B P7 C64 Therapy for Cardiac Arrhythmias Flashcards
The commonly used classification (_____) is still a useful framework for categorizing drug action but is limited because it is based on the electrophysiologic effects exerted by an arbitrary concentration of the drug, generally on a laboratory preparation of normal cardiac tissue.
Vaughan Williams
A more realistic but not widely used framework regarding AADs is provided by the “_____.” This approach to drug classification is an attempt to identify the mechanisms of a particular arrhythmia, to determine the vulnerable parameter of the arrhythmia most susceptible to modification, to define the target most likely to affect the vulnerable parameter, and then to select a drug that will modify the target
Sicilian Gambit
This class includes drugs that block the HCN channel mediated pacemaker current (If). Inhibition of the If channel (or “funny” current) _____
Class 0
Reduces:
Depolarization rate of the SN pacemaker cells
HR
___________ predominantly block the voltage gated fast sodium channel (INa)
Class I drugs
This class includes drugs that reduce V max (rate of rise in action potential upstroke [phase 0]) and prolong the action potential duration; onset and offset intermediate (<5 secs)
Class 1A - DOUBLE QUARTER POUNDER
Disopyrsmide
Quinidine
Procainamide
Class IA includes drugs that _____—quinidine, procainamide, and disopyramide.
Vmax: Reduce
APD: Prolong
This class of drugs does not reduce V max and shortens the APD; kinetics of onset and offset of these drugs in blocking the sodium channel is rapid (<500 milliseconds).
Class IB - LETTUCE, POTATO, MAYO, TOMATO
Lidocaine, Phenytoin, Mexelitine, Tocainide
Class IB drugs _____—mexiletine, phenytoin, and lidocaine.The kinetics of onset and offset of these drugs in blocking the sodium channel is rapid (<500 milliseconds)
Vmax: No reduction
APD: Shortens
This drugs reduce V max slow conduction velocity, and prolong refractoriness minimally. These drugs have slow onset and offset kinetics (10 to 20 seconds).
Class IC
MORE FRIES PLEASE
Moricizine
Flecainide
Propafenone
Class IC drugs, including flecainide and propafenone, can reduce V”max slow conduction velocity, and prolong refractoriness minimally. These drugs have slow onset and offset kinetics (10 to 20 seconds).
Vmax: Reduce
Slow conduction velocity
Refractoriness: prolong
Preferentially inhibits the late Na + current affecting APD and recovery and increases refractoriness and repolarization reserve; cause a reduction in early afterdepolarization-induced triggered activity.
Class ID
Ranolazine
Class ID drugs includes ranolazine, which preferentially inhibits the late Na+ current affecting APD and recovery and increases refractoriness and repolarization reserve.Class ID drugs cause a reduction in early afterdepolarization-induced triggered activity.
Refractoriness, Repolarization reserve: Increased
Drugs that block beta-adrenergic receptors
Propranolol, metoprolol, nadolol, carvedilol, nebivolol, and timolol.
This class of drugs predominantly blocks potassium channels (e.g., IKr) and prolongs repolarization.
Class III - “SAID”
Sotalol
Amiodarone
Ibutilide
Dronedarone
This class of drugs predominantly blocks potassium channels (e.g.,Ikr ) and prolongs _____. Included are sotalol, amiodarone, dronedarone, and ibutilide
Repolarization: prolong
This class of drugs predominantly blocks the L-type or slow calcium channel (ICa.L)
Class IV
Verapamil
Diltiazem
Examples of arrhythmias based on: Automaticity
Enhanced normal:
Inappropriate sinus tachycardia
Abnormal:
Atrial tachycardia
Accelerated Idioventricular rhythms
Examples of arrhythmias based on: Triggered activity
EAD: TdP
DAD:
Digitalis-induced arrhythmias
RVOT VT
Examples of arrhythmias based on: Reentry—Na+ Channel Dependent
Long excitable gap:
Sustained uniform VT
Atrial flutter (Typical)
Circus movement in WPWs
Short excitable gap:
Polymorphic and uniform ventricular tachycardia
Atrial flutter (Atypical)
Atrial fibrillation
Circus movement tachycardia in WPW
Bundle branch reentry
Ventricular fibrillation
Examples of arrhythmias based on: Reentry—Ca2+ Channel Dependent
AVNRT
Circus movement tachycardia in WPW
Verapamil-sensitive ventricular tachycardia
Some drugs exert greater inhibitory effects on the upstroke of the action potential at more rapid rates of stimulation and after longer periods of stimulation, a characteristic called ___________________
Use dependence
Drugs with this property depress V max to a greater extent after the channel has been “used” (i.e., after action potential depolarization rather than after a rest period).
