Dr P.V.Nishanth,MD,DNB.NIMS,Hyderabad.

A transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell

Caused by unequal distribution of ions inside vs. outside cell◦ Na+ higher outside than inside cell◦ Ca+ much higher “ “ “ “◦ K+ higher inside cell than outside

Maintenance by ion selective channels, active pumps and exchangers

Divided into five phases (0,1,2,3,4)◦ Phase 4 - resting phase (resting membrane potential)

Phase cardiac cells remain in until stimulated Associated with diastole portion of heart cycle

Addition of current into cardiac muscle (stimulation) causes ◦ Phase 0 – opening of fast Na channels and rapid

depolarization Drives Na+ into cell (inward current), changing membrane

potential Transient outward current due to movement of Cl- and K+

◦ Phase 1 – initial rapid repolarization Closure of the fast Na+ channels Phase 0 and 1 together correspond to the R and S waves of

the ECG

Phase 2 - plateau phase◦ sustained by the balance between the inward movement of Ca+

and outward movement of K + ◦ Has a long duration compared to other nerve and muscle tissue◦ Normally blocks any premature stimulator signals (other muscle

tissue can accept additional stimulation and increase contractility in a summation effect)

◦ Corresponds to ST segment of the ECG.

Phase 3 – repolarization ◦ K+ channels remain open, ◦ Allows K+ to build up outside the cell, causing the cell to

repolarize◦ K + channels finally close when membrane potential reaches

certain level◦ Corresponds to T wave on the ECG

Once an AP is initiated, there is a period (phase 0,1,2, part 3) that a new AP cannot be initiated.

Effective or Absolute refractory period (ERP or ARP)

Stimulation of cell by adjacent cell depolarizing does not produce new propagated APs

Prevents compounded APs from occurring & limits frequency of depolarization and HR

Fully repolarized -60mv No stable RMP Phase 4: Spontaneous

depolarization or pacemaker potential

Slow, inward Na+ channels open - "funny" currents

Cause the membrane potential to begin to spontaneously depolarize

During Ph4 there is also a slow decline in the outward movement of K+

-50mV T-type CaCh open Ca in: further depolarizes -40 mV L-type CaCh open More Ca in: further depol AP threshold -35mV Phase 0: Depolarization Primarily caused by Ca++

conductance through the L-type Ca++ channels

Movement of Ca++ through these is slow so the rate of depolarization (Phase 0 slope) is slower than in other cardiac cells

Phase 3: Repolarization

K+ channels open Increase the outward

hyperpolarizing K+ currents

At the same time the L-type Ca++ channels close

gCa++ decreases Inward depolarizing

Ca++ currents diminish

Repolarization

PCs - Slow, continuous depolarization during rest Continuously moves potential towards threshold

for a new action potential (called a phase 4 depolarization)

SNS - Increased with concurrent inhibition vagal tone: 

NA binds to B1 Rec Increases cAMP Increases Ca and Na in Decreases K out Increases slope phase 0 Non-Nodal tissue: More rapid depolarisation More forceful contraction Pacemaker current (If)

enhanced  Increase slope phase 4 Pacemaker potential more

rapidly reaches threshold Rate increased

PSNS (Vagal N) Ach binds M2 rec Increases gK+ Decreases inward Ca & Na Pacemaker current (If)

suppressed Decreases pacemaker rate Decrease slope of Phase 4 Hyperpolarizes in Phase 4 Longer time to reach

threshold voltage

Restore normal rhythm, rate and conduction or prevent more dangerous arrhythmias

1. Alter conduction velocity (SAN or AVN) Alter slope 0 depolarisation or refractoriness2. Alter excitability of cardiac cells by changing

duration of ERP (usually via changing APD) ERPinc – Interrupts tachy caused by reentry APDinc – Can precipitate torsades 3. Suppress abnormal automaticity

Block open ACTIVATED Na channels Slow phase 0 depolarisation - upstroke of AP Lengthen APD and ERP. Prolong QRS duration on ECG Anticholinergic S/E. Also blocks K Ch. Greater affinity for rapidly firing channels-

exhibit use dependence with intermediate kinetics

suppresses automaticity in normal Purkinje fibers

Little effect on normal sinus node Peripheral vasodilatation may reflexly

increase sinus node discharge rate(Anti chol.effect also)

