Cardiovascular withdrawal effects of clonidine and tiamenidine on abrupt cessation of oral treatment in conscious cats

Abstract

In conscious renal hypertensive cats prepared with permanent indwelling arterial catheters oral administration of clonidine (0·05 mg × 3 daily) clonidine (0·0125 mg × 3 daily), or tiamenidine (0·25 mg × 3 daily) induced hypotension and bradycardia during 6 days of treatment, although these responses were not well sustained. A pronounced tachycardia was demonstrated in all cats, 16–20 h after cessation of treatment with the higher dose of clonidine, however, only two cats in this group showed increased blood pressures above pre-dose levels at this time; these ‘withdrawal’ effects were absent 44 h after the final dose. No evidence of tachycardia, or blood pressure overshoot was seen up to 44 h after cessation of the low clonidine treatment regime, providing evidence for a dose-withdrawal effect relationship. Significant tachycardia was demonstrated in all cats 15–19 h after cessation of treatment with tiamenidine with no evidence of blood pressure elevation; the tachycardia was absent 48 h after the final dose. In four of these same cats clonidine (0·1 mg × 2 daily), in a long-acting, sustained release formulation (LA clonidine), elicited prolonged falls in blood pressure and heart rate over a 10 day period. No evidence of withdrawal effects were obtained 14–48 h after cessation of this treatment.