Glucocorticoids (GCs) have a wide and complex range of actions, and the glucocorticoids secreted in physiological situations with doses mainly affect the metabolism of normal substances. The classification of glucocorticoids is based on their duration of action in the body: short-acting is about 8-12 h, medium-acting is about 18-36 h, and long-acting is 36-54 h. As for the representative drugs of each category, the author has summarized a recipe for you to help you remember.
Cortisone, prednisone, and long-acting methylprednisolone, and medium-acting impact methylprednisolone.
Short-acting glucocorticoids: Most of them are related to “cortisone”, such as cortisone and hydrocortisone.
Medium-acting glucocorticoids: mostly with the word “prednisone”, such as prednisone, prednisolone, methylprednisone, etc. Methylprednisolone is the only drug that can be used in shock therapy, which will be described later.
Long-acting glucocorticosteroids: The so-called “long-acting glucocorticosteroids” are actually long-acting drugs containing the name “mizone”, such as dexamethasone and betamethasone.
However, the difference between the three is not only limited to the duration of action, but also differs in the following aspects.
1. Different biological efficacy
Glucose-raising effect: Glucocorticoids can promote glycogen xenobiogenesis, slow down glucose decomposition and reduce the use of glucose by body tissues, thus increasing the content of liver glycogen and muscle glycogen and raising blood sugar. However, it should be noted that as one of the important hormones for regulating glucose metabolism, steroidal diabetes mellitus may occur when they are used excessively.
Anti-inflammatory effects: Glucocorticoids have rapid, powerful and non-specific anti-inflammatory effects. They are effective against a wide range of inflammatory conditions. The relative efficacy of long-acting glucocorticoids is the strongest, followed by medium-acting and short-acting glucocorticoids for both glucose-raising and anti-inflammatory effects. However, it should be noted that while glucocorticoids treat infection and reduce symptoms, they also reduce the body’s defense function.
Therefore, sufficient amount of effective antibacterial drugs must be applied at the same time to prevent the spread of inflammation and deterioration of the original condition.
2. Effects on water and electrolyte metabolism
Glucocorticoids also have a weaker effect of salt corticoids: sodium retention and potassium excretion, and diuresis by increasing glomerular filtration rate and antagonizing antidiuretics. From long-acting to short-acting, all three have increasing sal corticosteroid activity: short-acting is the strongest, intermediate is the second strongest, and long-acting is the weakest.
3. Negative feedback effect on HPA axis
Negative feedback effect on hypothalamic-pituitary-adrenocortical axis (HPA axis): short-acting GC < medium-acting GC < long-acting GC.
4. Immunosuppression
Both long-acting and medium-acting have strong immunosuppressive effects, and medium-acting hormone is more commonly used in clinical immune transplantation treatment because of its shorter half-life.
5. Ability to penetrate the blood-brain barrier
From strong to weak: methylprednisolone (medium-acting), dexamethasone (long-acting), and hydrocortisone (short-acting), in that order.
6. Others
Long-acting hormones have more side effects, while medium-acting hormones have the least
Short-acting glucocorticoids
Representative drugs: cortisone, hydrocortisone
Clinical application characteristics.
The advantage of short-acting glucocorticoids is that they are less harmful to the HPA axis and their action state is closer to the physiological state. Therefore, they are generally used as replacement therapy in clinical practice, for example, after chronic hyperalgesia or subtotal nephrectomy.
The disadvantage is that its anti-inflammatory effect is weak and the duration of action of the drug is short. And because of the relatively strong activity of salt corticosteroids, they should also not be used for long-term treatment but mostly for short-term hormone replacement therapy, as they may lead to the risk of edema (sodium and water retention) and hypokalemia in patients.
It should be noted that cortisone needs to be metabolized by the liver into hydrocortisone before it can exert its physiological effects, so patients with poor liver function should use hydrocortisone directly.
Dosage
Hydrocortisone 20-30 mg/d twice daily, with the maximum dose of 2/3 of the daily dose in the morning and 1/3 in the afternoon, due to the fact that cortisol secretion in humans is highest between 6:00 a.m. and 9:00 a.m. and then decreases gradually to a minimum at midnight.
Tips
Generally speaking, hydrocortisone is chosen for oral administration and hydrocortisone succinate for intravenous application. The two are almost identical in that it is hydrocortisone that acts. The difference is that 100 mg of hydrocortisone needs to be diluted with 500 ml of physiological saline or sugar water due to the poor water solubility of hydrocortisone. In contrast, hydrocortisone succinate powder injections can be diluted directly with saline or sugar because the introduction of succinate in the structure increases the water solubility of hydrocortisone. It is also alcohol-free and has a better safety profile; it can also be used in large doses because no dilution concentration is specified
Medium-acting glucocorticoids
Representative drugs: Prednisone, prednisolone, prednisone (prednisolone acetate), methylprednisolone (methylprednisolone sodium succinate)
Drug characteristics
Medium-acting glucocorticosteroids are not optimal in terms of glucose-raising and anti-inflammatory effects, but they also have fewer side effects, and their negative feedback effects on the HPA axis and effects on water and electrolytes are within an acceptable range. Therefore, as a compromise between the anti-inflammatory effect of the drug and the effect on its own adrenocortical function, intermediate-acting glucocorticoids are the only hormones among the three that can be used for a long time, and are safe for long-term use. It is mostly used clinically for the long-term treatment of allergic and autoimmune inflammatory diseases: such as systemic lupus erythematosus, severe polymyositis, severe bronchial asthma, dermatomyositis, vasculitis and other allergic diseases, acute leukemia, malignant lymphoma.
Methylprednisolone, the “fighter” of the medium-acting hormones, is the only drug that can be used in shock therapy.
Tips
Did you know? Methylprednisolone is the only drug that can be used in shock therapy. This is because its binding rate to hormone receptors is significantly higher than that of other glucocorticoids, about 23 times that of prednisone, and its onset of action is rapid. Thus, it rapidly inhibits enzyme activity and saturates hormone-specific receptors.
Moreover, methylprednisolone has a weak inhibitory effect on the HPA axis and is highly water-soluble, so it can be used in large doses for rapid symptom control.
Long-acting glucocorticoids
Representative drugs: dexamethasone, betamethasone.
Clinical application characteristics
The advantages of long-acting glucocorticosteroids are that they are more anti-inflammatory (25 times stronger than hydrocortisone), have less effect on water and salt metabolism (almost none), and have a longer duration of action (3-6 times longer than hydrocortisone). The disadvantage is that it has a strong inhibitory effect on the HPA axis, so it is not suitable for long-term use and tends to affect its own adrenocortical function. It is mostly used for the diagnosis of Cushing’s syndrome – dexamethasone suppression test, as well as for patients in whom short-term treatment or application of other glucocorticoid preparations are ineffective or inefficient.
It is important to note that at higher doses, it is prone to diabetes, osteoporosis, peptic ulcers and Cushing’s-like syndrome symptoms, and it increases the risk of co-infection.