Exhibits use dependence and at slower rates exhibit reverse use dependence(on K channels)-TDP

Increases ERP of Atria,ventricles,HPS and HV interval

Suppresses premature SV/V ectopics Conversion and maintainence of atrial

flutter/fibrillation into sinus rhythm. Can prevent recurrence of AVNRT

I.V- 6 to 10 mg/kg at 0.3 to 0.5 mg/kg/min oral— 800 to1000mg-loading Maintainence- 300 to 600q6hr Half life- 5 to 9 hrs

syncope in 0.5 to 2.0 percent of patients, most often the result of a self-terminating episode of torsades de pointes

Significant QT prolongation (QT interval of 500 to 600 milliseconds) is often a characteristic of patients with quinidine syncope

most episodes occur within the first 2 to 4 days of therapy, often after conversion of atrial fibrillation to sinus rhythm.

Magnesium given intravenously (2 gm over 1 to 2 minutes, followed by an infusion of 3 to 20 mg/min) is the initial drug treatment of choice.

Atrial or ventricular pacing can be used to suppress the ventricular tachyarrhythmia, perhaps acting by suppressing early afterdepolarizations.

Isoproterenol can also be used to increase heart rate

Least anti cholinergic of class 1 agents Can depress myocardial contractility in high

doses

NAPA elimination half life is 7-8hrs and is excreted only by kidney

Procainamide is ecreted both by kidney and liver

Renal failure can cause accumulation of NAPA

SVT-convert AF to sinus In patients with AF and rapid conduction

over accessory pathway Can terminate sustained VT better than

lidocaine In EPS can be used to stress the his purkinje

system in evaluation for pacemaker and also for VT induction.

IV loading-6 to 13 mg/kg at 0.2 to 0.5 mg/kg/min

Maintainence-2 to 6 mg/min Oral loading-500 to 1000 mg Maintainence-250 to 1000 mg q4-6hr Half life-3-5 hrs

Noncardiac adverse effects from procainamide administration include rashes, myalgias, digital vasculitis, Raynaud's phenomenon, Fever and agranulocytosis

GI/cns side effects less common Drug induced Lupus developin 20-30% Cardiac-bradycardia,TDP

Doses are generally 100 to 200 mg orally every 6 hours, with a range of 400 to 1200 mg/day

Adverse effects-vagolytic TDP depression of cardiac

performance

Good Na channel block with weak K channel blocking property

mean elimination half-life of 13 min in most patients, making it poorly suited to longterm oral use.

dose for acute arrhythmia termination is generally 50 mg IV over 1 to 2 minutes

When administered IV at doses of 50 mg over 3 min, or 10 mg/minute, to a total dose of 1 mg/kg, ajmaline can have the following effects:

(1) delta wave disappearance in patients with Wolff- Parkinson-White syndrome (indicating an accessory pathway anterograde effective refractory period more than 250 milliseconds);

(2) ST-T abnormalities and interventricular conduction blocks in patients with occult chagasic cardiomyopathy

(3) heart block in patients with bundle branch block and syncope, but in whom no rhythm disturbance had been discovered

(4) right precordial ST elevation in patients with suspected Brugada syndrome in whom the resting electrocardiogram is normal

Block INACTIVATED Na channels Slow phase 0 depolarisation- Slows

upstroke of AP Shorten APD and ERP Ratio ERP/APD is increased Greater affinity for ischaemic tissue that

has more inactivated channels, little effect on normal cells – dissociates quickly (0.5sec)

does not affect normal sinus node automaticity

does depress other normal and abnormal forms of automaticity, as well as early and late afterdepolarizations in Purkinje fibers

can convert areas of unidirectional block into bidirectional block during ischemia and prevent development of VF by preventing fragmentation of organized large wave fronts into heterogeneous wavelets

Metabolised in liver ,metabolism inhibited in cardiac failure and half life increased to 4 hrs ,in uncomplicated MI and 10 hrs in cardiogenic shock.

