S3C23 - Pharmacology of Antiarrhythmics Flashcards
Class I
Fast Sodium Channel Blockers
Ia: quinidine, disopyramide, procainamide
Ib: lidocaine, phenytoin, mexiletine
Ic: encainide, flecainide, propafenone, indecainide, moricizine
Class II
Beta blockers
-propranolol, metoprolol, esmolol
Class III
Potassium efflux
-breytlium, amiodarone, sotalol, dofetilide
Class IV
Calcium Channel blockers
-verapamil, diltiazem
Class - unclassified
-digoxin, adenosine, magnesium sulfate
Lidocaine
Action:
- Class Ib antiarrhythmic
- little effect on peripheral vascular tone, contractility, CO
- causes CNS depression, sedation, anticonvulsant
- stabilized membranes, elevate v fib threshold and suppresses ventricular ectopy
Pharmacokinetics:
- onset 45-90sec
- duration 10-20mins
- elimination prolonged in CHF/liver dz
Indications:
- ventricular arrhythmias and ectopy
- second line to amiodarone for ACLS treatment of v fib and pulseless v tach
Dosing:
- loading dose 1-1.5mg/kg
- boluses 0.5-0.75mg/kg q5-10min
- NMT 3mg/kg total dose, reduce by 50% if CHF/liver dz
Adverse effects:
-toxicity: slurred speech, drowsiness, confusion, nausea, psychosis, seizures, respiratory depression
Procainamide
Action:
- Class Ia antiarrhythmic (same mechanism as quinidine) (binds to fast sodium channels)
- suppresses fibrillatory activity in the atria/ventricles and prevents ectopic or reentrant arrhythmias
- prolongs PR, QT, QRS
- large dose = proarrhythmic; vasodilation leads to hypotension and sinus tachy
- decreases force of myocardial contractility - negative inotrope
Pharmacokinetics:
- onset 5-10mins
- 1/2 life 4-5min (increased with CHF and renal dz)
- metabolized to active form in the liver, active metabolite has 1/2 life of 7h
Indications:
- ventricular arrhythmias - treat or prevent (stable VT)
- convert SVT
- contraindications: complete AV heart block or 2nd/3rd deg heart block (if no PM present), BBB, long QT, glycoside OD, torsades, myasthenia gravis
- use caution in SLE, CHF, bone marrow suppression
Dosing:
-continuous infusion for ventricular arrhythmias at 20mg/min for 25 mins then at 1-4mg/min
Adverse effects:
- QRS/QT prolongation, VT, VF, PVCs, complete AV block, torsades
- SLE - 50% pts on procainamide produce ANA
- agranulocytosis, leukopenia, hypoplastic anemia, thrombocytopenia
Propafenone
- class Ic
- can be used for pill-in-the-pocket for paroxysmal a. fib (600mg) - do as in patient with first trial
Flecainide
- class Ic
- can be used to treat a fib/flutter with preserved LV fxn
- 2mg/kg at 10mg/min IV
- -can be used for pill-in-the-pocket for paroxysmal a. fib (300mg)
Beta Blockers
- class II antiarrhythmics
- cardioselective (specific for B1 receptors): acebutolol, atenolol, esmolol, metoprolol (better for asthmatics and diabetes)
Indications
- HTN (except sotalol/esmolol), decrease mortality in ACS (metoprolol/atenolol) and non-acute CHF (bisoprolol, carvedilol, metoprolol)
Adverse Reactions
-n/v, light-headed, depression, bradycardia, hypotension, bronchospasm, hyperglycemia, pulmonary edema
Esmolol
Actions
- beta1 selective, short-acting
- negative inotropic and chronotropic effects
- increases sinus cycle, prolongs SA nodal recovery time, decreases conduction through AV node
Pharmacokinetics
- onset 1-4mins
- only available IV
- 1/2 life is 9 mins (quite short)
Indications: SVT
Dosing:
-loading 500mcg/kg bolus then infusion of 50mcg/kg/min for 4 mins
Adverse Effects: hypotension, bradycardia, syncope, heart block
Labetalol
Actions:
- class II antiarrhythmic
- non-cardioselective beta-adrenergic blocker and selective alpha 1 blocking agent
- decreases heart rate, contractility, cardiac output, cardiac work, total peripheral resistance
Pharmacokinetics:
- onset 2-5 mins IV or 20min-2h PO
- duration of action 2-4h IV and 8-24h PO
Indications: HTN
-markedly reduces BP with minimal effects on HR and CO
Dosing: 20mg IV with repeat of 40mg q10min (NMT 300mg)
- infusion 0.5-2mg/min
- PO: up to 2500mg/d divided BID/TID/QID
Adverse effects: orthostatic hypotn, light-headed, drowsy, nightmares
Propranolol
Actions:
- non-cardioselective BB
- decreases chronotropic, inotropy
- decreased sinus rate and CO, depresses AV conduction, and decrases myocardial oxygen consumption
Pharmacokinetics:
- onset is 1min after IV and 1h after PO
- 1/2 life ~3h
Indications:
- SVT (MAT), thyrotoxicosis, angina, HTN, HCM (=HOCM), migraine prophylaxis, essential tremor, anxiety, pheochr.
