest, augment NMB
Mexiletine - Class IB Agent
Oral agent has an amine side group so it avoids the 1st pass effect 150-200 mg q8h can be used for neuropathic pain needs cardiac clearance before surgery
Phenytoin - Class IB Agent
treat ventricular arrhythmias associated with digitalis toxicity, torsades de pointes
MIX IN NS not D5W!
Dose: 1.5 mg/kg IV q5min up to 10-15 mg/kg
Metabolized in the liver, excreted in urine
Elimination 1/2 time: 24 hours
Phenytoin
Therapeutic level, toxicity, A/E
Therapeutic level 10-18 mcg/mL
can cause pain or thrombosis, bone marrow depression, nausea, Steven’s Johnson Syndrome, partially inhibits insulin secretion
severe hypotension if given rapidly
toxicity: CNS disturbances, vertigo, ataxia, slurred speech
What arrhythmias are Class II agents used?
SVT, atrial and ventricular arrhythmias, ventricular dysrhythmias during MI and reperfusion, SVT, afib, aflutter, secondary to digoxin toxicity
Propranolol - Class II Agent`
Nonselective beta blocker Onset: 2-5mins Peak: 10-15mins Elimination 1/2 time: 2-4hours Cardiac effects: decreased HR, contractility, CO, increased PVR, coronary vascular resistance, lowered oxygen demand
What is Propranolol used for?
prevent reoccurrence of tachyarrhythmias precipitated by sympathetic stimulation
Metoprolol - Class II Agent
selective Beta 1 Dose: 5mg IV over 5 minutes, max 15 mg over 20 mins. Onset: 2.5 min Half life 3-4 hours metabolized by liver
Esmolol - Class II Agent
selective Beta 1 Dose: 0.5 mg/kg IV bolus over 1 min, 50-300 mcg/kg/min Duration: <10 minutes Effects HR w/o decreasing BP metabolized by plasma esterases
Class III Agents are used to treat which arrhythmias?
supraventricular and ventricular arrhythmias, prophylaxis in cardiac surgery patients who are at risk of afib, those who are not eligible for ICD, afib
Amiodarone - Class III Agent
also has Class I, II, and IV properties
used for prophylaxis or acute treatment for atrial and ventricular arrhythmias (refractory SVT, VTach, VFib, AF)
Which agent is the 1st line drug for refractory vtach/vfib to defibrillation?
Amiodarone
Amiodarone
Pharmacokinetics
Dose: bolus 150-300 mg IV over 2-5minutes up to 5mg/kg, 1mg/hr x 6 hours then 0.5 mg/hr x 18 hours elimination half life 29 DAYS! hepatic metabolism, active metabolite extensive protein bound large Vd
Amiodarone Adverse Effects
pulmonary toxicity, pulmonary edema, ARDS, photosensitive rashes, discoloration, thyroid abnormalities, corneal deposits, CNS/GI disturbance, proarrhythmic effects, heart block, hypotension, sleep disturbances, abnormal LFT, inhibits hepatic P450
Sotalol - Class II and III Agent
nonselective beta blocker and K+ channel blocker
treat severe sustained vtach/vfib, prevent reoccurrence of tachyarrhythmias (afib and flutter)
S/E: prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block
excreted in urine
Which agent(s) should be avoided in patients with asthma?
- sotalol d/t beta blocker effect on beta 2 receptors causing bronchoconstriction
- adenosine can cause bronchospasm, dyspnea
Dofetilide and Ibutilide - Class III Agents
used for conversion of afib or flutter to NSR
proarrhythmic - prolongs QT interval
Where are calcium ion channels?
cell membranes of skeletal muscle, vascular smooth muscle, cardiac muscle, mesenteric muscle, neurons, glandular cells
How are calcium channel blockers classified?
