A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

ADRENAL MEDULLA 305
injection may be useful, but if done repeatedly carries a substantial
risk of damage to the joint. Low doses of prednisolone may
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 suppositories
or enemas are used), and minimal-change nephrotic syndrome.
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 prednisolone
is 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
Aldosterone is 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 hydrocortisone
as 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.
Aldosterone acts on the distal nephron, promoting Na /K
exchange, causing sodium retention and urinary loss of potassium
and hydrogen ions. Primary hyperaldosteronism (Conn’s syndrome)
is due to either a tumour or hyperplasia of the zona
glomerulosa of the adrenal cortex. Clinical features include nocturia,
hypokalaemia, hypomagnesaemia, weakness, tetany,
hypertension and sodium retention. Spironolactone and
eplerenone are mineralocorticoid antagonists (see Chapters 31
and 36) that compete with aldosterone and other mineralocorticoids
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 synthetic
mineralocorticoid, being approximately 500 times more
powerful than hydrocortisone. It binds to the mineralocorticoid
steroid receptor and mimics the action of aldosterone. It undergoes
significant presystemic metabolism, but unlike aldosterone
is 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
potent α- and β-agonist activity (e.g. shock, beta-blocker overdose).
It is used to prolong the action of local anaesthetics (via
its vasoconstrictor action). Dipivefrine is a prodrug eye-drop
formulation of adrenaline used to treat chronic open angle
glaucoma (Chapter 52). Tumours of the adrenal medulla that
secrete adrenaline and other pharmacologically active catecholamines
(phaeochromocytoma) are treated surgically; in
these patients preoperative blockade with phenoxybenzamine,
a long-acting α-blocker, followed by β-blockade is essential.