C H A P T E R 3 6
Adrenocortical agents
547
M
ineralocorticoids
Mineralocorticoids
(Table 36.3) affect electrolyte levels
and homeostasis. These steroid hormones, such as
aldosterone, directly affect the levels of electrolytes in
the system. The classic mineralocorticoid is aldosterone.
Aldosterone holds sodium—and with it, water—in the
body and causes the excretion of potassium by acting
on the renal tubule. Aldosterone is no longer available
for pharmacological use. Mineralocorticoids that are
available include cortisone (
Cortate
), fludrocortisone
(
Florinef
) and hydrocortisone (
Solu-Cortef
).
Therapeutic actions and indications
The mineralocorticoids increase sodium reabsorption
in renal tubules, leading to sodium and water reten-
tion, and increase potassium excretion (see Figure 36.2).
Fludrocortisone is a powerful mineralocorticoid and
is preferred for replacement therapy over cortisone
and hydrocortisone; it is used in combination with
a glucocorticoid. Hydrocortisone and cortisone also
exert mineralocorticoid effects at high doses; however,
this effect is not usually enough to maintain electro-
lyte balance in adrenal insufficiency. These drugs are
indicated (in combination with a glucocorticoid) for
replacement therapy in primary and secondary adrenal
insufficiency. They are also indicated for the treatment
of salt-wasting adrenogenital syndrome when taken
with appropriate glucocorticoids. See Table 36.3 for
usual indications for each mineralocorticoid.
Pharmacokinetics
These drugs are absorbed slowly and distributed
throughout the body. They undergo hepatic metabolism
to inactive forms. They are known to cross the placenta
and to enter breast milk. They should be avoided during
pregnancy and breastfeeding because of the potential
for adverse effects in the fetus or baby.
Contraindications and cautions
These drugs are contraindicated in the presence of
any known allergy to the drug
to avoid hypersensitiv-
ity reactions
; with severe hypertension, heart failure
or cardiac disease
because of the resultant increased
blood pressure
; and with breastfeeding
due to potential
adverse effects on the baby
. Caution should be used in
pregnancy
because of the potential for adverse effects
to the fetus
, in the presence of any infection,
which will
alter adrenal response
, and with high sodium intake
because severe hypernatraemia could occur
.
Adverse effects
Adverse effects commonly associated with the use
of mineralocorticoids are related to the increased
fluid volume seen with sodium and water retention
(e.g. headache, oedema, hypertension, heart failure,
arrhythmias, weakness) and possible hypokalaemia.
Allergic reactions, ranging from skin rash to anaphy-
laxis, have also been reported.
Clinically important drug–drug interactions
Decreased effectiveness of salicylates, barbiturates,
hydantoins, rifampicin and anticholinesterases has been
reported when these drugs are combined with miner-
alocorticoids. Such combinations should be avoided if
possible, but if they are necessary, the person should be
monitored closely and the dose increased as needed.
• Because this drug affects your body’s natural defences,
you will need special care during any stressful situations.
You may want to wear or carry medical identification
showing that you are taking this medication. This
identification alerts any medical personnel taking care of
you in an emergency to the fact that you are taking this
drug.
• It is important to have regular medical follow-up. If
your drug dose is being tapered, notify your healthcare
provider if any of the following occurs: fatigue, nausea,
vomiting, diarrhoea, weight loss, weakness or dizziness.
• Keep this drug out of the reach of children. Do not
give this medication to anyone else or take any similar
medication that has not been prescribed for you.
Prototype summary: Fludrocortisone
Indications:
Partial replacement therapy in cortical
insufficiency conditions, treatment of salt-losing
adrenogenital syndrome; off-label use: treatment
of hypotension.
Actions:
Increases sodium reabsorption in the renal
tubules and increases potassium and hydrogen
excretion, leading to water and sodium retention.
Pharmacokinetics:
Route Onset
Peak
Duration
PO Gradual
1.7 hours
18–36 hours
T
1/2
:
3.5 hours; metabolised in the liver and excreted
in the urine.
Adverse effects:
Frontal and occipital headaches,
arthralgia, weakness, increased blood volume,
oedema, hypertension, heart failure, rash,
anaphylaxis.
