Thread: Corticosteroids

Oral Corticosteroids

* Cortisone
* Hydrocortisone (Cortef)
* Prednisone (Deltasone, Meticorten, Orasone)
* Prednisolone (Delta-Cortef, Pediapred, Prelone)
* Triamcinolone (Aristocort, Kenacort)
* Methylprednisolone (Medrol)
* Dexamethasone (Decadron, Dexone, Hexadrol)
* Betamethasone (Celestone)

Inhaled Corticosteroids

* Beclomethasone (Beclovent, Beconase, Vanceril, Vancenase)
* Budesonide (Pulmicort, Rhinocort)
* Mometasone (Nasonex)
* Triamcinolone (Azmacort, Nasacort)
* Flunisolide (AeroBid, Nasalide, Nasarel)
* Fluticasone (Flovent, Flonase)

Topical Corticosteroids

* Alclometasone (Aclovate)
* Amcinonide (Cyclocort)
* Augmented betamethasone (Diprolene)
* Betamethasone (Uticort, Diprosone, Maxivate, Teladar, Valisone)
* Clobetasol (Cormax, Embeline E, Temovate)
* Clocortolone (Cloderm)
* Desonide (DesOwen, Tridesilon)
* Desoximetasone (Topicort)
* Dexamethasone (Decadron, Decaspray)
* Diflorasone (Florone, Maxiflor, Psorcon)
* Flucinolone (Synalar, Fluonid)
* Fluocinonide (Lidex, Fluonex)
* Flurandrenolide (Cordran)
* Fluticasone (Cutivate)
* Halcinonide (Halog)
* Halobetasol (Ultravate)
* Hydrocortisone (Anusol-HC, Hytone, Cort-Dome, Cortenema, Cortifoam, Cortaind, Lanacort, Locoid, Westcort)
* Methylprednisolone (Medrol)
* Mometasone (Elocon)
* Prednicarbate (Dermatop)
* Triamcinolone (Aristocort, Kenalog, Flutex)

Hey frndz, t'was a list of drugs.
Lets continue the thread!!
we will start wiz mechanism of action!!!
will wait 4 u..

The corticosteroids:

• enter cells where they combine with specific steroid receptors in cytoplasm

• combination enters nucleus where it controls synthesis of protein, including enzymes that regulate vital cell activities over a wide range of metabolic functions including all aspects of inflammation

• formation of a protein that inhibits the enzyme phospholipase A2 which is needed to allow the supply of arachidonic acid. Latter is essential for the formation of inflammatory mediators

• also act on cell membranes to alter ion permeability

• also modify the production of neurohormones

gr8 job!! any pic?

General Mechanisms for Corticosteroid Effects.

Corticosteroids interact with specific receptor proteins in target tissues to regulate the expression of corticosteroid-responsive genes, thereby changing the levels and array of proteins synthesized by the various target tissues . As a consequence of the time required to modulate gene expression and protein synthesis, most effects of corticosteroids are not immediate but become apparent after several hours. This fact is of clinical significance, because a delay generally is seen before beneficial effects of corticosteroid therapy become manifest. Although corticosteroids predominantly act to increase expression of target genes, there are well-documented examples in which glucocorticoids decrease transcription of target genes (De Bosscher et al., 2003), as discussed below. In addition to these genomic effects, some immediate actions of corticosteroids may be mediated by membrane-bound receptors (Norman et al., 2004).

The receptors for corticosteroids are members of the nuclear receptor family of transcription factors that transduce the effects of a diverse array of small, hydrophobic ligands, including the steroid hormones, thyroid hormone, vitamin D, and retinoids. These receptors share two highly conserved domains: a region of approximately 70 amino acids forming two zinc-binding domains, called zinc fingers, that are essential for the interaction of the receptor with specific DNA sequences, and a region at the carboxyl terminus that interacts with ligand (the ligand-binding domain).

Carbohydrate and Protein Metabolism. Corticosteroids profoundly affect carbohydrate and protein metabolism. Teleologically, these effects of glucocorticoids on intermediary metabolism can be viewed as protecting glucose-dependent tissues (e.g., the brain and heart) from starvation. They stimulate the liver to form glucose from amino acids and glycerol and to store glucose as liver glycogen. In the periphery, glucocorticoids diminish glucose utilization, increase protein breakdown and the synthesis of glutamine, and activate lipolysis, thereby providing amino acids and glycerol for gluconeogenesis. The net result is to increase blood glucose levels. Because of their effects on glucose metabolism, glucocorticoids can worsen glycemic control in patients with overt diabetes and can precipitate the onset of hyperglycemia in patients who are otherwise predisposed.

