Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c25 CUFX213A/Peck 9780521618168 December 29, 2007 15:15

Section IVOther important drugs

facilitate the breakdown of membrane phospholipids to arachidonic acid, the pre-

cursor 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 suppres-

sion due to negative feedback on corticotrophin-releasing hormone and ACTH

(Figure25.1). The adrenal gland becomes atrophic and remains so for many months

after treatment has stopped. As a result the adrenal cortex cannot produce suffi-

cient glucocorticoid when exogenous glucocorticoid is withdrawn abruptly or dur-

ing 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 below).


Fluid retention – glucocorticoids have only weak mineralocorticoid activity. How-

ever, 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

Hypothalamus Corticotrophin releasing hormone

ACTH

Corticosteroids

Pituitary

Adrenal cortex

Figure 25.1.Feedback loops affecting corticosteroid production.——→,Stimulates; ,

inhibits.