TCAs are highly concentrated in myocardial tissue, which partly explains their interference with heart rate, cardiac rhythm, and myocardial contractility. These effects are mediated by several mechanisms, such as the anticholinergic and quinidine-like action of the TCAs, their interference with adrenergic amine reuptake, altered membrane permeability, and direct myocardial depression.
TCAs can induce second- and third-degree heart block, sick sinus syndrome, bundle branch block, and a prolonged QT interval. They can also be arrhyth-mogenic, probably by increasing the heterogeneity of the ventricular repolarization and/or by increasing myocardial norepinephrine levels, due to their peripheral inhibition of norepinephrine reuptake. Concomitant antiarrhythmic therapy contraindicates the use of TCAs.
TCAs elevate the heart rate by 5 to 20 beats per minute due to anticholinergic blockade. They also cause postural hypotension in up to 20% of patients, due to a combination of peripheral antiadrenergic action, myocardial depression, and a-blockade in the central nervous system.
The magnitude of the effect depends on the magnitude of pretreatment orthostatic hypotension; it is more likely to be clinically significant in patients with CHF or impaired left ventricular function, or in those on antihypertensive medications. It is less likely with nortriptyline than with amitriptyline or imipramine.
Most studies suggest that the effects of TCAs on left ventricular function have no major consequences on their applicability in everyday clinical practice. Nor is there convincing evidence that TCAs are likely to impair preexisting left ventricular dysfunction. However, as CHF is often associated with cardiac conduction disturbances or low blood pressure, clinicians should be aware that TCAs may have adverse cardiovascular effects in severe CHF, particularly given the scarcity of data on the longterm effect of TCAs on ventricular performance in CHF. A guiding principle in the elderly and those with heart disease is to initiate treatment with low doses, followed by slow” and careful uptitration. Tertiary amine TCAs (eg, imipramine and amitriptyline) tend to have more side effects in cardiac patients than secondary amines (eg, nortriptyline).
Selective serotonin reuptake inhibitors (SSRIs) cause fewer cardiovascular side effects. Probably their most important effect in cardiac patients is their potential to interact with drugs used for cardiac arrhythmias, CHF, and hypertension.