initial bolus of 1 to 2 mg/kg body weight at a rate of 20 to 50 mg/min, with a second injection of half the initial dose 20 to 40 minutes later

transient subtherapeutic plasma concentrations 30 to 120 minutes after initiation of therapy can be countered by giving asecond bolus of 0.5 mg/kg

To treat arecurtrence arrythmia 6-8 hrs later give another bolus and then increase infusion rate

If the initial bolus of lidocaine is ineffective, up to two more boluses of 1 mg/kg may be administered at 5-minute intervals

Maintenance infusion rates in the range of 1 to 4 mg/min produce steady-state plasma levels of 1 to 5 mg/ml

To treat ventricular arrythmias. Not useful for supra ventricular arrythmias dose-related manifestations of central

nervous system toxicity: dizziness, paresthesias, confusion, delirium, stupor, coma, and seizures..

Rarely, lidocaine can cause malignant hyperthermia

can result in severe bradycardia and abnormal sinus node recovery time in patients with sinus node disease

rapidly and almost completely absorbed after oral ingestion

Elimination half-life is approximately 10 hours

starting dose is 200 mg orally every 8 hours when rapid arrhythmia control is not essential

May be increased or decreased by 50 to 100 mg every 2 to 3 days

moderately effective antiarrhythmic agent for treating patients with acute and chronic ventricular tachyarrhythmias

Mexiletine may be very useful in children with congenital heart disease and serious ventricular arrhythmias

Most useful in combination with other agents

May be less danngerous in LQTS

Neurological Cardiac-bradycardia Dose related Therapeutic plasma levels - 0.5 to 2 mg/ml

In arrythmias caused by digitalis toxicity Prevents delayed after depolarisations 100 mg of phenytoin should be

administered intravenously every 5 minutes until the arrhythmia is controlled, 1 gm has been given, or adverse side effects result

Orally, phenytoin is given as a loading dose of 1000 mg the first day, 500 mg on the second and third days, and 300 to 400 mg daily thereafter(Half-life24 hrs)

Block Na channels. Most potent Na channel block Dissociate very slowly (10-20 sec) Strongly depress conduction in

myocardium Slow phase 0 depolarisation - upstroke of

AP No effect on APD No effect on QRS

marked drug effects can occur at physiological heart rates

Flecainide shortens the duration of the Purkinje fiber action potential but prolongs it in ventricular muscle(heterogenous effects)

Conduction time in the atria, ventricles, AV node, and His-Purkinje system is prolonged

Anterograde and retrograde refractoriness in accessory pathways can increase significantly in a use-dependent fashion

Cardiac contractility can be depressed

starting dose is 100 mg every 12 hours, increased in increments of 50 mg twice daily, no sooner than every 3 to 4 days, until efficacy is achieved, an adverse effect is noted, or to a maximum of 400 mg/day

Serum concentration should not exceed 1.0 mg/ml

ventricular tachyarrhythmias, SVTs, and paroxysmal atrial fibrillation

Useful as adiagnostic tool in brugada sybdrome

marked slowing of conduction precludes its use in patients with second-degree AV block without a pacemaker and warrants cautious administration in patients with ntraventricular conduction disorder

Worsening of existing ventricular arrhythmias or onset of new ventricular arrhythmias can occur in 5 to 30 percent of patients

PROPAFENONE conduction slowing is the major effect depresses sinus node automaticity and A-H,

H-V, PR, and QRS intervals increase, as do refractory periods of the atria, ventricles, AV node, and accessory pathways

Depreeses ventricular function 150 to 300 mg every 8 hours, not exceeding

1200 mg/day Used for VT,SVT and AF

dizziness, disturbances in taste, and blurred vision the most common and gastrointestinal side effects next.

Exacerbation of bronchospastic lung disease can occur

Proarrhythmic responses, which occur more often in patients with a history of sustained VT and decreased ejection fractions

prolongs AV node and His-Purkinje conduction times and QRS duration.

