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Antiarrhythmic Agent

Antiarrhythmic agent

Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation. While the use of antiarrhythmic agents to suppress atrial arrhythmias (atrial fibrillation and atrial flutter) is still in practice, it is unclear whether suppression of atrial arrhythmias will prolong life ^1,2. In the past, it was believed that suppression of the potentially dangerous ventricular arrhythmias, ventricular tachycardia and ventricular fibrillation would prolong life, but it was found in large clinical trials that suppression of these arrhythmias would paradoxically increase mortality^3,4, which may happen due to the increased workload these drugs place on the heart. In individuals with atrial fibrillation, antiarrhythmics are still used to suppress arrhythmias. This is often done to relieve the symptoms that may be associated with the loss of the atrial component to ventricular filling (atrial kick) that is due to atrial fibrillation or flutter. In individuals with ventricular arrhythmias, antiarrhythmic agents are often still in use to suppress arrhythmias. In this case, the patient may have frequent arrhythmic events or at high risk for ventricular arrhythmias. Antiarrhythmic agents may be considered the first-line therapy in the prevention of sudden death in certain forms of structural heart disease, and failure of these agents to suppress arrhythmias may lead to implantation of an implantable cardioverter-defibrillator (ICD). The use of antiarrhythmic agents in this population may be in conjunction with an ICD. In this case, the ICD is used to prevent sudden death due to ventricular fibrillation, while the antiarrhythmic agent(s) are used to suppress ventricular tachyarrhythmias so that the ICD doesn't shock the patient frequently. sudden death Many attempts have been made to classify antiarrhythmic agents. The problem arises from the fact that many of the antiarrhythmic agents have multiple modes of action, making any classification imprecise.

Vaughan Williams antiarrhythmic classification

The Vaughan Williams classification is one of the most widely used classification schemes for antiarrhythmic agents. This scheme classifies a drug based on the primary mechanism of its antiarrhythmic effect. However, its dependence on primary mechanism is one of the limitations of the VW classification, since many antiarrhythmic agents have multiple action mechanisms. Amiodarone, for example, has effects consistent with all of the first four classes. Another limitation is the lack of consideration within the VW classification system for the effects of drug metabolites. Procainamide, a class Ia agent whose metabolite – N-acetyl procainamide (NAPA) – has a class III action is one such example. A historical limitation was that drugs such as digoxin and adenosine – important antiarrhythmic agents – had no place at all in the VW classification system. This has since been rectified by the inclusion of class V. There are five main classes in the Vaughan Williams classification of antiarrhythmic agents:
- Class I agents interfere with the sodium (Na⁺) channel.
- Class II agents are anti-sympathetic nervous system agents. All agents in this class are beta blockers.
- Class III agents affect potassium (K⁺) efflux.
- Class IV agents affect the AV node.
- Class V agents work by other or unknown mechanisms.

Class I agents

The class I antiarrhythmic agents interfere with the sodium (Na⁺) channel. Class I agents are grouped by what effect they have on the Na⁺ channel, and what effect they have on cardiac action potentials.

Class Ia agents

action potential Class Ia agents block the fast sodium channel. Blocking this channel depresses the phase 0 depolarization (reduces V_max), which prolongs the action potential duration by slowing conduction. Agents in this class also cause decreased conductivity and increased refractoriness. Indications for Class Ia agents are supraventricular tachycardia, ventricular tachycardia, symptomatic ventricular premature beats, and prevention of ventricular fibrillation. Class Ia agents include quinidine, procainamide and disopyramide. Procainamide can be used in the treatment of atrial fibrillation in the setting of Wolff-Parkinson-White syndrome, and in the treatment of wide complex hemodynamically stable tachycardias. While procainamide and quinidine may be used in the conversion of atrial fibrillation to normal sinus rhythm, they should only be used in conjunction with an AV node blocking agent (ie: digoxin, verapamil, or a beta blocker), because procainamide and quinidine can increase the conduction through the AV node and may cause 1:1 conduction of atrial fibrillation, causing an increase in the ventricular rate.

Class Ib agents

beta blocker Class Ib antiarrhythmic agents are sodium channel blockers. Class Ib agents have fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. Class Ib agents shorten the action potential duration and reduce refractoriness. These agents will decrease V_max in partially depolarized cells with fast response action potentials. They either do not change the action potential duration, or they may decrease the action potential duration. Class Ib agents are indicated for the treatment of ventricular tachycardia and symptomatic premature ventricular beats, and prevention of ventricular fibrillation. Class Ib agents include lidocaine, mexiletine, tocainide, and phenytoin.

Class Ic agents

phenytoin Class Ic antiarrhythmic agents markedly depress the phase 0 repolarization (decreasing V_max). They decrease conductivity, but have a minimal effect on the action potential duration. Of the sodium channel blocking antiarrhythmic agents (the class I antiarrhythmic agents), the class Ic agents have the most potent sodium channel blocking effects. Class Ic agents are indicated for life-threatening ventricular tachycardia or ventricular fibrillation, and for the treatment of refractory supraventricular tachycardia (ie: atrial fibrillation). Class Ic agents include encainide, flecainide, moricizine, and propafenone.

Class II agents

Class II agents are conventional beta blockers. They act by slowing impulse induction in the Sinus node. Class II agents include esmolol, propranolol, and metoprolol.

Class III agents

metoprolol Class III agents predominantly block the potassium channels, thereby prolonging repolarization⁵. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is more like to interact with tissue that has become refractory). Class III antiarrhythmic agents exhibit reverse use dependent prolongation of the action potential duration (Reverse use-dependence)⁵. This means that the refractoriness of the ventricular myocyte increases at lower heart rates. This increases the susceptibility of the myocardium to early after-depolarizations (EADs) at low heart rates. Antiarrhythmic agents that exhibit reverse use-dependence are more efficacious at preventing a tachyarrhythmia that converting someone into normal sinus rhythm. Because of the reverse use-dependence of class III agents, at low heart rates class III antiarrhythmic agents may paradoxically be more arrhythmogenic. Class III agents include amiodarone, azimilide, bretylium, clofilium, dofetilide, ibutilide, sematilide, and sotalol. Amiodarone is indicated for the treatment of refractory VT or VF, particularly in the setting of acute ischemia. Amiodarone is also safe to use in individuals with cardiomyopathy and atrial fibrillation, to maintain normal sinus rhythm. However, it does not cardiovert individuals from atrial fibrillation to normal sinus rhythm. Sotalol is indicated for the treatment of atrial or ventricular tachyarrhythmias, and AV re-entrant arrhythmias. Ibutilide is the only antiarrhythmic agent currently approved by the FDA for acute conversion of atrial fibrillation to sinus rhythm.

Class IV agents

Class IV agents are slow calcium channel blockers. They decrease conduction through the AV node. Class IV agents include verapamil and diltiazem.

Class V agents

Class V agents include adenosine and digoxin.

