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Antiarrhythmics

General

  • Classified via the Vaughan Williams system
  • All are pro-arrhythmic
  • Ischemic or dysfunctional heart tissue is depolarized
  • All used to control arrythmias by decreasing conduction:
  • Class I and III work on Arial/Ventricular myocytes
  • Class II and IV work on the AV node
  • Alcohol
  • Promostes 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
    • Prolongation of the QRS
    • 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 coprescribed?
  • 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
    • Decreased contractility
  • Propafenone (Rythmol)
  • Acute: 600mg PO for convert, 300mg TID maintain
  • Chronic Use: AF/SVT/VT Prevention
    • Taste disturbances
  • 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 ionotropic) 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)
    • Hydrophilic
  • Timolol
  • Cardio-selective (B1 ≥ B2 blockers)
  • Atenolol
    • Hydrophilic
  • Bisprolol (Zebeta)
  • Esmolol
    • Acute Use: AF/AFL Rate Control
    • CI: Concurrent BB therapy, bradycardia, pulmonary edema, severe HF
  • Nebivolol (Bystolic)
    • B3 agonist also
  • 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 Torsade 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
    • Unlikely with ≤200mg/day
    • Most Common cause of Chronic Interstitial Pneumonitis
  • Check: LFTs (hepatoxic), TFTs (Thyroid disorders), PFTs (Interstitial lung disease)
  • Bretylium
  • Dofetilide (Tikosyn)
  • PubChem
  • 500mcg PO BID
  • Highly selective for delayed rectifier potassium current
  • 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%), torsade de pointes
  • Sotalol (Betapace)
  • Also has BB properties
  • Chronic Use: AF/VT Prevention
  • SE: Hypotension, bronchospasm, long QT, Torsade 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
  • 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