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Glossary of Drugs Related to ACTH and Glucocorticoid

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Cortrophin
- pig ACTH
- must administer iv or im
- half life: 15 mins
- can increase skin pigmentation and lipolysis in the absence of glucocorticoids
- repository injection: gelatin or zinc hydroxide complexes; slow absorption; longer acting; painful swelling at the site of injection (zinc hydroxide>gelatin)
Cosyntrophin
- synthetic human ACTH
- 1-24 aa only, reduces immunogenesis
- half life: 15 mins
- can increase skin pigmentation and lipolysis in the absence of glucocorticoids
- repository injection: gelatin or zinc hydroxide complexes; slow absorption; longer acting; painful swelling at the site of injection (zinc hydroxide>gelatin)
- contraindication: sensitivity to pig ACTH
Chronic Glucocorticoids Replacement
- oral cortisol (5-10 mg t.i.d., more when stress)
- mineralocorticoids (deoxycorticosterone, fludrocortisone)
Acute (Addisonian) Crisis
- cortisol (100 mg q.i.d. until patient is stable)
- iv fluid and NaCl
- glucose
Cortricorelin
- ovine CRH
- used to test for pituary vs. ectopic source of ACTH
Dexamethasone
- a synthetic glucocorticoids
- use for supression test, to document hypersecretion
Metyrapone
- a cortisol synthesis antagonist
- inhibits 11beta-hydroxylase (final enzyme in cortisol synthesis)
- administered orally
- used for diagnosis of HPA axix function and to treat Cushing's syndrome
- adverse effect: dizziness, GI disturbance, with chronic use: elevated mineralocorticoids and androgens
Mitotane
- general adrenocorticoid antagonist
- o,p-DDD (isomer of DDT)
- selective toxicity for adrenal cortex
- MOA not understood; cause mitochondrial degeneration
- sometimes used as anti-tumor agent for adrenal carcinoma
- need life-long glucocorticoid and mineralocorticoid after use
- adverse effects: GI disturbance, CNS depression, skin rashes
Aminoglutethimide
- general steroidogenesis antagonist
- inhibits P450scc
- used to: reduce gonadal hormone in breast cancer patient, reduce adrenal cortical hormones in adrenal carcinoma
- must add cortisone to block ACTH eleveation
Ketoconazole
- widely used steroidogenesis antagonist
- antifungal agent
- at higher dose, inhibit glucocorticoid synthesis
- block P450scc and other enzymes
- used to treat: Cushing's syndrome
Trilostane
- steroid hormone antagonist
- reversible inhibitor of 3beta-HSD
- block cortisol and aldesterone synthesis
- used when a more definitive treatment is not available

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