References

# Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1825-33. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=12466506&dopt=Abstract Medline abstract])
# Nichol G, McAlister F, Pham B, Laupacis A, Shea B, Green M, Tang A, Wells G. Meta-analysis of randomised controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation. Heart. 2002 Jun;87(6):535-43. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12010934 Medline abstract])
# The Cardiac Arrhythmia Suppression Trial (CAST): The CAST investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989, 321:406–412.
# The Cardiac Arrhythmia Suppression Trial II (CAST II): The CAST II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med. 1992 Jul 23;327(4):227-33. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1377359&dopt=Abstract Medline abstract])
# Lenz TL, Hilleman DE, Department of Cardiology, Creighton University, Omaha, Nebraska. Dofetilide, a New Class III Antiarrhythmic Agent. Pharmacotherapy 20(7):776-786, 2000. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10907968 Medline abstract])
- Category:Cardiac electrophysiology

Pharmaceutical

Pharmacology (in Greek: pharmacon (φάρμακον) is drug, and logos (λόγος) is science) is the study of how chemical substances interact with living systems. If these substances have medicinal properties, they are referred to as pharmaceuticals. The field encompasses drug composition, drug properties, interactions, toxicology, and desirable effects that can be used in therapy of diseases. Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main regulatory body is the Food and Drug Administration through its publication of the USP. Pharmacology as a science is practiced by pharmacologists. Subdisciplines are clinical pharmacology (the medical field of medication effects on humans), neuro- and psychopharmacology (effects of medication on behavior and nervous system functioning), and theoretical pharmacology.

Scientific background

The study of medicinal chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signalling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signalling pathways controlling cellular function). A chemical has, from the pharmacological point-of-view, various properties. Pharmacokinetics describes its behaviour in the body - particularly in the blood (e.g. its half-life and volume of distribution), and pharmacodynamics relates its behaviour in the blood to its effects (desired effects or toxic side-effects). When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in ADME:
- Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)?
- Distribution - How does it spread through the organism?
- Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic?
- Excretion - How is the medication eliminated (through the bile, urine, breath, skin)? Medication is said to have a narrow or wide therapeutic index or therapeutic window. This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to 1) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than 5) exerts its desired effect at a dose substantially below its toxic dose. Those with a narrow window are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumours.

Classification

Medication can be usually classified in various ways, e.g. by its chemical properties, mode of administration, or biological system affected. An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System.

Types of medication

For pain & consciousness (Analgesic drugs)

The main classes of painkillers are NSAIDs, opioids and various orphans such as paracetamol, tricyclic antidepressants and anticonvulsants.

For musculo-skeletal disorders

NSAIDs (including COX-2 selective inhibitors), muscle relaxant, neuromuscular drug
anticholinesterase

For the eye

- General: adrenergic neurone blocker, astringent, ocular lubricant
- Diagnostic: topical anesthetics, sympathomimetics, parasympatholytics, mydriatics, cycloplegics
- Anti-bacterial: antibiotics, topical antibiotics, sulfa drugs, aminoglycosides, fluoroquinolones
- Anti-viral:
- Anti-fungal: imidazoles, polyenes
- Anti-inflammatory: NSAIDs, corticosteroids
- Anti-allergy: mast cell inhibitors
- Anti-glaucoma: adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors/hyperosmotics, cholinergics, miotics, parasympathomimetics, prostaglandin agonists/prostaglandin inhibitors. nitroglycerin

For the ear, nose and oropharynx

sympathomimetic, antihistamine, anticholinergic, NSAIDs, steroid, antiseptic, local anesthetic, antifungal, cerumenolytic

For the respiratory system

bronchodilator, NSAIDs, anti-allergic, antitussive, mucolytic, decongestant
corticosteroid, beta-receptor antagonist, anticholinergic, steroid

For endocrine problems

androgen, antiandrogen, gonadotropin, corticosteroid, growth hormone, insulin, antidiabetic (sulfonylurea, biguanide/metformin, thiazolidinedione, insulin), thyroid hormones, antithyroid drugs, calcitonin, diphosponate, vasopressin analogues

For the reproductive system or urinary system

antifungal, alkalising agent, quinolones, antibiotic, cholinergic, anticholinergic, anticholinesterase, antispasmodic, 5-alpha reductase inhibitor, selective alpha-1 blocker, sildenafil

For contraception

contraceptive, oral contraceptives, spermicide, depot contraceptives

For obstetrics and gynaecology

NSAIDs, anticholinergic, haemostatic drug, antifibrinolytic, Hormone Replacement Therapy, bone regulator, beta-receptor agonist, follicle stimulating hormone, luteinising hormone, LHRH
gamolenic acid, gonadotropin release inhibitor, progestogen, dopamine agonist, oestrogen, prostaglandin, gonadorelin, clomiphene, tamoxifen, Diethylstilbestrol

For the skin

emollient, anti-pruritic, antifungal, disinfectant, scabicide, pediculicide, tar products, vitamin A derivatives, vitamin D analogue, keratolytic, abrasive, systemic antibiotic, topical antibiotic, hormones, desloughing agent, exudate absorbent, fibrinolytic, proteolytic, sunscreen, antiperspirant, corticosteroid

For infections and infestations

antibiotic, antifungal, antileprotic, antituberculous drug, antimalarial, anthelmintic, amoebicide, antiviral, antiprotozoal, antiserum

For immunology

vaccine, immunoglobulin, immunosuppressant, interferon, monoclonal antibody

For allergic disorders

anti-allergic, antihistamine, NSAIDs

For nutrition

tonic, iron preparation, electrolyte, parenteral nutritional supplement, vitamins, anti-obesity drug, anabolic drug, haematopoietic drug, food product drug

For neoplastic disorders

cytotoxic drug, sex hormones, aromatase inhibitor, somatostatin inhibitor, recombinant interleukins, G-CSF, erythropoietin

For diagnostics

contrast media

For euthanasia

A euthanaticum is used for euthanasia and physician-assisted suicide, see also barbiturates.

Other

Zoopharmacognosy: Animal usage of drugs and non-foods.

External links

- [http://www.ich.org/ International Conference on Harmonisation]
- [http://www.usp.org US Pharmocopea]
- [http://www.davabazaar.co.in Davabazaar.co.in]

Cardiac arrhythmias

Cardiac arrhythmia is a group of conditions in which the muscle contraction of the heart is irregular or is faster or slower than normal. Cardiac dysrhythmia is technically more correct, as arrhythmia would imply that there is "no rhythm," but this term is not used frequently. Some arrhythmias are life-threatening medical emergencies that can cause cardiac arrest and sudden death. Others cause aggravating symptoms, such as an awareness of the heart beat palpitation that can be annoying. Some are quite benign and normal. Sinus arrhythmia is the mild acceleration followed by slowing of the normal rhythm that occurs with breathing. In adults the normal heart rate ranges from 60 beats per minute to 100 beats per minute. The normal heart beat is controlled by a small area in the upper chamber of the heart called the sinus node. The sinus node contains specialized cells that have spontaneous electrical activity that starts each normal heart beat.

Frequency too high/low

A heart rate faster than 100 beats/minute is considered a tachycardia. With exercise the sinus node increases its rate of electrical activity to accelerate the heart rate. The normal fast rate that develops is called sinus tachycardia. Arrhythmias that are due to fast, abnormal electrical activity can cause tachycardias that are dangerous. If the ventricles of the heart experiences one of these tachycardias for a long period of time, there can be deleterious effects. Individuals may sense a tachycardia as a pounding sensation of the heart, known as palpitations. If a tachycardia lowers blood pressure it may cause lightheadedness or dizzinesses, or even fainting [syncope]. If the tachycardia is so fast that the heart can not function, it leads to death, which may occur suddenly. Most tachycardias are not dangerous. Anything that increases adrenaline or its effects on the heart will increase the heart rate and potentially cause palpitations or tachycardias. Causes include stress, ingested or injected substances (ie: caffeine, alcohol (see Holiday heart syndrome), and an overactive thyroid gland hyperthyroidism. Individuals who have a tachycardia are often advised to limit or remove exposure to any causative agent. A slow rhythm, known as bradycardia (less than 60 beats/min), is usually not life threatening, but may cause symptoms. When it causes symptoms implantation of a permanent pacemaker may be needed. Either dysrhythmia requires medical attention to evaluate the risks associated with the arrhythmia.

