Treatment of Chronic Symptomatic Supraventricular Bradyarrhythmias with Transdermal Scopolamine: Discussion

Treatment of Chronic Symptomatic Supraventricular Bradyarrhythmias with Transdermal Scopolamine: DiscussionScopolamine (hyoscine) is a competitive inhibitor of the muscarinic receptors of acetylcholine and has pharmacologic actions similar to those of atropine. The usefulness of this drug has been limited by its relatively short duration of action and high incidence of side effects when administered orally or parenterally. The transdermal system of administration is designed to deliver the scopolamine into the systemic circulation over an extended period similar to a slow intravenous infusion. The patch itself is 2.5 cm2 in area and has a reservoir layer containing 1.5 mg of scopolamine. About 0.5 mg of the drug passes from this reservoir through a micro-porous polypropylene membrane and the intact skin to enter the systemic circulation at a steady rate over a period of 72 hours. A continuous controlled release of scopolamine occurs to maintain the plasma concentration at a steady level. The transdermal system of administration of scopolamine is currently used for the prevention of nausea and vomiting associated with motion sickness.

The cardiovascular response to antimuscarinic agents depends upon the dose used and the physiologic state of the heart. Atropine, in low doses, may initially produce a decrease in the sinus rate due to central vagal stimulation, but the onset of peripheral muscarinic cholinergic blockade typically causes the sinus rate to rise and the AV conduction time and PR interval to shorten. In patients with second and third degree AV nodal block, atropine may lessen the degree of block and may rarely accelerate the idioventricular rate in patients with trifascicular block. The physiologic state of the heart, in particular the magnitude of vagal tone, seems to be an important determinant of antimuscarinic response. Thus, in the setting of acute myocardial infarction, low doses of atropine are commonly employed to treat sinus and AV junctional bradyarrhythmias without encountering any noticeable worsening of the bradycardia.
Small doses of scopolamine may also cause slowing of the sinus rate in normal individuals and this effect may be more marked than with atropine. In a recent study by Dibner-Dunlap et al, transdermal scopolamine patches (doses of Vi, 1 or V/2 patches) were applied to 16 healthy young men. Twenty-four hours after application there was an average increase in cycle length by 13 percent. With higher doses of scopolamine (above 0.2 mg orally or parenterally), cardioac-celeration occurs. Plasma scopolamine levels cannot be directly measured, although a reversed-phase liquid chromatography and radioreceptor assay has recently been developed and may be performed in certain research laboratories. This assay was not available to us.
The success of transdermal scopolamine in accelerating the heart rate and reducing the frequency and duration of asystolic periods in our patient suggests that it may be useful in the treatment of chronic, symptomatic supraventricular bradyarrhythmias. This may be particularly important in the management of patients who are not candidates for a permanent pacemaker such as those who are terminally ill or severely demented. In our patient, the increase in heart rate was sustained over a period of two months. Since the cardiovascular response to antimuscarinic agents is unpredictable and sometimes paradoxic, the patient should be monitored for some time after application of the patch to determine its effectiveness.

Category: Transdermal Scopolamine

Tags: supraventricular bradyarrhythmias, transdermal scopolamine, treatment