Disease relevance of fludrocortisone

• Fludrocortisone in orthostatic hypotension [1].
• Clinically, hypertension in the recumbent position is an important risk of fludrocortisone treatment in patients with orthostatic hypotension [2].
• Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism [3].
• Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial [4].
• Evidence that patients with Addison's disease are undertreated with fludrocortisone [5].

Psychiatry related information on fludrocortisone

• Subjects with PTSD had higher raw cortisol and higher normed (baseline-related) ACTH and 11-deoxycortisol values after metyrapone independent of treatment with fludrocortisone or placebo [6].
• However, after she was switched to a regimen of cortisol (CORT) and fludrocortone (FLUD) the psychopathology disappeared [7].

High impact information on fludrocortisone

• Seven patients received fludrocortisone (0.1 or 0.2 mg per day) before, during, and after the trial of erythropoietin [8].
• The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001) [9].
• To assess the frequency and mechanism of mineralocorticoid escape in cirrhosis, 9-alpha-fluorohydrocortisone (0.6 mg/day) was administered to 19 patients with compensated cirrhosis, portal hypertension, and no history of ascites who were able to maintain sodium balance on a 250 mmol Na+ diet [10].
• Hyponatremia responsive to fludrocortisone acetate in elderly patients after head injury [11].
• After long-term blood volume expansion with florinef (E.R. Squibb, Princeton, New Jersey), 0.1 mg twice a day, and a high-salt diet, the head-up tilt test was repeated in five patients [12].

Chemical compound and disease context of fludrocortisone

• These results suggest that patients with Addison's disease on 0.05-0.1 mg of fludrocortisone with undetectable plasma aldosterone levels are currently being undertreated with fludrocortisone [5].
• CONCLUSION: Low-dose combination therapy of hydrocortisone and fludrocortisone was not effective in patients with chronic fatigue syndrome [13].
• We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone provides effective control of congenital adrenal hyperplasia with reduced risk of glucocorticoid excess [14].
• Pretreatment supine plasma norepinephrine (but not plasma renin activity or aldosterone excretion) correlated with blood pressure changes during fludrocortisone dosing, which suggests participation of the sympathetic nervous system in the blood pressure elevations reported during exogenous steroid administration or primary aldosteronism [15].
• Hyperkalemia persisted despite furosemide-induced diuresis in the other two patients, but resolved with fludrocortisone treatment [16].

Biological context of fludrocortisone

• Chronically, this can be accomplished with increased salt and water intake in conjunction with fludrocortisone [17].
• Two subjects with adrenocortical insufficiency, who were followed for 45-60 days during treatment with dexamethasone and 9alpha-fluorocortisol acetate, also showed a transient rise in sodium space and plasma volume [18].
• The patient did not respond to therapeutic doses of mineralocorticoid (fludrocortisone), but treatment with water restriction, increased salt intake, and large doses of mineralocorticoids resulted in a normal serum sodium level and blood pressure [19].
• This hypothesis was tested using explant cultures derived from the GR-/- transplants in which the mineralocorticoid fludrocortisone was able to synergistically induce beta-casein gene expression in the presence of prolactin and insulin [20].
• CONCLUSION--This association of hyperkalemic periodic paralysis with CMO-II deficiency and resolution of paralytic episodes with fludrocortisone therapy suggests a contribution of defective mineralocorticoid-mediated potassium homeostasis to the pathogenesis of hyperkalemic periodic paralysis [21].

Anatomical context of fludrocortisone

• Mineralocorticoid (fludrocortisone or aldosterone), in doses that did not decrease thymus weight, also increased thiazide diuretic receptor density to or above normal [22].
• Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly [23].
• Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha-fluorocortisol by human liver microsomes and cytosol [24].
• The oxidative and reductive biotransformations of 9 alpha-fluorocortisol (fluorocortisol) by human liver microsomes and cytosol have been characterized [24].
• Immediately after discontinuing 9 alpha-fludrocortisone, the adrenal glomerulosa was able to respond to stimulation by the renin-angiotensin system as shown by the ability to achieve renal sodium conservation on a restricted sodium intake (less than 10 mEq/d for 5 d) [25].

Associations of fludrocortisone with other chemical compounds

• Treatment was beta-blockers (8), Na/fludrocortisone (9), both (6), and DDD pacemakers (2) [26].
• We treated these children with daily sc injections of a LHRH analog (LHRHa) for 6-18 months in addition to the standard hydrocortisone and fludrocortisone therapy for CAH [27].
• OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis [28].
• However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses [29].
• Each patient was receiving cortisone acetate, 20.6 to 22.6 mg/m2 body surface area per day, divided into three doses, and 9 alpha-fluorohydrocortisone, 0.05 to 0.1 mg/day [30].

Gene context of fludrocortisone

• MRs and GRs were activated using either MR specific (9 alpha fluorohydrocortisone) or GR specific (dexamethasone) exogenous steroids, respectively [31].
• In rats on low-salt diet, ramipril further increased renin mRNA ninefold, COX-2 mRNA fourfold, and nNOS 2.5-fold in the absence of fludrocortisone [32].
• The crystal structure of a mutant androgen receptor (AR) ligand-binding domain (LBD) in complex with the agonist 9alpha-fluorocortisol has been determined at 1.95 A resolution [33].
• Plasma AVP remained in the normal range after fludrocortisone withdrawal, but was slightly elevated after increasing salt intake without fludrocortisone administration [34].
• All patients with PCAF also received 0.005-0.01 mg/day of 9alpha-fluorocortisol [35].

Analytical, diagnostic and therapeutic context of fludrocortisone

• A double-blind crossover study of fludrocortisone, 0,1 mg. twice daily, and placebo is reported in six diabetics with troublesome symptoms of postural hypotension due to autonomic neuropathy [36].
• Initial treatments with elastic stockings, fludrocortisone acetate, and dihydroergotamine mesylate resulted in no obvious improvement of his orthostasis [37].
• The mineralocorticoid responsiveness of electrogenic Na(+) absorption was evaluated in the two groups by measuring amiloride sensitive electrical potential difference (PD) in the proximal rectum before and 24 hours after oral administration of 1 mg of fludrocortisone [38].
• The mainstay of drug therapy is fludrocortisone acetate, but edema, supine hypertension, and heart failure occur frequently [39].
• DESIGN: A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone [40].

References