Therapies replacement

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

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The compound shown is diethylstilbestrol (DES) it has a number of therapeutic uses in estrogen replacement therapy DES is not a steroid but can adopt a shape that allows it to mimic estrogens such as estradiol (p 1100) and bind to the same receptor sites Construct molecular models of DES and estradiol that illustrate this similanty in molecular size shape and location of polar groups... 

Thyroid-stimulating hormone can be used clinically to test thyroid function but has not found practical apphcation in the treatment of human thyroid insufficiency. Direct replacement therapy with thyroid hormone is easy and effective, owing to a simple molecular stmcture. TSH has been used in the veterinary treatment of hypothyroidism, and preparations of TSH ate produced by Cooper Animal Health, Inc. and Armour Pharmaceuticals. 

Hormonal effects on the aging process have been areas of current interest. The intricacies of the interaction of the various hormones are undoubtedly involved in the aging process and hence these hormones could be called antiaging agents. Both androgens and estrogens have been studied. Low level estrogen replacement therapy (ERT) has been used to treat postmenopausal women. 

Oral mucosal membranes provide a port for systemic therapy as weU. Nitroglycerin sublingual tablets (Nitrostat) abort acute mgina attacks methyl-testosterone [58-18-4] buccal tablets (Android 5) are indicated for testosterone [58-22-0] replacement therapy (39) md nicotine [54-11-5] gum (Nicorette) aids in smoking cessation. 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Although both estrone and estradiol are available for replacement therapy, they suffer the disadvantage of poor activity on oral administration and short duration of action even when administered parenterally, because of ready metabolic disposition. In order to overcome these deficiencies, there was developed a series of esters of estradiol with long-chain fatty acids. These esters are oil-soluble and correspondingly water-insoluble compounds. 

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