Antiarrhythmics General A good thing to note is that all anti-arrhythmics are "pro-arrhythmic" Classified via the Vaughan Williams system All used to control arrhythmias by decreasing conduction: Class I and III work on Arial/Ventricular myocytes Class II and IV work on the AV node Alcohol Promotes SNS stimulation, shortens atrial effective refractory period, increased interatrial electromechanical delays, acts via vagal pathways Class I (Na+ Channel Blockers) General Inhibit phase 0 of the AP (initial depolarization) Prolonged QRS at faster HR (use dependence) Increase in QRS duration during stress test/exercise Makes them useful Use dependence (enhanced effect at faster heart rates due to tighter drug binding), seen most frequently with IC ≥ IA and rarely IB, this is why they're so good in SVTs Class Ia General Slow conduction throughout the His-Purkinje system, atria, and ventricles and prolong the refractory state Lengthens the action potential: Right shift Preferentially binds sodium Act on Phase 0 of the action potential No potassium blocking effects No QT prolongation usually SE: PVT Procainamide Acute Use: Convert/prevent AF/VT, WPW SE: Lupus like syndrome, increased ventricular rate in AF or AFL Prolonged QT and prolonged QRS but also causes blood dyscrasias, agranulocytosis, neutropenia, thrombocytopenia, Torsades de pointes Caution in HF Hypotension, pleural effusions, rash, myalgia Pericarditis Quinidine Acute Use: Convert/Prevent AF/VT Chronic Use: AF/SVT/VT Prevention SE: Diarrhea, nausea, vomiting, cinchonism, thrombocytopenia Prolongs QRS and the QT, hearing loss, tinnitus, psychosis Disopyramide Chronic Use: AF/SVT Prevention SE: Anticholinergic, urinary retention, constipation, dry mouth Prolonged QT, QRS, Torsades de pointes Class Ib Phenytoin, Mexiletine, Tocainide General Preferentially binds sodium after initial depolarization Therefore, tends to work better in ischemia Shortens the action potential: Left shift Weaker binding than Class IA agents Widen QRS and produce Bradycardia Prolong PR interval SE: Ventricular tachycardia Lidocaine Acute Use: VT SE: Seizures, Dizziness, confusion, delirium, slow VT in patients with HD Class Ic General Used in AFib w/ normal hearts Slowest rate of drug binding and slowest dissociation from Na channel receptor (works better when heart rates are high) Slows atrial conduction, may result in 1-1 AV conduction AV node blocking agents co-prescribed? No significant action potential effect: Left squeeze, no shift Normally no QRS/QT prolongation More likely to prolong QRS ≥ QT, but both are possible Greatest Use Dependence Flecainide Acute: 300mg PO for conversion, 150mg BID maintain Chronic Use: AF/SVT/VT Prevention Propafenone (Rythmol) Acute: 600mg PO for convert, 300mg TID maintain Chronic Use: AF/SVT/VT Prevention Moricizine (Ethmozine) Class II (Beta-Adrenergic Blockers) General Work purely by blocking Beta-Adrenergic stimulation of the cardiac myocytes Decreases Sinus and AV nodal conduction Reduces intracellular cAMP, reducing Ca2+ influx Anti-anginal effects mediated by reducing myocardial contractility (negative inotropic) and HR (negative chronotropic), decreasing myocardial oxygen demand Membrane stabilizers: Carvedilol, propranolol ≥ labetalol, metoprolol SE: taper slowly, decreased libido, impotence Non-Selective (B1 = B2 blockers) Can trigger bronchoconstriction in asthmatics due to B2 blockade Carvedilol (Coreg) Also has alpha-1 blocking ability Target dosage in HFrEF is 25mg BID or 