Mechanism of action and pharmacokinetics
Natural corticotropin is a 39-amino-acid polypeptide obtained from the pituitary gland of cattle. The drug is administered parenterally (primarily intramuscularly), and the duration of its effect ranges from 6 to 8 hours.
The pharmacological action is based on the following algorithm:
- The drug binds to specific receptors in the adrenal cortex.
- Synthesis of own (endogenous) glucocorticoids is stimulated.
The main drawback of the natural substance is its protein origin, which can lead to the formation of antibodies during therapeutic use.
Synthetic analogue: tetracosactide
To reduce the risk of immune reactions, tetracosactide (Tetracosactidum) was created — a synthetic polypeptide analogue of ACTH. It consists of 24 amino acids and completely replicates the N-terminal fragment of the native hormone, retaining all its biological properties.
Comparison of natural and synthetic preparations:
| Parameter | Corticotropin (Corticotropinum) | Tetracosactide (Tetracosactidum) |
|---|---|---|
| Origin | Natural (bovine pituitary) | Synthetic polypeptide |
| Molecular structure | 39 amino acid residues | 24 amino acid residues |
| Duration of effect | 6–8 hours | Longer (up to once daily) |
| Safety | Antibodies are formed | Less prone to causing allergic reactions |
Indications and dosing regimen
The main indication for the use of natural corticotropin and tetracosactide is the prevention and treatment of secondary drug-induced adrenal cortical atrophy (relieving "withdrawal syndrome") occurring against the background of long-term glucocorticoid therapy.
Additional indications for tetracosactide as part of combination therapy:
- Collagenoses;
- Bronchial asthma;
- Dermatoses;
- Ulcerative colitis.
Important rule of administration: therapy with ACTH preparations is carried out strictly in courses. Prolonged continuous administration is prohibited, as it leads to adrenal cortex depletion.
Side effects and contraindications
Side effects are due to excessive stimulation of the adrenal cortex and high levels of endogenous glucocorticoids and mineralocorticoids.
Main adverse effects:
- Vascular and water-electrolyte: fluid retention (edema), arterial hypertension.
- Metabolic: hyperglycemia, increased protein catabolism.
- Immunological: antibody production and allergic reactions (characteristic of natural ACTH).
Contraindications:
- Diabetes mellitus (due to diabetogenic effect);
- Peptic ulcer of the stomach and duodenum (risk of perforation and bleeding);
- Heart failure (risk of worsening edema due to water retention);
- Severe forms of arterial hypertension.
Briefly: answers to topical questions
Which specific adrenal cortex receptors does corticotropin bind to?
Corticotropin binds to specific G-protein-coupled membrane receptors located on the plasma membrane of adrenal cortex cells. The interaction of the hormone with these receptors leads to the activation of the adenylate cyclase system. As a result of this process, ATP molecules are converted into a secondary messenger — cyclic adenosine monophosphate (cAMP). Subsequent accumulation of cAMP triggers a cascade of intracellular reactions that activate steroidogenesis enzymes and stimulate the hydrolysis of cholesterol esters in lipid droplets.
The synthesis of which adrenal cortex hormones is stimulated by ACTH?
Adrenocorticotropic hormone stimulates the synthesis of corticosteroids in various zones of the adrenal cortex. The main action is directed at the production of glucocorticoids, but the hormone also affects the production of other steroids.
ACTH stimulates the synthesis of the following hormones:
- Glucocorticoids — synthesized by the cells of the zona fasciculata (main representative is cortisol).
- Mineralocorticoids — synthesized by the cells of the zona glomerulosa (main representative is aldosterone).
- Androgens — synthesized by the cells of the zona reticularis (include dehydroepiandrosterone, androstenedione, and testosterone).
Synthetic Tetracosactide consists of 24 amino acids and is administered once a day, eliminating the risk of antibody formation.
Class and exam questions
Why is tetracosactide preferred over natural corticotropin?
Natural corticotropin is obtained from the pituitary gland of cattle, which is why it is immunogenic and causes antibody formation. Synthetic tetracosactide consists of 24 amino acids, causes allergic reactions much less frequently, and has a longer duration of action.
Why are ACTH stimulants prescribed after long-term glucocorticoid therapy?
Long-term intake of exogenous glucocorticoids suppresses adrenal function. ACTH preparations stimulate the production of own hormones, preventing and eliminating secondary drug-induced adrenal cortical atrophy ("withdrawal syndrome").
Why is treatment with tetracosactide administered only in courses?
Prolonged uncontrolled administration of ACTH stimulants leads to the exhaustion of the functional reserves of the adrenal cortex, which is why a course-based regimen is mandatory.
In which diseases is corticotropin contraindicated?
The drug is contraindicated in diabetes mellitus, peptic ulcer of the stomach and duodenum, severe arterial hypertension, and heart failure.
What else to study on this topic
- Structural differences: 39 amino acids of natural ACTH vs. 24 amino acids of tetracosactide
- Mechanism of hyperglycemia and protein catabolism development upon adrenal cortex stimulation
- Use of tetracosactide in the treatment of bronchial asthma, collagenoses, and ulcerative colitis
- Risks of gastrointestinal complications (perforation and bleeding) during glucocorticoid hypersecretion
- Pathophysiology of adrenal cortex exhaustion during continuous ACTH administration
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