Pharmacology of Antidysrhythmic and Vasoactive Medications

Class I Antidysrhythmics Lidocaine (Xylocaine) Procainamide (Pronestyl) Propafenone (Rythmol) Flecainide (Tambocor)

Lidocaine (Class Ib) Binds fast sodium channels, inhibiting

recovery after repolarization Suppresses spontaneous depolarization of

the ventricles during diastole Acts on ischemic myocardium

Lidocaine Onset of action: 45-90 seconds Indications:

Ventricular dysrhythmias and ectopy Sinus maintenance after pulseless VT/VF Second-line for hemodynamically stable VT

Lidocaine Dosing:

Load 1-1.5 mg/kg, max of 3 mg/kg Infuse at 1-4 mg/min (maintenance usually 2

mg/min) Adverse effects:

Above 9 mg/min, may cause CNS depression, seizures, respiratory depression

Procainamide (Class Ia)

Prevents ectopic or reentrant dysrhythmias Anticholinergic properties in large doses Potentially pro-dysrhythmic

Prolonged QRS and QT intervals, PVCs, VT, VF, complete AV block

Beware hypotension secondary to peripheral vasodilation

Procainamide

Onset: 5-10 min

Indications: Recurrent ventricular dysrhythmias

stable VT & wide complex tachycardia Pulseless VT/VF Converting PSVT, a fib, a flutter

Procainamide

Contraindications: Torsades & all blocks except first degree Myasthenia gravis (will increase weakness)

Dosing: Load 20 mg/min up to 17 mg/kg then

infuse at 1-4 mg/min to maintain suppression

Class II Antidysrhythmics BETA BLOCKERS

Treatment of hypertension Decrease morbidity and mortality:

Acute MI (metoprolol and atenolol)CHF (metoprolol and carvedilol)

Beta Blockers Cardioselective (specific for β1

receptors): atenolol, esmolol, metoprolol Useful with asthma, COPD, or diabetes Cardioselectivity lost at high doses

Labetalol (Normodyne) Non-cardioselective β-blocker and

selective α1-adrenergic blocker The β-blocker effects exceed the α1-

blocking effects at a 7:1 ratio if given IV Decreases heart rate, contractility, cardiac

output, cardiac work, and peripheral resistance

Labetalol Onset: 2-5 min; duration 2-4 hrs Indications:

HTN in patients with myocardial ischemia Minimally changes heart rate and cardiac output

Acute neurological emergencies little effect on cerebral perfusion pressure or ICP

Labetalol Dosing:

IV bolus 20 mg, repeat 40-80 mg q10 min prn up to 300 mg

Infuse 0.5-2 mg/min to desired effect Adverse effects:

orthostatic hypotension, heart failure, lethargy, increased liver enzymes

Class III Antidysrhythmics Amiodarone (Cordarone) Dofetilide (Tidosyn) Ibutilide (Corvert)

Amiodarone Inhibits sodium channels and β-adrenergics Prolongs action potential duration &

effective refractory period delays repolarization

Impairs SA and AV nodal function and prolongs refractory period in accessory pathways

Amiodarone Indications:

Ventricular and supraventricular dysrhythmias

Recurrent VF and VT, atrial fib/flutter, and junctional & wide-complex tachycardias

Pulseless VT/VF and atrial dysrhythmias with LVEF<40%

Amiodarone Dosing:

Pulseless VT/VF: Load 300 mg IV, repeat 150 mg IV

Other dysrhythmias: Load 150 mg IV, then infuse 1 mg/min X 6 hours,

then 0.5 mg/min thereafter Adverse effects:

Hypotension, bradycardia, asystole, cardiac arrest, shock

Contains iodine – avoid if allergic to iodine or shellfish

Class IV Antidysrhythmics: Calcium Channel Antagonists

Diltiazem (Cardizem) Verapamil (Verelan, Calan, Isoptin)

Diltiazem1) Interferes slow channel extracellular

calcium influx in cardiac smooth muscle

2) Inhibits sodium influx through fast channels

Slows AV nodal conduction/prolongs refraction Dilates coronary vasculature

decreases O2 consumption/ improves O2 delivery

Diltiazem Onset: 2-3 min IV; 15-60 min PO

Indications: Rapid conversion of PSVT to NSR Ventricular slowing in atrial fib/flutter Do NOT use for wide-complex

tachydysrhythmias suggesting an accessory bypass tract (i.e. WPW syndrome)

Diltiazem Dosing:

Load 0.25 mg/kg (max 20 mg) IV push over 2 min, repeat in 15 minutes with 0.35 mg/kg (max 25 mg) IV push over 2 minutes if patient not responsive

Infuse at 5 mg/hr (max 15 mg/hr) Adverse effects:

Angina, bradycardia, asystole, CHF, AV block, bundle branch block, hypotension, peripheral edema

Verapamil Action & Adverse Effects similar to Diltiazem Indications:

As in Diltiazem Essential HTN Avoid in WPW patients (may accelerate

bypass tract conduction) Dosing:

For PSVT: 5-10 mg IV push over 2 min

Other Dysrhythmics/Vasoactives Adenosine Digoxin Atropine Dobutamine Vasopressin

Adenosine (Adenocard) Transient AV nodal block

breaks re-entrant circuit of AV nodal atrial tachydysrhythmia

No effect on non-AV nodal re-entrant SVTs or anterograde conduction over accessory pathways in WPW

As rapid IV bolus - slows cardiac conduction and restores sinus rhythm

Infused - acts as a potent vasodilator.

