Clonidine Withdrawal in Hypertension

Reid, John L.; Dargie, H. J.; Davies, D. S.; Wing, L. M. H.; Hamilton, CA; Dollery, C T

doi:10.1016/s0140-6736(77)92715-5

Cited by 140 publications

(17 citation statements)

References 13 publications

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“…However, standing plasma noradrenaline levels were greater by day 4 after cessation of guanfacine than before treatment (P < 0.05). The decrease in plasma and urinary noradrenaline levels on treatment is similar to that observed after clonidine (Hokfelt et al, 1970;Reid et al, 1977) and is consistent with a central sympathetic inhibitory action for guanfacine. The increase in standing plasma noradrenaline may indicate an increase in sympathetic activity at that time.…”

Section: Discussionsupporting

confidence: 77%

Guanfacine: Effects of long‐term treatment and withdrawal.

Reid¹,

Zamboulis²,

Hamilton³

1980

Brit J Clinical Pharma

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1Guanfacine 3-6 mg daily lowered blood pressure in five essential hypertensives and also reduced saliva production. 2 Plasma and urinary noradrenaline values were significantly reduced throughout the 8-10 weeks of treatment.3 On substitution of placebo tablets for guanfacine, blood pressure increased over a 2-4d period to reach but did not significantly exceed pretreatment levels. 4 After withdrawal of guanfacine plasma noradrenaline standing was significantly higher than the pretreatment level (P < 0.05) after 4 days. Saliva production was significantly higher than the pretreatment level on day 3 and day 4 of withdrawal. 5Guanfacine is an effective antihypertensive drug with a spectrum of actions similar to clonidine.However, in abrupt withdrawal blood pressure returned to the pretreatment level over a 2-4d period.

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Section: Discussionsupporting

confidence: 77%

Guanfacine: Effects of long‐term treatment and withdrawal.

Reid¹,

Zamboulis²,

Hamilton³

1980

Brit J Clinical Pharma

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“…Initially the withdrawal phenomenon was thought Table 5 Plasma renin activity (,ug angiotension 1/3 h tiamenidine or clonidine to be rare, but it is becoming clear that it occurs rather frequently (Geyskes, Boer & Dorhout Mees, 1979;Reid, Dargie, Davies, Wing, Hamilton & Dollery, 1977). The severity of the reaction bears some relationship albeit inconsistent to the dose or the duration of therapy.…”

Section: Discussionmentioning

confidence: 99%

Changes in blood pressure, plasma catecholamines and plasma renin activity during and after treatment with tiamenidine and clonidine.

Hansson¹,

Hökfelt²

1981

Brit J Clinical Pharma

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1 Tiamenidine (Hoe 440) is an imidazoline with blood pressure lowering properties. Its pharmacology resembles that of clonidine. 2 The effect of both drugs on blood pressure, plasma noradrenaline (NA), plasma adrenaline (Ad), urinary catecholamines and plasma renin activity (PRA) was assessed in four previously untreated male hypertensive patients in a cross over study. 3 The maximum daily dose of tiamenidine was 3 mg. The maximum daily dose of clonidine was 450 micrograms. 4 During treatment, blood pressure, systolic and diastolic, supine and erect, fell on average between 12 and 15%. Levels of NA, Ad, PRA were reduced during treatment. 5 During withdrawal of either drug there was rebound of blood pressure and NA, Ad, PRA, overshooting baseline levels. 6 The withdrawal effects caused by clonidine were similar for tiamenidine.

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“…Physical dependence on clonidine, expressed as hyperactivity or hypertension after withdrawal of the drug, has been described in experimental animals (Meyer, El-Azhary, Bierer, Hanson, Robbins & Sparber, 1977;Jennewein, Stockhaus & Hoefke, 1980) and in man (Hansson, Hunyor, Julius & Hoobler, 1973;Reid, Dargie, Davies, Wing, Hamilton & Dollery, 1977;Geyskes, Boer & Dorhout-Mees, 1979). In the whole animal, many variables confuse the analysis of the molecular mechanisms underlying dependence, which requires models of clonidine dependence in isolated cells or organs.…”

Section: Introductionmentioning

confidence: 99%

Clonidine Dependence in the Guinea‐pig Isolated Ileum

Collier

Cuthbert

Francis

1981

British J Pharmacology

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1 Compared with the response of preparations incubated in solutions without clonidine, a three to four fold increase in the magnitude of the contracture of the longitudinal muscle to challenge with phentolamine (1.0 1aM) was induced by incubating the guinea-pig isolated ileum at 22°C for 24 h with clonidine (1.0 ,UM) in Krebs solution containing hexamethonium (70 ,M). Incubation of the ileum with clondine (1.0 ,UM) for 0.5 h at 37°C did not increase responsiveness to phentolamine. 2 The increase in responsiveness to phentolamine was directly related to the clonidine concentration in the incubation fluid over the range 0.01 to 1.0 p.M. 3 The magnitude of the contracture to phentolamine of ilea incubated with clonidine (1.0 ,uM) (withdrawal contracture) was directly related to the challenge dose of phentolamine over the range 0.3 to 1.0 pM. 8 Ileal segments incubated with clonidine (1.0 pM) were unresponsive to challenge with naloxone (100 nm); and segments incubated with normorphine (1.0 FM) were unresponsive to phentolamine (1.0 pM), although responsive to naloxone. 9 Normorphine (1.0 AM) restored to resting level the tension of the clonidine withdrawal contracture; and clonidine (0.1 pM) restored to resting level the tension of the contracture to naloxone in ileal segments incubated with normorphine. 10 These experiments indicate that incubation with clonidine induces, in the final cholinergic motor neurones of the myenteric plexus of the isolated ileum, a dependence the withdrawal from which is expressed as a contracture in response to a-adrenoceptor antagonists. 11 Although opiate receptors are not involved in clonidine dependence nor a-adrenoceptors in opiate dependence, the findings that normorphine suppresses the clonidine withdrawal-contracture and that clonidine suppresses the contracture of opiate-dependent ileum to naloxone, suggest that the withdrawal effect studied in both clonidine and normorphine dependence in this preparation is mediated by release of acetylcholine from the final motor neurone.

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Clonidine Withdrawal in Hypertension

Cited by 140 publications

References 13 publications

Guanfacine: Effects of long‐term treatment and withdrawal.

Guanfacine: Effects of long‐term treatment and withdrawal.

Changes in blood pressure, plasma catecholamines and plasma renin activity during and after treatment with tiamenidine and clonidine.

Clonidine Dependence in the Guinea‐pig Isolated Ileum

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