Decreased secretion of cortisol and ACTH after oral clonidine administration in normal adults

Lanes, Roberto; Herrera, Ana Lucia; Palacios, Anselmo; Moncada, Gustavo

doi:10.1016/0026-0495(83)90026-4

Cited by 63 publications

(25 citation statements)

References 18 publications

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“…GH deficiency or ACTH deficiency) in combination with prolonged fasting for the clonidine test, rather than a generic clonidine effect, is an explanation for the occurrence of hypoglycemia. In contrast to previous reports suggesting that low serum cortisol levels may play a role in the risk of hypoglycemia [16,17], serum cortisol in our patients who developed hypoglycemia was similar to that of the others. It has to be kept in mind that the procedure is performed under fasting conditions, so under these circumstances this individual susceptibility might become apparent independent of clonidine administration.…”

Section: Discussioncontrasting

confidence: 53%

Pharmacokinetics and Pharmacodynamics of Orally Administered Clonidine: A Model-Based Approach

Álvarez-Jiménez

Sukhai²,

Oostdijk³

et al. 2013

Horm Res Paediatr

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Background/Aims: The oral clonidine test is a diagnostic procedure performed in children with suspected growth hormone (GH) deficiency. It is associated with untoward effects, including bradycardia, hypotension and sedation. Serum clonidine levels have not previously been assessed during this test. Methods: In 40 children referred for an oral clonidine test, blood samples were drawn for clonidine and GH. Vital statistics and sedation scores were recorded until 210 min post-dose. We explored the relationship between clonidine concentrations and effects such as GH peak and blood pressure. Results: Of 40 participants, 5 children were GH deficient. Peak clonidine concentrations of 0.846 ± 0.288 ng/ml were reached after 1 h. Serum levels declined slowly, with concentrations of 0.701 ± 0.189 ng/ml 210 min post-dose. A large interindividual variation of serum levels was observed. During the procedure, systolic blood pressure dropped by 12.8%, diastolic blood pressure by 19.7% and heart rate by 8.4%. Moderate sedation levels were observed. Concentration-effect modeling showed that the amount of GH available for secretion as determined by previous bursts was an important factor influencing GH response. Conclusion: Clonidine concentrations during the test were higher than necessary according to model-based predictions. A lower clonidine dose may be sufficient and may produce fewer side effects.

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Section: Discussioncontrasting

confidence: 53%

Pharmacokinetics and Pharmacodynamics of Orally Administered Clonidine: A Model-Based Approach

Álvarez-Jiménez

Sukhai²,

Oostdijk³

et al. 2013

Horm Res Paediatr

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“…Catecholaminergic systems and especially the noredrenergic system have long been regarded as inhibitors of the hypotha-lamic-pituitary-adrenal (HPA)' axis (1)(2)(3)(4)(5)(6)(7)(8). However, recent data obtained from experimental animals and humans indicate that the brainstem noradrenergic (i.e., locus coeruleus [LC]) system and the HPA axis are both activated during physical (e.g., surgery, trauma, hemorrhage, and exercise) and emotional (e.g., depression, panic anxiety attacks, bereavement, examinations, and experimentally induced inescapable shock stress) (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro.