Fibrillation

A serious variety of arrhythmia is known as fibrillation. Fibrillation occurs when the heart muscle begins a quivering motion instead of a normal, healthy pumping rhythm. Fibrillation can affect the atrium (atrial fibrillation) or the ventricle (ventricular fibrillation); ventricular fibrillation is imminently life-threatening. Atrial fibrillation is the quivering, chaotic motion in the upper chambers of the heart, known as the atria. Atrial fibrillation is often due to serious underlying medical conditions, and should be evaluated by a physician. It is not typically a medical emergency. Ventricular fibrillation occurs in the ventricles (lower chambers) of the heart, it is always a medical emergency. If left untreated, ventricular fibrillation (VF, or V-fib) can lead to death within minutes. When a heart goes into V-fib, effective pumping of the blood stops. V-fib is considered a form of cardiac arrest, and an individual suffering from it will not survive unless cardiopulmonary resuscitation (CPR) and defibrillation are provided immediately. CPR can prolong the survival of the brain in the lack of a normal pulse, but defibrillation is the intervention which is most likely to restore a more healthy heart rhythm. It does this by applying an electric shock to the heart, after which sometimes the heart will revert to a rhythm that can once again pump blood. Almost every person goes into ventricular fibrillation in the last few minutes of life as the heart muscle reacts to diminished oxygen or general blood flow, trauma, irritants, or depression of electrical impulses themselves from the brain.

Origin of impulse

When an electrical impulse begins in any part of the heart, it will spread throughout the myocardium and cause a contraction; see Electrical conduction system of the heart. Abnormal impulses can begin by one of two mechanisms: automaticity or reentry.

Automaticity

Automaticity refers to a cardiac muscle cell firing off an impulse on its own. Every cardiac cell has this potential: if it does not receive any impulses from elsewhere, its internal "pacemaker" will fire off an impulse after a certain amount of time. A single specialized location in the atria, the sinoatrial node, has a higher automaticity (a faster pacemaker) than the rest of the heart, and therefore is usually the one to start the heartbeat. Any part of the heart that initiates an impulse without waiting for the sinoatrial node is called an ectopic focus, and is by definition a pathological phenomenon. This may cause a single premature beat now and then, or, if the ectopic focus fires more often than the sinoatrial node, it can produce a sustained abnormal rhythm. Rhythms produced by an ectopic focus in the atria, or by the atrioventricular node, are the least dangerous dysrhythmias; but they can still produce a decrease in the heart's pumping efficiency, because the signal reaches the various parts of the heart muscle with slightly different timing than usual and causes a poorly coordinated contraction. Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia. The resulting heart rhythm depends on where the first signal begins: if it is the sinoatrial node, the rhythm remains normal but rapid; if it is an ectopic focus, many types of dysrhythmia can result.

Reentry

Reentrant dysrhythmias occur when an electrical impulse travels in a circle within the heart, rather than moving outward and then stopping. Every cardiac cell is able to transmit impulses in every direction, but will only do so once within a short period of time. Normally the impulse spreads through the heart quickly enough that each cell will only respond once, but if conduction is abnormally slow in some areas, part of the impulse will arrive late and will be treated as a new impulse, which can then spread backward. Depending on the timing, this can produce a sustained abnormal rhythm, such as atrial flutter, a self-limiting burst of supraventricular tachycardia, or the dangerous ventricular tachycardia. By analogy, imagine a room full of people all given these instructions: "If you see anyone starting to stand up, then stand up for three seconds and sit back down." If the people are quick enough to respond, the first person to stand will trigger a single wave which will then die out; but if there are stragglers on one side of the room, people who have already sat down will see them and start a second wave, and so on.

Diagnosis

Cardiac dysrhythmias are often first detected by simple but nonspecific means: auscultation of the heartbeat with a stethoscope, or feeling for peripheral pulses. These cannot usually diagnose specific dysrhythmias, but can give a general indication of the heart rate and whether it is regular or irregular. Not all the electrical impulses of the heart produce audible or palpable beats; in many cardiac arrhythmias, the premature or abnormal beats do not produce an effective pumping action and are experienced as "skipped" beats. The simplest specific diagnostic test for assessment of heart rhythm is the electrocardiogram (abbreviated ECG or EKG). A Holter monitor is an ECG recorded over a 24-hour period, to detect dysrhythmias that may happen briefly and unpredictably throughout the day.

SADS

SADS, or sudden arrhythmia death syndrome, is a term used to describe sudden death due to cardiac arrest brought on by an arrhythmia. The most common cause of sudden death in the US is coronary artery disease. Approximately 300,000 people die suddenly of this cause every year in the US. SADS can also occur from other causes. Tragically there are many inherited condictions and heart diseases that can affect young people that can cause sudden death. Many of these victims have no symptoms before dying suddenly. The most common causes of SADS in young people are long QT syndrome, Brugada syndrome, and hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia.

List of common cardiac dysrhythmias

- Atrial Arrhythmias
- Atrial fibrillation
- Atrial Dysrhythmias
- Premature atrial contraction
- Atrial flutter
- Supraventricular tachycardia
- Sick sinus syndrome
- Ventricular Arrhythmias
- Ventricular fibrillation
- Ventricular Dysrhythmias
- Premature ventricular contraction
- Pulseless electrical activity
- Ventricular tachycardia
- Asystole
- Junctional Dysrhythmias
- Premature junctional contraction
- Junctional tachycardia
- Heart Blocks
- First degree heart block
- Second degree heart block
- Type 1 Second degree heart block a.k.a. Mobitz I or Wenckebach
- Type 2 Second degree heart block a.k.a. Mobitz II
- Third degree heart block a.k.a. complete heart block

Antiarrhythmic therapies

There are many classes of antiarrhythmic medications and many individual drugs within these classes. See the article on antiarrhythmic agents. Dysrhythmias may also be treated electrically. Cardioversion is the application of electrical current across the chest wall to the heart and it is used for treatment of supraventricular or pulsed ventricular tachycardia. Defibrillation differs in that it is used for ventricular fibrillation and pulseless ventricular tachycardia, and more electricity is delivered with defibrillation than with cardioversion. In cardioversion, the recipient is either sedated or lightly anesthetized for the procedure. In defibrillation, the recipient has lost consciousness so there is no need for sedation. Electrical treatment of dysrhythmia includes cardiac pacing. Temporay pacing may be done for very slow heartbeats, or bradycardia, from drug overdose or myocardial infarction. A pacemaker may be placed in situations where the bradycardia is not expected to recover. Atrial fibrillation can also be treated through a procedure, e.g. pulmonary vein isolation. This is performed by a cardiologist who specializes in electrophysiology and is done percutaneously with catheters. Alternatively, a maze procedure can be performed through cardiothoracic surgery.

