Corticosteroid - AbsoluteAstronomy.com

Corticosteroids are a class of steroid hormone

Steroid hormone

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...

s that are produced in the adrenal cortex

Adrenal cortex

Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...

. Corticosteroids are involved in a wide range of physiologic

Physiology

Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

systems such as stress response

Stress (medicine)

Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

, immune response

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

and regulation of inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, carbohydrate

Carbohydrate

A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

, protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

catabolism

Catabolism

Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...

, blood electrolyte

Electrolyte

In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

levels, and behavior.

Glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

s such as cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

release, decreasing eosinophil
Eosinophil granulocyte
Eosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...

action and a number of other mechanisms.
Mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...

s such as aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

control electrolyte and water levels, mainly by promoting sodium retention in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

.

Some common natural hormones are corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

(C₂₁H₃₀O₄), cortisone
Cortisone
Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

(C₂₁H₂₈O₅, 17-hydroxy-11-dehydrocorticosterone) and aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

.

Biosynthesis

The corticosteroids are synthesized from cholesterol

Cholesterol

Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

within the adrenal cortex

Adrenal cortex

. Most steroidogenic reactions are catalysed by enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s of the cytochrome

Cytochrome

Cytochromes are, in general, membrane-bound hemoproteins that contain heme groups and carry out electron transport.They are found either as monomeric proteins or as subunits of bigger enzymatic complexes that catalyze redox reactions....

P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).

Aldosterone

Aldosterone

Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

and corticosterone

Corticosterone

Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

share the first part of their biosynthetic pathway. The last part is mediated either by the aldosterone synthase

Aldosterone synthase

Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone....

(for aldosterone

Aldosterone

) or by the 11β-hydroxylase (for corticosterone

Corticosterone

). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions), but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa

Zona glomerulosa

The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...

at the outer edge of the adrenal cortex

Adrenal cortex

; 11β-hydroxylase is found in the zona fasciculata

Zona fasciculata

The zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles"....

and zona glomerulosa

Zona glomerulosa

The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...

By chemical structure

In general, corticosteroids are grouped into four classes, based on chemical structure. Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. This is known as the "Coopman classification", after S. Coopman, who defined this classification in 1989.

The highlighted steroids are often used in the screening of allergies to topical steroids.

Group A - Hydrocortisone Type

Hydrocortisone

Cortisol

Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

, hydrocortisone acetate

Cortisol

, cortisone acetate

Glucocorticoid

Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

, tixocortol pivalate
Tixocortol pivalate
Tixocortol pivalate is a corticosteroid. It is has anti-inflammatory properties similar to hydrocortisone. It is marketed under the brand name Pivalone.It is sometimes used in patch testing in atopic dermatitis....

, prednisolone

Prednisolone

Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

, methylprednisolone

Methylprednisolone

Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....

, and prednisone

Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

(Short- to medium-acting glucocorticoids).

Group B - Acetonides

Triamcinolone acetonide

Triamcinolone acetonide is a synthetic corticosteroid used to treat various skin conditions and to relieve the discomfort of mouth sores. It is a more potent type of triamcinolone, being about 8 times as effective as prednisone.-Medical use:...

, triamcinolone alcohol, mometasone, amcinonide

Amcinonide

Amcinonide is a topical glucocorticoid steroid used to treat itching, redness and swelling associated with several dermatologic conditions such as atopic dermatitis and allergic contact dermatitis.See also fluocinonide....

, budesonide
Budesonide
Budesonide is a glucocorticoid steroid for the treatment of asthma and non-infectious rhinitis , and for treatment and prevention of nasal polyposis...

, desonide

Desonide

Desonide is the generic name of a low potency topical corticosteroid that has been available since the 1970s. It is primarily used to treat atopic dermatitis , seborrheic dermatitis, psoriasis and contact dermatitis in both adults and children. It has a fairly good safety profile and is available...

, fluocinonide

Fluocinonide

Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema and seborrhoeic dermatitis...