Ventricular refractoriness is prolonged slightly, with no consistent atrial change

usual adult dose is 600 to 900 mg/day, given every 8 hours in divided doses, with increments of 150 mg/day at 3- day intervals

designed as a multicenter, randomized, placebo-controlled trial to test the hypothesis that in patients with prior myocardial infarction, the suppression of ventricular premature depolarizations improves survival free of arrhythmic death

As data were gathered, it became evident that encainide and flecai nide worsened survival, and these two arms of the trial (called CAST-I) were stopped

moricizine arm of the trial was contin ued as CAST-II.

But it had to be prematurely terminated as it also worsened survival.

Role of tachycardia in precipitating arrythmias

Increased sympathetic activity in patients with sustained VT

Role of C AMP in causation of ischemia related VF

Associated anti hypertensive and anti ischemic effects of these drugs

Hyperpolarisation (if) current-proarrythmic depolarisation in damaged to heart tissue

Inward (L type) calcium current indirectly inhibited as level of tissue C AMP falls

slows spontaneous automaticity in the sinus node or in Purkinje fibers that are being stimulated by adrenergic tone, producing If block

block ICa.L stimulated by beta agonists high concentrations of propranolol slow

normal automaticity in Purkinje fibers, probably by a direct membrane action

Membrane stablising effect cannot be discounted.

sinus discharge rate in humansdecreases by 10 to 20 percent

The PR interval lengthens, as do AV nodal conduction time and AV nodal effective and functional refractory periods (at a constant heart rate), but refractoriness and conduction in the normal His- Purkinje system remain unchanged

No effect on ventricular muscle as seen by lack of effect on QRS and QT interval

Propanolol,sotalol acebutolol approved Metoprolol was tried in arrythmia

suppression trials like the one by stienbeck Esmolol with short half life of 9 min can be

used in situations where b blockers are otherwise contraindicated.

Pharmacokinetics:Propranolol is almost 100 percent absorbed, but the effects of first-pass hepatic metabolism reduce bioavailability to about 30 percent and produce significant interpatient variability of plasma concentration for a given dose

Beta blockers eliminated by liver have more inpatient variability than those eliminated by liver.

Arrhythmias associated with thyrotoxicosis, pheochromocytoma, and anesthesia with cyclopropane or halothane or arrhythmias largely related to excessive cardiac adrenergic stimulation, such as those initiated by exercise, emotion, or cocaine.

Terminate or prevent recurrence of tachycardias like-AVNRT and orthodromic reciprocating tachycardias in the Wolff-Parkinson-White syndrome or inappropriate sinus tachycardia, or for Ats

Metoprolol and esmolol may be useful in patients with multifocal AT(bronchospasm is a problem as underlying lung disease is a risk)

effective for digitalis-induced arrhythmias(watch for AV block)

arrhythmias associated with the prolonged QT interval syndrome,MVP,in setting of ischemic heart disease.

ADVERSE EFFECTS unacceptable hypotension, bradycardia,

and congestive heart failure Raynauds,bronchospasm,insomnia,loss of

diabetes control,intermittent claudication,vivid dreams,decreased libido, hypoglycemia unawareness.

CASH EVSEM

CASH (Randomized Comparison of Antiarrhythmic Drug Therapy With Implantable Defibrillators in Patients Resuscitated From Cardiac Arrest: The Cardiac Arrest Study Hamburg)

This study was designed to evaluate impact of the ICD vs antiarrhythmic drugs (amiodarone, metoprolol, propafenone), on overall survival rates in survivors of cardiac arrest

Number of patients: 288 pts: 99 pts (ICD); 92 pts (amiodarone); 97 pts (metoprolol)

23% reduction (statistically nonsignificant) in the all-cause mortality rate was seen in the ICD group compared with the amiodarone/metoprolol group.