Agents with class IB action exhibit rapid binding and unbinding from their receptor site on the channel protein, or exhibit use-dependent block of the fast channel at fast rates
With increased time spent in diastole (slower rate), a greater proportion of receptors unbind drug, and the drug exerts less effect.
Some drugs exert greater effects at slow rates than at fast rates, a property known as ___________________
Reverse use dependence
This is particularly true for drugs that lengthen repolarization; in the ventricle the QT interval becomes more prolonged at slow rather than at fast rates
_______________ depends critically on the interrelationships between refractoriness and conduction velocity, the presence of unidirectional block in one of the pathways, and other factors that influence refractoriness and conduction, such as excitability
Reentry
An effective agent that can stop reentry that is already present or can prevent it from starting if the drug _____________ or, alternately, ___________________
Depresses conduction
Improves conduction
Improving conduction can (1) eliminate unidirectional block so that reentry cannot begin or (2) facilitate conduction in the reentrant loop so that the returning wavefront reenters too quickly, encounters cells that are still refractory, and is extinguished
A drug that depresses conduction can transform unidirectional block into bidirectional block and thus terminate reentry or prevent it from starting by creating an area of complete block in the reentrant pathway.
A drug that slows conduction without producing block or significantly lengthening refractoriness can actually promote reentry.
If a drug prolongs the refractoriness of fibers in the reentrant pathway, the pathway may not recover excitability in time to be depolarized by the reentering impulse, and reentrant propagation ceases.
Examples of idiosyncratic adverse drug effects
Amiodarone pulmonary fibrosis and some arrhythmias, such as quinidine-induced TdP
Genetic variants can underlie susceptibility to idiosyncratic reactions.
Drugs that care considered safe in pregnancy
Adenosine (C)
Propranolol (C)
Metoprolol (C)
Lidocaine (B)
Digoxin * (C)
Sotalol (B)
Verapamil (C)
Antiarrhythmic drugs contraindicated in pregnancy
Amiodarone
Dronedarone
Proarrhythmia can manifest as _____.
(1) Increase in frequency of a preexisting arrhythmia
(2) Sustaining of a previously non-sustained arrhythmia (even making it incessant)
(3) Development of arrhythmias that the patient has not previously experienced
Electrophysiologic mechanisms of proarrhythmia are probably related to:
(1) Prolongation of repolarization or an increase in transmural dispersion
(2) Development of EADs with resultant TdP
(3) Alterations in reentry pathways to initiate or sustain tachyarrhythmias
Proarrhythmic events can occur in as many as _____% of patients receiving antiarrhythmic agents; heart failure increases this risk
5% to 10%
_____identify patients who experience AAD-induced ventricular fibrillation (VF)
Reduced LV function
Treatment with digitalis and diuretics
Bradycardia
Longer pretreatment QT interval
In the _____ Trial, however, researchers found that encainide and flecainide reduced spontaneous ventricular arrhythmias but were associated with a total mortality of 7.7%, versus 3.0% in the placebo group. Deaths were equally distributed throughout the treatment period, indicating that another type of proarrhythmic response can occur sometime after the beginning of drug therapy.