The mechanisms by which glucocorticoids inhibit glucose utilization in peripheral tissues are not fully understood. Glucocorticoids decrease glucose uptake in adipose tissue, skin, fibroblasts, thymocytes, and polymorphonuclear leukocytes; these effects are postulated to result from translocation of the glucose transporters from the plasma membrane to an intracellular location. These peripheral effects are associated with a number of catabolic actions, including atrophy of lymphoid tissue, decreased muscle mass, negative nitrogen balance, and thinning of the skin.

Similarly, the mechanisms by which the glucocorticoids promote gluconeogenesis are not fully defined. Amino acids mobilized from a number of tissues in response to glucocorticoids reach the liver and provide substrate for the production of glucose and glycogen. In the liver, glucocorticoids induce the transcription of a number of enzymes involved in gluconeogenesis and amino acid metabolism, including phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, and the bi-functional enzyme fructose-2,6-bisphosphatase. Analyses of the molecular basis for regulation of PEPCK gene expression have identified complex regulatory influences involving an interplay among glucocorticoids, insulin, glucagon, and catecholamines. The effects of these hormones and amines on PEPCK gene expression mirror the complex regulation of gluconeogenesis in the intact organism.

Lipid Metabolism. Two effects of corticosteroids on lipid metabolism are firmly established. The first is the dramatic redistribution of body fat that occurs in settings of endogenous or pharmacologically induced hypercorticism, such as Cushing's syndrome. The other is the permissive facilitation of the lipolytic effect of other agents, such as growth hormone and b adrenergic receptor agonists, resulting in an increase in free fatty acids after glucocorticoid administration. With respect to fat distribution, there is increased fat in the back of the neck ("buffalo hump"), face ("moon facies"), and supraclavicular area, coupled with a loss of fat in the extremities.

One hypothesis for this redistribution is that peripheral and truncal adipocytes differ in their relative sensitivities to insulin and to glucocorticoid-facilitated lipolytic effects, that truncal adipocytes respond predominantly to elevated levels of insulin resulting from glucocorticoid-induced hyperglycemia, whereas peripheral adipocytes are less sensitive to insulin and respond mostly to the glucocorticoid-facilitated effects of other lipolytic hormones. This differential sensitivity may reflect differences in the expression of the type 1 isozyme of 11bHSD that converts inactive cortisone into active cortisol in target tissues. Consistent with this idea, overexpression of 11bHSD1 in adipocytes causes obesity in a transgenic mouse model. The potential role of this enzyme in adipocyte function has prompted speculation that 11bHSD1 inhibitors may have a role in the treatment of obesity.

Electrolyte and Water Balance. Aldosterone is by far the most potent endogenous corticosteroid with respect to fluid and electrolyte balance. Thus, electrolyte balance is relatively normal in patients with adrenal insufficiency due to pituitary disease, despite the loss of glucocorticoid production by the inner cortical zones. Mineralocorticoids act on the distal tubules and collecting ducts of the kidney to enhance reabsorption of Na+ from the tubular fluid; they also increase the urinary excretion of K+ and H+. Conceptually, it is useful to think of aldosterone as stimulating a renal exchange between Na+ and K+ or H+, although this does not involve a simple 1:1 exchange of cations in the renal tubule.

These actions on electrolyte transport, in the kidney and in other tissues (e.g., colon, salivary glands, and sweat glands), appear to account for the physiological and pharmacological activities that are characteristic of mineralocorticoids. Thus, the primary features of hyperaldosteronism are positive Na+ balance with consequent expansion of extracellular fluid volume, normal or slight increases in plasma Na+ concentration, hypokalemia, and alkalosis. Mineralocorticoid deficiency, in contrast, leads to Na+ wasting and contraction of the extracellular fluid volume, hyponatremia, hyperkalemia, and acidosis. Chronically, hyperaldosteronism can cause hypertension, whereas aldosterone deficiency can lead to hypotension and vascular collapse. Because of the effects of mineralocorticoids on electrolyte handling by sweat glands, patients who are adrenal insufficient are especially predisposed to Na+ loss and volume depletion through excessive sweating in hot environments.

