Summary
1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
Similar content being viewed by others
References
Barber ND, Reid JL (1978) Comparison of the actions of central and peripheral administration of clonidine and BS 100–141 in the rabbit. Br J Pharmacol 63: 395
Barber ND, Zamboulis C, Reid JL (1978) Comparison of cardiovascular and other effects of clonidine and BS 100–141. 7th International Congress of Pharmacology (IUPHAR), Paris
Campbell BC, Elliott HL, Hamilton CA, Reid JL (1980) Changes in blood pressure, heart rate and sympathetic activity on abrupt withdrawal of tiamenidine. Paper presented at World Congress of Clinical Pharmacology & Therapeutics, London
Dubach UC, Huwyler R, Radielovic P, Singeisen M (1977) A new centrally acting antihypertensive agent guanfacine (BS 100–101). Arzneim Forsch 27: 674–676
Henry DP, Starman BJ, Johnson DG, Williams RH (1975) A sensitive radioenzymatic assay for norepinephrine in tissues and plasma. Life Sci 16: 375–384
Hökfelt B, Hedeland H, Dymling JF (1970) Studies on catecholamines, renin and aldosterone following catapres in hypertensive patients. Eur J Pharmacol 10: 389–397
Hunyor SN, Hansson L, Harrison TS, Hoobler SW (1973) Effects of clonidine withdrawal: possible mechanisms and suggestions for management. Br Med J 2: 209–211
Jäättelä A (1976) Clinical efficacy of BS 100–141 in essential hypertension. A single blind pilot study. Eur J Clin Pharmacol 10: 69–72
Kirch W, Distler A (1978) Antihypertensive effect of N-Amidino 2- (2–6 dichlorophenyl) acetamide hydrochloride. A double blind crossover trial versus clonidine. Int J Clin Pharmacol 16: 132–135
Oates HF, Stoker LM, Stokes GS (1979) Studies in the rat on the haemodynamic overshoot response to withdrawal of guanfacine or clonidine treatment. Clin Exp Pharmacol Physiol 6: 61–68
Rand MJ, Rush M, Wilson S (1969) Some observations on the inhibition of salivation by ST 155. Eur J Pharmacol 5: 168–172
Reid JL, Wing LMH, Dargie HJ, Hamilton CA, Davies DS, Dollery CT (1977) Clonidine withdrawal in hypertension. Lancet 2: 1171–1174
Salzmann R (1979) The effects of treatment and of withdrawal of treatment with guanfacine and clonidine on blood pressure and heart rate in normotensive and renal hypertensive rats. J Pharm Pharmacol 31: 212–216
Scholtysik G, Lauener H, Eichenberger E (1975) Pharmacological actions of the antihypertensive agent N-amidino-2-(2,6 dichlorophenyl) acetamide hydrochloride (BS 100, 101). Arzneim Forsch 25: 1483–1491
Seedak YK (1978) Long-term treatment of hypertension with guanfacine alone and in combination therapy. Curr Ther Res 24: 288–298
von Euler U, Lishajko F (1961) Improved technique for fluorimetric estimation of catecholamines. Acta Physiol Scand 51: 348–356
Wing LMH, Reid JL, Hamilton CA, Sever PS, Davies DS, Dollery CT (1977a) Effects of clonidine on biochemical indices of sympathetic function and plasma renin activity in normotensive man. Clin Sci Mol Med 53: 45–53
Wing LMH, Reid JL, Davies DS, Neill EAM, Tippett P, Dollery CT (1977b) Pharmacokinetic and concentration effect relationships of clonidine in essential hypertension. Eur J Clin Pharmacol 12: 463–469
Zamboulis C, Reid JL, Hamilton CA (1978) BS 100–141: a centrally acting and hypertensive drug: effects on blood pressure and plasma and urinary catecholamines in essential hypertension. 7th International Congress of Pharmacology (IUPHAR) Paris
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zamboulis, C., Reid, J.L. Withdrawal of guanfacine after long-term treatment in essential hypertension. Eur J Clin Pharmacol 19, 19–24 (1981). https://doi.org/10.1007/BF00558376
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00558376