Cardiac Arrhythmia Suppression Trial (CAST)
________ blocks several channels, including the rapid inward sodium channel (INa ), IKr , Ito , and to a lesser extent the slow inward calcium channel, IKs , and the adenosine triphosphate (ATP)–sensitive potassium current (KATP ). Quinidine causes alpha-adrenergic and cholinergic blockade
For tx of primary (idiopathic) VF, ventricular arrhythmias in patients with Brugada syndrome and short-QT syndrome
Quinidine
Oral dose - 300 to 600 mg four times daily
LD: of 600 to 800 mg produces an earlier effective concentration
Adverse effects:
Prolongation of the QRS duration or as sinoatrial (SA) or AV nodal conduction; syncope as a result of self-terminating episode of TdP; prolongs the QT interval in most patients (not dose related)
Quinidine induces vasodilation by blocking alpha-adrenergic receptors and can cause significant hypotension. It does not cause significant direct myocardial depression.
Syncope - the first 2 to 4 days
Inidcations for using Quinidine
Primary (idiopathic) VF
Ventricular arrhythmias in patients with BrS
Short-QT syndrome
Quinidine crosses the placenta so it can be used to treat fetal arrhythmias
The most common adverse effects of chronic oral quinidine therapy are _____.
Gastrointestinal (GI) and include nausea, vomiting, diarrhea, abdominal pain, and anorexia (milder with the gluconate form)
Quinidine prolongs the QT interval in most patients (not dose related), regardless of whether ventricular arrhythmias occur, but significant QT prolongation (QT interval of _____ milliseconds) is often a characteristic of patients with quinidine-related syncope, who may have a genetic predisposition underlying such a response
500 to 600 msec
Therapy of proarrhythmia due to Quinidine requires immediate discontinuation of use of the drug; magnesium given intravenously _____ is the initial drug treatment of choice
Magnesium 2 g over 1 to 2 minutes, followed by an infusion of 3 to 20 mg/min
_____ can be used to suppress the ventricular tachyarrhythmia, perhaps by suppressing EADs. When pacing is not available, _____ can be given with caution
Atrial or ventricular pacing
isoproterenol
__________________ predominantly blocks the inactivated state of INa . It also blocks IKr , IK1 , and IK.ATP . Like quinidine, procainamide usually prolongs the ERP more than it prolongs the APD and thus may prevent reentry. Procainamide exerts the least anticholinergic effects among type IA drugs.
Procainamide
Convert recent-onset AF to sinus rhythm; can block conduction in the accessory pathway of patients with Wolff Parkinson-White (WPW) syndrome
Can depress myocardial contractility
Dose - IV 10 to 15 mg/kg are used at a rate of up to 50 mg/min until the arrhythmia has been controlled; oral 3- to 4-hour dosing interval at a total daily dose of 2 to 6 g
AE: rash, myalgia, digital vasculitis, and Raynaud phenomenon, fever and agranulocytosis, systemic lupus erythematosus (SLE)-like syndrome (reversible; but if positive anti-DNA antibody g ally indicates that drug therapy should be discontinued), brain and kidneys are typically spared, and there is no predilection for women.
Indications of using Procainamide
SVT
VT
Conversion of recent-onset AF to SR
AF with RVR
WPWs
Administered during an EPS to stress the His-Purkinje system and evaluate the need for a pacemaker
The drug also has diagnostic applications when given intravenously (10 mg/kg over 5 to 10 minutes). In patients with suspected Brugada syndrome who have a normal resting electrocardiogram (ECG), drug infusion can result in the characteristic _____, whereas in patients with WPW syndrome, the drug can cause _____.
BrS: “Brugada sign”
WPWs: Sudden loss of preexcitation
In patients with sinus node dysfunction, however, procainamide can prolong sinus node recovery time and worsen symptoms in some patients with _____.