Adenosine Onset: 20-30 seconds; Half-life <10 seconds Indications: Emergency treatment of SVT

Distinguish Afib/AFlutter from other tachydysrhythmias

Contraindications: 2nd and 3rd degree AV block or sick sinus

syndrome

Adenosine Dosing:

6 mg rapid IV bolus, most proximal port then 12 mg rapid IV bolus every 1-2 min prn x2 doses

Follow bolus immediately with 10-20 cc flush

Adverse effects (usu. minor and well-tolerated) Dyspnea, syncope, vertigo, metallic taste, flushing,

chest pain, bradycardia, and sense of impending doom.

Bronchospasm in asthmatics.

Digoxin 3 basic actions:

Positive inotrope = Increases force, strength, and velocity of contractions

Negative chronotrope = Slows heart rate, improving coronary blood flow and myocardial perfusion

Negative dromotrope = Slows conduction velocity through AV node

Digoxin Inhibits Na+K+ATPase pump gain of

intracellular Na+

Extra Na+ removed via Na+Ca2+ exchange channel

Increased intracellular Ca2+ improves myocyte contractility

Onset: 5-30 min IV; 30-120 min PO

Digoxin Indications:

Improve cardiac output in CHF Control ventricular response in atrial

fib/flutter and PSVT

Digoxin Dosing:

10-15 μg/kg or 0.75-1.5 mg IV 0.125-0.5 mg/day PO

Adverse effects:

GI: abdominal pain, N/V, diarrhea Cardiac: sinus bradycardia, AV or SA nodal

block, ventricular dysrhythmias

Digoxin Toxicity:

Can be fatal if not properly treated Symptoms are varied and can be vague

Altered mentation, visual disturbances, seizures PVCs, VT, junctional tachycardia, high-degree

AV block, SVT, and sinus arrest Hyperkalemia

Digoxin Toxicity Treatment:

Lidocaine, phenytoin and/or atropine Digibind (antibody fragments) IF:

Tachydysrhythmias Sinus bradycardia Severe AV blocks K+ >5mEq/L secondary to digoxin use

Atropine Antagonizes acetylcholine & muscarinic agents Increases sinus node automaticity and AV

conduction by blocking vagal activity (parasympatholytic)

Onset: 2-4 minutes Indications:

Symptomatic sinus bradycardia PEA and asystole

Atropine Dosing:

For bradycardia = 0.5mg IVP q 3-5min For PEA/asystole = 1mg IVP q 3-5min Maximum total dose of 0.04 mg/kg

produces complete vagal blockade

Atropine Adverse effects:

Dry mouth, CNS stimulation, hallucinations, blurred vision, and tachycardia

Potential ischemia and ventricular tachydysrhythmia in hemodynamically stable bradycardic patients

Dobutamine (Dobutrex) Sympathomimetic - inotropic and

chronotropic effects β1/ β2-adrenergic and α-adrenergic offset

by α-adrenergic antagonist activity increase in myocardial contractility and

systemic vasodilation

Dobutamine Onset: 1-2 min Indications:

Positive inotropic support for cardiovascular decompensation secondary to ventricular dysfunction or low-output heart failure.

Preferred agent to manage cardiogenic shock. increases CO and renal/mesenteric blood flow w/o direct stimulation of the heart rate.

Dobutamine Dosing:

2-20 μg/kg/min Monitor patient with CVP or pulmonary

artery catheter. Adverse effects:

Increases in heart rate, blood pressure, and ectopic dysrhythmias

Nitroglycerin Enters vascular smooth muscle Converts to nitric oxide

direct vasodilator produces systemic venodilatation

Venodilation at <100 μg/min Arteriolar vasodilation >200 μg/min

Nitroglycerin Indications:

Angina pectoris Acute decompensated CHF Hypertensive crisis Perioperative hypertension in CV procedures

Dosing: SL, lingually, intrabuccaly, topically or IV Multiple formulations with specific dosing

regimens

Nitroglycerin Adverse effects:

Headache, dizziness, hypotension, syncope Remove transdermal patches and ointments

before defibrillation or cardioversion Concurrent use of sildenafil (Viagra) has

been reported to cause excessive refractory hypotension

Vasopressin (Pitressin) Directly stimulates smooth muscle V1

receptors vasoconstriction Decreased splanchnic, coronary, GI, skin, and

muscular system blood flow May be beneficial during resuscitation

attempts

Vasopressin Onset = immediate Indications:

Alternative to epinephrine as nonadrenergic peripheral vasoconstrictor during CPR

Pulseless VT/VF

Vasopressin Dosing:

Cardiac arrest: 40 units IV push single dose Epinephrine 1 mg IV should be given after 10

minutes if adequate response is not seen. Adverse effects:

HTN, bradycardia, dysrhythmias, PACs, heart block, peripheral vascular constriction, and decreased cardiac output

Questions 1. Which of the following is indicated for symptomatic sinus bradycardia?

A. Labetalol B. Atropine C. Neseritide D. Vasopressin E. Digoxin

2. Nitroglycerin may not be given: A. Sublingually B. Topically with cardioversion C. Via IV infusion D. With concomitant Viagra use E. B & D

3. True or False?

Amiodarone is a good treatment choice for wide-complex tachydysrhythmias in patients with unknown underlying EF.

4. Which of the following is false regarding adenosine? A. Is indicated for emergency treatment of SVT. B. Has a half-life of about 10 seconds. C. Blocks anterograde conduction over accessory pathways. D. Produces transient AV nodal block. E. A sense of impending doom is a common side effect.

5. What is the appropriate dose of vasopressin for pulseless VT/VF? A. 40 units IV push B. 1 mg IV C. 1mg/kg/min D. 6 mg rapid IV push E. 300 mg IV

Answers 1. B 2. E 3. T 4. C 5. A