External links

- [http://www.sads.org/ SADS Foundation]
- [http://www.c-r-y.org.uk Cardiac Risk in the Young] (UK) Category:Cardiac electrophysiology Category:medical emergencies ko:부정맥 ja:不整脈

Atrial flutter

Atrial flutter is a rhythmic, fast rhythm that occurs in the atria of the heart. This rhythm occurs most often in individuals with organic heart disease (ie: pericarditis, coronary artery disease, and cardiomyopathy). Atrial flutter is typically not a stable rhythm, and frequently degenerates to atrial fibrillation. However, it may persist for months to years.

Overview

atrial fibrillation

Atrial flutter with 4:1 block. Flutter waves (red triangles) at rate of 240 / minute. QRS complexes (yellow triangles) at rate of 60 / minute.

Atrial flutter is a regular, rhythmic tachycardia originating in the atria. The rate in the atria is over 220 beats/minute, and typically about 300 beats/minute. The morphology on the surface EKG is typically a sawtooth pattern. The ventricles do not beat as fast as the atria in atrial flutter. The AV node acts as a safety valve in the event of any fast rhythm of the heart, including atrial fibrillation and atrial flutter. The AV node slows down conduction of the electrical activity, and if it receives the next action potential before it is ready, the impulse will be blocked at the AV node level, and never reach the ventricles. In the case of atrial flutter, there is a very particular block pattern at the AV node level. In atrial flutter, the AV node typically will block every other electrical impulse, or three out of four impulses. If every other impulse is blocked, known as 2:1 block, while the atrial rate is 300 beats/minute, the ventricular rate will be 150 beats/minute. If three out of four beats are blocked, known as 4:1 block, while the atrial rate is 300 beats/minute, the ventricular rate will be 75 beats/minute. In many individuals, the degree of block is variable - sometimes every other beat is transmitted, sometimes two beats are dropped before the third is transmitted, etc. This is known as varying block. For reasons that are not well understood, a stable 3:1 block is not commonly seen in individuals with atrial flutter. A single individual can have varying degrees of block at different times. The varying degree of block is due to a multitude of factors, including catecholamine release and the use of any drugs that inhibit conduction through the AV node, such as beta blockers, digitalis, and calcium channel blockers. The term 2:1 block comes from the fact that for every two electrical impulses that reach the AV node, only one is transmitted to the ventricle. Similarly, 4:1 block comes from the fact that for every four impulses that reach the AV node, only one is transmitted to the ventricle.

Mechanism of action

Atrial flutter is caused by a reentrant rhythm in either the right or left atrium.

Types of atrial flutter

There are two types of atrial flutter, known as type I and type II.¹ Most individuals with atrial flutter will manifest only one of these types of atrial flutter. Rarely someone may manifest both types of flutter; however, they can only manifest one type at a time.

Type I flutter

reentrant rhythm

Type I atrial flutter, counterclockwise rotation with 4:1 AV nodal block.

Type I atrial flutter, also known as common atrial flutter or typical atrial flutter, has an atrial rate of 240 to 350 beats/minute. However, this rate may be slowed by antiarrhythmic agents. Type I flutter can be entrained by rapid atrial pacing. This means that the re-entrant rhythm of the flutter can be broken if a stimulus enters the re-entrant cycle at just the right point, breaking the cycle and thereby terminating the atrial flutter. While this can be performed with a pacemaker, it is performed almost exclusively in the electrophysiology lab by pacing the atrium at a rate just above the rate of the atrial flutter. While entrainment may break atrial flutter and cause the individual to revert to a normal sinus rhythm, the rapid atrial pacing may cause the individual to go into atrial fibrillation. Type I flutter has two subtypes, known as counterclockwise atrial flutter and clockwise atrial flutter.

Counterclockwise atrial flutter

Couterclockwise atrial flutter (known as cephalad-directed atrial flutter) is more commonly seen than clockwise atrial flutter. The flutter waves in this rhythm are inverted in II, III, and aVF.

Clockwise atrial flutter

Clockwise atrial flutter is less common than counterclockwise atrial flutter. The flutter waves are upright in II, II, and aVF in this rhythm.

Type II flutter

Type II flutter is faster than type I flutter, and usually is 340-430 beats/minute. Unlike type I flutter, the rhythm of type II flutter cannot be entrained by rapid atrial pacing.

Complications

Clot formation

In atrial flutter, as in atrial fibrillation, there is no effective contraction of the atria. In individuals with structural heart disease, this causes stasis of blood in the atria. The stasis of blood leads to formation of thrombus material (clots) within the heart. In the left side of the heart, thrombus is most likely for form in the left atrial appendage. This is important because, since the left side of the heart supplies blood to the entire body, any thrombus material that dislodges from the left side of the heart can potentially embolize to the brain, causing a stroke. Of course, the thrombus material can also embolize to any other portion of the body.

Sudden death

Sudden death is not directly associated with atrial flutter. However, in individuals with a pre-existing accessory conduction pathway, such as the bundle of Kent in Wolff-Parkinson-White syndrome, the accessory pathway may conduct activity from the atria to the ventricles much faster than the AV node. In this case, the atrial rate of 300 beats/minute will lead to a ventricular rate of 300 beats/minute. The ventricles, unable to sustain a ventricular tachycardia at such a high rate, will go into ventricular fibrillation, which will quickly lead to hemodynamic collapse and death.

Treatment

In general, atrial flutter should be treated the same as atrial fibrillation. Both rhythms do not provide effective contraction of the atria. Because of this, there is stasis of blood in the atria. This stasis of blood leads to the potential formation of thrombus material in the atria. Therefore, individuals with atrial flutter require some form of anticoagulation or anti-platelet agent. In addition to the treatments available to individuals in atrial fibrillation, there are a couple of treatment considerations that are particular to individuals with atrial flutter.

Ablation

Because of the reentrant nature of atrial flutter, it is possible to ablate the circuit that causes atrial flutter. This is done in the electrophysiology lab by causing a ridge of scar tissue that crosses the path of the circuit that causes atrial flutter.

Rate control

Control of the ventricular rate in atrial flutter may be more difficult than if the individual was in atrial fibrillation. This is because of properties of the AV node. In atrial fibrillation, the AV node is typically bombarded with signals from the atria at rates in excess of 400 beats/minute. This causes a high degree of block within the AV node, with many signals partially penetrating the node and blocking at the lower levels of the AV node. This phenomenon is known as concealed conduction. In atrial flutter, on the other hand, the AV node receives signals very rhythmically at a rate of about 300/minute. Since the atrial flutter is an organized rhythm of the atria, the block at the AV node will be consistently at the same level, and paradoxically a higher number of impulses will get through per minute. Because of this, it may be easier to control the rate of some individuals if they are converted from atrial flutter to atrial fibrillation. While there are no guidelines for this procedure at this time, this may be attempted in the electrophysiology lab by pacing the atria at rates well over 300 beats/minute.

References

#Chou's Electrocardiography in Clinical Practice, Fifth Edition, Surawicz & Knilans, ISBN 0-7216-8697-4 #Electrophysiologic Testing, Richard N. Fogoros, Blackwell Science, ISBN 0-632-04325-3

Ventricular tachycardia

Tachycardia is an abnormally rapid beating of the heart, defined as a resting heart rate of over 100 beats per minute. It can have harmful effects in two ways. First, when the heart beats too rapidly, it performs inefficiently (since there is not enough time for the ventricles to fill completely), causing blood flow and blood pressure to diminish. Second, it increases the work of the heart, causing it to require more oxygen while also reducing the blood flow to the cardiac muscle tissue, increasing the risk of ischemia and resultantly infarction. Tachycardia is a general symptomatic term that does not describe the cause of the rapid rate. Common causes are autonomic nervous system or endocrine system activity, hemodynamic responses, and various forms of cardiac arrhythmia.

