Hydrocortisone is the name for the hormone

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

when supplied as a medication. It is a

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

and works as an anti-inflammatory and by immune suppression. Uses include conditions such as adrenocortical insufficiency,

adrenogenital syndrome Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...

, high blood calcium, thyroiditis,

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

dermatitis Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

, and COPD. It is the treatment of choice for adrenocortical insufficiency. It can be given

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, topically, rectally or by injection. Stopping treatment after long-term use should be done slowly. Common side effects may include mood changes, increased appetite, hyperglycemia,

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, and edema (swelling). With long-term use, common side effects include

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...

, adrenal insufficiency, upset stomach, physical weakness, easy bruising, and candidiasis (yeast infections). It is unclear if it is safe for use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. Hydrocortisone was patented in 1936 and approved for medical use in 1941. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2022, it was the 202nd most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses

Hydrocortisone is the pharmaceutical term for cortisol used in

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of

prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...

in patients needing steroid treatment but unable to take oral medication, and perioperatively in patients on long-term steroid treatment to prevent an adrenal crisis. It may also be injected into inflamed joints resulting from diseases such as

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...

. It may be used topically for allergic rashes,

eczema Dermatitis is a term used for different types of skin inflammation, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened ...

, psoriasis, itching, and other inflammatory skin conditions. Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only. It may also be used rectally in suppositories to relieve the swelling, itch, and irritation in hemorrhoids. It may be used as an acetate form ( hydrocortisone acetate), which has slightly different pharmacokinetics and pharmacodynamics. File:Cortisol for injection.jpg, Cortisol for injection File:Tube of hydrocortisone cream.jpg, A tube of hydrocortisone cream, purchased over-the-counter File:Hydrocortisone Cortef 10 mg Кортеф Гидрокортизон.jpg, Hydrocortisone 10 mg oral tablets (depicted a package for Russian market)

Pharmacology

Pharmacodynamics

Hydrocortisone is a

, acting specifically as both a

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

and as a mineralocorticoid. That is, it is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

and mineralocorticoid receptors. Hydrocortisone has low potency relative to synthetic corticosteroids. Compared to hydrocortisone,

is about 4times as potent and dexamethasone about 40times as potent in terms of anti-inflammatory effect. Prednisolone can also be used as cortisol replacement, and at replacement dose levels (rather than anti-inflammatory levels), prednisolone is about 8times more potent than cortisol. The equivalent doses and relative potencies of hydrocortisone compared to various other synthetic corticosteroids have also been reviewed and summarized. The endogenous production rate of cortisol is approximately 5.7 to 9.9mg/m² per day, which corresponds to an oral hydrocortisone dose of approximately 15 to 20mg/day (for a 70-kg person). One review described daily cortisol production of 10mg in healthy volunteers and reported that daily cortisol production could increase up to 400mg in conditions of severe stress (e.g.,

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

). The total and/or free concentrations of cortisol/hydrocortisone required for various glucocorticoid effects have been determined.

Pharmacokinetics

Absorption

The bioavailability of oral hydrocortisone is about 96% ± 20% ( SD). The pharmacokinetics of hydrocortisone are non-linear. The peak level of oral hydrocortisone is 15.3 ± 2.9 (SD) μg/L per 1mg dose. The time to peak concentrations of oral hydrocortisone is 1.2 ± 0.4 (SD) hours. The topical percutaneous absorption of hydrocortisone varies widely depending on experimental circumstances and has been reported to range from 0.5 to 14.9% in different studies. Some skin application sites, like the scrotum and

vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...

, absorb hydrocortisone much more efficiently than other application sites, like the forearm. In one study, the amount of hydrocortisone absorbed ranged from 0.2% to 36.2% depending on the application site, with the ball of the foot having the lowest absorption and the scrotum having the highest absorption. The absorption of hydrocortisone by the vulva has ranged from 4.4 to 8.1%, relative to 1.3 to 2.8% for the arm, in different studies and subjects.

Distribution

Most cortisol in the blood (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and

serum albumin Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chem ...

. A pharmacokinetic review stated that 92% ± 2% (SD) (92–93%) of hydrocortisone is plasma protein-bound. Free cortisol passes easily through cellular membranes. Inside cells it interacts with corticosteroid receptors.

Metabolism

Hydrocortisone is metabolized by 11β-hydroxysteroid dehydrogenases (11β-HSDs) into

cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase ...

, an inactive

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

. It is additionally 5α-, 5β-, and 3α-reduced into dihydrocortisols, dihydrocortisones, tetrahydrocortisols, and tetrahydrocortisones.

Elimination

The elimination half-life of hydrocortisone ranges from about 1.2 to 2.0 (SD) hours, with an average of around 1.5hours, regardless of oral versus parenteral administration. The duration of action of systemic hydrocortisone has been listed as 8 to 12hours.

Chemistry

Hydrocortisone, also known as 11β,17α,21-trihydroxypregn-4-ene-3,20-dione, is a

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

pregnane

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. A variety of hydrocortisone esters exist and have been marketed for medical use.

Society and culture

Legal status

In March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Efmody, intended for the treatment of congenital adrenal hyperplasia (CAH) in people aged twelve years and older. The applicant for this medicinal product is Diurnal Europe BV. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Hydrocortisone (Efmody) was approved for medical use in the European Union, in May 2021, for the treatment of

congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...

(CAH) in people aged twelve years and older. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Anti-competitive practices

In the UK, the Competition and Markets Authority (CMA) concluded an investigation into the supply of hydrocortisone tablets, finding that from October 2008 onwards, drug suppliers Auden McKenzie and Actavis plc had charged "excessive and unfair prices" for 10mg and 20mg tablets and entered into agreements with potential competitors, paying companies who agreed not to enter the hydrocortisone market and enabling Auden McKenzie and Actavis to supply the drugs as " generic" rather than branded products and thereby escape price controls until eventually other companies entered the market. Auden and Actavis overcharged the UK's

National Health Service The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...

for over ten years. Fines totalling over £255m were levied against the companies involved in this breach of

competition law Competition law is the field of law that promotes or seeks to maintain market competition by regulating anti-competitive conduct by companies. Competition law is implemented through public and private enforcement. It is also known as antitrust ...

Research

Chronic fatigue syndrome

Cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

levels have been found to be altered in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Hydrocortisone has been clinically studied in the treatment of ME/CFS. A 2016

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

found that it had been assessed for this purpose in six clinical studies. Its clinical effectiveness was conflicting in the studies, ranging from not effective, to slightly or mildly effective, to moderately effective. Four of the studies came from one research group. The systematic review called for higher-quality trials. A 2015 systematic review found that the clinical data on hydrocortisone for ME/CFS was inconclusive.

COVID-19

Hydrocortisone was found to be effective in reducing mortality rate of critically ill

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...

patients when compared to other usual care or a placebo.

References

{{Authority control Alcohols Antipruritics CYP3A4 inducers Glucocorticoids Ketones Mineralocorticoids Orphan drugs Pregnanes World Health Organization essential medicines Wikipedia medicine articles ready to translate