Glucocorticoids also exert effects on fluid and electrolyte balance, largely due to permissive effects on tubular function and actions that maintain glomerular filtration rate. Glucocorticoids play a permissive role in the renal excretion of free water; the ability to excrete a water challenge was used at one time to diagnose adrenal insufficiency. In part, the inability of patients with glucocorticoid deficiency to excrete free water results from the increased secretion of AVP, which stimulates water reabsorption in the kidney.

In addition to their effects on monovalent cations and water, glucocorticoids also exert multiple effects on Ca2+ metabolism. Steroids interfere with Ca2+ uptake in the gut and increase Ca2+ excretion by the kidney. These effects collectively lead to decreased total body Ca2+ stores.

Cardiovascular System. The most striking effects of corticosteroids on the cardiovascular system result from mineralocorticoid-induced changes in renal Na+ excretion, as is evident in primary aldosteronism. The resultant hypertension can lead to a diverse group of adverse effects on the cardiovascular system, including increased atherosclerosis, cerebral hemorrhage, stroke, and hypertensive cardiomyopathy. Consistent with the known actions of mineralocorticoids in the kidney, restriction of dietary Na+ can lower the blood pressure considerably in mineralocorticoid excess.

Studies also have shown direct effects of aldosterone on the heart and vascular lining; aldosterone induces hypertension and interstitial cardiac fibrosis in animal models. The increased cardiac fibrosis is proposed to result from direct mineralocorticoid actions in the heart rather than from the effect of hypertension, because treatment with spironolactone, a MR antagonist, blocked the fibrosis without altering blood pressure. Similar effects of mineralocorticoids on cardiac fibrosis in human beings may explain, at least in part, the beneficial effects of spironolactone in patients with congestive heart failure (see Chapter 33).

The second major action of corticosteroids on the cardiovascular system is to enhance vascular reactivity to other vasoactive substances. Hypoadrenalism is associated with reduced response to vasoconstrictors such as norepinephrine and angiotensin II, perhaps due to decreased expression of adrenergic receptors in the vascular wall. Conversely, hypertension is seen in patients with excessive glucocorticoid secretion, occurring in most patients with Cushing's syndrome and in a subset of patients treated with synthetic glucocorticoids (even those lacking any significant mineralocorticoid action).

The underlying mechanisms in glucocorticoid-induced hypertension also are unknown; in hypertension related to the endogenous secretion of cortisol, as seen in patients with Cushing's syndrome, it is not known if the effects are mediated by the GR or MR. Unlike hypertension caused by high aldosterone levels, the hypertension secondary to excess glucocorticoids is generally resistant to Na+ restriction

Cardiovascular System. The most striking effects of corticosteroids on the cardiovascular system result from mineralocorticoid-induced changes in renal Na+ excretion, as is evident in primary aldosteronism. The resultant hypertension can lead to a diverse group of adverse effects on the cardiovascular system, including increased atherosclerosis, cerebral hemorrhage, stroke, and hypertensive cardiomyopathy. Consistent with the known actions of mineralocorticoids in the kidney, restriction of dietary Na+ can lower the blood pressure considerably in mineralocorticoid excess.

Studies also have shown direct effects of aldosterone on the heart and vascular lining; aldosterone induces hypertension and interstitial cardiac fibrosis in animal models. The increased cardiac fibrosis is proposed to result from direct mineralocorticoid actions in the heart rather than from the effect of hypertension, because treatment with spironolactone, a MR antagonist, blocked the fibrosis without altering blood pressure. Similar effects of mineralocorticoids on cardiac fibrosis in human beings may explain, at least in part, the beneficial effects of spironolactone in patients with congestive heart failure (see Chapter 33).

The second major action of corticosteroids on the cardiovascular system is to enhance vascular reactivity to other vasoactive substances. Hypoadrenalism is associated with reduced response to vasoconstrictors such as norepinephrine and angiotensin II, perhaps due to decreased expression of adrenergic receptors in the vascular wall. Conversely, hypertension is seen in patients with excessive glucocorticoid secretion, occurring in most patients with Cushing's syndrome and in a subset of patients treated with synthetic glucocorticoids (even those lacking any significant mineralocorticoid action).

The underlying mechanisms in glucocorticoid-induced hypertension also are unknown; in hypertension related to the endogenous secretion of cortisol, as seen in patients with Cushing's syndrome, it is not known if the effects are mediated by the GR or MR. Unlike hypertension caused by high aldosterone levels, the hypertension secondary to excess glucocorticoids is generally resistant to Na+ restriction