Chapter 47 - Antidysrhythmic Drugs

CHAPTER 47

ANTIDYSRHYTHMIC DRUGS

Dysrhythmia – an abnormality in the rhythm of the heartbeat - in their most sever forms, dysrhythmias can so disable the heart that no blood is pumped at all - also known as arrhythmias, since the term denotes an absence of cardiac rhythm Types: tachydysrhythmias – heart rate is increased bradydysrhythmias – heart rate is slowed Drugs of Choice: atropine and isoproterenol - virtually all of the drugs used to treat dysrhythmias can also cause the dysrhythmias - antidysrhythmic drugs should be employed only when the benefits of treatment clearly outweigh the risks

I.

PRODYSRHYTHMIC EFFECTS

OF

ANTIDYSRHYTHMIC DRUGS

Prodysrhythmic – all of these drugs can worsen existing dysrhythmias and generate new ones Because of their prodysrhymthmic actions, antidysrhythmic drugs should be used only when dysrhythmias are symptomatically significant, and only when the potential benefits clearly outweigh the risks. - regardless of the particular circumstances of drug use, all patients must be followed closely

II.

OVERVIEW

OF

COMMON DYSRHYTHMIAS

AND

THEIR TREATMENT

MAJOR GROUPS: supraventricular dysrhythmias ventricular dysrhythmias – more dangerous than supraventricular dysrhythmias TREATMENT PHASES: 1) termination of the dysrhythmias, with electrical countershock, drugs or both 2) long-term suppression with drugs FIRST LINE

OF

TREATMENT

FOR:

ventricular premature beats (VPBs) digoxin-induced ventricular dysrhythmias

- for several dysrhythmias, direct current (DC) cardioversion (electrical countershock) is the preferred therapy - for supraventricular tachycardia (SVT), maneuvers that increase vagal tone are the treatment of choice

- even after a dysrhythmias has been identified, we cannot predict with certainty just which drugs will be effective A.

SUPRAVENTRICULAR DYSRHYTHMIAS - dysrhythmias that arise in areas of the heart above the ventricles (atria, SA node, AV node) - per se are not especially harmful because dysrhythmic activity within the atria does not significantly reduce cardiac output except in patients with valvular disorders and heart failure - can be dangerous, however, in that atrial impulses are likely to traverse the AV node, resulting in excitation of the ventricles - if atria drive the ventricles at an excessive rate, diastolic filling will be incomplete and cardiac output will decline - objective is frequently one of blocking impulse conduction through the AV node and not elimination of the dysrhythmias itself - acute treatment is accomplished with vagotonic maneuvers, DC cardioversion, and certain drugs: class II agents, class IV agents, adenosine, and digoxin 1. Sustained SVT - usually caused by an AV nodal reentrant circuit - heart rate is increased to 150 to 20 beats/min - best treated by maneuvers that increase vagal tone, such as carotid sinus massage or the Valsalva maneuver - if ineffective, intravenous adenosine or verapamil should be given - once controlled, long-term prophylaxis with quinidine may prevent its recurrence 2.

Atrial Flutter - caused by ectopic atrial focus discharging at a rate of 250 to 350

beats/min - ventricular rate is considerably slower, however, because the AV node is unable to transmit impulses at such a high rate - typically one atrial impulse out of three manages to reach the ventricles - treatment of choice is cardioversion which almost always converts a-fib to normal sinus rhythm - if ineffective, drugs may be employed - objective is to decrease the number of atrial impulses that pass to the ventricles - digoxin is the drug of choice - verapamil, diltiazem or a beta blocker may also effective - long-term therapy with quinidine

3.

Atrial Fibrillation - caused by multiple atrial ectopic foci firing randomly - each focus stimulates a small area of atrial muscle - depending on the extent of impulse transmission through the AV node, ventricular rate may be rapid or nearly normal - DC cardioversion is the preferred therapy - carries a high risk of intracardiac thrombus formation - this occurs because some blood can become trapped in the atria - when normal sinus rhythm is restored, intracardiac thrombi may become dislodged, creating a risk of embolism - patients are usually given warfarin (an anticoagulant drug) for 3 – 4 weeks prior to and another 4 weeks after treating the dysrhythmias B.

VENTRICULAR DYSRHYTHMIAS - objective is to abolish the dysrhythmias - cardioversion is often the treatment of choice 1.

Sustained Ventricular Tachycardia - arises from a single, rapidly firing ventricular ectopic focus, typically located at the border of an old infarction - rate of 150 – 250 beats/min - immediate treatment is required - cardioversion is the treatment of choice - if conversion fails to normalize rhythm, lidocaine should be administered - if lidocaine is also ineffective, bretylium, procainamide, or amiodarone should be tried - whichever drug converts the patient is the one that is hung as a drip - for long-term management, drugs or an implantable cardioverter/defibrillator (ICD) may be employed 2.