There is a 61% reduction in the sudden death rate in the ICD group compared with the amiodarone/metoprolol group

Propranolol 0.25 to 0.5 mg q5 min to 0.20 mg/kg

Oral-10 to 200 q6- 8hr Time to peak conc.-4 Effective serum conc.-1 to 2.5 Half life--3 to6 hrs

Esmolol-IV 500µg/min loading dose over 1min

Use steps of 50/100/150/200µ/min over 4 min each

Half life-9 min Onset-2min Removal of effect within 18-30 min Esmolol is metabolised in RBC without

renal/hepatic metabolism

Block K channels Prolong repolarisation Prolong APD and ERP Useful in Re-Entry tachycardias AMIODARONE (also Class IA, II BB) SOTALOL (also Class II BB)

Initially developed in the early 1960s as a treatment for angina pectoris, since it produces coronary vasodilation and decreases cardiac oxygen demand

Pronounced antiarrhythmic effects redirected its use

Structural similarities to the thyroid hormones

Absorption is limited (30-50%) Metabolised in the liver to produce the

active metabolite desethylamiodarone Relatively slow distribution, a steady state

of tissue concentrations is reached only after 2 months.

Lipophilic nature –large volume of distribution-concentrates in fatty tissue,liver and lung

elimination half-life after oral long term treatment is 50-60 days

200mg dose-7mg /d of iodine is released Into body(150-200 µg)

Class-3-acts on K channels-prolongs action potential and prolongs ERP

Class-1-blocks inactivated Na channels-more at high heart rates

Class-2-non competetive β and α antagonist Class-4- calcium channel blocker.

slows sinus rate and atrioventricular conduction

prolongs the QRS duration ,notably prolongs the QT interval.

Abnormal automaticity is inhibited

Useful for both SVT and VT AF- two trials-canadian trial and DIONOSYS

trial showed superior efficacy of amiodarone in decreasing recurrence rate compared to sotalol and dronedarone.

Increses refractory period both upperrlobe pulmonary veins

Excellent choice for decreasing recurrences in patients with structural heart disease and reduced ejection fraction

Ventricular arrythmias- Useful in out of hospital VF and refractory

VT following cardiac surgery Similar/superior efficacy to lidocaine in

cardiac resuscitation Reduces need for and inappropriate shocks

in ICD patients-OPTIC trial-superior to sotalol

Primary prevention-in patients with reduced EF<35%-decreased arrythmic death without overall effect on mortality

SCD-HeFT-EF<35%-similar all cause mortality to placebo but higher compared to ICD

EMIAT- SCD In post MI with decreased EF-decreased arrythmic deaths ,total deaths remained unchanged

CAMIAT-post MI with frequent VPC or nonsustained VT-reduced mortality-SCD and mortality reduced.

IV- 15 mg/min for 10 min, 1 mg/min for 3 hr, 0.5 mg/min thereafter till 24hrs

Maintainence doses-1 mg/min Oral loading- 800 to 1600 qd for 7-14 days maintainence-200 to 600 qd Serum therapeutic level-0.5-1.5 mg% Half life-56 days.

Increase serum levels-digoxin anticoagulants statins CCBS Tacrolimus Quinidine fentanyl flecainide

Prevalence of 15% in the first year, increasing up to 50% during long term use.

20 -50% of patients, the drug must be discontinued due to side effects

Discontinuation rate was 35% for amiodarone versus 22% for placebo

200 mg the incidence is0.1-1.6%, which increases with

higher doses18-24 months after initiation

of treatment.dyspnoea, dry cough, weight loss,

malaise, low grade fever, and sometimes pain due to Pleuritis

earliest abnormality is a decreasedcarbon monoxide diffusion

capacity. Arterial hypoxaemia and restrictive lung function tests

Treatment consists of termination of amiodarone and long term use of

corticosteroidsEarly diagnosis, mortality is 10%

but with late diagnosis or when hospitalisation is necessary,

mortality is reported to be as high as 20e33%

Erythematous iscoloration with a b

luish shadeDue to prolonged high

dose tretment and lipofuscin deposition resolves in 2 yrs of

cessation

corneal deposits-excretion in lacrimal

fluidHalo vision-

necessiate withdrawlOptic neuritis-occurs

4 mon -1 yr later warrants withdrawl.

First licensed for control of severe ventricular arrythmias

Non cardio selective water soluble protien bound agent with renal excretion and half life of 12 hours.

Racemic mixture L-sotalol has class 2 effects-SA and AV node

depression D- sotalol has class 3 effects-prolongs APD

in atrial ,ventricular refractory periods ,inhibition of conduction in by pass tracts in any direction.

