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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
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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