, fluocinolone acetonide

Fluocinolone acetonide

Fluocinolone acetonide is a corticosteroid primarily used in dermatology to reduce skin inflammation and relieve itching. It is a synthetic hydrocortisone derivative. The fluorine substitution at position 9 in the steroid nucleus greatly enhances its activity. A typical dosage strength used in...

, and halcinonide

Halcinonide

Halcinonide is a corticosteroid. It is used topically in the treatment of certain skin conditions....

Group C - Betamethasone Type

Betamethasone
Betamethasone
Betamethasone is a potent glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. Unlike other drugs with these effects, betamethasone does not cause water retention. It is applied as a topical cream, ointment, foam, lotion or gel to treat itching...

, betamethasone sodium phosphate, dexamethasone

Dexamethasone

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

, dexamethasone sodium phosphate, and fluocortolone

Fluocortolone

Fluocortolone is a glucocorticoid used in the treatment of several conditions, including hemorrhoids.It is similar to fluocortin, but with one less keto group....

Group D₁ - Halogenated (Less Labile)

hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate

Betamethasone dipropionate

Betamethasone dipropionate is a glucocorticoid steroid with anti-inflammatory and immunosuppressive abilities. It is applied as a topical cream, ointment, lotion or gel to treat itching and other minor skin conditions such as eczema....

, prednicarbate

Prednicarbate

Prednicarbate is a relatively new topical corticosteroid drug. It is similar in potency to hydrocortisone. Compared to other topical corticosteroids, like betamethasone, repeated prednicarbate use does not cause skin atrophy as quickly...

, clobetasone-17-butyrate

Clobetasone

Clobetasone is a corticosteroid used in dermatology, for treating such skin inflammation as seen in eczema and other forms of dermatitis, and ophthalmology....

, clobetasol-17-propionate

Clobetasol propionate

Clobetasol propionate is a corticosteroid used to treat various skin disorders including eczema and psoriasis. It is also highly effective for contact dermatitis caused by exposure to poison ivy/oak. Clobetasol belongs to US Class I of the corticosteroids, making it one of the most potent...

, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate

Fluprednidene acetate

Fluprednidene acetate is a corticosteroid....

Group D₂ - Labile Prodrug Esters

Hydrocortisone-17-butyrate
Hydrocortisone-17-butyrate
Hydrocortisone-17-butyrate is a form of hydrocortisone butyrate....

, 17-aceponate, 17-buteprate, and Prednicarbate.

Topical steroids

For use topically on the skin, eye, and mucous membrane

Mucous membrane

The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

s.

Topical corticosteroids are divided in potency classes I to IV, with the additional complication that in Europe class IV is the most potent, while in the US this is called Class I.

Inhaled steroids

for use to treat the nasal mucosa, sinuses, bronchii, and lungs.
This group includes:

Flunisolide
Flunisolide
Flunisolide is a corticosteroid often prescribed as treatment for allergic rhinitis....
Fluticasone propionate
Fluticasone propionate
Fluticasone propionate is a synthetic corticosteroid derived from fluticasone used to treat asthma and allergic rhinitis . It is also used to treat eosinophilic esophagitis....
Triamcinolone acetonide
Triamcinolone acetonide
Triamcinolone acetonide is a synthetic corticosteroid used to treat various skin conditions and to relieve the discomfort of mouth sores. It is a more potent type of triamcinolone, being about 8 times as effective as prednisone.-Medical use:...
Beclomethasone dipropionate
Budesonide
Budesonide
Budesonide is a glucocorticoid steroid for the treatment of asthma and non-infectious rhinitis , and for treatment and prevention of nasal polyposis...

There is also a combination preparation (trade name Advair), containing fluticasone propionate and
salmeterol xinafoate (a long-acting bronchodilator). It is approved for children over 12 years old.

Uses of corticosteroids

Synthetic pharmaceutical drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumor

Brain tumor

A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal...

s to skin diseases. Dexamethasone

Dexamethasone

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

and its derivatives are almost pure glucocorticoids, while prednisone

Prednisone

and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone

Fludrocortisone

Fludrocortisone is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.-Uses:...

(Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency

Adrenal insufficiency

Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

and congenital adrenal hyperplasia

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....