Bradycardia-tachycardia syndrome
As with quinidine, prior treatment with _____ is recommended to prevent acceleration of the ventricular response during atrial flutter or fibrillation after procainamide therapy
Beta or calcium channel blockers
In _____% of patients receiving long-term procainamide therapy, anti-nuclear antibodies (ANAs) develop, with clinical symptoms occurring in 20% to 30%;this is reversible when procainamide is stopped
60-70%
Causes use-dependent block of I Naand non–use-dependent block of IKr
Muscarinic blocker and can increase the sinus node discharge rate and shorten AV nodal conduction time and refractoriness when the nodes are under cholinergic (vagal) influence
Avoided in patients with reduced left ventricular systolic function
Helps prevent recurrence of AF after successful cardioversion as effectively as quinidine and may terminate atrial flutter.
Disopyramide
Dose: 100 to 300 mg orally every 6 hours, with a range of 400 to 1200 mg/day
Treating patients with AF, particularly atrial flutter, the ventricular rate must be controlled before disopyramide is administered, or the combination of a decrease in atrial rate with vagolytic effects on the AV node can result in 1:1 AV conduction during atrial flutter.
It has been used in patients with hypertrophic cardiomyopathy for both AF therapy and its negative inotropic effect
AE:
MC: Parasympatholytic properties and include urinary hesitancy or retention, constipation, blurred vision, closed-angle glaucoma, and dry mouth.
Produce ventricular arhythmias frequently associated with QT prolongation and TdP.
Disopyramide suppresses _____perforance and is a _____. The drug should generally be avoided in patients with reduced left ventricular systolic function because they tolerate its negative inotropic effects poorly.
Ventricular systolic performance
Mild arterial vasodilator
_____, a rauwolfia derivative, has been used extensively to treat patients with ventricular and supraventricular arrhythmias in Europe and Asia but is not available in the United States.
Ajmaline
When administered intravenously at doses of 50 mg over a 3-minute period, or 10 mg/min, to a total dose of 1 mg/kg, ajmaline can have the following effects:
(1) delta wave disappearance in patients with WPW syndrome (indicating an accessory pathway anterograde ERP longer than 250 milliseconds);
(2) ST-T abnormalities and interventricular conduction block 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; and
(4) right precordial ST elevation in patients with suspected Brugada syndrome in whom findings on the resting ECG are normal.
Ajmaline can _____ the defibrillation threshold.
Increase
______________ Blocks INa, predominantly in the open or inactivated state. It has rapid onset and offset kinetics and does not affect normal sinus node automaticity in usual doses but does depress other normal and abnormal forms of automaticity, as well as EADs and DADs in Purkinje fibers in vitro
Modest depressant effect on Vmax; however, faster rates of stimulation, acidosis, increased extracellular K + concentration, and reduced membrane potential (changes that can result from ischemia) increase the ability of ___________ to block INa.
Moderate efficacy against ventricular arrhythmias of diverse causes; it is generally ineffective against supraventricular arrhythmias and rarely terminates monomorphic VT.
Lidocaine
Dose: initial bolus of 1 to 2 mg/kg body weight at a rate of 20 to 50 mg/min and a second injection of half the initial dose 20 to 40 minutes later; infusion rates in the range of 1 to 4 mg/min
Clinically significant adverse hemodynamic effects are rarely noted unless with severe LVD
AE: CNS toxicity, d ness, paresthesias, confusion, delirium, stupor, coma, and seizures, dose related; rarely malignant hyperthermia
Lidocaine can convert areas of unidirectional block into bidirectional block during _____ and inhibit the development of _____ by preventing fragmentation of organized large wavefronts into heterogeneous wavelets.
Ischemia
VF
Lidocaine has only a modest depressant effect on Vmax; however,_____ increase the ability of lidocaine to block INa
Faster rates of stimulation
Acidosis
Increased extracellular K+ concentration
Reduced membrane potential (changes that can result from ischemia)
If the initial bolus of lidocaine is ineffective, up to ____.
