Antiarrythmics Flashcards
Classes of antiarrythmics
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.)
Phases of cardiac cycle
Phase 0 rapid depolarization (fast sodium channels open; fast inward flow of Na+ ) Phase 1 begin repolarization (sodium channels close) Phase 2 plateau (slow calcium channels open; slow inward flow of Ca2+) Phase 3 repolarization (calcium channels close; potassium channels open; slow outward K+ current) Phase 4 pacemaker potential; return to resting membrane potentials Refractory period (phases 1-3) (periods of repolarization)
Sympathetic stimulation effects
(ß1 receptors activated) Increases catecholamines Increased heart rate (positive chronotropic effect) Increased automaticity Facilitation of conduction of AV node
Parasympathetic system effects
(M2 muscarinic receptors)
Decreases heart rate
Inhibits AV conduction
Classification of arrythmias
Site of origin of abnormality (atrial/ junctional / ventricular)
Complexes on ECG (narrow/broad)
Heart rhythm (regular/irregular)
Heart rate is increased or decreased
Mechanisms of Arrhythmia Production
Altered automaticity - latent pacemaker cells take over the SA node’s role; escape beats
Delayed after-depolarization - normal action potential of cardiac cell triggers a train of abnormal depolarizations
Re-entry - refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit
Conduction block – impulse fail to propagate in non-conducting tissue
Reasons for arrythmias
Arterial hypoxemia Electrolyte imbalance Acid-base abnormalities Myocardial ischemia Altered sympathetic nervous system activity Bradycardia Administration of certain drugs Enlargement of a failing ventricle
Class I agents
Block sodium channels which depresses Phase O in depolarization of the cardiac action potential with resultant decreases in action potential propagation (decrease in depolarization rate) and slowing of conduction velocity
Class IA
Quinidine - Class IA Prototype
Procainamide
Disopyramide
Moricizine
Intermediate Na+ channel blocker (intermediate dissociation) Decreased depolarization rate (phase 0) Decreased conduction velocity Prolonged repolarization Increased AP duration
Disopyramide
Suppresses atrial and ventricular tachyarrhythmias
Oral agent
Has significant myocardial depressant effects and can precipitate congestive heart failure and hypotension
Class IB Agents
Lidocaine - Class IB Prototype
Mexiletine
Tocainide
Phenytoin
Fast Na+ channel blocker (fast dissociation)
Alters the action potential by inhibiting sodium ion influx via rapidly binding to and blocking sodium channels (fast)
Produces little effect on maximum velocity depolarization rate, but shortens AP duration and shortens refractory period
Decreases automaticity
Lidocaine
Class IB Antiarrhythmic Drug- Prototype
Sodium channel blocker (fast)
Used in acute treatment and prevention of ventricular dysrhythmias in immediate aftermath of MI
Ventricular tachycardia, fibrillation, PVCs, especially associated with ischemia; Pulseless VT and VF
Pharmacokinetics: Lidocaine
Elimination half-time (h) 1.4-8.0
Therapeutic plasma concentration 1-5 ug/mL
Dose: 1-1.5 mg/kg IV, infusion 1-4 mg/min (max dose 3 mg/kg)
50% protein binding
Hepatic metabolism
Active metabolite, which prolongs elimination half-time.
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
10% renal elimination
Adverse effects: Lidocaine
hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment preexisting neuromuscular blockade
Mexiletine
Chronic suppression of ventricular cardiac tachyarrhymias
Oral agent
Class IC Agents
Flecainide - Class IC Prototype
Propafenone
Slow Na+ channel blocker (slow dissociation), so does not vary much during the cardiac cycle
Potent decrease of depolarization rate phase 0 and decreased conduction rate, with increased AP
Markedly inhibit conduction through the His-Purkinje system
Flecainide
Effective in the treatment of suppressing ventricular PVCs and ventricular tachycardia; also atrial tachyarrhythmias; Wolff-Parkinson-White syndrome (reentry rhythm)
Oral agent
Has proarrhythmic side effects
Propafenone
Suppression of ventricular and atrial tachyarrhythmias
Oral agent
Has proarrhythmic side effects
Class II Agents
Propanolol – Prototype
Metoprolol
Esmolol
Labetolol (off-label use)
Class II drugs - Beta-adrenergic antagonists. Depress spontaneous phase 4 depolarization resulting in SA node discharge decrease
Drug-induced slowing of heart rate with resulting decreases in myocardial oxygen requirements is desirable in patients with CAD
Slow speed of conduction of cardiac impulses through atrial tissues and AV node resulting in prolongation of the P-R interval on ECG, increased duration of the action potential in atria
Decreased automaticity
Class II agent used for?
Used to treat SVT, atrial and ventricular arrhythmias
Used to suppress and treat ventricular dysrhythmias during MI and reperfusion
To treat tachyarrhythmias secondary to digoxin toxicity, and SVT (atrial fibrillation or flutter).
