Pharmacology I
(NURS2125)
Corticosteroids
Dr. Raya Al Maskari
Email: r.maskari@squ.edu.om
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Agenda
1. Introduction
2. Glucocorticoids
3. Inhibitors of corticosteroids
4. Mineralocorticoids
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Corticosteroids
Steroid hormones produced by
the adrenal cortex. They consist
of two major physiologic and
pharmacological groups:
1. Glucocorticoids: important
roles on metabolism,
catabolism, immune
responses and inflammation
2. Mineralocorticoids: regulate
sodium and potassium
reabsorption in the kidneys
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Synthesis Pathway
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Glucocorticoids
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Regulation of Cortisol Circadian
The hypothalamic-pituitary-adrenal axis: corticotropin- rhythm
releasing hormone (CRH) released from the
hypothalamus stimulates anterior pituitary
release adrenocorticotropic hormone (ACTH)
stimulates adrenal cortex
The negative feedback
mechanism: when
cortisol level in the
blood increases it
switches off the
release of CRH and
ACTH
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Mechanism of Action
- Enter the cell bind to
glucocorticoid receptors in
the cytoplasm transport
the steroids into the nucleus
- The steroid-receptor
complex bind glucocorticoid
response elements (GRE) on
the DNA activate or
inhibit genes changes in
protein synthesis by various
target tissues
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Classification
Endogenous Synthetic
glucocorticoids glucocorticoids
Cortisol betamethasone
dexamethasone
Cortisone prednisone
prednisolone
methylprednisolone
fludrocortisone
triamcinolone
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Individual glucocorticoids
have different anti-
inflammatory and
immunosuppressive effects
as well as different half-lives
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Actions
Metabolic effects Catabolic effects
- Stimulate gluconeogenesis - Muscle protein catabolism
increased blood glucose - Lymphoid, connective tissue,
and insulin secretion fat and skin wasting
- Stimulate lipolysis and - Catabolic effect on bones
lipogenesis increased fat osteoporosis
deposition in certain areas
(e.g. face, shoulders and Immunosuppressive effects
back) Inhibit cell-mediated
immunologic functions, esp.
those dependent on
lymphocytes
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Actions
Anti-inflammatory effects
- Major effect on distribution and functions of leukocytes
- neutrophils
- lymphocytes, eosinophils, basophils, monocytes
- Inhibit migration of leukocytes
Anti-inflammatory Mechanism:
- Inhibit phospholipase A2 blocks the release of arachidonic acid,
PGs and LTs
- Decrease production and release of proinflammatory cytokines (IL-1,
IL-6 and TNF-alpha)
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Actions
Electrolytes Other effects
- Sodium and water retention - Stomach: increase gastric
edema and hypertension acidity increase risk of
- Loss of potassium replace ulcer formation
with potassium supplements - Psychological: produce a
in patients receiving large feeling of well being
doses (euphoria) followed by
subsequent depression
- Adrenal cortical
hypertrophy: with prolonged
therapy
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Cushing’s Syndrome
- Set of symptoms resulting
from exposure to high levels
of glucocorticoids
(endogenous or synthetic)
- Causes: long term therapy
with glucocorticoids, adrenal
tumor, pituitary tumor
Dose should be tapered down
gradually and patient
monitored for adrenal
insufficiency syndrome 14
Therapeutic Uses
Adrenal Disorders-
Replacement Therapy
- Primary adrenocortical
insufficiency (e.g. Addison’s
disease)
- Secondary and tertiary
adrenocortical insufficiency
(caused by defects in CRH or
corticotropin production)
Hydrocortisone drug of choice
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Therapeutic Uses Relief of Inflammatory Symptoms
- Dramatically reduce manifestations
Treatment of Allergies of inflammation (e.g. systemic
- Asthma: long-term management lupus, rheumatoid arthritis,
of persistent asthma through vasculitis) – prednisolone
the inhalation route (e.g. commonly used
beclomethasone, fluticasone,
mometasone) Others
- Eczema: applied topically (e.g. - Accelerate lung maturation in
hydrocortisone) or orally in premature infants (betamethasone
severe cases (e.g. or dexamethasone)
methylprednisolone) - Diagnosis of Cushing’s syndrome
- Hay fever: applied topically (ear (dexamethasone suppression test)
drops or eye drops) - Leukemia and multiple myeloma
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Therapeutic considerations
1. Corticosteroids should not be given to patients with systemic fungal
infections as they may be exacerbated
2. Diabetics may experience an exacerbation of their disease
3. Symptoms of gastritis or peptic ulcer may be masked, and patients
may bleed without warning
4. Patients for whom edema may be hazardous (e.g. those with chronic
heart failure or impaired renal function) should be monitored closely
5. Use cautiously in pregnancy. If needed, prednisone or prednisolone
are less likely to cross the placental barrier
6. Long term therapy leads to impaired bone formation and
osteoporosis – patients should be regularly monitored for bone
density, vitamin D and 24-hour urinary Ca2+.
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Therapeutic considerations
7. The major adverse effects on the cardiovascular system include
dyslipidemia and hypertension, especially in the elderly.
8. Patients are at increased susceptibility to serious infections
(bacterial, viral, fungal)
9. Patients are at increased risk of wound infections and delayed
healing of open wounds
10. Patients may develop hyperglycemia – mild cases can be managed
with oral hypoglycemic agents
11. Patients may develop cataracts and ocular hypertension – regular
ophthalmological examination recommended
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Inhibitors of corticosteroids
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Ketoconazole
Mechanism of action:
Interact with cytochrome P450
block hydroxylating enzyme
systems inhibit steroid and
androgen synthesis
Therapeutic Uses:
Palliative treatment for Cushing’s
syndrome
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Aminoglutethimide
Mechanism of action:
Competitive inhibitor of desmolase,
the enzyme that catalyzes the
conversion of cholesterol to
pregnenolone reduced synthesis
of all steroid hormones
Therapeutic Uses:
- Cushing’s syndrome
- Metastatic breast and prostate
cancer
- Cancers of the adrenal cortex
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Mifepristone
Mechanism of action:
Progesterone receptor
antagonist that has a high
affinity for glucocorticoid
receptors
Therapeutic Uses:
Management and treatment
of hyperglycemia in patients
with Cushing’s syndrome
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Mineralocorticoids
Actions:
Act on kidney tubules and collecting
ducts to increase reabsorption of Na+
and water in exchange for K+
Endogenous:
Aldosterone
Synthetic:
Fludrocortisone (high mineralocorticoid
activity)
Therapeutic uses:
- Addison’s disease
- Replacement therapy post
adrenalectomy 23
Spironolactone
Mechanism of Action:
Aldosterone antagonist cause
increased amount of Na+ and
water excretion while K+ is
retained
Therapeutic Uses:
- Primary aldosteronism
(adrenal glands produce
excessive aldosterone)
- Hypertension
- Heart failure
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Q&A
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