50mg BID if ≥85kg Labetalol Also has alpha-1 blocking ability Highly lipophilic CI: Asthma, COPD, Heart Block, may worsen heart failure Nadolol (Corgard) Chronic Use: Same as Metoprolol Hydrophilic Propranolol (Inderal) Sotalol (Betapace) Timolol Cardio-selective (B1 ≥ B2 blockers) Atenolol Bisprolol (Zebeta) Esmolol Acute Use: AF/AFL Rate Control CI: Concurrent BB therapy, bradycardia, pulmonary edema, severe HF Nebivolol (Bystolic) Metoprolol (Lopressor, Toprol XL) Acute Use: SVT, AF Rate Control, Exercise-induced VT, Long QT Chronic Use: AF Rate Control/SVT, Long QT/RVQT VT BB, inhibits sympathetic activity, leading to decrease in rate of impulse generation and increase in refractory period of the AV node No QRS prolongation SE: bradycardia, bronchospasm, hypotension, nasal congestion CI: Sinus bradycardia, 1st degree AV block (PR ≥0.24), cardiogenic shock, SSS, WPW Class III (K+ Channel Blockers) General Inhibit potassium channels and prolong the refractory state of cardiac tissue (decreasing automaticity) All prolong QT and can cause Torsades de pointes Amiodarone MOA: Inhibits alpha receptors, beta receptors, sodium channels, and calcium channels in addition to potassium channels Has partial action of all classes May produce QRS prolongation, QT prolongation, and/or a decrease in heart rate (bradycardia) Lipophilic = likes to attach to internal organs Acute Use: AF, AFL, SVT, VT/VF Chronic Use: AF/VT Prevention (100-400 qd) SE: Sinus brady, AV block, proarrhythmic, hypo/hyperthyroid, hepatitis, optic neuropathy, blue-gray skin, elevated LFTs, corneal microdeposits (98% of pts), peripheral neuropathy, QT prolonagion, Torsades de points Hyper/hypothyroidism Pulmonary fibrosis deadly 10% of the time, usually occurs within the 1st year of treatment and in older patients with low DLCO Most Common cause of Chronic Interstitial Pneumonitis Check: LFTs (hepatoxic), TFTs (Thyroid disorders), PFTs (Interstitial lung disease) Bretylium Dofetilide (Tikosyn) PubChem 500mcg PO BID Requires special training Highly selective for delayed rectifier potassium current Goal K: >3.5 (correct before initiation) IV Magnesium enhances the ability of dofetilide to cardiovert AF or AFL Chronic Use: AF Prevention SE: Headache (11%), Chest Pain (10%), Dizziness (8%), Nausea (5%), QT prolongation CI: QTc >440ms prior to initiation, <60 BPM CI: Cimetidine, Verapamil, Ketoconazole, Trimethoprim, TMP/SMX, Prochlorperazine, Megestrol, HCTZ, Triamterene Alternatives: Omeprazole, ranitidine, antacids Trials: DIAMOND-MI, DIAMOND-AF, and DIAMOND-CHF Dronedarone (Multaq) Chronic Use: AF Prevention Lacks iodine molecule of amiodarone (less effective, less harmful), 2x increased mortality in permanent AF and class III/IV HF Ibutilide (Corvert) Acute Use: Terminate (cardiovert) AF/AFL Within 7 days (CI in hypokalemic or QT prolong) Check magnesium and potassium to minimize risk IV Magnesium enhances the ability of ibutilide to cardiovert AF or AFL IV 4g magnesium sulfate Increases odds of conversion by 78% SE: Nausea, QT prolongation (8%), torsades de pointes Sotalol (Betapace) Also has BB properties Chronic Use: AF/VT Prevention SE: Hypotension, bronchospasm, long QT, Torsades de Pointes Class IV (Calcium Channel Blockers (CCBs)) General Delay conduction in the SA and AV nodes Non-Dihydropyridine CCBs (Non-DHP) General Block non-DHP L type channels at SA/AV node Prolonged PR interval at faster HR (use dependence) Use dependence with an increase in CCB with increasing ventricular