Antiarrhythmia Drug

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Common antidysrhythmic drugs



Contractile cell Pacemaker

cell









Class II Antiarrhythmics: ß-Blockers

In general all beta-blockers are active at both ß1 and ß2 receptors but to varying degrees

slow SA node impulse formation and depress myocardial

contractility to varying degrees

Effect on ECG is slowing of HR and PR prolongation, withno effect on QRS and QT interval



ß adrenergic receptors and responses tophamacologic manipulation Response toreceptors Location Stimulation Antagonism

ß1Heart Increased HR

and ectopy

Increasedcontractility

Decreased HR

and ectopy

Decreasedcontractility

ß2 Airway (smooth

muscle)

Peripheral

vasculature

Decreased

tone(relaxation)

Decreased

tone(relaxation)

Increased

tone(contraction

)

Increasedtone(contraction)



Class II Antiarrhythmics: ß-Blockers

Relative contraindication include asthma or COPD,advanced CHF, third-trimester pregnancy

Should not be used in pt with bradycardia or greater

than 1o AV block





Indication

Esmolol best suited to control ventricular responserates and break a reentrant circuit in supraventricular

dysrhythmia

Some –blockers decrease morbidity & mortality in

patients with acute myocardial infarction (e.g., metoprolol and

atenolol)

CHF (bisoprolol, carvedilol, and extended-releasemetoprolol)



Esmolol

Action: short-acting drug selectively blocking ß 1-receptors in the myocardium

available only in a parenteral formulation with an

onset of action of 1-4 min, elimination t1/2 9 min

Indications: treatment of supraventricular arrhythmias, including atrial fibrillation/flutter and

sinus tachycardia in acute myocardial ischemia



Esmolol

Dosing and Administration:The loading dose is a 500micrograms/kg bolus over 1 minute, followed by an

infusion at 5micrograms/kg/min for 4 minutes

Adverse Effect: Hypotension is the most common

adverse effect



Labetalol

noncardioselective alpha-adrenergic blocking agentand a selective ß1-adrenergic blocking agent

The alpha-blocking effects > ß1-blocking effects

It is a good choice for treating HT in patients with

myocardial ischemia. It has little effect on cerebral perfusion pressure or

intracranial pressure and can be used in patientswith acute neurologic emergencies



Propranolol

Noncardioselective ß -blocker without intrinsicsympathomimetic activity

Propranolol slows the sinus rate, depresses AV

conduction, decreases cardiac output

prevents exercise-induced increases in BP, andreduces supine and standing blood pressures

Propranolol also decreases myocardial oxygenconsumption



Propanolol

Propranolol is indicated for a wide variety of supraventricular arrhythmias

include MAT , in particular, those arrhythmias

induced by digoxin or catecholamines; rate control of

atrial flutter or fibrillation with preserved LV function Not commonly use in ED setting because it relatively

long effect



Class III Antiarrhythmic Drugs

Prolong the action potential and refractory periodduration, thus exhibiting a clinical antifibrillatoryeffect



Amiodarone

it also exhibits traits of Class I, II, and IVantiarrhythmics

Amiodarone prolongs the action potential duration

and refractory period ,slow automaticity in

pacemaker cell and slows conduction in the AV node Also displays a noncompetitive blockage of

adrenergic receptors causes smooth musclerelaxation



Amiodarone

When given IV, amiodarone may cause a mild dropin BP and HR

Amiodarone is metabolized in the liver andeliminated by biliary excretion



Indication

Amiodarone effectively in the suppression andprevention of recurrent Vfib and Vtach, atrial

fibrillation and flutter, and junctional and wide-

complex tachycardias

It is the first-line antiarrhythmic drug in the ACLSpathways for pulseless Vtach and Vfib

it is also indicated to treat atrial arrhythmias in

patients with a significantly ↓ EF (i.e., 40%).