2 more boluses of 1 mg/kg may be administered at 5-minute intervals
Lidocaine has moderate efficacy against _____ of diverse causes; it is generally ineffective against supraventricular arrhythmias and rarely terminates monomorphic VT.
Ventricular arrhythmias: moderate
SVT: ineffective
Monomorphic VT: rare termination
Although once used in an attempt to prevent VF in the first 2 days after acute MI, its efficacy was marginal, and because it can produce side effects such use is now not recommended.
The most frequently reported adverse effects of lidocaine are dose-related manifestations of _____.
CNS toxicity: dizziness, paresthesias, confusion, delirium, stupor, coma, and seizures
Occasional sinus node depression and His-Purkinje block have been reported.
Rarely, lidocaine can cause malignant hyperthermia.
Local anesthetic congener of lidocaine with anticonvulsant properties, is used for the oral treatment of patients with symptomatic ventricular arrhythmias. It is rarely used as a single agent
Shortens the APD and ERP of Purkinje fibers and, to a lesser extent, ventricular muscle. It depresses the V max of phase 0 by blocking INa , especially at faster rates, and depresses the automaticity of Purkinje fibers
Moderately effective tx in cute and chronic ventricular t rhythmias, but not SVTs; combined with other drugs such as procainamide, beta blockers, quinidine, disopyramide, propafenone, or amiodarone
Mexiletine
Dose: 200 mg orally every 8 hours; inc or dec 50 to 100 mg every 2 to 3 days
Mexiletine exerts no major hemodynamic effects
Mexiletine can result in severe bradycardia and abnormal sinus node recovery time in patients with sinus node disease, but not in those with a normal sinus node. It does not affect AV nodal conduction and can depress His-Purkinje conduction, does not affect the QT interval
In treating patients with a long QT interval, mexiletine may be safer
AE: 40% of patients may require a change in dose or discontinuation of mexiletine therapy as a result of adverse effects, including tremor, dysarthria, dizziness, paresthesia, diplopia
Lidocaine use as an AAD should be avoided in patients receiving mexiletine.
Mexiletine is a moderately effective antiarrhythmic agent for the treatment of acute and chronic ventricular tachyarrhythmias, but not _____. Success rates vary from 6% to 60% and can be increased in some patients if mexiletine is combined with other drugs such as procainamide, beta blockers, quinidine, disopyramide, propafenone, or amiodarone.
SVTs
Phenytoin was used originally to treat seizure disorders. Its value as an AAD is limited to rare cases of _____.
(1) Digitalis-toxic atrial and ventricular tachyarrhythmias (for which more rapid and effective control can be achieved with digitalis-specific antibodies)
(2) occasional cases of ventricular arrhythmias when used in combination with other agents
Exhibits marked use-dependent depressant effects on the rapid sodium channel by decreasing V max and has slow onset and offset kinetics; profoundly slows conduction in all cardiac fibers and, in high concentrations, inhibits the slow Ca2+ channel; Conduction time in the atria, ventricles, AV node, and His-Purkinje system is prolonged.
Can depresses cardiac performance, particularly in patients with compromised ventricular systolic function
Indicated for lifethreatening ventricular tachyarrhythmias, SVTs, and paroxysmal AF, particularly effective in suppressing PVCs and short runs of non-sustained VT, atrial tachycardia (AT), atrial flutter, and AF (including oral loading to terminate episodes acutely)
Can produce ST elevation in lead V1, c acteristic of Brugada syndrome, in susceptible patients and has been used as a diagnostic tool
Flecainide
Dose: 100 mg every 12 hours, increased in increments of 50 mg twice daily, no sooner than every 3 to 4 days,
Increases in serum concentrations of digoxin (15% to 25%) and propranolol (30%)
Flecainide and propafenone may both be used in c tion with beta or calcium channel blockers as a “pill in the pocket”
AE:
Worsening of existing ventricular arrhythmias or the onset of new ventricular arrhythmias can occur in 5% to 30%
Negative inotropic effects can precipitate or worsen heart failure episodes
In CAST, patients treated with flecainide had higher mortality or nonfatal cardiac arrest compared to the placebo group, possibly related to an interaction between the drug and myocardial ischemia. Exercise can amplify the conduction slowing in the ventricle produced by flecainide and in some cases can precipitate a proarrhythmic response. Therefore, exercise testing has been recommended to screen for proarrhythmia (as well as occult ischemia) before and periodically during treatment.
