A Textbook of Clinical Pharmacology and Therapeutics

ADRENALMEDULLA 305

injection may be useful, but if done repeatedly carries a substan-
tial risk of damage to the joint. Low doses of prednisolonemay
be symptomatically useful in the short-term management of
patients with severe articular symptoms from systemic lupus
erythematosus and larger doses may be appropriate for limited
periods in such patients with steroid-responsive forms of
glomerulonephritis or with progressive central nervous system
involvement.
Other diseases where prednisolone may be indicated
include severe asthma and some interstitial lung diseases, e.g.
fibrosing alveolitis and some patients with sarcoidosis (Chapter
33), some forms of acute hepatitis and chronic active hepatitis,
acute and chronic inflammatory bowel disease (where supposi-
tories or enemas are used), and minimal-change nephrotic syn-
drome. The immunosuppressant effect of prednisolone is
further utilized in transplantation, usually in combination with
ciclosporin or azathioprine, in order to prevent rejection
(Chapter 50). Benign haematological disorders for which pred-
nisoloneis indicated include autoimmune haemolytic anaemia
and idiopathic thrombocytopenic purpura and is an essential
component of chemotherapeutic regimens for lymphoma and
Hodgkin’s disease (Chapters 48 and 49).

DEXAMETHASONE

Uses

Dexamethasone is powerfully anti-inflammatory, but is
virtually devoid of mineralocorticoid activity. It is generally
reserved for a few distinct indications, including:

• as a diagnostic agent in the investigation of suspected
  Cushing’s syndrome (low- and high-dose dexamethasone
  suppression tests) as it does not cross-react with
  endogenous cortisol in conventional radioimmunoassays;


• in the symptomatic treatment of cerebral oedema
  associated with brain tumours;


• to prevent respiratory distress syndrome in premature
  babies by administration to pregnant mothers;


• in combination with other anti-emetics to prevent
  cytotoxic chemotherapy-induced nausea and vomiting;


• when a corticosteroid is indicated, but fluid retention is
  problematic.

MINERALOCORTICOIDS

ALDOSTERONE

Aldosteroneis the main mineralocorticoid secreted by the zona
glomerulosa of the adrenal cortex. It has no glucocorticoid
activity, but is about 1000 times more active than hydrocorti-
soneas a mineralocorticoid. The main factors that control its
release are plasma sodium, plasma potassium and angiotensin II.
Pituitary failure, which results in a total absence of ACTH and
of cortisol secretion, allows aldosterone production to
continue.
Aldosteroneacts on the distal nephron, promoting Na/K
exchange, causing sodium retention and urinary loss of potassium

and hydrogen ions. Primary hyperaldosteronism (Conn’s syn-

drome) is due to either a tumour or hyperplasia of the zona

glomerulosa of the adrenal cortex. Clinical features include noc-

turia, hypokalaemia, hypomagnesaemia, weakness, tetany,

hypertension and sodium retention. Spironolactone and

eplerenoneare mineralocorticoid antagonists (see Chapters 31

and 36) that compete with aldosteroneand other mineralocorti-

coids for the cytoplasmic mineralocorticosteroid receptor. They

are used as potassium-sparing diuretics and to treat primary or

secondary hyperaldosteronism in the contexts of hypertension

and/or heart failure (Chapters 28 and 36).

FLUDROCORTISONE

Fludrocortisone(9-α-fluorohydrocortisone) is a potent syn-

thetic mineralocorticoid, being approximately 500 times more

powerful than hydrocortisone. It binds to the mineralocorticoid

steroid receptor and mimics the action of aldosterone. It under-

goes significant presystemic metabolism, but unlike aldos-

teroneis active by mouth. It is used as replacement therapy in

patients with adrenocortical insufficiency. It is sometimes used

to treat patients with symptomatic postural hypotension, but at

the cost of causing features of Conn’s syndrome.

Key points

Mineralocorticoids

• Mineralocorticoids mimic aldosterone’s effects on the
  distal nephron, causing sodium retention and
  potassium excretion.


• The synthetic mineralocorticoid fludrocortisone, is
  effective orally.


• Fludrocortisone is used when mineralocorticoid
  replacement is needed in patients with adrenal
  insufficiency.


• Occasionally, fludrocortisone is used to treat severe
  postural hypotension.


• Mineralocorticoid antagonists (e.g. spironolactone,
  Chapter 36) are used to treat mineralocorticoid excess
  (e.g. Conn’s syndrome).

ADRENAL MEDULLA

Adrenaline(epinephrine) is the main hormone produced by

the adrenal medulla. It is used in emergency situations, such as

cardiac arrest (Chapter 32), anaphylactic shock (Chapter 50)

and other life-threatening disorders that require combined

potentα- and β-agonist activity (e.g. shock, beta-blocker over-

dose). It is used to prolong the action of local anaesthetics (via

its vasoconstrictor action). Dipivefrineis a prodrug eye-drop

formulation of adrenalineused to treat chronic open angle

glaucoma (Chapter 52). Tumours of the adrenal medulla that

secrete adrenaline and other pharmacologically active cate-

cholamines (phaeochromocytoma) are treated surgically; in

these patients preoperative blockade with phenoxybenzamine,

a long-acting α-blocker, followed by β-blockade is essential.