Calogero¹,

Gallucci²,

Chrousos³

et al. 1988

J. Clin. Invest.

190

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To further our understanding of the functional role of catecholaminergic systems in regulating hypothalamic corticotropinreleasing hormone (CRH) secretion, we assessed the direct effects of a multiplicity of catecholamine agonists and antagonists on hypothalamic CRH secretion. To accomplish this, we used an in vitro rat hypothalamic organ culture system in which CRH secretion from single explants was evaluated by a specific RIA (IR-rCRH). Norepinephrine (NE) stimulated IRrCRH secretion dose dependently, with peak effects in the nanomolar range. The effect of NE was antagonized by the mixed a antagonist phentolamine, the a, antagonist prazosin, and the a2 antagonist yohimbine, but not by the ,B blocker, L-propanolol. Compatible with these data were the findings that the a, agonist phenylephrine and the a2 agonist clonidine both stimulated IR-rCRH secretion in a dose-dependent fashion. On the other hand, whereas the fi agonist, isoproterenol, caused a weak, non-dose-dependent increase in IR-rCRH secretion, this effect could not be antagonized by L-propanolol. Despite pretreatment with serotonin and acetylcholine antagonists, the effect of NE upon IR-rCRH secretion was undiminished, suggesting that NE-induced CRH secretion is not mediated by either neurotransmitter. On the other hand, pretreatment with y-aminobutyric acid (GABA) attenuated NE-induced IR-rCRH secretion. Whereas epinephrine (E) stimulated IR-rCRH secretion, this occurred only at higher concentrations, and was antagonized by phentolamine, but not by L-propanolol. Dopamine (DA) had a weak stimulatory effect that could be antagonized by the DA, receptor antagonist, SCH 23390, but not by phentolamine.We conclude that NE and E stimulate hypothalamic IRrCRH secretion via a, and a2 receptors. The effect of NE upon IR-rCRH secretion is not apparently mediated by serotonergic or cholinergic interneurons, but is modulated by the inhibitory neurotransmitter, GABA. These data support the idea that the central catecholaminergic systems are excitatory rather than inhibitory upon CRH secretion when acting directly at the hypothalamic level.

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“…Clonidine is an alpha-adrenoceptor ago nist [1] that has been shown to stimulate the release of growth hormone (GH) in normal subjects [2], and has been suggested as a test of GH reserve in children and adolescents with suspected GH deficiency [3], However, a more detailed analysis of alpha-adrenocep tors has subdivided them into alphar and alphao-subtypes; on this classification cloni dine has been shown to activate both alphar and alpha2-subtypcs, although its preferen tial activity is at alpha2-adrenoceptors [4], It has been unclear as to whether the GH-stimulatory effects of clonidine in man are ex erted at alphar or alphai-adrenoceptors, al though studies in other species suggest that the alphai-adrenoceptor is the more likely candidate [5][6][7], Clonidine has also been variously reported to inhibit circulating cor tisol in man [8,9], while others have found either no effect of clonidine on cortisol, or even stimulation [2,10,11], Part of the problem may have been the fact that cloni dine activates both alphai-and alphai-adrenoceptors and different receptor subtypes may have different effects. Studies in our department have shown that a highly se lective alphai-adrenoceptor agonist, such as methoxamine, stimulates the release of ACTH and cortisol [ 12], so that the effects of clonidine have been difficult to interpret.…”

Section: Introductionmentioning

confidence: 99%

Alpha<sub>2</sub>-Adrenoceptor Agonists Stimulate Growth Hormone Secretion but Have No Acute Effects on Plasma Cortisol under Basal Conditions

et al. 1987

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Ten normal male subjects were administered clonidine (0.1 and 0.2 mg) or a highly-selective alpha₂-adrenoceptor agonist S 3341 (1 and 2 mg) on separate occasions in a double-blind randomised placebo-controlled study; blood samples were obtained for measurement of serum GH and plasma cortisol via an indwelling venous cannula for 4 h after each drug administration. Both clonidine and S 3341 were equally effective at lowering supine, and particularly standing BP; both also caused mild sedation, although this was slightly less marked for S 3341. High doses of both clonidine and S 3341 significantly increased serum GH (peak increment after clonidine: 18.8 ± 5.5 mU/1 (mean ± SEM); peak increment after S 3341: 21.1 ± 4.8 mU/1). Neither drug affected plasma cortisol. It is concluded that GH release may be stimulated by alpha2-adrenoceptor agonism. As S 3341 has slightly less central activity than clonidine at the doses employed, but is at least equally potent at stimulating GH release, it is probable that the alpha₂-adrenoceptor stimulation of GH release occurs outside the blood-brain barrier. The pituitary-adrenal axis appears resistant to manipulation of alpha2-adrenoceptors under basal conditions.

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Decreased secretion of cortisol and ACTH after oral clonidine administration in normal adults

Cited by 63 publications

References 18 publications

Pharmacokinetics and Pharmacodynamics of Orally Administered Clonidine: A Model-Based Approach

Pharmacokinetics and Pharmacodynamics of Orally Administered Clonidine: A Model-Based Approach

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro.

Alpha<sub>2</sub>-Adrenoceptor Agonists Stimulate Growth Hormone Secretion but Have No Acute Effects on Plasma Cortisol under Basal Conditions

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