Veterinary Medicine - February 2008 - (Page 110) Hyperadrenocorticism and trilostane tion may protect patients from these debilitating problems. When selecting a treatment for hyperadrenocorticism, consider likely ef cacy, the cost of care (including monitoring), and the risk of adverse events. In general, both ketoconazole and selegiline demonstrate low ef cacy and are not widely regarded as appropriate rst-line therapies. Choosing between mitotane and trilostane requires careful thought; complications can occur with both drugs, and regular patient evaluations will be necessary. In experienced hands, mitotane is often successful, but its variable intestinal absorption, long half-life, and cytotoxic effects can be problematic. Deciding when to switch from induction to maintenance therapy with mitotane can be dif cult, and clients must promptly identify changes in thirst and appetite to prevent overdose. In contrast, trilostane has more predictable pharmacokinetics and is not directly cytotoxic. Daily medication costs may be higher with trilostane, but monitoring expenses may be lower. TRILOSTANE Trilostane (4-alpha, 5-alpha-epoxy17-beta-hydroxy-3-oxoandrostane2-alpha-carbonitrile) is a synthetic steroid analogue. It is a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase, an enzyme that catalyses several crucial steps in the synthesis of cortisol from cholesterol (Figure 1).6 When therapeutic concentrations of trilostane are present, cortisol synthesis is dramatically reduced. Although 3-beta-hydroxysteroid dehydrogenase is also required for the synthesis of aldosterone, production of this mineralocorticoid is generally spared at standard therapeutic doses.7 It is thought that the zona glomerulosa (the site of aldosterone production) may be less sensitive to trilostane or that cellular uptake by this region of the adrenal cortex is different. Trilostane was previously licensed for use in the United States for people with adrenal disorders but was volun- 110 VETERINARY MEDICINE
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