Autonomic and endocrine causes

An increase in sympathetic nervous system stimulation causes the heart rate to increase, both by the direct action of sympathetic nerve fibers on the heart, and by causing the endocrine system to release hormones such as epinephrine (adrenaline) which have a similar effect. Increased sympathetic stimulation is usually due to physical or psychological stress (the so-called "fight or flight" response), but can also be induced by stimulants such as caffeine. Endocrine disorders such as pheochromocytoma can cause epinephrine release and tachycardia independent of the nervous system.

Hemodynamic responses

The body contains several feedback mechanisms to maintain adequate blood flow and blood pressure. If blood pressure decreases, the heart beats faster in an attempt to raise it. This can happen in response to a decrease in blood volume (through dehydration or bleeding), or an unexpected change in blood flow. The most common cause of the latter is orthostatic hypotension (also called postural hypotension), a sudden drop of blood pressure that occurs with a change in body position (e.g., going from lying down to standing up). When tachycardia occurs for this reason, it is called postural orthostatic tachycardia syndrome (POTS).

Tachycardic arrhythmias

An electrocardiogram tracing can distinguish several different forms of rapid abnormal heartbeat: If the heart's electrical system is functioning normally, except that the rate is in excess of 100 beats per minute, it is called sinus tachycardia. This is caused by any of the factors mentioned above, rather than a malfunction of the heart itself. Supraventricular tachycardia (SVT) occurs when an abnormal electrical impulse originates above the ventricles, but instead of causing a single beat and a pause, it travels in circles and causes many rapid beats. To distinguish SVT from Sinus Tachycardia one must simply look at the rate: If the rate of contraction is more than 150 bpm, then it is considered SVT. Otherwise it is Sinus Tachycardia. Ventricular tachycardia (VT or "V-tach") is a similar phenomenon occurring within the tissue of the ventricles, causing an extremely rapid rate with poor pumping action. Both of these rhythms normally last for only a few seconds (paroxysmal tachycardia), but if VT persists it is extremely dangerous, often leading to ventricular fibrillation. Arrhythmias can be treated using drugs, intervention or implantable devices. See also: Bradycardia. The vagus reflex may help as a first-aid measure. Category:Cardiology ko:빠른맥

Atrial fibrillation

Atrial fibrillation (AF or afib) is a cardiac arrhythmia (an abnormality of heart rate or rhythm) originating in the atria. Abnormal electrical impulses in the atria cause the ventricles to contract erratically. AF is the most common cardiac arrhythmia. If rapid, it may compromise blood flow and cause fainting, orthostatic hypotension (low blood pressure on standing up) or low blood pressure. In addition, the erratic wall motion of the atria leads to blood stasis which predisposes to thrombosis and embolism to the brain and other areas, being a prime risk factor for stroke, the most feared complication of atrial fibrillation.

Signs and symptoms

Atrial fibrillation is usually accompanied by symptoms related to either the rapid heart rate or embolization. Rapid and irregular heart rates may be perceived as palpitations, exercise intolerance, and occasionally produce angina and congestive symptoms of shortness of breath or edema. Sometimes the arrhythmia will be identified with the onset of a stroke or a TIA. It is not uncommon to identify atrial fibrillation on a routine physical examination or electrocardiogram. Paroxysmal atrial fibrillation is the episodic occurrence of the arrhythmia and may be difficult to diagnose. Episodes may occur with sleep or with exercise, and their episodic nature may require prolonged ecg monitoring for diagnosis.

Diagnosis

Electrocardiogram

Image:Afib.gif Atrial fibrillation is diagnosed on an electrocardiogram, an investigation performed routinely whenever irregular heart beat is suspected. Characteristic findings are (a "rhythm strip" of lead II is shown):
- absence of P waves
- unorganized electrical activity in their place
- irregularity of R-R interval due to irregular conduction of impulses to the ventricles

Other investigations

While many cases of AF have no definite cause, it may be the result of various other problems (see below). Hence, renal function and electrolytes are routinely determined, as well as thyroid-stimulating hormone (commonly suppressed in hyperthyroidism and of relevance if amiodarone will be administered) and a blood count. A chest X-ray is generally performed. In acute-onset AF associated with chest pain, cardiac troponins or other markers of damage to the heart muscle may be ordered. Coagulation studies (INR/aPTT) are usually performed, as anticoagulant medication may be commenced.

Causes

AF is linked to several cardiac causes, but may occur in otherwise normal hearts. Known associations include:
- Arterial hypertension
- Mitral valve disease (e.g. due to rheumatic heart disease or mitral valve prolapse)
- Heart surgery
- Coronary heart disease
- Excessive alcohol consumption ("binge drinking" or "holiday heart")
- Hyperthyroidism
- Hyperstimulation of the vagus nerve, usually by having large meals ("binge eating") In turn, AF with a rapid rate that goes untreated can cause further damage to the heart muscle. This weakened condition, termed chronotropic cardiomyopathy, is usually a result of a long period of tachycardia(fast heart rate).

Pathophysiology

In atrial fibrillation, the regular impulses produced by the sinus node to provide rhythmic contraction of the heart are overwhelmed by the rapid randomly generated discharges produced by larger areas of atrial tissue. It can be distinguished from atrial flutter, which is a more organized electrical circuit usually in the right atrium that produces characteristic saw toothed waves on the electrocardiogram. Often, the rhythm produced is more rapid than normal, but the difficulty is in obtaining control of the heart rate both at rest and with exercise. Good rate control will usually require two drugs, and can only be checked by observing heart rate response to exercise. An organized electrical impulse in the atrium produces atrial contraction; the lack of such an impulse, as in atrial fibrillation, produces stagnant blood flow, especially in the atrial appendage and predisposes to clotting. The dislodgement of a clot from the atrium results in an embolus, and the damage produced is related to where the circulation takes it. An embolus to the brain produces the most feared complication of atrial fibrillation, stroke, while an embolus may also lodge in the mesenteric circulation (the circulation supplying the abdominal organs) or digit, producing organ-specific damage.

Treatment

Rate and rhythm control

AF can cause disabling and annoying symptoms. Palpitations, angina, lassitude (weariness), and decreased exercise tolerance are related to rapid heart rate and inefficient cardiac output caused by AF. There are two ways to approach these symptoms: rate control and rhythm control. Rate control treatments seek to reduce the heart rate to normal, usually 60 to 100 beats per minute. Rhythm control seeks to restore the normal heart rhythm, called normal sinus rhythm. Studies suggest that rhythm control is mainly a concern in newly diagnosed AF, while rate control is more important in the chronic phase. Rate control with anticoagulation is as effective a treatment as rhythm control in long term mortality studies, the AFFIRM Trial. AF can cause a form of heart failure called tachycardia-induced cardiomyopathy. This can significantly increase mortality and morbidity. The early treatment of AF through either rate-control or rhythm-control can prevent this condition and thereby improve mortality and morbidity.