Flecainide _____ cardiac performance, particularly in patients with compromised ventricular systolic function, and should be used cautiously or not at all in those with moderate or severe ventricular systolic dysfunction.
Depresses
Flecainide is indicated for the treatment of _____
Life- threatening ventricular tachyarrhythmias
SVTs
Paroxysmal AF
Proarrhythmic effects are some of the most important adverse effects of flecainide. Its marked slowing of conduction precludes its use in patients with _____ and warrants cautious administration in patients with intraventricular conduction disorders
Second-degree AV block with-out a pacemaker
Exercise can amplify the conduction slowing in the ventricle pro- duced by flecainide and in some cases can precipitate a proarrhythmic response. Therefore, _____ testing has been recommended to screen for proarrhythmia (as well as occult ischemia) before and periodically during treatment.
Exercise testing
_____, represent the most frequent non-cardiac adverse effects of flecainide
CNS complaints, including confusion and irritability
High doses of class IC agents can result in a _____
Markedly prolonged QRS duration
Bundle branch block
Wide and bizarre QRS morphologies during tachycardia
Blocks the fast sodium current in a use-dependent manner in Purkinje fibers and to a lesser degree in ventricular muscle
Treatment of paroxysmal SVT, AF, and life-threatening ventricular tachyarrhythmias, and effectively suppresses spontaneous PVCs and nonsustained and sustained VT. Acute termination of AF episodes occurred with a single 600mg oral dose of propafenone in 76%
Propafenone
Dose: 150 to 300 mg every 8 hours, not to exceed 1200 mg/day (
In patients with left ventricular e tion fraction (EF) exceeding 40%, the negative inotropic effects are well tolerated, but patients with preexisting left ventricular dysfunction and congestive heart failure may exhibit worsening of their symptoms.
Increases the pacing threshold but minimally affects the defibrillation threshold
AE:
Exacerbation of bronchospastic lung disease can occur because of mild beta-blocking effects.
Cardiovascular side effects develop in 10% to 15% of patients - AV block, sinus node depression, and worsening of heart failure
Beta Blocking Agents - Class II
Metoprolol, carvedilol, atenolol, propranolol, and esmolol have been most widely used to treat supraventricular and ventricular arrhythmias
In low doses, ___________________ can block β1 receptors more than they block β2 receptors and might be preferable for the treatment of patients with pulmonary or peripheral vascular disease. In high doses, the “selective” β 1 blockers also block β 2 receptors.
________________ also exerts alpha-blocking effects and is used primarily in patients with heart failure
___________ induce less depression of left ventricular function than do beta blockers without intrinsic sympathomimetic activity.
Selective beta blockers
Carvedilol
Beta blockers with intrinsic sympathomimetic
Arrhythmias associated with thyrotoxicosis or pheochromocytoma and arrhythmias largely related to excessive cardiac adrenergic stimulation, such as those initiated by exercise or emotion
Beta-blocking drugs do not usually convert chronic atrial flutter or AF to normal sinus rhythm
Beta blockers exert negative inotropic effects and can precipitate or worsen heart failure. However, beta blockers clearly improve survival in patients with heart failure
_____ decrease overall mortality and sudden death after MI
Propranolol
Atenolol
Carvedilol
Timolol
Metoprolol
Adverse cardiovascular effects from beta blockers include unacceptable _____.
