Fludrocortisone

Sample preparation Condition a 3 mL 500 mg Sep-Pak Vac CIS SPE cartridge with 3 mL MeOH and 3 mL water. Mix 500 p-L 200 mM pH 3.85 acetate buffer with 1 mL serum, add 400 p.L 2.5 p,M IS in mobile phase, centrifuge, add to the SPE cartridge, wash with 3 mL acetone water 20 80, wash with 3 mL water, wash with 3 mL hexane, elute with 3 mL diethyl ether. Vortex the eluate with 1 mL 200 mM NaOH, centrifuge. Evaporate the organic layer to dryness under a stream of nitrogen, reconstitute the residue with 250 (J.L mobile phase, place on a rotary mixer for 5 min, inject a 60 xL aliquot. (Fludrocortisone is IS. Extraction from serum has not been strictly demonstrated.) 

Mobile phase MeOH THF water 3 25 72 Flow rate 1 Injection volume 60 Detector UV 254 

McWhinney, B.C. Ward, G. Hickman, P.E. Improved HPLC method for simultaneous analysis of cortisol, 11-deoxycortisol, prednisolone, methylprednisolone, and dexamethasone in serum and urine, Clin.Chem., 1996, 42, 979-981. 

Sample preparation Condition a 3 ml. 200 mg Clean-Up C18 SPE cartridge (Worldwide Monitoring) with two 2 mL portions of MeOH and two 2 mL portions of water. Centrifuge plasma at 2000 rpm for 5 min prior to analysis. Mix 2 mL plasma with 40 aL MeCN, add 1 mL water, vortex until homogeneous, add to the SPE cartridge, wash with two 2 mL portions of acetone water 20 80, wash with 1 mL 50 mM pH 2.7 phosphate buffer, place under vacuum for 3 min, elute with two 2.5 mL portions of ethyl acetate. Evaporate the eluate to dr5mess under reduced pressure at 40°, reconstitute the residue with 75 jlL mobile phase B, vortex, add 100 aL 50 mM pH 3 phosphate buffer, centrifuge at 5000 rpm for 5 min, inject a 145 aL aliquot. 

Mobile phase Gradient. A B 20 80 for 1 min, to 50 50 over 7 min, to 65 35 over 3 min, to 100 0 (step gradient), maintain at 100 0 for 1 min, return to initial conditions, reequilibrate for 4 min. A was MeCN 50mM pH 3.0 potassium dihydrogen phosphate buffer 50 50. B was MeOH 50 mM pH 3.0 potassium dihydrogen phosphate buffer 20 80. Flow rate 0.3 Injection volume 145 Detector UV 246 

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Amphotericin B. Amphotericin B (3), an important polyene antibiotic, is administered almost exclusively via the intravenous route and is therefore discussed in more detail under the systemic antimycotics. The vaginal tablets contain 50 mg amphotericin B, and 100 mg tetracycline base per tablet (see also Antibiotics, tetracyclines). The tablets for oral use contain 50 mg amphotericin B, 250 mg tetracycline base, and 125 mg sodium hexametaphosphate. A combination ointment contains 1 mg fludrocortisone acetate, 2.5 mg neomycin, 0.25 mg gramicidin, and 1 g plastibase in addition to 30 mg amphotericin B (see also Antibiotics, peptides). 

The main mineralocorticoid agonist in humans is aldosterone. Additionally, cortisol, corticosterone, and DOC have also mineralocorticoid agonistic activity. The synthetic steroid fludrocortisone (9a-fluorocorti-sol) is extremely potent and usually chosen for replacement mineralocorticoid therapy. In contrast, aldosterone and DOC are not useful in oral therapy due to rapid degradation in liver after absorption. 

Hypoaldosteronism is defined as a deficiency of aldosterone. Renal secretion of potassium is decreased, causing hyperkalaemia. The treatment is replacement of a mineralocorticoid, e.g. fludrocortisone. 

The antidiuretic effects of vasopressin may be decreased when die agent is taken witii die following drugs lithium, heparin, norepinephrine, or alcohol. Antidiuretic effect may be increased when die drug is used witii carbamazepine, clofibrate, or fludrocortisone... 

Fludrocortisone (Florinef) is a drug that has both glucocorticoid and mineralocorticoid activity and is the only currently available mineralocorticoid drug. 

Fludrocortisone is used for replacement therapy for primary and secondary adrenocortical deficiency. Even though this drug lias both mineralocorticoid and glucocorticoid activity, it is used only for its mineralocorticoid effects. 

Fludrocortisone is contraindicated in patients with hypersensitivity to fludrocortisone and those with systemic fungal infections. Fludrocortisone is used cautiously in patients with Addison s disease infection, and during pregnancy (Pregnancy Category C) and lactation. Fludrocortisone decreases the effects of the barbiturates, hydantoins, and rifampin. There is a decrease in serum levels of the salicylates when those agents are administered with fludrocortisone... 

When administering fludrocortisone, the nurse monitors the patient s blood pressure at frequent intervals. Hypotension may indicate insufficient dosage. The nurse weighs the patient daily and assesses for edema, particularly swelling of the feet and hands. The lungs are auscultated for adventitious sounds (eg, rales/crackles). 

Daily oral doses are generally given before 9 00 am to minimize adrenal suppression and to coincide with normal adrenal function. However, alternate-day therapy may be prescribed for patients receiving long-term therapy (see below). Fludrocortisone is given orally and is well tolerated in the GI tract. 

Some clinicians would add fludrocortisone 50 meg enterally daily to hydrocortisone pharmacotherapy... 

Monitor electrocardiogram continuously in patients with cardiac abnormalities until serum potassium levels drop below 5 mEq/L (5 mmol/L) or cardiac abnormalities resolve. Evaluate serum potassium and glucose levels within 1 hour in patients who receive insulin and dextrose therapy. Evaluate serum potassium levels within 2 to 4 hours after treatment with SPS or diuretics. Repeat doses of diuretics or SPS if necessary until serum potassium levels fall below 5 mEq/L (5 mmol/L). Monitor blood pressure and serum potassium levels in 1 week in patients who receive fludrocortisone. 

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