The drug #dexamethasone is a steroid. Now the word "steroid" evokes all manner of reactions, but in essence medics use "steroids" mainly in exchange for a specific subgroup of the huge class of hormones and their analogues, namely the #glucocorticoid group.
All steroid hormones are produced in the body from cholesterol (don't worry statin users, there's plenty for everyone). They are converted by enzymes in various organs to specific hormones that are released and controlled by all manner of systems. (O)estrogen, progesterone...
... testosterone, cortisol and aldosterone are the main members. Each of these has intracellular receptors in their target tissues. They are fat-soluble and most of them need a carrier protein in the bloodstream to actually circulate around the body (e.g. SHBG, sex hormone...
... binding globulin). Inside cells the receptors activate all sorts of processes depending on the hormone and the cell type involved, but mostly DNA transcription or suppression thereof.
Cortisol is the hormone that is mimicked by dexamethasone.
Cortisol is the hormone that is mimicked by dexamethasone.
Cortisol has awide range of actions in the body that seem to correlate with liberating energy for increased activity. It is therefore a catabolic hormone. It is raised in chronic stress
One of features of high doses of steroids, recognised since the 1950s is immune suppression.
One of features of high doses of steroids, recognised since the 1950s is immune suppression.
Cortisol and its pharmaceutical analogues are called "glucocorticoids" mainly because they raise blood sugar. In people with diabetes it messes up blood sugars and some people without diabetes might temporarily get diabetes while receiving them.
Other complications exist...
Other complications exist...
In short term use the main risks are insomnia, polyphagia (eating a lot) and occasionally psychotic symptoms (rare but recognised).
Long-term glucocorticoid use affects bone health, fat distribution and may cause cataracts and hypertension.
Long-term glucocorticoid use affects bone health, fat distribution and may cause cataracts and hypertension.
Cushing's syndrome is said to occur of the body produces too much cortisol for no good reason. It is usually caused by hormone-producing tumours of the adrenal gland or the pituitary gland (sometimes elsewhere). The latter drives cortisol secretion with a hormone called ACTH.
Glucocorticoid steroids include hydrocortisone, prednisone & prednisolone, triamcinolone, betamethasone, methylprednisolone and a whole lot more. They have been used since the 1950s. Their main use is immunosuppression either topically (skin cream, asthma inhaler) or systemically
But there are multiple other uses such as lung maturation in premature delivery.
People who lack normal adrenal function may receive steroid replacement (Addison's syndrome, congenital adrenal hyperplasia etc.)
People who lack normal adrenal function may receive steroid replacement (Addison's syndrome, congenital adrenal hyperplasia etc.)
The hypothetical mode of action of dexamethasone in COVID19 is in reducing the immune response well recognised in severe cases ("cytokine storm"). This also underpins its use in bacterial meningitis, where an overexuberant immune response is considered to often be present.
The #RECOVERYtrial only examined dexamethasone use in hospitalised patients. It has no role in prevention of infection with SARS-NCoV2 and is probably pointless in mild disease where risks may even outweigh any hypothetical benefits (6mg is actually a fairly high dose).
Here ends a brief explainer on dexamethasone. Apologies for the lack of images. I might try that in the future if there is an appetite.
Postscript: I have not discussed the issue that some steroids (especially hydrocortisone) have some mineralocorticoid (aldosterone-like) activity. My understanding is that dexamethasone has very little MC activity and is therefore not so prone to cause salt and water retention.