Hypotension
Bradycardia
Congestive heart failure
Indications for using Beta blockers
(1) Arrhythmias associated with thyrotoxicosis or pheochromocytoma and arrhythmias largely related to excessive cardiac adrenergic stimulation
(2) AF of recent onset and in patients who have recently undergone cardiac surgery
(3) Reentrant SVTs using the AV node as one of the reentrant pathways, such as AV nodal reentrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia in WPW syndrome or inappropriate sinus tachycardia, or for AT, beta blockers can slow or terminate the tachycardia and can be used prophylactically to prevent a recurrence
(4) Digitalis-induced arrhythmias such as AT, nonparoxysmal AV junctional tachycardia, PVCs, or VT
(5) Ventricular arrhythmias associated with prolonged–QT interval syndrome and MVP
Sudden withdrawal of _____ in patients with angina pectoris can precipitate or worsen angina and cardiac arrhythmias and cause acute MI, possibly as a result of the heightened sensitivity to beta agonists caused by previous beta blockade (receptor upregulation). Heightened sensitivity may begin several days after cessation of beta-blocker therapy and can last _____ days
Propranolol
5-6 days
Other adverse effects of beta blockers include _____.
Worsening of asthma or COPD
Intermittent claudication
Raynaud phenomenon
Mental depression
Increased risk for hypoglycemia in insulindependent diabetic patients
Easy fatigability
Dsturbingly vivid dreams or insomnia
Impaired sexual function
___________________ is an iodinated benzofuran derivative approved by the FDA for the treatment of patients with life-threatening ventricular tachyarrhythmias when other drugs are ineffective or not tolerated.
This drug and its metabolite ________________ prolong the APD of ventricular muscle but shorten the APD of Purkinje fibers. It depresses Vmax in ventricular muscle in a rate- or use-dependent manner by blocking inactivated sodium channels. The ERP of all cardiac tissues is prolonged. The H-V interval increases, and the QRS duration lengthens, especially at fast rates
This has class I (blocks INa ), class II (antiadrenergic), and class IV (blocks ICa.L ) actions in addition to its class III effects (blocks IK)
Amiodarone
Desethylamiodarone
Decreases the heart rate, systemic vascular resistance, and left ventricular dP/dt when administered IV
Dose: 800 to 1200 mg/day for 1 to 3 weeks, 400 to 800 mg/day for 1 to 2 weeks, and finally after 2 to 3 months of treatment, a maintenance dose of 200 mg per day
To achieve more rapid loading and effect in emergencies, amiodarone can be administered intravenously at initial doses of 15 mg/min for 10 minutes, followed by 1 mg/min for 6 hours and then 0.5 mg/min for the remaining 18 hours and the next several days as necessary
The efficacy of amiodarone equals or exceeds that of all other AADs and may be in the range of 60% to 80% for most supraventricular tachyarrhythmias and 40% to 60% for ventricular tachyarrhythmias
Amiodarone has been shown to result in inferior survival compared with ICD therapy, and in the SCD-HeFT population (New York Heart Association [NYHA] class II or III heart failure; EF, 35%), survival of amiodarone-treated patients was no different than for the placebo group. The drug may still be used adjunctively in ICDtreated patients to decrease the frequency of shocks from VT and VF episodes or to control supraventricular tachyarrhythmias that elicit device therapy
Effects of Amiodarone
Long term administration:
amiodarone prolongs the APD and refractoriness of all cardiac fibers without affecting resting membrane potential
Acute:
Desethylamiodarone prolong the APD of ventricular muscle but shorten the APD of Purkinje fibers
_____
Depresses V”max in ventricular muscle in a rate- or use-dependent manner by blocking inactivated sodium channels
Noncompetitively antagonizes alpha and beta receptors and blocks conversion of thyroxine (T4) to triiodothyronine (T3)
Exhibits slow channel–blocking effects; with oral administration, it slows the sinus rate by 20% to 30% and prolongs the QT interval, at times changing the contour of the T wave and producing U waves
Amiodarone is a peripheral and coronary vasodilator. When administered intravenously (150 mg over 10 minutes, then a 1-mg/min infusion), amiodarone _____.
