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Transcript
Pharmacology of
Antidysrhythmic and Vasoactive
Medications
Tintinalli: Chapter 29
Lecture prepared by
Jack Hay, DO
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 α1blocking 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)
Diltiazem
1) 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.
2.
3.
4.
5.
B
E
T
C
A