ABSTRACT
The incidence and pathogenesis of withdrawal phenomena with the centrally acting drugs clonidine (CLON) and tiamenidine (TIAM) were evaluated. Thirty subjects with hypertension on hydrochlorothiazide (HCTZ) were randomized to TIAM or CLON. Blood pressure and integrated plasma catecholamine levels fell equally in response to both drugs. On withdrawal, blood pressure and pulse rose in both groups with no difference between them. Three subjects had symptoms of withdrawal, four had blood pressure overshoot above pretreatment levels of 10 mm Hg or more, and eight had a rise in blood pressure of 30 mm Hg systolic or 20 mm Hg diastolic. There was no difference between TIAM and CLON in these effects. There was a direct correlation between blood pressure rise and increase in integrated plasma norepinephrine levels. We conclude that the incidence of withdrawal phenomena in subjects on TIAM or CLON is infrequent and that there is a direct relationship between the rise in blood pressure and the loss of suppression of catecholamines by these drugs.
Subject(s)
Clonidine/adverse effects , Hypertension/chemically induced , Substance Withdrawal Syndrome , Thiophenes/adverse effects , Adult , Blood Pressure/drug effects , Clonidine/pharmacology , Epinephrine/blood , Humans , Hydrochlorothiazide/therapeutic use , Male , Middle Aged , Norepinephrine/blood , Norepinephrine/urine , Pulse/drug effects , Random Allocation , Thiophenes/pharmacologyABSTRACT
Abrupt clonidine withdrawal may be associated with sharp marked increases in catecholamine levels, heart rate, and blood pressure, which may induce nausea, vomiting, and palpitations. Relatively little information is available on the incidence of cardiac arrhythmias in this setting. With continuous ambulatory ECG recordings, we determined the incidence of arrhythmias in seven male hypertensive patients (without active heart disease) after abrupt clonidine withdrawal. Serious ventricular arrhythmias, including brief ventricular tachycardia, developed in two patients who had greater increases in mean systolic blood pressure (28 +/- 3 vs 10 +/- 8 mm Hg) and double product (552 +/- 681 vs 333 +/- 195) than the others. The differences were not significant. Ventricular arrhythmias were not related to age, dose, withdrawal symptoms, initial blood pressure, urinary norepinephrine levels, or ECG abnormalities. We conclude that serious ventricular arrhythmias may be relatively common but unpredictable during clonidine withdrawal, even in patients with no clinically apparent heart disease. The triggering of ventricular arrhythmias should be added to the list of components of clonidine withdrawal syndrome.