D-sotalol showed increased mortality In SWORD study-due to after depolarisations

Indications-PSVT,WPW, preventing recurrence of AF,ischemic VT,

Major trial was EVSEM trial-in decreasing death and arrythmias in patients with EP induced sustained monomorphic VT –better than Class1 agents

It is as effective as Flecainide in preventing recurrences of AF and can be used in patients with structural heart disease where flecainide cannot be used.

Comparable to amiodarone

oral dose is 80 to 160 mg every 12 hours, allowing 2 to 3 days between dose adjustments to attain a steady state and to monitor the electrocardiogram for arrhythmias and QT prolongation.

Doses exceeding 320 mg/day can be used in patients when the potential benefits outweigh the risk of proarrhythmia.

Major side effect-torsades de pointes increases to 4 percent in patients with a history of sustained VT and is dose related, reportedly only 1.6 percent at 320 mg/day but 4.4 percent at 480 mg/day

prolongs repolarization it also activates a slow inward sodium

current along with block outward potassium currents, such as Ikr

mild slowing of the sinus rate and has minimal effects on AV conduction or QRS

Given intravenously and has a large volume of distribution.

Clearance is renal, with a half-life of 6 hours IV infusion of 1 mg over 10 minutes, second

1-mg dose may be given after the first dose is finished if the arrhythmia persists

Watch the patient for atleast 4 hrs in hospital

termination of an established episode of atrial flutter or fibrillation,but not for short paroxysms or prevention of recurrences.

Up to 60 percent of patients with atrial fibrillation and 70 percent of those with atrial flutter convert to sinus rhythm after 2 mg of ibutilide has been administered

prolongs accessory pathway refractoriness and can temporarily slow the ventricular rate during preexcited atrial fibrillation.

Can also terminate episodes of organized atrial tachycardia as well as sustained uniform morphology VT

Side effects and precautions Torsades is imp. Side effectoccur in

approximately 2 percent of patients given the drug (twice as often in women as in men).

The adverse effect occurs within the first 4 to 6 hours of dosing, after which the risk is negligible

Avoid in patients with QTc>440ms,un stable heart disease,k<4meq/l

approved for acute conversion of atrial fibrillation to sinus rhythm, as well as chronic suppression of recurrent atrial fibrillation

block of the rapid component of the delayed rectifier potassium current (IKr), which is important in repolarization

more prominent in the atria than in the ventricles—30 percent increase in atrial refractory period versus 20 percent in the ventricle

absorbed well, with over 90 percent bioavailability.

Fifty to 60 percent of the drug is excreted unchanged in urine, with a mean elimination half-life of 7 to 13 hours

Dosing is from 0.125 to 0.5 mg twice daily and must be initiated in a hospital

should not be given to patients with a creatinine clearance less than 20 ml/min or a baseline corrected QT interval longer than 440 milliseconds.

prevention of episodes of supraven-tricular tachyarrhythmias, particularly atrial flutter and fibrillation

Chemical cardioversion in AF<6mo More data in favor of cardioversion than

maintainence Devoid of negative ionotropic effect hence

can be used in patients with decreased EF

Drugs which increase its concentration are ketoconazole,macrolides,protease inhibitors

Additive effect with other drugs that prolong QT interval

balanced blockade of both rapid and slow components of IK.

effect is responsible for the lower rate of proarrhythmia and better preservation of drug efficacy at higher heart rates with this agent compared with pure IKr blockers

orally once daily, and its absorption is nearly complete and unaffected by food intake

once daily at a dosage of 100 to 200 mg. The drug is well tolerated, and dosing need

not be adjusted in the presence of renal or hepatic disease

likely to be indicated for long-term prevention of atrial flutter and fibrillation.

