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

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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.