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Content Update
December 5, 2019
Istradefylline: an Adenosine A2A Receptor Antagonist to Treat Off Episodes in Parkinson Disease: Istradefylline (Nourianz) is the first adenosine A2A receptor antagonist approved in the U.S. to treat off episodes in Parkinson disease. Adenosine A2A receptors are located in GABAergic (γ-aminobutyric acid) neurons within the indirect pathway of the basal ganglia system. Blocking of A2A receptors (ie, inhibition of the indirect pathway) can result in prolongation of dopaminergic action. In randomized, placebo-controlled trials, istradefylline resulted in statistically significant reductions in daily off time. The most common adverse reaction to istradefylline is dyskinesia followed by dizziness, nausea, hallucinations, and insomnia. The recommended dosage is 20 mg orally once daily with or without food. The dosage may be increased to a maximum of 40 mg once daily.
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CHAPTER SUMMARY FROM THE PHARMACOTHERAPY HANDBOOK
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For the chapter in the Wells Handbook, please go to Chapter 18. Adrenal Gland Disorders.
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KEY CONCEPTS
Glucocorticoid secretion from the adrenal cortex is stimulated by adrenocorticotropic hormone (ACTH) or corticotropin that is released from the anterior pituitary in response to the hypothalamic-mediated release of corticotropin-releasing hormone (CRH).
To ensure the proper treatment of Cushing syndrome, diagnostic procedures should (a) establish the presence of hypercortisolism and (b) discover the underlying etiology of the disease.
The rationale for treating Cushing syndrome is to reduce the morbidity and mortality resulting from disorders such as diabetes mellitus, cardiovascular disease, and electrolyte abnormalities.
The treatment of choice for both ACTH-dependent and ACTH-independent Cushing syndrome is surgery, whereas pharmacologic agents are reserved for adjunctive therapy, refractory cases, or inoperable disease.
Pharmacologic agents that may be used to manage the patient with Cushing syndrome include steroidogenesis inhibitors, adrenolytic agents, neuromodulators of ACTH release, and glucocorticoid-receptor blocking agents.
Spironolactone, a competitive aldosterone-receptor antagonist, is the drug of choice in bilateral adrenal hyperplasia (BAH)–dependent hyperaldosteronism.
Addison disease (primary adrenal insufficiency) is a deficiency in cortisol, aldosterone, and various androgens resulting from the loss of function of all regions of the adrenal cortex.
Secondary adrenal insufficiency usually results from exogenous steroid use, leading to hypothalamic–pituitary–adrenal (HPA)–axis suppression followed by a decrease in ACTH release, and low levels of androgens and cortisol.
Virilism results from the excessive secretion of androgens from the adrenal gland and often manifests as hirsutism in females.
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The adrenal glands were first characterized by Eustachius in 1563. After Addison identified a case of adrenal insufficiency in humans, adrenal anatomy and physiology flourished. Most of the work done in the early and mid-1900s centered on the glucocorticoid cortisol. With the discovery of aldosterone by Simpson and Tait in 1952, adrenal pharmacology turned toward the mineralocorticoid. Conn1 followed with his classical description of primary aldosteronism (PA) in 1955, and numerous clinicians and investigators have continued to explore the variety of disease processes promoted through the adrenal gland.
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PHYSIOLOGY, ANATOMY, ...