Dose

For Vfib and pulseless Vtach 300-milligram IV bolus, Another 150-milligram bolus

can be given if needed

For stable Vtach or SVT

150 milligrams IV in 100 mL D5W over 10 minutes Follow the loading dose by an infusion at 1 mg/min

for 6 hours, and then 0.5 mg/min thereafter



Amiodarone

For cardioversion of AF the loading dose is 5 to 7 milligrams per kg over 30 -

60 minutes, followed by a continuous infusion of 1.2

-1.8 grams per day until a total dose of 10 grams has

been administered



Adverse Effect Profile

After IV administration, adverse effects are typicallylimited to hypotension and bradycardia



Amiodarone

Long-term oral therapy is associated with thyroid disorders

pulmonary fibrosis

skin discoloration

hepatic dysfunction

corneal infiltrates

Before long-term treatment, patients need baselineophthalmologic and pulmonary function tests



Amiodarone

Several clinically significant drug interactions increases serum concentrations of many drugs,

including digoxin, procainamide, quinidine,

theophylline

Concurrent use of amiodarone with calcium channelor ß-blockers may potentiate sinus bradycardia,

sinus arrest, and AV block.

Coadministration with simvastatin is associated with

an increased risk of rhabdomyolysis



Ibutilide

An alteranative to IV procainamide for pharmacologic conversion of atrial fibrillation and

atrial flutter in ED

When give in dose of 0.015-0.02 mg/kg

approcimately 50-65% of pt convert to sinus rhythmwithin 20 min

Easier use and a good safety profile offset by higher

cost



Class IV agent: calcium blocker

Block the influx of extracellular calcium through"slow" channels in the cardiac smooth muscle

Verapamil and diltiazem exhibit the most potent

effects on myocardial cell > peripheral vascular

smooth muscle The net result is a slowing of AV nodal conduction

and a prolongation of AV nodal refractoriness



Calcium blocker

effective for rapid conversion of PSVT to NSR and toslow ventricular response in atrial fibrillation or atrial

flutter ( 90% of pt)

Do not use to treat a wide-complex tachyarrhythmia

suggesting an accessory bypass tract (e.g., WPWsyndrome) ), because life-threatening adverseeffects (e.g., Vfib and/or cardiac arrest) may occur



Calcium blocker Adverse effect: hypotension and congestive heart

failure, nausea, vomiting, constipation,

dizziness,nervousness and, pruritus



Diltiazem

Onset 2-3 min after iv administration, peak response

2-7 min, duration 1-3 hr

0.25 mg/kg over 2 min, followed by 0.35 mg/kg 15

min later if the first dose is unsuccessful



Verapamil

The onset of action of verapamil is within 5 minutes,

the peak response is 10 -20 minutes, and the

duration of action is 30 - 60 minutes after IV

administration

the initial dose is 5 to 10 mg(0.1mg/kg )IV bolusgiven over 2 minutes

Reduced to 2.5 to 5.0 mg (0.05mg/kg) in elderly

patients and those with hepatic dysfunction

Check BP immediately before and after verapamiladministration



Verapamil

For the prevention of recurrent PSVT

The dosage is 240 - 480 milligrams/day PO of a

short-acting preparation in four divided doses

long acting is available but not approved for the

treatment of dysrhythmias



Miscellaneous agents Digitalis

Adenosine

Magnesium



Digitalis

Digoxin has three basic actions:

it increases the force, strength, and velocity of

cardiac contractions (positive inotropic effect)

it slows the heart rate (negative chronotropic effect)

it slows conduction velocity through the AV node(negative dromotropic effect)



Digoxin



Digoxin

In therapeutic doses, characteristic ST segment

depress and shortening and T wave inversion

Because it is slow onset and narrow therapeutic

index ,it is not a first line agent for emergencytherapy



Digoxin

Emergently, the first dose iv digoxin dose is 0.5 mg

in adults(Rosen) , 0.25 milligram (Tintinalli)

maximum total dose of 1.5 milligrams

Clinical effect may be seen in 30 min, but the peak

effect is 1.5-2 hr Digoxin is excreted 50-75% unchanged in the urine



Digoxin

The usual oral maintenance dose is 0.125 to 0.375

mg per day

The therapeutic serum digoxin level is 0.8 to 2.0

nanograms/mL

The t1 /2 of digoxin in patients with normal renalfunction is 1.5 -1.8 days and can be extended up to4 - 6 days in patients with renal insufficiency