Decreases:
HR
SVR
Left ventricular dP/dt
Dosing of amiodarone
There is no standard dosng schedule for amiodarone applicable to all patients.
One recommended approach is to treat with:
800 to 1200 mg/day for 1 to 3 weeks,
400 to 800 mg/day for 1 to 2 weeks,
and finally after 2 to 3 months of treatment,
a maintenance dose of 200 mg per day
To achieve more rapid loading and effect in emergencies, amiodarone can be administered intravenously at initial doses of _____ and the next several days as necessary.
15 mg/min for 10 minutes
followed by 1 mg/min for 6 hours
and then 0.5 mg/min for the remaining 18 hours
Supple- mental infusions of 150 mg over a 10-minute period can be used for breakthrough VT or VF. Intravenous infusions can be continued safely for _____ weeks.
2-3 weeks
Patients with depressed EF should receive IV amiodarone with great caution because of hypotension. High-dose oral loading (_____)may suppress ventricular arrhythmias in _____ days.
800 to 2000 mg/day to maintain trough serum concentrations of 2 to 3 μg/mL
5-7 days
However, amiodarone has been shown to result in inferior survival compared with ICD therapy, and in the SCD-HeFT population (New York Heart Association [NYHA] class II or III heart failure; EF, 35%), survival of amiodarone-treated patients was _____t than for the placebo group
No different
Adverse effects are reported by about 75% of patients treated with amiodarone for 5 years, and these effects compel stopping the drug in 18% to 37%. The most frequent side effects requiring drug discontinuation involve _____complaints or abnormal test results. Most adverse effects are reversible with dose reduction or cessation of treatment. .Adverse effects are more common when therapy is continued in the long term and at higher doses
Pulmonary and GI
Of the non-cardiac adverse reactions of amiodarone, _____ toxicity is the most serious; in one study, it occurred in 33 of 573 patients between 6 days and 60 months of treatment, with three deaths. The mechanism is unclear but may involve a _____.
Pulmonary toxicity
Hypersensitivity reaction, widespread phospholipidosis, or both
_____ are the most common symptoms of amiodarone-induced pulmonary toxicity, along with_____ on examination, _____.
Dyspnea and nonproductive cough
Fine crackles
Hypoxia
Abnormal gallium scan results,
Reduced carbon monoxide diffusion capacity (DLCO)
Radiographic evidence of pulmonary infiltrates
Because amiodarone appears to inhibit the peripheral conversion of T4 to T3, chemical changes result and are characterized by a slight increase in _____ and a slight decrease in ___ levels.The reverse T3 concentration has been used as an index of drug effect.
Slight increase in:
T4
reverse T3 - used as an index of drug effect
TSH
Slight decrease in:
T3
In amiodarone-induced thyroid disease, during hypothyroidism the ___ level increases greatly, whereas the level of __ increases in hyperthyroidism.
Hypothyroidism: TSH
Hyperthyroidism: T3
Thyroid function tests should be performed approximately every ____ months for the first year while amiodarone is being taken and _____ yearly thereafter, or sooner if symptoms develop that are consistent with thyroid dysfunction
1st year: every 3 months
Thereafter: 1-2x yearly
Corneal microdeposits occur in almost 100% of adults receiving the drug longer than _____ months. More serious ocular reactions, including optic neuritis and atrophy with visual loss, have been reported but are rare, and causation by amiodarone has not been firmly established
> 6 months
Among the most common side effects limiting long-term drug use are _____, and these side effects are both dose and duration related as well as idiosyncratic. Lowering the dose of amiodarone frequently decreases the severity of the side effect.A wide variety of neurologic toxicities have been described including tremor, ataxia, peripheral neuropathy, and rarely myopathy and encephalopathy.
Neurologic