- not indicated for hypertensive emergencies
Dosing:
-loading 0.5-1mg IV at 1mg/min
Adverse Effect: (same as other BB)
-contraindicated in SA/AV block and intermittent claudication, CHF
Sotalol
Actions:
- class II antiarrhythmic - non-cardioselective BB
- has some class III properties (prolongs repol and refractoriness w/o affecting conduction)
Pharmacokinetics:
- onset 2-3h
- duration 24h
- elimination depends on renal fxn
Indications:
- life-threatening ventricular arrhythmias
- suppresses a fib and SVT
Dosing: 80mg PO BID
-NMT 640mg/d
Adverse Effect: bradycardia, hypotension, hyperglycemia
-can be proarrhythmic in long QT, torsades, hypokalemia
Amiodarone
Actions:
- class III antiarrhythmic, but also traits of class I, II and IV
- slows the heart by impairing SA node, dperesses AV node conduction, modifies purkinje firing and prolongs the refracotry period in an accessory pathway (eg. WPW)
- inhibits potassium channels to incrase repolarization in the mycocardium, blocks fast Na channels, and decreases HR and AV node conduction by BB and CCB properties
Pharmacokinetics:
Indications: ventricular and SVT arrhythmias, VF/VT, AFib A flutter, junctional and wide complex tachy
Dosing:
- Vfib/pulseless VT: 300mg followed by 150mg (ACLS)
- stable VT or SVT: 150mg IV in 100cc 5% dextrose in water (D5W) over 10 mins followed by an infusion
- cardioversion: 5-7mg/kg over 30-60min followed by infusion until total dose of 10g has been given (or PO 1.2-1.8g/d in divided doses until 10g given total) (NMT 0.9mg/d for out pt PO tx)
** before starting long-term tx must get baseline ophtho and PFT tests
Adverse effects:
- thyroid d/o, pulmonary fibrosis, skin discoloration, hepatic dysfxn, corneal infiltrates, paroxysmal VTach, CHF
- hypotension/bradycardia
- CI: iodine allergy
- MANY drug interactions (simvastatin, warfarine, dig, CCB, BB)
Dofetilide
Actions:
- pure class III antiarrhythmic
- prolongs repolarization without affecting conduction velocity via K+ channel inhibition
- suppresses arrhythmias related to reentry mechanisms
- negative chronotropy
Pharmacokinetics:
- onset = 2h (PO)
- duration = 4h (PO)
Indications:
- conversion of A fib/flutter to NSR for very symptomatic pts
- strict prescribing patterns - quite proarrhythmic
Dosing:
- CI if QTc >440msec
- 500mcg PO BID depending on Creatinine clearance
Adverse Effects: QTc prolongation, Vtach, h/a, dizzy, c/p
Ibutilide
Actions:
- Class III antiarrhythmic
- prolongs action potential duration and effective refractory period
- activates the slow inward Na current (as opposed to inhibiting the outward K+ current)
Pharmacokinetics:
- onset 20-30mins if IV
- duration 24h if IV
Indications:
-rapid conversion of recent onset a fib/flutter
Dosing:
- IV only, loading dose 1mg IV in 50cc D5W over 10 mins or 0.01mg/kg IV in 50cc D5W
- may rpt after 10 mins
- continue ECG monitor for 4h after or until QTc normalized
Adverse Effects:
-hypotension, HTN, bradycardia, sinus arrest, syncope, QTc prolongation, CHF
Diltiazem
Actions:
- class IV antiarrhythmic - CCB
- nondihydropyridine CCB (interfers with influx of ECF Ca+ through slow channels)
- slows AV conduction and prolongs AV refractoriness
- minimal systemic vasodilation, preferentially dilates the coronary vasculature
- helps in SSS with SA automaticity
Pharmacokinetics:
- onset IV is 2-3min (peak response 2-7min)
- onset PO is 15-60mins (peak response 1.5-4h)
- duration = 1-3h if IV
Indications:
- rapid conversion of PSVT
- slow ventricular response in A fib/flutter
- vasospastic angina
- HTN
Dosing:
- load with 0.25mg/kg (max 20mg) IV over 2min, rpt in 15 mins with 0.35mg/kg if needed
- infusion rate 5-15mg/h
- max antihypertensive effect seen w/in 14d
Adverse effect:
-angina, bradycardia, asystole, CHF, AV block, BBB, flushing, hypotension, palpitations, edema, h/a, dizzy, nausea, constipation, rash, diarrhea, dry mouth, pruritus, insomnia, tinnitus, depression, sexual dysfxn, hyperglycemia, photosensitivity
Verapamil
Actions:
- class IV antiarrhythmic - nondihydropyridine CCB