Digoxin

Side effects of digoxin are enhanced by

hypokalemia, hypomagnesemia, and hypercalcemia,

increased catecholamine

Several drugs can increase serum digoxin levels,

including amiodarone, verapamil, nifedipine,diltiazem, flecainide, quinidine, erythromycin, andtetracycline



Digoxin toxicity

Symptoms of digoxin toxicity

include mental status changes

confusion,

headache, drowsiness

anorexia, nausea,vomiting

Weakness

visual disturbances

Delirium

seizures

Type of arrhythmia can

manifest an increased number of

unifocal or multifocalPVCs

Vtach

junctional tachycardia high-degree AV block

SVT with block

sinus arrest

Atrial fibrillation bradycardia

bidirectional Vtach Vfib



Digoxin toxicity

significant digoxin toxicity itself may produce

hyperkalemia

Lidocaine and phenytoin are antiarrhythmic drugs

that have classically been used in digoxin toxicity,but their efficacy has not been proven



Digoxin toxicity

Digoxin antibody fragments (Digibind, DigiFab) are

indicated for

life-threatening tachyarrhythmia

sinus bradyarrhythmia

severe AV blocks serum potassium >5 mEq/L

Ad i



Adenosine

is an endogenous nucleoside produced by the

degradation of adenosine triphosphate

Adenosine produces a transient AV nodal block,

which breaks the reentrant circuit of atrial

tachyarrhythmia involving the AV node. Adenosine has no effect on anterograde conduction

over accessory pathways in patients with WPWsyndrome



Adenosine

onset of action of adenosine is 20 to 30 seconds,

with a duration of action lasting approximately 60 to

90 seconds

Adenosine is used for the emergency treatment of

SVT recurrence of the arrhythmia may occur within

minutes after conversion

not effective in converting atrial fibrillation or flutter to

NSR, but it can be used to distinguish these rhythmsfrom other tachyarrhythmias



Dose

The initial is 6 mg given as a very rapid IV bolus over

1 - 2 seconds directly into the vein or in the most

proximal port of the IV tubing

If the arrhythmia persists, give 12 mg IV rapid bolus

2 minutes later The 12-mg dose can be repeated once, 2 more

minutes later

Follow the bolus dose immediately with a 10- to 20-

mL normal saline flush



Adenosine

The adverse effects minor and well tolerated, due to

the short half-life

The most common AE include dyspnea, cough,

syncope, vertigo, paresthesias, numbness, nausea,

and metallic taste Cardiovascular AE include facial flushing, headache,

palpitations, retrosternal chest pain, sinusbradyarrhythmia

M i



Magnesium

directly activating the Na+K+ ATPase pump and

indirectly by calcium channel blockade

It increases membrane potential, prolongs AV

conduction, and increases the absolute refractoryperiod



Magnesium

The onset is immediate, with a duration of action of

approximately 30 minutes after IV administration

Magnesium is indicated for torsades de pointes and

refractory Vtach/Vfib, regardless of prearrest serum

magnesium levels



Magnesium

The loading dose is

1 - 4 gm in 50 - 100 mL D5W over 20-60 minutes in

patients with spontaneous circulation

1 -2 gm in 10 mL D5W over 1 to 2 minutes in

patients in cardiac arrest. The rate should be reduced or the infusion stopped

temporarily if hypotension develops



Magnesium

Hypotension is the predominant adverse effect but is

surprisingly uncommon, even when a 1- to 2-gram IVbolus dose is given over 1 to 2 minutes

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Antiarrhythmia Drug