.

Synthetic glucocorticoids are used in the treatment of joint pain or inflammation (arthritis

Arthritis

Arthritis is a form of joint disorder that involves inflammation of one or more joints....

), temporal arteritis

Temporal arteritis

Giant-cell arteritis or Horton disease is an inflammatory disease of blood vessels most commonly involving large and medium arteries of the head...

, dermatitis

Dermatitis

-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...

, allergic reactions, asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

, hepatitis

Hepatitis

Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

, systemic lupus erythematosus

Systemic lupus erythematosus

Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

, inflammatory bowel disease

Inflammatory bowel disease

In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

(ulcerative colitis

Ulcerative colitis

Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...

and Crohn's disease

Crohn's disease

Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

), sarcoidosis

Sarcoidosis

Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

and for glucocorticoid replacement in Addison's disease

Addison's disease

Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

or other forms of adrenal insufficiency

Adrenal insufficiency

. Topical formulations are also available for the skin, eyes (uveitis

Uveitis

Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....

), lungs (asthma

Asthma

), nose (rhinitis

Rhinitis

Rhinitis , commonly known as a stuffy nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or...

), and bowels

Inflammatory bowel disease

In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g. ondansetron

Ondansetron

Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic , often following chemotherapy. Its effects are thought to be on both peripheral and central nerves...

).

Typical undesired effects

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome

Cushing's syndrome

Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

. Typical mineralocorticoid side-effects are hypertension (abnormally high blood pressure), hypokalemia

Hypokalemia

Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

(low potassium levels in the blood), hypernatremia

Hypernatremia

Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...

(high sodium levels in the blood) without causing peripheral edema

Peripheral edema

Peripheral edema is the swelling of tissues, usually in the lower limbs, due to the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, trauma, alcoholism, altitude sickness, pregnancy,...

, metabolic alkalosis

Metabolic alkalosis

Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...

and connective tissue weakness. There may also be impaired wound healing or ulcer formation because of the immunosuppressive effects.

Clinical and experimental evidence indicates that corticosteroids can cause permanent eye damage by inducing central serous retinopathy

Central serous retinopathy

Central serous retinopathy , also known as central serous chorioretinopathy , is an eye disease which causes visual impairment, often temporary, usually in one eye, mostly affecting males in the age group 20 to 50 but which may also affect women...

(CSR, also known as central serous chorioretinopathy, CSC). A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex

Tobradex

Tobramycin/dexamethasone is a prescription medication in the form of eye drops and eye ointment, marketed by Alcon. The active ingredients are tobramycin 0.3% and dexamethasone 0.1% . It is prescribed for a wide spectrum of bacterial eye infections...

), to prednisone have been implicated in the development of CSR.

Corticosteroids have been widely used in treating people with traumatic brain injury. A systematic review

Systematic review

A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...

identified 20 randomised controlled trials and included 12,303 participants, compared patients who received corticosteroids with patients who received no treatment. The authors recommended people with traumatic head injury should not be routinely treated with corticosteroids.

History

First known use in 1944 according to: http://www.merriam-webster.com/dictionary/corticosteroid
Tadeusz Reichstein together with Edward Calvin Kendall

Edward Calvin Kendall

Edward Calvin Kendall was an American chemist. In 1950, Kendall was awarded the 1950 Nobel Prize for Physiology or Medicine along with Swiss chemist Tadeus Reichstein and Mayo Clinic physician Philip S. Hench, for their work with the hormones of the adrenal gland...

and Philip Showalter Hench

Philip Showalter Hench

Philip Showalter Hench was an American physician. Hench, along with his Mayo Clinic co-worker Edward Calvin Kendall and Swiss chemist Tadeus Reichstein was awarded the Nobel Prize for Physiology or Medicine in 1950 for the discovery of the hormone cortisone, and its application for the treatment...

were awarded the Nobel Prize

Nobel Prize

The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

for Physiology

Physiology

and Medicine

Medicine

Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

in 1950 for their work on hormones of the adrenal cortex, which culminated in the isolation of cortisone

Cortisone

Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

.

Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co.

Merck & Co.

Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...

was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox

An ox , also known as a bullock in Australia, New Zealand and India, is a bovine trained as a draft animal. Oxen are commonly castrated adult male cattle; castration makes the animals more tractable...

bile

Bile

Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

. The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker

Russell Marker

Russell Earl Marker was an American chemist who invented the octane rating system when he was working at the Ethyl Corporation. Later in his career, he went on to found a steroid industry in Mexico when he successfully made synthetic progesterone from chemical constituents found in Mexican yams...

, at Syntex

Syntex

Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam....

, discovered a much cheaper and more convenient starting material, diosgenin

Diosgenin

Diosgenin, a steroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscorea wild yam, such as the Kokoro...

from wild Mexican yams. His conversion of diosgenin into progesterone

Progesterone

Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

by a four-step process now known as Marker degradation

Marker degradation

The Marker degradation is a three-step synthetic route in steroid chemistry developed by American chemist Russell Earl Marker in 1938–40. It is used for the production of cortisone and mammalian sex hormones from plant steroids, and established Mexico as a world center for steroid production in...

was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception

Hormonal contraception

Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...

. In 1952, D.H. Peterson and H.C. Murray of Upjohn

Upjohn

The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Kalamazoo, Michigan by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make friable pills, which were specifically designed to be easily digested...

developed a process that used Rhizopus

Rhizopus

Rhizopus is a genus of common saprobic fungi on plants and specialized parasites on animals. They are found on a wide variety of organic substrates, including "mature fruits and vegetables", faeces, jellies, syrups, leather, bread, peanuts and tobacco. Some Rhizopus species are opportunistic agents...

mold to oxidize progesterone into a compound that was readily converted to cortisone. The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $0.46 per gram by 1980. Percy Julian's research also aided progress in the field. The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2

Phospholipase A2

Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids...

in the production of prostaglandin

Prostaglandin

A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....

s and leukotriene

Leukotriene

Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...

s was fully understood in the early 1980s.

Side-effects

Long-term corticosteroids use has several severe side-effects as for example: hyperglycemia

Hyperglycemia

Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...

, insulin resistance

Insulin resistance

Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...

, diabetes mellitus

Diabetes mellitus

Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

, osteoporosis

Osteoporosis

Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

, cataract

Cataract

A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...

, anxiety

Anxiety

Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, depression

Depression (mood)

Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, colitis

Colitis

In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...

, hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, ictus

Ictus

-Medicine:*ictus, a sudden event such as a stroke, seizure, collapse, or faint-Music and poetry:*ictus, in music and conducting, the instant when a beat occurs*ictus, in poetry, a way of indicating a stressed syllable...

, erectile dysfunction

Erectile dysfunction

Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....

, hypogonadism

Hypogonadism

Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...

, hypothyroidism

Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...

, amenorrhoea

Amenorrhoea

Amenorrhoea , amenorrhea , or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy and lactation , the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method...

, and retinopathy

Retinopathy

Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...

.

While the evidence for corticosteroids causing peptic ulcer

Peptic ulcer

A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...

ation is relatively poor except for high doses taken for over a month, the majority of doctors still believe this is the case and would consider protective prophylaxis measures.

Pregnancy

Corticosteroids have a small but significant teratogenic effect, causing a few birth defects per 1,000 pregnant women treated.

Safety

Corticosteroids were voted Allergen of the Year

Allergen of the Year

Allergen of the Year is an annual 'award' of dubious distinction voted upon by the American Contact Dermatitis Society. It is "designed to draw attention to allergens that are very common and/or under-recognized and merit more attention because they are causing significant allergic contact...

in 2005 by the American Contact Dermatitis Society.

Biosynthesis

By chemical structure

Group A - Hydrocortisone Type

Group B - Acetonides

Group C - Betamethasone Type

Group D1 - Halogenated (Less Labile)

Group D2 - Labile Prodrug Esters

Topical steroids

Inhaled steroids

Uses of corticosteroids

History

Side-effects

Pregnancy

Safety

See also

Group D₁ - Halogenated (Less Labile)

Group D₂ - Labile Prodrug Esters