CLINICAL PHARMACOLOGY 2003 (PART 26)

The pathophysiology of cardiac arrhythmias is complex and the actions of drugs that are useful in stopping or controlling them may seem equally so. Nevertheless many patients with arrhythmias respond well to therapy with drugs and a working knowledge of their effects and indications pays dividends, for irregularity of the heart-beat is at least inconvenient and at worst fatal.The mechanisms by which the failing heart may be sustained are now better understood; carefully selected and monitored drugs can have a major impact on morbidity and mortality in this condition. Drugs for cardiac arrhythmias. Principal drugs by class •...
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CLINICAL PHARMACOLOGY 2003 (PART 26) 24 Cardiac arrhythmia and cardiac failure SYNOPSIS • To reduce morbidity and • To reduce mortality. The pathophysiology of cardiac arrhythmias is complex and the actions of drugs that are Arrhythmias are frequently asymptomatic but useful in stopping or controlling them may may be fatal. Indeed an estimated 70 000 deaths per seem equally so. Nevertheless many patients year are ascribed to ventricular arrhythmias in the with arrhythmias respond well to therapy with United Kingdom. In addition, all antiarrhythmics drugs and a working knowledge of their effects are also capable of generating arrhythmias and should and indications pays dividends, for irregularity be used only in the presence of clear indications. In of the heart-beat is at least inconvenient and at addition, antiarrhythmic agents are to a variable worst fatal.The mechanisms by which the degree negatively inotropic (except for digoxin and failing heart may be sustained are now better amiodarone). understood; carefully selected and monitored A second reason for a careful approach to anti- drugs can have a major impact on morbidity arrhythmic treatment is the gulf between knowledge and mortality in this condition. of their mechanism of action and their clinical uses. On the side of normal physiology, we can see the • Drugs for cardiac arrhythmias spontaneous generation and propagation of the • Principal drugs by class cardiac impulse requiring a combination of specialised • Specific treatments, including those for conducting tissue and inter-myocyte conduction. cardiac arrest The heart also has backstops in case of problems • Drugs for cardiac failure with the variety of pacemakers. By contrast, the available drugs may be considered still to be at an early stage of evolution, and useful antiarrhythmic actions — such as that of adenosine — continue to be discovered by chance.Drugs for cardiac Doctors and drugs interfere with cardiac electro- physiological actions at their peril. In emergencies,arrhythmias action often needs to be taken by the most junior doctor in the team, and some rote recommendations are then necessary. The diagnosis and electiveOBJECTIVES OF TREATMENT treatment of chronic, or episodic arrhythmias requireIn almost no other condition is it as important to greater skill to ensure that the correct balance betweenremember the dual objectives which are: risk and benefit is achieved. As will become clear, 49724 CARDIAC ARRHYTHMIA AND CARDIAC FAILUREantiarrhythmic drugs have a hard time proving disposition of ions (mainly sodium, potassium andsuperior safety or efficacy over other therapeutic calcium) across its membrane, i.e. it is polarised. The(non-drug) options. ionic changes of the action potential first result in a rapid redistribution of ions such that the potential alters to positive within the cell (depolarisation);SOME PHYSIOLOGY AND subsequent and slower flows of ions then restorePATHOPHYSIOLOGY the resting potential (repolarisation). These ionicThere are broadly two types of cardiac tissue. movements may be separated into phases which The first type is ordinary myocardial (atrial and are briefly described here and in Figure 25.1, forventricular) muscle, responsible for the pumping they help to explain the actions of antiarrhythmicaction of the heart. drugs.1 The second type is specialised conducting tissuethat initiates the cardiac electrical impulse and ...