Chapter 26 – Corticosteroids and Other Hormone Preparations




Abstract




The main endogenous glucocorticoid in humans is hydrocortisone. Synthetic glucocorticoids include prednisolone, methylprednisolone, betamethasone, dexamethasone and triamcinolone. They have metabolic, anti-inflammatory (see Table 26.1) and immunosuppressive effects.





Chapter 26 Corticosteroids and Other Hormone Preparations




Glucocorticoids


The adrenal cortex releases two classes of steroidal hormones into the circulation:




  • Glucocorticoids (from the zona fasciculata and zona reticularis)



  • Mineralocorticoids (from the zona glomerulosa).


The main endogenous glucocorticoid in humans is hydrocortisone. Synthetic glucocorticoids include prednisolone, methylprednisolone, betamethasone, dexamethasone and triamcinolone. They have metabolic, anti-inflammatory (see Table 26.1) and immunosuppressive effects.




Table 26.1 Anti-inflammatory potential of various steroids
































Drug Relative anti-inflammatory potency Equivalent anti-inflammatory dose (mg)
Hydrocortisone 1 100
Prednisolone 4 25
Methylprednisolone 5 20
Triamcinolone 5 20
Dexamethasone 25 4


Metabolic Effects


Glucocorticoids facilitate gluconeogenesis (i.e. synthesis of glucose from a non-carbohydrate source, e.g. protein). Glycogen deposition and glucose release from the liver are stimulated but the peripheral uptake of glucose is inhibited. Protein catabolism is stimulated and synthesis inhibited.


When exogenous glucocorticoid is given in high doses or for prolonged periods, the altered metabolism causes unwanted effects. Increased protein catabolism leads to muscle weakness and wasting. The skin becomes thin leading to striae, and gastric mucosa becomes susceptible to ulceration. Dietary protein will not reverse these changes. Altered carbohydrate metabolism leads to hyperglycaemia and glycosuria. Diabetes may be provoked. Fat is redistributed from the extremities to the trunk, neck and face. Bone catabolism leads to osteoporosis.



Anti-Inflammatory Effects


Glucocorticoids reduce the production of tissue transudate and cell oedema in acute inflammation. Circulating polymorphs and macrophages are prevented from reaching inflamed tissue. The production of inflammatory mediators (prostaglandins, leukotrienes and platelet-activating factor) is suppressed by the stimulation of lipocortin, which inhibits phospholipase A2. Normally phospholipase A2 would facilitate the breakdown of membrane phospholipids to arachidonic acid, the precursor of inflammatory mediators, in particular prostaglandins.


These effects may reduce the patient’s resistance to infection (latent tuberculosis may become reactivated), and the normal clinical features usually present may be absent until the infection is advanced.



Immunosuppressive Effects


Glucocorticoids depress macrophage function and reduce the number of circulating T-lymphocytes. The transport of lymphocytes and their production of antibodies are also reduced. Interleukin 1 and 2 production is inhibited, which reduces lymphocyte proliferation.



Other Effects




  • Adrenal suppression – during long-term steroid therapy there is adrenal suppression due to negative feedback on corticotrophin-releasing hormone and adrenocorticotrophic hormone (ACTH) (see Figure 26.1). The adrenal gland becomes atrophic and remains so for many months after treatment has stopped. As a result the adrenal cortex cannot produce sufficient glucocorticoid when exogenous glucocorticoid is withdrawn abruptly or during periods of stress, that is, infection or surgery. If supplementary hydrocortisone is not administered in such patients peri-operatively, they are at risk of hypotension and possibly cardiovascular collapse (see ‘Peri-Operative Steroid Supplementation’ below).



  • Fluid retention – glucocorticoids have only weak mineralocorticoid activity. However, some do act on the distal renal tubule, leading to Na+ retention and K+ excretion. In very large doses, water retention may cause oedema, hypertension and cardiac failure. Mineralocorticoid (sodium retaining) activity is greatest with hydrocortisone and cortisone, lesser with prednisolone and least with methylprednisolone and dexamethasone.



  • Vascular reactivity – glucocorticoids have a ‘permissive action’ on vascular smooth muscle, allowing them to respond efficiently to circulating catecholamines. Therefore, glucocorticoid deficiency leads to an ineffective response by vascular smooth muscle to circulating catecholamines. In sepsis there may be an inappropriately reduced production of cortisol so that higher levels of inotropic support are required. This may be improved by the administration of intravenous hydrocortisone.





Figure 26.1 Feedback loops affecting corticosteroid production. , Stimulates; , inhibits.


Other ‘permissive actions’ of glucocorticoids include the calorigenic effects of glucagon and catecholamines, and the lipolytic and bronchodilator effects of catecholamines.



Peri-Operative Steroid Supplementation


Patients with adrenal insufficiency (AI) require peri-operative steroid supplementation. AI may be Primary (adrenal gland disease / failure), Secondary (deficient ACTH or CRH production) or most commonly Tertiary (the result of glucocorticoid therapy, sometimes classified within Secondary). Peri-operative steroid supplementation is in addition to the patient’s usual steroid medication. Recent guidelines highlight that doses as low as 5 mg prednisolone and standard doses of inhaled glucocorticoids taken for more than 1 month can cause an inadequate response to the short synacthen test. As the side effects of peri-operative steroid supplementation are minimal compared to an inadequate glucocorticoid stress response it is recommended that this group of patients has peri-operative steroid supplementation. Tables 26.2 & 26.3 summarise the recommendations.


It should be noted that dexamethasone is not recommended in Primary AI due to its lack of mineralocorticoid effect.


Mar 7, 2021 | Posted by in ANESTHESIA | Comments Off on Chapter 26 – Corticosteroids and Other Hormone Preparations
Premium Wordpress Themes by UFO Themes