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Chemistry – A 39 amino acid polypeptide, corticotropin is secreted from the anterior pituitary. The first 24 amino acids (from the N-terminal end of the chain) define its biologic activity. While human, sheep, cattle and swine corticotropin have different structures, the first 24 amino acids are the same and, therefore, biologic activity is thought to be identical. Commercial sources of ACTH generally are obtained from porcine pituitaries. One USP unit of corticotropin is equivalent to 1 mg of the international standard.
Corticotropin is available commercially as corticotropin for injection, repository corticotropin for injection, and corticotropin zinc hydroxide suspension. Corticotropin is commonly called ACTH (abbreviated from adrenocorticotropic hormone ). Repository corticotropin is often called ACTH gel and is the most commonly used ACTH product in veterinary medicine.
Storage/Stability/Compatibility – Corticotropin for injection (aqueous) can be stored at room temperature (15-30°C) before reconstitution. After reconstitution, it should be refrigerated and used within 24 hours. Repository corticotropin injection should be stored in the refrigerator (2-8°C). To allow ease in withdrawing the gel into a syringe, the vial may be warmed with warm water prior to use.
Pharmacology – ACTH stimulates the adrenal cortex (principally the zona fasiculata) to stimulate the production and release of glucocorticoids (primarily cortisol in mammals and corticosterone in birds). ACTH release is controlled by corticotropin-releasing factor (CRF) activated in the central nervous system and via a negative feedback pathway, whereby either endogenous or exogenous glucocorticoids suppresses ACTH release.
Uses/Indications – In veterinary medicine, an ACTH product (Adrenomone®—Summit Hill) is approved for use in dogs, cats, and beef or dairy cattle for stimulation of the adrenal cortex when there is a deficiency of ACTH, and as a therapeutic agent in primary bovine ketosis. In practice however, it tends to be used most often in the diagnosis of hyper- or hypoadrenocorticism (ACTH-stimulation test) and to monitor the response to mitotane therapy in Cushing’s syndrome.
ACTH has been used for several purposes in human medicine for its corticosteroid stimulating properties, but as it must be injected, it is not commonly employed.
Pharmacokinetics – Because it is rapidly degraded by proteolytic enzymes in the gut, ACTH cannot be administered PO. It is not effective if administered topically to the skin or eye. After IM injection in humans, repository corticotropin injection is absorbed over 8-16 hours. The elimination half-life of circulating ACTH is about 15 minutes, but because of the slow absorption after IM injection of the gel, effects may persist up to 24 hours.
Contraindications/Precautions – When used for diagnostic purposes, it is unlikely that increases in serum cortisol levels induced by ACTH will have significant deleterious effects on conditions where increased cortisol levels are contraindicated (e.g., systemic fungal infections, osteoporosis, peptic ulcer disease, etc.). ACTH gel should not be used in patients hypersensitive to porcine proteins.
ACTH should only be used during pregnancy when the potential benefits outweigh the risks. It may be embryocidal. Neonates born from mothers receiving ACTH should be observed for signs of adrenocortical insufficiency.
Adverse Effects/Warnings – Prolonged use may result in fluid and electrolyte disturbances and other adverse effects. If using on a chronic basis, refer to the human literature for an extensive listing of potential adverse reactions. The veterinary manufacturer suggests giving potassium supplementation with chronic therapy. Do not administer the repository form (gel) IV.
Overdosage – When used for diagnostic purposes, acute inadvertent overdoses are unlikely to cause any significant adverse effects. Monitor as required and treat symptomatically if necessary.
Drug Interactions – Glucocorticoids may alter the insulin requirements of diabetics. When used chronically, there are several potential interactions with ACTH including barbiturates, phenytoin, rifampin, cyclophosphamide, estrogens, ulcerogenic drugs (e.g., ASA, NSAIDs), potassium-depleting diuretics/drugs (e.g., amphotericin B) and oral anticoagulants. If the drug is to be used for purposes other than diagnostic purposes and the animal is receiving or will receive one of drugs listed above, refer to an appropriate reference (see bibliography) for further information.
Drug/Laboratory Interactions – ACTH may decrease 131I uptake by the thyroid gland. ACTH may suppress skin test reactions and interfere with urinary estrogen determinations.
Doses – Obtain specific information from the laboratory on sample handling and laboratory normals for cortisol when doing ACTH stimulation tests. ACTH is quite unstable in unfrozen plasma.
ACTH Stimulation Test:
a) Draw baseline blood sample for cortisol determination and administer 1 Unit/kg IM of ACTH gel. Draw second sample 8 hours later. Normal stimulation will result in serum cortisol levels will increase 2-3 times. Horses with pituitary tumors will increase cortisol fourfold after ACTH. (Beech 1987b)
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Corticotropin, Repository for Injection; 40 Units/ml and 80 Units/ml in 5 ml an d10 ml vials; ACTH Gel (Anthony); Adrenomone® (Summit Hill) (Rx) Approved for use in dogs, cats, and beef or dairy cattle.
Corticotropin Powder for Injection; 25 Units per vial, and 40 Units per vial
Acthar® (Rorer) (Rx) ACTH ® (Parke-Davis); (Rx); generic (Rx)
Corticotropin, Repository for Injection; 40 Units/ml and 80 Units/ml in 1 ml and 5 ml vials
H.P. Acthar® Gel (Rorer) (Rx), ACTH-80® (Various); (Rx)