- substantial inhibitory effects on the cardiac conduction system as well as slowing AV node
Pharmacokinetics:
- onset in 5 min (IV)
- peak response 10-20 min (IV)
- duration 30-60 min (IV)
- PO: onset= 1-2h peak response = 4-11h duration = 6-12h
Indications:
- as effective as adenosine in terminating narrow-complex PSVT and for controlling the ventricular response in a fib/flutter
- angina
- HTN
Dosing:
- PSVT: 5-10mg IV bolus over 2mins
- check BP before and after administration
- consider pretreatment with CaCl/Gluconate
- max effects seen w/in 48h
- PO 240-280mg/d div TID for angina/HTN
Adverse Effects:
-hypotension, bradycardia, AV block, BBB, pulmonary edema, constipation, dizzy, h/a, nausea
Atropine
Actions;
- other antiarrhythmic class
- antimuscarininc - antagonizes acetylcholine
- increases sinus node automaticity and AV conduction by blocking vagal activity
Pharmacokinetics:
-rapid onset, peak affect 2-4min, duration up to 5h
Indications:
- reverses cholinergic-mediated decreases in HR
- symptomatic sinus brady, AV block
Dosing:
- loading dose 0.5mg bolus q3min (NMT 0.04mg/kg)
- PEA/asystole 1mg rapid IV bolus q3min
- IV/IM/ET/SC/IO (if ET then increase dose by 2x)
Adverse effect:
-anticholinergic symptoms - blurred vision, dry mouth, hallucinations, mydriasis, tachycardia
Adenosine
Actions:
- transient negative inotropic, dromotropic, chronotropic effects on SA and AV nodal tissues
- transient AV nodal block, breaks a reentrant circuit involving the AV node
Pharmacokinetics:
- onset 20-30sec
- duration 60-90sec
- metabolized by adenosine deaminase to inosine
Indications:
- SVT
- contraindicated: 2nd/3rd deg heart block or SSS if no PM present
- NOT effective for converting a fib/flutter
Dosing: 6mg over 1-2sec then 12mg if need repeating (x2)
Adverse effect:
-dyspnea, cough, syncope, vertigo, paresthesias, numbness, nausea, metallic taste, flushing, h/a, palpitiations, c/p, sinus brady, PVC, hypotension
Digoxin
Actions:
- increases force, strength, velocity of cardiac contractions (positive inotropy)
- slow HR (negative chronotropic)
- slows conduction velocity through AV node (negative dromotropy)
- inhibits NaK+ATPase enzyme pump system, leads to loss of K+ in ICF in increase in Na+, which causes influx of Ca+ through Na/Ca pump, this improves contractions
- increases conduction in accessory paths therefore do not use in WPW
Pharmacokinetics:
- onset 5-30mins IV and 30-120mins PO
- peak effect 1.5-4h IV and 4h PO
- dialysis is ineffective in removing dig
Indications:
- improves CO in CHF, reduces hospitilization for CHF but not mortality
- controls ventricular response in a fib/flutter/PSVT
Dosing:
- 0.125-0.375mg OD PO
- serum level target of 0.8-2 nanograms/ml
- IV: 0.25mg q2h NMT 1.5mg
Adverse effects: (mostly GI)
- abdo pain, diarrhea, n/v, gynecomastia, rash, eosinophilia, thrombocytopenia, arrhythmias
- dig toxicity: mental status change, confusion, h/a, drowsy, anorexia, n/v, weak, visual disturbance, delirium, seizure, hyperkalemia
- digibind/digifab indicated for tachyarrhythmia, sinus brady, severe AV block, K+ >5mEq/L
Isoproterenol
Actions:
- sympathomimetic agonist (beta 1 and beta 2)
- increased chronotropy and inotropy and vasodilation
Pharmacokinetics:
- onset 1-5min
- duration 1-2h
Indications:
-refractory torsades and temporary control of refractory symptomatic brady
Dosing: 2-10mcg/min IV infusion
Adverse Effect: ischemia
Magnesium
Actions:
- increases skeletal and smooth msc contractility, vasomotor tone, neuronal transmission
- activates NaK+ATPase pump and does some CCB
- prolongs AV, increases refractory period
Pharmacokinetics:
-duration 30mins IV
Indications:
- torsades
- refractory VTach, VFib
- seizures: toxemia, eclampsia, nephritis, hypomagnesema, acute asthma exac
Dosing: 1-4g in 50-100cc D5W over 20-60 mins
-or 1-2g IV bolus in 10cc D5W over 1-2min if arrested
Adverse effect:
- hypotension
- flushing, sweating, n/v, CNS, depressed DTR, paralysis, depressed cardiac vxn, resp dpn, circulatory collapse