Calcium Channel Blockers Bind to L-type Ca channels Vascular SmM, Cardiac nodal & non-nodal

cells Decrease firing rate of aberrant PM sites Decrease conduction velocity Prolong repolarisation Especially active at the AVN VERAPAMIL DILTIAZEM

Narrow complex tachycardias Terminates PSVT/SVT Rate control in AFib/Aflutter NOT WPW or VT or high degree block NOT with BBlockers Negative Inotropy Vasodilation – Hypotension Dose: 5mg IV bolus. Rpt 15 min max 30 mg Diltiazem less adverse effects

• Acts via the adenosine A1 receptor• activation of an outward potassium current

(IKADO and IKACH) present in the atrium, sinoatrial and atrioventricular nodes

• Activation of the IKADO channel -shortening of the atrial action potential and hyperpolarization of the – depression of sinus node rate and transient AV block

• indirect actions via inhibition of intracellular CAMP generation

In the N region of the AV node, conduction is depressed, along with decreases in action potential amplitude, duration, and V.max.

Transient prolongation of the AH interval results, often with transient first-, second-, or third-degree AV node block.

Delay in AV nodal conduction is rate dependent.

His-Purkinje conduction is generally not directly affected.

Adenosine does not affect conduction in normal accessory pathways

• Pharmacokinetics: • Half life-10-30sec• Metabolised by erythrocytes and vascular

endothelial cells.• Dose-• 6mg-rapid IV,repeat 2 12 mg doses at 1-2

min intervals if ineffective.• Children-0.0375-0.25mg/kg• Pharmacodynamics- transient (less than 10

seconds) sinus slowing, AV nodal and conduction block

Interactions: methylxanthines are competitive

antagonists, and therapeutic concentrations of theophylline totally block the exogenous adenosine effect.

Dipyridamole is a nucleoside transport blocker that blocks reuptake of adenosine, delaying its clearance from the circulation or interstitial space and potentiating its effect.

AV node and AV reentry Can terminate SA node reentry RVOT VT-inhibition of catecholamine

stimulated calcium currents

Useful in distinction between SVT with aberancy and VT

differentiating conduction over the AV node from that over an accessory pathway during ablative procedures designed to interrupt the accessory pathway

Side effects: most commonly flushing, dyspnea, and

chest pressure-lasting less than 1 minute, and are well tolerated.

PVCs, transient sinus bradycardia, sinus arrest, and AV block are common when an SVT abruptly terminates.

Atrial fibrillation (12 percent )- adenosine administration, perhaps because of the drug's effect in shortening atrial refractoriness-can be problematic in patients with WPW.

Asthma or h/o asthma 2nd or 3rd degree AV block Sick sinus syndrome

enhancing both central and peripheral vagal tone

actions are largely confined to slowing the sinus node discharge rate, shortening atrial refractoriness, and prolonging AV nodal refractoriness

Electrophysiological effects on the His-Purkinje system and ventricular muscle are minimal, except in toxic concentrations

Serum half-life of digoxin is 36 to 48 hours, and the drug is excreted unchanged by the kidneys

Acute Loading dose is 0.5 – 1mg Oral maintainence doses are 0.125-0.25mg Routine monitoring of serum levels not

wararnted Quinidine increases concentration of lanoxin

Mainly for control of ventricular rate in Aflu/Afib

In exercise diminution of vagal tone and increase in sympathetic tone overrides the effect of digoxin and patient will experience tachycardia with minimal exertion

headache, nausea and vomiting, altered color perception, halo vision, and generalized malaise

Cardiac –digitalis effect-reverse tick sign ectopic beats of AV junctional or ventricular

origin, first-degree AV block, an excessively slow ventricular rate response to atrial fibrillation, or an accelerated AV junctional pacemaker-monitoring

bradycardias relatedto a markedly enhanced vagal effect (e.g., sinus bradycardia or arrest, AV node block)-withdrawal of digoxin; atropine or temporarypacing

Tachyarrhythmias-DAD-PAT with varying block, junctional, and fascicular or ventricular tachycardia-Phenytoin can be used for control of atrial tachyarrhythmias

lidocaine -treating infranodal tachycardias Potassium administration should be

considered for patients with evidence of increased AV junctional or ventricular automaticity

Life-threatening arrhythmias can be treated with digoxin-specific antibody fragments

Worsening renal function, advanced age, hypokalemia, chronic lung disease, hypothyroidism, and amyloidosis