Rate control

Rate control methods include:
- Beta blockers (e.g. metoprolol)
- Digoxin
- Calcium channel blockers (e.g. verapamil) In refractory cases where none of the above drugs are sufficient, a variety of other antiarrhythmic drugs, most commonly including quinidine, flecainide, propafenone, disopyramide, sotalol, or amiodarone may be used. Of these, only propafenone, sotalol, and amiodarone (which possess some beta blocking activity) control the ventricular rate; the others may maintain sinus rhythm, but may actually increase the ventricular rate. Many of these drugs are less frequently used today than in the past. All (with the possible exception of amiodarone) increase the risk of ventricular tachycardia, which can be fatal. In symptomatic patients with normal heart function, however, the small increase in risk is usually felt to be acceptable. In the presence of heart failure, the only antiarrhythmic drugs thought to be safe are amiodarone and dofetilide. These medications work by slowing the generation of impulses from the atria and the conduction of those impulse from the atria to the ventricles. In patients with AF where rate control drugs are ineffective and it is not possible to restore sinus rhythm using cardioversion, non-pharmacological alternatives are available. For example, to control rate it is possible to destroy the bundle of cells connecting the upper and lower chambers of the heart - the atrioventricular node - which regulates heart rate, and to implant a pacemaker instead. A more complex technique involves ablating groups of cells near the pulmonary arteries where atrial fibrillation is thought to originate, or creating more extensive lesions in an attempt to prevent atrial fibrillation from establishing itself..

Rhythm control

Rhythm control methods include electrical and chemical cardioversion:
- Electrical cardioversion involves the restoration of normal heart rhythm either through the application of a DC electrical shock (electrical cardioversion)
- Chemical cardioversion is performed with drugs, such as amiodarone, propafenone or flecainide. The anti-arrhythmic medications often used in either pharmacological cardioversion or in the prevention of relapse to AF alter the flux of ions in heart tissue, making them less excitable, setting the stage for spontaneous and durable cardioversion. These medications are often used in concert with electrical cardioversion. However, the AFFIRM study showed no difference in risk of stroke in patients who have converted to a normal rhythm with anti-arrhythmic treatment, compared to those who have only rate control.. The main risk of cardioversion is systemic embolization by a bloodclot from the previously fibrillating left atrium. It should not be performed without adequate anticoagulation in patients who have been in atrial fibrillation for more than 48 hours. Whichever method of cardioversion is used, approximately 50% of patient relapse within one year, although the continued daily use of oral antiarrhythmic drugs may extend this period. The key risk factor for relapse is duration of AF, although other risk factors that have been identified include the presence of structural heart disease, and increasing age.

Radiofrequency ablation

Radiofrequency ablation (RFA) uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue. It is used in recurrent AF. The energy emitting probe (electrode) is placed into the heart through a catheter. The practitioner first "maps" an area of the heart to locate the abnormal electrical activity before the responsible tissue is eliminated. Ablation is a newer technique and has shown some promise for cases unresponsive to conventional treatments. New techniques include the use of cryoablation (tissue freezing using a coolant which flows through the catheter), and microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue. The abnormal electrophysiology can also be modified in a similar way surgically, and this procedure referred to as the "Cox maze procedure", is commonly performed concomitantly with cardiac surgery. This is an area of active research, especially with respect to the RF ablation technique and emphasis on isolating the pulmonary veins that enter into the left atrium.

Anticoagulation

In confirmed AF, anticoagulant treatment is a crucial way to prevent stroke. Treatment of AF patients over age 60 with warfarin (also known as Coumadin®) results in a significant reduction in the subsequent risk of stroke. Patients under age 65 who have any structural heart disease (ie: valvular heart disease, ejection fraction <= 35%, history of heart attack) also benefit from warfarin. Patients under age 65 who do not have structural heart disease do not require warfarin, and can be treated with aspirin. Other guidelines are also used. The new anticoagulant ximelagatran has been shown to prevent stroke with equal efficacy as warfarin, without the difficult monitoring process associated with warfarin and with possibly fewer adverse haemorrhagic events. Unfortunately, ximegalatran and other similar anticoagulant drugs (commonly referred to as direct thrombin inhibitors), have yet to be widely licensed. License applications made by AstraZeneca, who developed Ximegalatran, have been rejected by both American and European licensing authorities, and its evaluation has been suspended in the UK. This is primarily due to concerns over possible liver toxicity.

References

- Fuster V, Ryden LE, Asinger RW, Cannom DS, Crijns HJ, Frye RL, Halperin JL, Kay GN, Klein WW, Levy S, McNamara RL, Prystowsky EN, Wann LS, Wyse DG, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC, Klein WW, Alonso-Garcia A, Blomstrom-Lundqvist C, De Backer G, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A; American College of Cardiology/American Heart Association/European Society of Cardiology Board. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation): developed in Collaboration With the North American Society of Pacing and Electrophysiology. J Am Coll Cardiol 2001;38:1231-66. [http://www.acc.org/clinical/guidelines/atrial_fib/af_index.htm ACC/AHA/ESC Fulltext]. PMID 11583910.
- Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-33. PMID 12466506.
- [http://www.cardiologychannel.com/afib/longterm.shtml Long term management of Atrial Fibrillation]

External links

- [http://www.italheartj.org/abstract/I_H_J_2002_3_571-578.htm Hybrid therapy of Atrial Fibrillation] Category:Cardiac electrophysiology

Cardiac arrest

A cardiac arrest is the cessation of normal circulation of the blood due to failure of the ventricles of the heart to contract effectively during systole. The resulting lack of blood supply results in cell death from oxygen starvation. Cerebral hypoxia, or lack of oxygen supply to the brain, causes victims to lose consciousness and stop breathing. Cardiac arrest is a medical emergency that, if left untreated, invariably leads to death within seconds to minutes. The primary first-aid treatment for cardiac arrest is cardiopulmonary resuscitation.

Etiology

Coronary artery disease (CAD) is the predominant disease process associated with sudden cardiac death in the United States. The incidence of CAD in individuals who suffer sudden cardiac death is between 64 and 90%. Other causes of cardiac arrest include electrocution and near-drowning, as well as other cardiac conditions such as the cardiomyopathies. In children, cardiac arrest is typically caused by hypoxia from other causes such as near-drowning. With prompt treatment survival rates are high. Every fatal injury or illness ultimately terminates in cardiac arrest, which is a natural part of the processes of death.

Treatable causes

The potentially treatable causes of cardiac arrest (4 Ts and 4 Hs) are:
- Cardiac Tamponade
- Tension pneumothorax
- Toxins or drug overdoses
- Pulmonary Thromboembolism (or other mechanical obstruction to cardiac outflow)
- Hypoxia (lack of oxygen)
- Electrolyte disturbances (such as hypokalemia, hyperkalemia, and hypocalcaemia)
- Hypovolemia (decreased blood volume) due to haemorrhage or dehydration
- Hypothermia

Diagnosis

The state of cardiac arrest is diagnosed in an unconscious (unresponsive to vigorous stimulation) person who does not have a pulse. An ECG clarifies the exact diagnosis and guides treatment. but treatment should begin without awaiting an ECG. The ECG may reveal:
- asystole (known colloquially as a flatline)
- pulseless electrical activity (formerly called electromechanical dissociation)
- ventricular fibrillation
- ventricular tachycardia
- severe bradycardia
- complete heart block with a slow ventricular escape rate
- agonal rhythm

Treatment

First aid

Seconds count. Call for help immediately or send someone for help. Begin cardiopulmonary resuscitation (CPR) immediately. CPR only buys time for help to arrive but does not restart the heart. If an automated external defibrillator is available, use it immediately.

