CORTICOTROPIN (ACTH)

Chemistry - A 39 amino acid polypeptide, corticotropin is secreted from the anterior pituitary. Thefirst 24 amino acids (from the N-terminal end of the chain) define its biologic activity. Whilehuman, sheep, cattle and swine corticotropin have different structures, the first 24 amino acids arethe same and, therefore, biologic activity is thought to be identical. Commercial sources of ACTHgenerally are obtained from porcine pituitaries. One USP unit of corticotropin is equivalent to 1 mgof the international standard.
Corticotropin is available commercially as corticotropin for injection, repository corticotropin forinjection, and corticotropin zinc hydroxide suspension. Corticotropin is commonly called ACTH(abbreviated from adrenocorticotropic hormone). Repository corticotropin is often called ACTH geland is the most commonly used ACTH product in veterinary medicine.

Storage, Stability, Compatibility

Corticotropin for injection (aqueous) can be stored at roomtemperature (15-30°C) before reconstitution. After reconstitution, it should be refrigerated and usedwithin 24 hours. Repository corticotropin injection should be stored in the refrigerator (2-8°C). Toallow ease in withdrawing the gel into a syringe, the vial may be warmed with warm water prior touse.

Pharmacology - CORTICOTROPIN (ACTH)

ACTH stimulates the adrenal cortex (principally the zona fasiculata) to stimulatethe production and release of glucocorticoids (primarily cortisol in mammals and corticosterone inbirds). ACTH release is controlled by corticotropin-releasing factor (CRF) activated in the centralnervous system and via a negative feedback pathway, whereby either endogenous or exogenousglucocorticoids suppresses ACTH release.Uses, Indications - In veterinary medicine, an ACTH product (Adrenomone®¯Summit Hill) isapproved for use in dogs, cats, and beef or dairy cat le for stimulation of the adrenal cortex whenthere is a deficiency of ACTH, and as a therapeutic agent in primary bovine ketosis. In practicehowever, 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 stimulatingproperties, but as it must be injected, it is not commonly employed.

Pharmacokinetics - CORTICOTROPIN (ACTH)

Because it is rapidly degraded by proteolytic enzymes in the gut, ACTHcannot 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. Theelimination half-life of circulating ACTH is about 15 minutes, but because of the slow absorptionafter IM injection of the gel, effects may persist up to 24 hours.
Contraindications/Precautions - When used for diagnostic purposes, it is unlikely that increasesin serum cortisol levels induced by ACTH will have significant deleterious effects on conditionswhere 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 porcineproteins.
ACTH should only be used during pregnancy when the potential benefits outweigh the risks. Itmay be embryocidal. Neonates born from mothers receiving ACTH should be observed for signsof adrenocortical insufficiency.

Adverse Effects, Warnings

Prolonged use may result in fluid and electrolyte disturbances andother adverse effects. If using on a chronic basis, refer to the human literature for an extensivelisting of potential adverse reactions. The veterinary manufacturer suggests giving potassiumsupplementation with chronic therapy.
Do not administer the repository form (gel) IV.
Overdosage - When used for diagnostic purposes, acute inadvertent overdoses are unlikely tocause 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.