Ventricular Fibrillation - life-threatening emergency that required immediate treatment - results from asynchronous discharge of multiple ventricular ectopic

foci - because each foci initiates contraction in its immediate vicinity, localized twitching takes place all over the ventricles, making coordinated ventricular contraction impossible - pumping action of the heart stops

- in the absence of blood flow, the patient becomes unconscious and cyanotic - if heartbeat is not restored rapidly, death soon follows - electrical countershock (defibrillation) is applied to eliminate fibrillation and restore cardiac function - if necessary, lidocaine can be used to enhance the effects of defibrillation - procainamide and bretylium may also be helpful - whichever drug converts the patient is the one that is hung as a drip - amiodarone can be used for long-term suppression - as an alternative, ICD may be employed 3. Ventricular Premature Beats – also known as premature ventricular complexes - beats that occur before they should in the cardiac cycle - caused by ectopic ventricular foci - benign and not usually treated - in the presence of acute myocardial infarction, may predispose the patient to v-fib for which treatment is required - beta blocker is the agent of choice 4.

Digoxin-Induced Ventricular Dysrhythmias - digoxin toxicity can mimic practically all types of dysrhythmias - varying degrees of AV block are among the most common - v-flutter and v- fib are the most dangerous - digoxin causes dysrhythmias be increasing automaticity in the atria, ventricles, and HisPurkinje system and by decreasing conduction through the AV node - can almost always be controlled - lidocaine and phenytoin are the agents of choice - DC cardioversion may bring on v-fib 5.

Torsades de Pointes - an atypical, rapid, undulating, ventricular tachydysrhythmias that can evolve into potentially fatal v-fib - main factor associated with development is prolongation of the QT interval, which can be caused by a variety of drugs - preferred treatment is IV magnesium

III.

CLASS I: SODIUM CHANNEL BLOCKERS

A.

CLASS IA AGENTS

1.

QUINIDINE – oldest and most frequently used - administered orally - has antimalarial and antipyretic properties - by blocking sodium channels, slows impulse conduction in the atria, ventricles, and HisPurkinje system - depolarization is delayed at these sites by blocking potassium channels - actions contribute to suppression of dysrhythmias - strongly anticholinergic (atropine-like) and blocks vagal input to the heart - increase in SA nodal automaticity and AV conduction can drive the ventricles at an excessive rate - to prevent excessive ventricular stimulation, usually pretreated with digoxin, verapamil, or a beta blocker, all of which suppress AV conduction Adverse Affects: be immediate and intense)

diarrhea and other GI symptoms (reactions can - can be reduced by administering quinidine with

food cinchonism is characterized by tinnitus (ringing in the ears), headache, nausea, vertigo, and disturbed vision severe cardiotoxicity (sinus arrest, AV block, v-tach, asystole) can occur at high concentrations - occur secondary to increased automaticity of Purkinje fibers and reduced conduction throughout all regions of the heart embolism can occur in the treatment of a-fib - during a-fib, thrombi may form in the atria - when sinus rhythm is restored, the thrombi may dislodge and cause embolism - warfarin (anticoagulant) is given 3-4 weeks prior to quinidine alpha-adrenergic blockade, resulting in vasodilation and subsequent hypotension (more serious in IV therapy than oral) Drug Interactions: can double digoxin levels which is caused by displacing digoxin from plasma albumin and by decreasing digoxin elimination last choice drug for treating digoxin-induced dysrhythmias

2.

PROCAINAMIDE - pronestyl, procanbid - active against a broad spectrum of dysrhythmias - administered orally, IV and IM - short half life, requires more dosing than quinidine Adverse Effects:

systemic lupus erythematosus-like syndrome

(SLE) - prolonged treatment is associated with sever immuno-logic reactions - symptoms include pain and inflammation of the joints, pericarditis, fever, and hepatomegaly - therapy can continue if SLE can be controlled with a nonsteroidal anti-inflammatory agent (aspirin) or a glucocorticoid blood dyscrasias – including neutropenia, thrombocytopenia, and agranulocytosis - reactions usually develop during the first 12 weeks of treatment - complete blood counts should be obtained weekly during this time and periodically thereafter - should be obtained at the first signs of infection, bruising or bleeding cardiotoxicity – danger signs are QRS widening and excessive prolongation of the QT interval GI symptoms, hypotension and arterial embolism B.

CLASS IB AGENTS 1.

LIDOCAINE - xylocaine - IV agent used only for ventricular dysrhythmias, including those associated with myocardial infarction, cardiac surgery, and digoxin toxicity - employed as a local anesthetic - whenever used, equipment for resuscitation must be available Adverse Effects: generally well tolerated central nervous system (CNS) effects can occur drowsiness, confusion, and paresthesias (skin irritation) can occur at high therapeutic doses convulsion and respiratory arrest can occur at toxic doses

IV.