Field care

Appropriately trained personnel apply advanced cardiac life support protocols as soon as they arrive, unless there is a valid do not resuscitate order or advance health directive. If so, it is ethically appropriate to permit natural death to occur in accordance with the wishes of the patient. Do not use an AED unless you hold current qualifications to do so. The incorrect usage can lead to more harm than good. Also legally you will be held accountable.

Hospital treatment

In many hospitals, cardiac arrest results in one of the carers announcing a "Code Blue" (or the local equivalent) for immediate response by a trained team of nurses and doctors. The resuscitating team continues advanced cardiac life support until the patient recovers or a doctor declares the patient's death.

Ethical Issues

Cardiopulmonary resuscitation and advanced cardiac life support are not always in a person's best interest. This is particularly true in the case of terminal illnesses when resuscitation will not alter the outcome of the disease. Properly performed CPR often fractures the rib cage, especially in older patients or those suffering from osteoporosis. Defibrillation, especially repeated several times as called for by ACLS protocols, may also cause electrical burns. Internal cardiac massage, an ACLS procedure performed by emergency medicine physicians requires splitting open the rib cage, which is painful during the weeks of recovery. While such treatment is worthwhile when it saves a life, it is undignified and simply adds to the suffering of a victim with a terminal illness who wishes to die peacefully. It is not surprising that some people with a terminal illness choose to avoid such "heroic" measures and die peacefully. People with views on the treatment they wish to receive in the event of a cardiac arrest should discuss these views with both their doctor and with their family. It is also important that these views are written down somewhere in the medical record. In the event of cardiac arrest, health professionals need to act quickly on the information that is available to them. As cardiac arrest often happens out of regular hours, the resuscitation team rarely includes anybody who actually knows the patient. A patient may ask their doctor to record a do not resuscitate (DNR) order in the medical record. Alternatively, in many jurisdictions, a person may formally state their wishes in an "advance directive" or "advance health directive". See also death and hospice. Category:Cardiovascular diseases Category:medical emergencies ja:心停止

Cardiac arrest

Etiology

Treatable causes

Diagnosis

Treatment

First aid

Field care

Hospital treatment

Ethical Issues

Amiodarone

Amiodarone belongs to a class of drugs called Vaughan-Williams Class III antiarrhythmic agent. It is used in the treatment of a wide range of cardiac tachyarhthmias, including both ventricular and supraventricular (atrial) arrhythmias. The chemical name for amiodarone is 2-butyl-3-benzofuranyl 4-[2-(diethylamino)-ethoxyl]-3,5-diiodophenyl ketone hydrochloride.

History

Amiodarone was initially developed in 1961 in Belgium as a treatment for angina. It was widely used throughout Europe as an anti-anginal medication, and was soon found to suppress arrhythmias. Dr. Bramah Singh determined that amiodarone and sotalol belonged to a new class of antiarrhythmic agents (what would become the class III antiarrhythmic agents) that would prolong repolarization of the cardiac action potential. Based on this, the Argentinian physician Dr. Mauricio Rosenbaum began using amiodarone to treat his patients who suffered from supraventricular and ventricular arrhythmias, with impressive results. Based on papers written by Dr. Rosenbaum, physicians in the United States began prescribing amiodarone to their patients with potentially life-threatening arrhythmias in the late 1970s. By that time, amiodarone was commonly prescribed throughout Europe for the treatment of arrhythmias. Because amiodarone was not approved by the FDA for use in the United States at the time, physicians were forced to directly obtain amiodarone from pharmaceutical companies in Canada and Europe. The FDA was reluctant to officially approve the use of amiodarone, since initial reports had shown increased incidence of serious pulmonary side-effects of the drug. In the mid 1980s, the European pharmaceutical companies began putting pressure on the FDA to approve amiodarone by threatening to cut the supply to the American physicians if it was not approved. In December of 1985, amiodarone was approved by the United States FDA for the treatment of arrhythmias. This makes amiodarone one of the few drugs approved by the FDA without rigorous randomized clinical trials.

Dosing

Amiodarone is available in oral and intravenous formulations. Orally, it is available under the trade names Pacerone^® (produced by Upsher-Smith Laboratories, Inc.) and Cordarone^® (produced by Wyeth-Ayerst Laboratories) in 200 mg and 400 mg tablets. It is also available in intravenous ampules and vials, typically in 150mg increments. The dose of amiodarone administered is tailored to the individual and the dysrhythmia that is being treated. When administered orally, the bioavailability of amiodarone is quite variable. Absorption ranges from 22 to 95%, with better absorption when it is given with food. Amiodarone is fat-soluble, and tends to concentrate in tissues including fat, muscle, liver, lungs, and skin. This confers a high volume of distribution (5000 liters in a 70kg adult) and a long half-life. Due to the long half-life of amiodarone, oral loading typically takes days to weeks. An oral loading dose is typically a total of 10 grams, divided over one to two weeks. Once an individual is loaded, a typical maintenance dose of amiodarone is 100 or 200 mg either once or twice daily. An intravenous loading dose is typically 300mg in 20-30cc D5W for cardiac arrest. The loading infusion for dysrhythmias is typically 150mg in a 100cc bag of D5W given over 10 minutes. Both can be followed by a 360mg slow infusion over 6 hours then a maintenance infusion of 540mg over 18 hours.

Mechanism of action

Amiodarone is categorized as a class III antiarrhythmic agent, and prolongs phase 3 of the cardiac action potential. It has numerous other effects however, including actions that are similar to those of antiarrhythmic classes Ia, II, and IV. Amiodarone shows beta blocker-like and calcium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.

Indications for use

Because amiodarone has a low incidence of pro-arrhythmic effects, it has been used both in the treatment of acute life-threatening arrhythmias as well as the chronic suppression of arrhythmias. It is useful both in supraventricular arrhythmias and ventricular arrhythmias.

Ventricular fibrillation

The treatment of choice for ventricular fibrillation (VF) is electrical defibrillation. However amiodarone can be useful in shock-refractory VF. In the ARREST trial, amiodarone was shown to improve survival to hospital admission (when compared to placebo) in individuals who suffer cardiac arrest with shock-refractory VF. It is on the basis of this study that the guidelines created by the American Heart Association for the treatment of VF include amiodarone as a second line agent (after epinephrine or vasopressin). ARREST was not adequately powered to demonstrate survival to hospital discharge.

Ventricular tachycardia

Amiodarone may be used in the treatment of ventricular tachycardia in certain instances. Individuals with hemodynamically unstable ventricular tachycardia should not initially receive amiodarone. These individuals should be defibrillated out of their unstable rhythm. Amiodarone can be used in individuals with hemodynamically stable ventricular tachycardia. In these cases, amiodarone can be used regardless of the individual's underlying heart function and the type of ventricular tachycardia; it can be used in individuals with monomorphic ventricular tachycardia as well as individuals with polymorphic ventricular tachycardia. The dose of amiodarone is 150 mg IV administered over 10 minutes.

Atrial fibrillation

Individuals who have undergone open heart surgery are at an increased risk of developing atrial fibrillation (or AF) in the first few days post-procedure. In the ARCH trial, intravenous amiodarone (2 grams administered over 2 days) has been shown to reduce the incidence of atrial fibrillation after open heart surgery when compared to placebo. However, clinical studies have failed to demonstrate long-term efficacy and have shown potentially fatal side effects such as pulmonary toxicities. While Amiodarone is not approved for AF by the FDA, it is a commonly prescribed off-label treatment due to the lack of efficacious treatment alternatives.