Based on structure:
Phenyl-alkyl-amines AV node (Verapamil)
Benzothiazepines-AV node (Diltiazem)
1,4-dihydropyridines-arterial beds (Nifedipine)
Vascular uses for calcium channel blockers
angina, systemic HTN, pulmonary HTN, cerebral arterial spasm, Raynaud’s disease, migraine
Nonvascular uses for calcium channel blockers
bronchial asthma, esophageal spasm, dysmenorrhea, premature labor
Which agents are complementary to nitrates and good at dilating the coronary arteries?
Class IV Agents - Calcium channel blockers
decrease contractility
Which Calcium channel subtype is important in determining vascular tone and cardiac contractility?
L type channels
Calcium channel blocker effects
decreased contractility, HR, SA node activity, rate of conduction of impulses via AV node, vascular smooth muscle relaxation (decreased SVR and BP), decreased O2 demand
What arrhythmias are treated by Class IV agents?
SVT and ventricular rate control in afib/flutter, prevent reoccurrence of SVT
NOT used in ventricular arrhythmias
Verapamil - Class IV Agent
depresses the AV node, negative chronotropy, inotropy, moderate vasodilation
used for SVT, vasospastic angina pectoris, HTN, HCM, premature onset of labor
highly protein bound
hepatic first pass metabolism, active metbolite
oral peak: 30-45 mins, 15 mins IV
elimination 1/2 time: 6-12 hours
Verapamil
Dosing, Side Effects
Dose: 2.5-10 mg IV over 1-3min (max 20mg), 5 mcg/kg/min infusion
Side effects: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMB
What can we give to decrease the chance of hypotension with administration of Verapamil?
Calcium gluconate
Which class of drugs should not be given with Verapamil?
Beta blockers = will cause heart block
Which drug has local anesthetic activity?
Verapamil, increases the risk of local anesthetic toxicity
Diltiazem - Class IV Agent
1st line for SVT, also used for HTN, vasospastic angina, HCM
minimal CV depressant effects
Dose: 0.25-0.35 mg/kg over 2 mins can repeat in 15 minutes, 10 mg/hour infusion
Onset: 15 minutes
Peak: 30 minutes
highly protein bound
elimination 1/2 time 4-6 hours
Nifedipine - Class IV Agent
used for angina pectoris coronary and peripheral vasodilator properties little to no effect on SA and AV node Onset: 20 minutes Peak: 60-90 minutes highly protein bound hepatic metabolism elimination 1/2 time: 3-7 hours
Calcium Channel Blockers Drug interactions
- myocardial depression and vasodilation with inhalational agents
- potentiate NMB
- verapamil and beta blockers = heart block
- verapamil increases risk of LA toxicity
- verapamil and dantrolene = hyperkalemia d/t slowing of K+ movement = cardiac collapse
- CCBs interact w/ calcium mediated platelet function
- digoxin w/ CCB increases plasma concentration of digoxin
- H2 antagonists increase plasma levels of CCB
Toxicity of CCB can be reversed by
IV admin of calcium or dopamine
Abrupt discontinuation of CCB can cause
coronary vasospasm
Adenosine MOA
binds to A1 purine nucleotide receptors to open K+ channels and increase K+ currents, slows AV nodal conduction
used for SVT/diagnosis of VT
Adenosine
Pharmacokinetics/Dosing
Dose: 6 mg rapid bolus, after 3 minutes 6-12 mg
onset: <10 seconds
eliminated by plasma and vascular enzymes in RBCs
S/E: excessive AV or SA node inhibition, flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm
Digoxin - cardiac glycoside
increases vagal activity, decreases SA node activity and prolongs conduction of impulses thru the AV node
positive inotrope by blocking the Na+/K+ ATP pump, increasing Ca++
Digoxin Dosing and Pharmacokinetics
dose: 0.5-1 mg over 12-24 hours
onset: 30-60 mins
elimination 1/2: 36 hours
weak protein binding
excreted by kidneys
narrow therapeutic index: 0.5-1.2 ng/mL
Digoxin Adverse Effects
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
How to treat digoxin toxicity
phenytoin, pacing, atropine
Magnesium
works at Na+, K+, Ca++ channels
used for torsades de pointes
dose: 1 gm over 20 minutes
