Clinical Pharmacology and Therapeutics

304 ADRENAL HORMONES
Table 40.2: Relative potencies of glucocorticosteroids and mineralocorticosteroids
Compound
Relative potency
Anti-inflammatory Mineralocorticoid
Glucocorticosteroids
Cortisol (hydrocortisone) 1 1
Cortisone 0.8 1
Prednisolone and prednisone 4 0.8
Methylprednisolone 5 0.5
Triamcinolone 5 0
Dexamethasone 25–30 0
Betamethasone 25–30 0
Mineralocorticosteroids
Aldosterone 0 1000 a
Fludrocortisone 10 500
a Injected (other preparations administered as oral doses).
inflamed bursae to provide a localized anti-inflammatory
effect. Hydrocortisone cream is relatively low in potency and
is of particular use on the face where more potent steroids are
contraindicated.
Pharmacokinetics
Hydrocortisone is rapidly absorbed from the gastro-intestinal
tract, but there is considerable inter-individual variation in
bioavailability due to variable presystemic metabolism. It is
metabolized in the liver (by CYP3A) and other tissues to tetrahydrometabolites
that are conjugated with glucuronide before
being excreted in the urine. The plasma t 1/2 is approximately 90
minutes, but the biological t 1/2 is longer (six to eight hours).
Key points
Glucocorticosteroids – major side effects
• Adrenal suppression, reduced by once daily morning or
alternate-day administration.
• After chronic therapy – slow-dose tapering is needed,
otherwise an adrenal crisis is likely to be precipitated.
• Metabolic effects including hyperglycaemia and
hypokalaemia occur rapidly, as does insomnia and
mood disturbances.
• Chronic side effects include Cushingoid appearance,
hypertension, osteoporosis and proximal myopathy.
• Immunosuppression – susceptibility to infections.
• Mask acute inflammation (e.g. perforated intraabdominal
viscus).
• Patients on chronic steroid treatment require an
increased dose for stresses, such as infection or surgery.
Key points
Glucocorticosteroids – pharmacodynamics and
pharmacokinetics
• They have a potent anti-inflammatory action
which takes six to eight hours to manifest after
dosing.
• They act as positive transcription factors for proteins
involved in inhibition of the production of
inflammatory mediators (e.g. lipocortin) and they
inhibit the action of transcription factors for proinflammatory
cytokines.
• Mineralocorticoid effects decrease as the antiinflammatory
potency of synthetic glucocorticoids
increases.
• Glucocorticosteroids have relatively short half-lives and
are metabolized to inactive metabolites.
• Used in a wide range of inflammatory disorders of
lung, gut, liver, blood, nervous system, skin and
musculoskeletal systems, and for immunosuppression in
transplant patients.
PREDNISOLONE
Uses
Prednisolone is an analogue of hydrocortisone that is approximately
four times more potent than the natural hormone with
regard to anti-inflammatory metabolic actions, and involution of
lymphoid tissue, but slightly less active as a mineralocorticoid.
The anti-inflammatory effect of prednisolone can improve
inflammatory symptoms of connective tissue and vasculitic diseases
(see Chapter 26), but whether this benefits the underlying
course of the disease is often unclear. Treatment must therefore
be re-evaluated regularly and if long-term use is deemed essential,
the dose reduced to the lowest effective maintenance dose.
Alternate-day dosing produces less suppression of the pituitary–adrenal
axis, but not all diseases are adequately treated in
this way (e.g. giant cell arteritis). Prednisolone is considered in
progressive rheumatoid arthritis when other forms of treatment
have failed, or as an interim measure while a disease-modifying
drug, such as methotrexate, has time to act. Intra-articular