activation. Prolongation of the refractory period of the av node, leading to an increased PR No QRS prolongation (doesn't work on phase 0) Diltiazem (Cardizem) PubChem David Drug Guide Weight based Acute Use: SVT, AF/AFL Rate Control Acute Afib: 0.25mg/kg/IV over 2 mins Chronic Use: AF Rate Control/SVT Chronic Afib: 120-360mg/day PO divided QID Verapamil (Isoptin) Acute Use: SVT, AF Rate Control Chronic Use: AF Rate Control/RVQT VT, Idiopathic LV VT Avoid in: Afib or flutter in WPW, wide complex tachycardias, with BBs, asymptomatic HCM Can use in: Afib/Flutter w/RVR, SVT(2nd to amio), MAT, symptomatic HHCM. Severe/concentric LVH, hypertension Dihydropyridine CCBs (DHP) General Increase myocardial oxygen supply via Coronary artery vasodilation Decreases afterload via systemic vasodilation, reducing myocardial oxygen demand Amlodipine No use dependence or prolongation of QT SE: Elevated Uric Acid Felodipine Do not combine with Nitrates May worsen angina by decreasing coronary perfusion pressure Class V (Adenosine, Digoxin, Magnesium Sulfate) Adenosine (Adenocard) Alpha1 agonist Decreases conduction through the AV and SA node Lasts only seconds Acute Use: terminate Reentrant SVT involving AV Node Cough flushing, chest pain, Profound pauses, Afib Digoxin (Lanoxin) MOA: Inhibits ATPase-dependent Na-K pump, increases sodium intracellularly, increasing ca+2 inside (indirect inhibition of Na/Ca exchanger) Enhances vagal tone and slows AV nodal conduction (decrease HR), SA node rate, and shortens atrial refractory period Positive inotropy Amiodarone, Verapamil, quinidine, spironolactone, and propafenone increase Digoxin levels (Verapamil increases by 70-100%) Acute Use: AF/AFL Rate Control Chronic Use: AF Rate Control Used in patients with HF and low EF for symptomatic management Does not decrease mortality but decreases hospitalizations SE: N/V, AV block, atrial tachycardia with av block, JET, EAT, fascicular tachycardia and ventricular tachycardia Can cause bradyarrhythmia in younger, healthy patients or enhance automaticity and delayed after-depols leading to ventricular ectopy and tachyarrhythmias in old people with HD Toxicity Cholinergic: Vision changes (color vision), diarrhea, anorexia, nausea, vomiting, ST segments on EKG, confusion Hyperkalemia indicates poor prognosis CI: Renal Failure, Decreased clearance, hypokalemia Antidote: Slowly normalize K+, cardiac pacer, anti-digoxin FAB, Mg2+ Other Antiarrhythmic Agents Digitalis Can increase ectopy in the arteria or ventricles Can be used to increase vagal tone and sometimes to treat atrial fibrillation if BBs or CCBs have not been effective Toxicity Focal Atrial tachycardia with AV block is specific Increases ectopy and increased vagal tone Dobutamine Ivabradine MOA: Inhibits the hyperpolarization-activated nucleotide-gated funny channels (If) in the sinus node Use: Chronic Symptomatic HF w/LVEF \<35% on maximally tolerated BB who are in sinus rhythm and HR ≥70 Shown to reduce hospitalizations in patients with NYHA III to IV on maximally tolerated B-Blocker therapy (maximize BB first) Milrinone PDE inhibitor, same as above (camp ca influx) Less likely to stimulate the heart than dobutamine More likely for hypotension, renally dosed (nephrotoxic) Levosimendan Enhance contractility via sensitization Promotes vasodiation Cardioprotective no myocardial o2 increase nly one with survival benefit tachy and hypotension Dopamine Epinephrine Norepinephrine Isopro Anti-Arrhythmics Beta-Blockers Calcium Channel Blockers