CLASS II:

BETA BLOCKERS

A.

PROPRANOLOL - inderal - a nonselective beta-adrenergic antagonist - blocks beta1-adrenergic receptors that affect the heart - blocks beta2-adrenergic receptors that affect the bronchi - useful for treating dysrhythmias caused by excessive sympathetic stimulation of the heart - among these are sinus tach, severe recurrent v-tach, exercise induced tach, and paroxysmal atrial tach - in supraventricular tach, beneficial effects are: suppression of excessive discharge of the SA node slowing of ventricular rate by decreasing transmission of atrial impulses through the AV node - can be administered orally and, in life threatening emergencies, by IV injection Adverse Effects: generally well tolerated by blocking cardiac beta1 receptors, can cause heart failure, AV block, and sinus arrest hypotension can occur secondary to reduced cardiac output blockade of beta2 receptors in the lung can cause bronchospasm

V. A.

CLASS III: POTASSIUM CHANNEL BLOCKERS (DRUGS

THAT

DELAY REPOLARIZATION)

AMIODARONE - corarone, pacerone - highly effective against both atrial and ventricular dysrhythmias - serious toxicities (lung damage, visual impairment) are common - approved only for life-threatening ventricular dysrhythmias that have been refractory to safer agents - being used with increasing frequency against a variety of atrial and ventricular dysrhythmias Oral Use: approved only for long-term therapy of two life-threatening ventricular dysrhythmias: recurrent v-fib and recurrent hemodynamically unstable v-tach

- treatment reserved for patients who have not responded to safer drugs used with success to convert a-fib to normal sinus rhythm and to maintain normal sinus rhythm following conversion Adverse Effects:

pulmonary toxicity (pneumonitis, alveolitis,

pulmonary fibrosis) - symptoms (dyspnea, cough, chest pain) resemble those of heart failure and pneumonia paradoxical increase in dysrhythmic activity - by suppressing the SA and AV nodes, can cause sinus brady and AV block - by reducing contractility, can precipitate heart failure corneal microdeposits which may cause photophobia or blurred vision - optic neuropathy sometimes progresses to blindness blue-gray discoloration of the skin gastrointestinal reactions (anorexia, nausea, vomiting) CNS reaction include ataxia, dizziness, tremor, mood alteration, and hallucinations hepatitis and thyroid dysfunction Drug Interactions:

can increase plasma levels of several

drugs, including quinidine, procainamide, phenytoin, digoxin, diltiazem, and warfarin Intravenous Therapy: of recurrent v-fib and

approved only for initial treatment and prophylaxis

hemodynamically unstable v-tach used with success against other dysrhythmias including a-fib, AV nodal reentrant tach, and shock resistant v-fib Adverse Effects:

VI.

hypotension and bradydysrhythmias

CLASS IV: CALCIUM CHANNEL BLOCKERS

VERAPAMIL (calan, Isoptin) and DILTIAZEM (Cardizem, others) are able to block calcium channels in the heart. - can slow ventricular rate in patients with a-fib or a-flutter - can terminate SVT caused by an AV nodal reentrant circuit - benefits derive from suppressing AV nodal conduction Administration: verapamil = IV or oral diltiazem = IV, continuous IV infusion Adverse Effects: generally safe bradycardia, AV block, and heart failure by blockade of cardiac calcium channels vasodilation, resulting in hypotension and peripheral edema by blocking vascular smooth muscle calcium channels constipation by blocking calcium channels in intestinal smooth muscle Drug Interactions: elevate levels of digoxin, increasing the risk of digoxin toxicity - combining with digoxin increases the risk of AV block combining with a beta blocker increases the risk of bradycardia, AV block, and heart failure

VII. OTHER ANTIDYSRHYTHMIC DRUGS A.

ADENOSINE - adenocard - a naturally occurring nucleotide - current drug of choice for terminating paroxysmal SVT - EXTREMELY short half-life (less than 10 secs), hence must be administered IV as close to the heart as possible Adverse Effects: sinus bradycardia, dyspnea (from bronchoconstriction), hypotension and facial flushing (from vasodilation) and chest discomfort (perhaps from stimulation of pain receptors in the heart) Drug Interactions: methylxanthines (aminophylline, theophylline, caffeine) block receptors for adenosine B.

DIGOXIN - lanoxin - primary indication is heart failure

- also used to treat supraventricular dysrhythmias Adverse Effects: cardiotoxicity (dysrhythmias), increased by hypokalemia, which can result from concurrent therapy with diuretics GI disturbances (anorexia, nausea, vomiting, abdominal discomfort) CNS responses (fatigue, visual disturbances) C.

IBUTILIDE - corvert - IV agent used to terminate a-flutter and a-fib of recent onset - dosage is 1 mg infused over 10 minutes - if ineffective, a second 1 mg infusion may be made