Adrenal system

Data of animal experiments discussed in this chapter suggest a variety of potential pharmacological targets for the treatment of pathological anxiety (Fig. 1). As the occurrence of traumatic events is usually unpredictable, it seems more promising to interfere with consolidation than with acquisition processes. In this context, the sympatho-adrenergic and the hypothalamic-pituitary-adrenal system are of particular interest. Both noradrenaline and corticosterone/cortisol are known to facilitate memory consolidation, in par-... 

CORTISOL ANTACONISTS AND LIMBIC-HYPOTHALAMIC-PITUITARY-ADRENAL SYSTEM STABILIZERS... 

Reus VI, Berlant JR Behavioral disturbances associated with disorders of the hypothalamic-pituitary-adrenal system, in Medical Mimics of Psychiatric Disorders. Edited by Extein I, Gold MS. Washington, DC, American Psychiatric Press,... 

Because of its effects on the pituitary/adrenal system, ketoconazole has been used in the long-term control of hypercortisolism of either pituitary or adrenal origin (SED-12, 677). In seven patients with Cushing s disease and one with an adrenal adenoma, ketoconazole 600-800 mg/day for 3-13 months produced rapid persistent clinical improvement (585). Plasma dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid and cortisol excretion fell soon after the start of treatment, and remained normal or nearly so throughout treatment. Urinary tetrahydro-ll-deoxycortisol excretion rose... 

Krishnan R, Ellinwood EH Jr, Laszlo J, Hood L, Ritchie J. Effect of gamma interferon on the hypothalamic-pituitary-adrenal system. Biol Psychiatry 1987 22(9) 1163-6. 

Many clinical observations indicate that neurogenic factors in some way influence the development and maintenance of essential hypertension. It has long been recognized that stressful situations may induce marked increases in both systolic and diastolic pressures which persist for varying periods of time (21, 38), and that hypertensives tend to have a characteristic type of personality (2, 99. Such individuals usually exhibit important components of repressed antagonism and anxiety. They do not find emotional outlets in overt acts, but rather their emotions are expressed through an increased activity of the sympatho-adrenal system with a consequent increase in blood pressure. Relief of psychic tension frequently produces salutary effects in these patients. Individuals who show hyperactive sympathetic vasomotor reflexes (as measured by the cold pressor test) are much more prone than the average individual to develop hypertension in later life (57). 

Figure 1 illustrates the principal nervous pathways involved in the maintenance of blood pressure. Under normal conditions the afferent pathways from the carotid sinus and aortic arch areas carry tonic impulses which depress the activity oi the vasomotor centers. Consequently, section of these moderator nerves in animals (51, 56) or man (103) brings about a sustained hypertension. Of more importance to an analysis of clinical hypertension, however, is the fact that increased activity of the sympatho-adrenal system may arise on a central basis. In animals such hypertension may be induced by electrical stimulation of or injury to the hypothalamus (59, 98) in both animals (17, 26, 39) and man (16) it may result from an increased intracranial pressure, at least in part because of the cerebral ischemia that results (16, 46). 

At the present time, pheochromocytoma and intracranial lesions are the only causes of human hypertension which are definitely known to involve overactivity of the sympatho-adrenal system. However, presumptive evidence is accumulating to indicate that neurogenic factors may be involved in early essential hypertension, and it is possible that adequate adrenergic blockade early in the course of such hypertension may be effective in aborting its development. Only additional evidence regarding the etiology of essential... 

Not much is known about hallucinogens in general and mescaline in particular. While much of the research has pointed to the close ties with serotonin, others are now looking at the similarity between mescaline and amphetamine, with which it shares an even closer similar structure. This is especially evident in the mescaline analogs such as ecstasy, which has an extreme amphetamine-like effect on users. Amphetamines affect the adrenal system. 

The opioids may modulate the actions of the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. Natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. In general, these effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids. 

L. Mathematical modeling of the hypothalamic-pituitary-adrenal system activity. Math Biosci 2005,197 173-187. 

The methods described here are applied for Supplemental Safety Pharmacology Studies (ICH S7A), if the test substance has shown indications of effects on the hypothalamic-pituitary-adrenal system in the preceding pharmacology studies. The in vitro studies are generally performed with several increasing doses to investigate concentration-effect relationships. The preliminary information from these in vitro studies is then compared with the biological information available from in vivo for studies, to assess the need for additional animal studies based on repeated dose administration of the test compound. 

In the endocrine safety pharmacology for the hypothalamic pituitary adrenal system, the levels to be examined are ... 

Interestingly, a marine-derived peptide product called Stabilium 200 has been reported to reduce anxiety in humans and to improve memory and learning performances in both rats and humans. Stabilium 200 is a derivative of the commercial product PC 60, which is a mixture of fish protein hydrolysates from mainly cod and mackerel. Bernet et al. (2000) reported that the marine-derived Gabolysat PC 60 showed anxiolytic properties by exhibiting diazepam-like effects on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity. 

Bemet, F., Montel, V., Noel, B., and Dupouy, J. P. 2000. Diazepam-like effects of a fish protein hydrolysate (Gabolysat PC60) on stress responsiveness of the rat pituitary-adrenal system and sympathoadrenal activity. Psychopharma., 149,... 

Adrenal steroids chronic corticosteroid therapy with the equivalent of prednisolone 10 mg daily within the previous 3 months suppresses the hypothalamic-pituitary-adrenal system. Without steroid supplementation perioperatively the patient may fail to respond appropriately to the stress of surgery and become hypotensive (see Ch. 34). A single dose of etomidate depresses the hypothalamic-pituitary-adrenal axis for a few hours but this is not associated with an adverse outcome. 

In all these situations an i.v. infusion should be available for immediate use in case the above is not enough. These precautions should be used in patients who have received substantial treatment with corticosteroid within the past year, because their hypothalamic/pituitary/adrenal system, though sufficient for ordinary life, may fail to respond adequately to severe stress. If steroid... 

Grobecker HF, Riebel K, Wellenhofer T. Cyclosporine A-induced hypertension in SHR and WKY role of the sympatho-adrenal system. Clin Exp Pharmacol Physiol 1995 22 Supp11 S94-S95. 

The evidence in favour of a relationship between non-steroidal antirheumatic activity and the pituitary-adrenal system is based mainly on experiments involving salicylates and phenylbutazone. No attempt will be made to discuss these problems in detail since they have been adequately reviewed by Smith and Done for salicylates, and by Rechenburg for phenylbutazone. Smith argued persuasively that the available experimental evidence on salicylates does not support the view that they either mimic or reinforce the actions of the natural adrenocortical hormones, and that the similar clinical effects of salicylates and these steroids in rheumatic diseases must therefore be produced by different mechanisms. Done, on the other hand, suggests that the concept cannot be prematurely dismissed and believes that the possibility that salicylate simultaneously affects the production and disposition of adrenocortical hormones deserves further consideration. He emphasizes that the antirheumatic effects of salicylates are not dependent on the maintenance of elevated circulating levels of corticoids. 

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