Contraindications

The only absolute contraindications to the administration of amiodarone is allergic reaction (ie: anaphylaxis) to the compound. However, because of the wide spectrum of the mechanism of action of amiodarone and the numerous side effects possible, there are a number of groups for which care should be taken when administering the drug. Individuals who are pregnant or may become pregnant are strongly advised to not take amiodarone. Since amiodarone can be expressed in breast milk, women taking amiodarone are advised to stop nursing. It is contraindicated in individuals with sinus nodal bradycardia, atrioventricular block, and second or third degree heart block who do not have an artificial pacemaker. Individuals with baseline depressed lung function should be monitored closely if amiodarone therapy is to be initiated.

Metabolism

Amiodarone is extensively metabolized in the liver, and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone.

Interactions with other drugs

The pharmacokinetics of numerous drugs, including many that are commonly administered to individuals with heart disease, are effected by amiodarone. Particularly, doses of digoxin should be halved in individuals taking amiodarone. Amiodarone potentiates the action of warfarin. Individuals taking both of these medications should have their warfarin dose halved and their anticoagulation status (measured as prothrombin time (PT) and international normalized ratio (INR)) measured more frequently. The effect of amiodarone in the warfarin concentration can be as early as a few days after initiation of treatment, or can be delayed a few weeks. Amiodarone inhibits the action of the cytochrome P450 isozyme family. This reduces the clearance of many drugs, including the following: -
- Cyclosporin
- Digoxin
- Flecainide
- Procainamide
- Quinidine
- Sildenafil
- Simvastatin
- Theophylline
- Warfarin

Excretion

Unlike most other drugs, which are excreted via the urine or feces, amiodarone is excreted via shedding of epithelial cells. This includes loss of skin cells and loss of the cells of the lining of the gastrointestinal system. While the human body sheds millions of cells a day, the amount of amiodarone lost per day is small, giving a long half life (13 to 103 days). Therefore, if an individual was taking amiodarone on a chronic basis, if it is stopped it will remain in the system for months.

Side effects

Amiodarone has numerous side effects. Most individuals administered amiodarone on a chronic basis will experience at least one side effect.

Thyroid

Due to the iodine content of the agent (37.3% by weight), abnormalities in thyroid function are common. Amiodarone is structurally similar to thyroxine (a thyroid hormone), which contributes to the effects of amiodarone on thyroid function. The incidence of hypothyroidism is about 6%, while the incidence of hyperthyroidism is about 2%. They are called Wolff-Chalkoff and Jodbasedow effect separately. Measurement of free thyroxine (FT4) alone may be unreliable and thyroid-stimulating hormone (TSH) should therefore also be checked every 6 months .

Eye

Corneal micro-deposits are almost universally present (over 90%) in individuals taking amiodarone for at least 6 months. These deposits typically do not cause any symptoms. About 1 in 10 individuals may complain of a blueish halo.

Gastrointestinal system

Liver toxicity due to amiodarone is quite rare. A drug-induced hepatitis (inflammation of the liver) may occur and is sometimes reversible by lowering the dose.

Skin

Long-term administration of amiodarone is associated with a blue-grey discoloration of the skin. This is more commonly seen in individuals with lighter skin tones. The discoloration may revert upon cessation of the drug. However, the skin color may not return completely to normal. Individuals taking amiodarone may become more sensitive to the harmful effects of UV-A light. Taking sunblock that also blocks UV-A rays appears to prevent this side effect.

Lung

The most serious reaction that is due to amiodarone is idiopathic pulmonary fibrosis. The incidence of pulmonary fibrosis is not dose related. Some individuals were noted to develop pulmonary fibrosis after a week of treatment, while others did not develop it after years of continuous use. There are no known factors that increase the incidence of amiodarone-induced pulmonary fibrosis in a particular individual. Common practice is to avoid the agent if possible in individuals with decreased lung function. The most specific test of pulmonary toxicity due to amiodarone is a dramatically decreased DL_CO noted on pulmonary function testing.

References

# Siddoway LA. Amiodarone: Guidelines for Use and Monitoring. American Family Physician Dec. 1, 2003. ([http://www.aafp.org/afp/20031201/2189.html Full text]) # Kudenchuk PJ, Cobb LA, Copass MK, Cummins RO, Doherty AM, Fahrenbruch CE, Hallstrom AP, Murray WA, Olsufka M, Walsh T. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999 Sep 16;341(12):871-8. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10486418 Medline abstract]) # Guarnieri T, Nolan S, Gottlieb SO, Dudek A, Lowry DR. Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial. J Am Coll Cardiol. 1999 Aug;34(2):343-7. ([http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10440143 Medline abstract]) # British National Formulary guidance on thyroid function monitoring ([http://www.bnf.org/bnf/bnf/49/openat/2417.htm?q=%22amiodarone%22 BNF Amiodarone])

External links

- [http://www.medicinenet.com/amiodarone/article.htm Amiodarone (MedicineNet.com)]
- [http://www.fpnotebook.com/CV192.htm Amiodarone (FamilyPracticeNotebook.com)]
- [http://www.thyroidmanager.org/Chapter13/Ch-13-5.htm Iodine-induced thyrotoxicosis]
- [http://tiscali.medicdirect.co.uk/tests/default.asp?step=4&pid=1561 Amiodarone (Tiscali.com)]
- [http://www.anaesthetist.com/icu/manage/drugs/heart/amiodarone.htm Amiodarone (The WorldWide Intensivist)]
- [http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00288.txt DrugBank Amiodarone DrugCard] University of Alberta Bioinformatics Drug Database
- Category:Amines Category:Antiarrhythmic agents Category:Aromatic compounds Category:Ethers Category:Heterocyclic compounds Category:Ketones

Procainamide

Procainamide (trade names Pronestyl®, Procan®, Procanbid®) is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia. It blocks open sodium (Na⁺) channels and prolongs the cardiac action potential (outward potassium (K⁺) currents may be blocked). This results in slowed conduction, and ultimately the decreased rate of rise of the action potential, which may result in widening of QRS on electrocardiogram (EKG). This <

Antiarrhythmic agent

Vaughan Williams antiarrhythmic classification

Class I agents

Class Ia agents

Class Ib agents

Class Ic agents

Class II agents

Class III agents

Class IV agents

Class V agents

Related topics

References

Pharmaceutical

Scientific background

Classification

Types of medication

For the gastrointestinal tract or digestive system

For the cardiovascular system

For the central nervous system

For pain & consciousness (Analgesic drugs)

For musculo-skeletal disorders

For the eye

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For the respiratory system

For endocrine problems

For the reproductive system or urinary system

For contraception

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See also

Cardiac arrhythmias

Frequency too high/low

Fibrillation

Origin of impulse

Automaticity

Reentry

Diagnosis

SADS

List of common cardiac dysrhythmias

Antiarrhythmic therapies

Related topics

External links

Atrial flutter

Overview

Mechanism of action

Types of atrial flutter

Type I flutter

Counterclockwise atrial flutter

Clockwise atrial flutter

Type II flutter

Complications

Clot formation

Sudden death

Treatment

Ablation

Rate control

References

Related topics

Ventricular tachycardia

Autonomic and endocrine causes

Hemodynamic responses

Tachycardic arrhythmias

Atrial fibrillation

Signs and symptoms

Diagnosis

Electrocardiogram

Other investigations

Causes

Pathophysiology

Treatment

Rate and rhythm control