Prevents catecholamine binding to beta receptors
Slowing of heart rate
Decrease myocardial oxygen requirements
Propranolol
Class II Antiarrhythmic Drug- Prototype
Beta-adrenergic antagonist (nonselective)
Used to prevent reoccurrence of tachyarrhythmias, both supraventricular and ventricular precipitated by sympathetic stimulation
Pharmacokinetics: Propranolol
Dose: 1 mg/min (total dose of 3-6 mg) IV or 10-80 mg po
Onset: 2-5 minutes
Peak effect 10-15 minutes, duration 3-4 hours
Elimination half-time 2-4 hours
Cardiac effects: decreased HR, contractility, CO; increased PVR, coronary vascular resistance; however, oxygen demand lowered
Highly protein bound 90-95%
Hepatic metabolism, with weak metabolite
Therapeutic plasma level 10-30 ng/mL
Side effects: bradycardia, hypotension, myocardial depression, fatigue, and worsening bronchospasm, drug fever, rash, nausea, worsening Raynauds, interferency with glucose metabolism
Caution with reactive airway disease, hypovolemia, CHF, AV block
Metoprolol
Class II Antiarrhythmic Drug- Prototype
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
Can be used in mild CHF
Esmolol
Class II Antiarrhythmic Drug
Beta-adrenergic antagonist (selective B1)
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
Rapidly hydrolyzed by plasma esterases
Not the same esterases as cholinesterases responsible for metabolism of sux, therefore no effect on sux metabolism
Class III agents
Amiodarone – Class III Prototype
Dronedarone
Sotalol
Class III drugs block potassium ion channels resulting in prolongation of cardiac depolarization and increasing action potential duration, and lengthening repolarization.
Decrease the proportion of the cardiac cycle during which myocardial cells are excitable and thus susceptible to a triggering event
Used to treat 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
Amiodarone
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)
1st line drug VT/ VF when resistant to electrical defibrillation
Amiodarone Pharmacokinetics
Dose: Bolus 150-300 mg IV over 2-5 minutes, up to 5 mg/kg, then 1 mg/hr x 6 hrs, then 0.5 mg/hr x 18 hrs
Prolonged elimination half-life (29 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
Amiodarone Adverse Effects
Pulmonary toxicity Pulmonary edema ARDS Photosensitive rashes Grey/blue discolouration of skin Thyroid abnormalities 2% Corneal deposits CNS/GI disturbance Pro-arrhythmic effects (torsades de pointes) Heart block Hypotension Nightmares 25% Abnormal LFT 20% Inhibits hepatic P450
Class IV
Calcium channel blockers Verapamil – Class IV Prototype Diltiazem * Block slow calcium channels *primary site AV node Block slow calcium channels, which decreases conduction through AV node and shortens Phase 2 (the plateau) of the action potential in ventricular myocytes Contractility of the heart decreases 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
Verapamil
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)
T1/2 6-8 hours
Highly protein bound
Hepatic metabolism, with active metabolite
Excreted in the urine, and bile
Side effects: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular blockers
Caution with Verapamil
Caution:
Myocardial depression and vasodilation with inhalational agents
Can potentiate neuromuscular blockers
Can increase risk of local anesthetic toxicity
Together with Dantrolene can cause hyperkalemia
Causes decreased clearance of Digoxin
Diltiazem
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 T1/2 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
Other class V agents
Adenosine
Digoxin
Phenytoin
Atropine
Adenosine
Not in Vaughan Williams class
Binds to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels and increase K+ currents)
Slows AV nodal conduction
Used for acute Rx only
Used for termination of SVT/ diagnosis of VT
Dose 6mg IV, rapid bolus
Repeated if necessary after 3 minutes, 6-12 mg IV
T1/2 < 10 seconds
Eliminated by plasma and vascular endothelial cell enzymes
Side effects: excessive AV or SA nodal inhibition, facial flushing, headache, dyspnea, chest discomfort, nausea, bronchospasm
Contraindicated in asthma, heart block
Digoxin
Not in Vaughan Williams class
Cardiac glycoside
Increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses thru the AV node
Decreases HR, preload and afterload
Slows AV conduction by increasing AV node refractory period
Positive inotrope- used to treat CHF
Digoxin Pharmacokinetics
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
Digoxin Adverse Effects
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
Phenytoin, class, use, and route
Effects resemble Lidocaine
Class IA agent
Used in suppression of ventricular arrhythmias associated with digitalis toxicity
Can also be used other ventricular tachycardias or torsades de pointes
Given IV (can precipitate in D5W; mix in NS)
Can cause pain or thrombosis when given in peripheral IV
Dose: 1.5 mg/kg IV every 5 min. up to 10-15 mg/kg
Therapeutic blood levels 10-18 mcg/mL
Phenytoin Metabolization and Elimination, adverse effects
Metabolized by liver
Excreted in urine
Elimination ½ time @24 hours
Adverse effects: CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea
Atropine Dose, Route, Receptor, Use
Muscarinic receptor antagonist Used to treat unstable bradyarrhythmias Option for asystolic patients; PEA 0.4 to 1.0 mg IV and repeat as necessary 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
