Corticosteroids

Question 0

What is the endogenous control mechanism of corticosteroids?

Answer 0

HPA axis

Question 1

Where are corticosteroids produced?

Answer 1

The adrenal cortex produces corticosteroids.
Mineralocorticoids- aldosterone (ZG)
Glucocorticoids- cortisol and corticosterone (ZF and ZR)
Synthesised from cholesterol.

Question 2

What is the structure of glucocorticoids?

Answer 2

It is a four ring 21 carbon basic structure.

It must have a double bond at C4-5 and a ketone at C3 to be active.

Question 3

What are the pharmacokinetics of Corticosteroids?

Answer 3

90% PPB to albumin and corticotrophin binding globulin.
CBG high affinity but low capacity.
Metabolism occurs in liver and it is excreted in the urine.
There are pro-drugs- cortisone and prednisone.

Question 4

What are the mechanisms of action of corticosteroids?

Answer 4

1) cross the cell by diffusion
2) bind to the cytosolic receptor
3) steroid complex translocates to the nucleus
4) increases or decreases mRNA transcription
5) up/down regulation of genes

Question 5

What are 2 examples of proteins induced by corticosteroids?

Answer 5

1) Angiotensin converting enzyme (drives RAAS)
2) B2-adrenoreceptor (bronchodilation- B2 agonist) It enhances action and is an anti-inflammatory
Also induce mineralocorticoids

Question 6

What are 3 proteins that are inhibited by cortiosteroids?

Answer 6

Cytokines
Cyclo-oxygenase
Collagenase

Question 7

What are the four actions that glucocorticoids have?

Answer 7

1) metabolic effects
2) systemic effects
3) anti-inflammatory effects
4) immune suppressive effects

Question 8

What effects do glucocorticoids have on metabolism?

Answer 8

Mainly on carbohydrate and proteins.

1) inc. gluconeogenesis
2) inhibit utilisation of glucose= hyperglycaemia
3) protein breakdown and reduced synthesis
4) negative calcium balance
5) redistribution of fat.

Question 9

What are the systemic effects of glucocorticoids?

Answer 9

1) elevation of liver enzymes
2) induction of parturition
3) alteration of CNS function (behaviour)
4) mineralocorticoid activity

Question 10

When do glucocorticoids have an inflammatory effect and what is there effect?

Answer 10

Only at pharmacological concentrations.

Act on early and late inflammation stages, affect all inflammatory reactions, decrease vasodilation and fluid exudation.

Question 11

What is the inflammatory effect on cells?

Answer 11

decrease T helper cells, decrease leukocytes, decrease macrophages, increase fibroblasts, decrease osteoblasts and increase osteoclasts. (not all are good!)

Question 12

What is there effect on inflammatory mediators?

Answer 12

Inhibit COX, inhibit PLA2 by inducing lipocortin (higher up in pathway), decrease inflammatory cytokines and decrease histamine release.

Question 13

What effects do glucocorticoids have on the immune system?

Answer 13

At low doses: cellular response inhibited e.g. lymphocytes, eosinophils, monocytes and basophils. Increase in neutrophils.
At high doses the humoral response is inhibited.

Question 14

What are three examples of short acting glucocorticoids?

Answer 14

Prednisolone, prednisone and methylprednisolone (pro-drug).

<24hrs

Question 15

What are examples of long acting glucocorticoids?

Answer 15

Dexamethasone, Betamethasone, Triamcinolone >24hrs

Question 16

What formulations are glucocorticoids available in?

Answer 16

Water soluble salts- IV e.g. Dexamethasone

Insoluble esters- acetate for s/c, i/m or orally.

Question 17

How can glucocorticoids be used topically?

Answer 17

On the eyes, ears and skin. Opthalmic preparations can cause adrenal suppression as they are highly lipid soluble and get into the systemic circulation.

Question 18

What are the 5 clinical uses of glucocorticoids?

Answer 18

Inflammatory disease- acute and chronic (osteoarthritis).
Immune-mediated disease (high to low dose)
Shock (prevent degranulation)
Cerebral oedema
Neoplasia (2ndary problems e.g. hypercalcaemia)

Question 19

What are Methylprednisolone acetate and Triamcinolone used for?

Answer 19

Intra-articular steroids.

1) maintained for 39d 2)no alteration on bone remodelling but undetectable after 2 weeks.

Question 20

What is Addison’s Disease and what are the presenting signs?

Answer 20

Deficiency of adrenocortical steroid production, both glucocorticoid and mineralocorticoid deficiency. Present collapsed, bradycardic (would expect tachycardia-WARNING!), hyperkalaemic, hyponatraemic and dehydrated. (aldosterone deficiency).

Question 21

What are the two treatments for Addison’s disease?

Answer 21

Acutely with hydrocortisone and long term with fludrocortisone.
DOCP- US, more long term than fludrocortisone