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Adrenocorticosteroids
Adrenocorticosteroids
and
Adrenocortical Antagonists
Classification:
A. Mineralocorticoids
B. Glucocorticoids
C. Adrenal Androgens
A. Mineralocorticoids
Aldosterone – electrolyte-balance regulating, salt-
retaining activity
- promotes reabsorption of Na+ from the distal convoluted tubules and proximal
collecting tubules; loosely coupled with K+ and H+ ions excretion
- increase Na reabsorption in sweat, salivary glands. Gastric mucosa
- MOA: binds with mineralocorticoid receptor
- secreted at a rate of 100-200ug/d
- t ½ 15-20mins
- excreted in the urine as tetrahydroaldosterone and 3-oxo-glucoronide in 5-
15mcg/24 hr
Mineralocorticoids (cont.)
Deoxycortisone (DOC)
- 200 mcg/d; t ½ : 70mins.
- ↑ levels with adrenocortical carcinoma; CAH
Fludrocortisone
- both mineralocorticoid and glucocorticoid activity;
potent salt-retaining activity
- most widely used mineralocorticoid
- treatment of adrenocortical insufficiency
- oral dose: 0.1 mg 2 to 7X weekly
B. Glucocorticoids
Cortisol – carbohydrate metabolism regulating,; intermediary
metabolism; immune function; synthesis and secretion is tightly
regulated by the CNS
- Hydrocortisone; compound F
- 10-20 mg daily; circadian rhythm (24-hour cycles)
- bound to CBG (90%); albumin (5%), free (5%) exerts effect in target cells; if plasma
cortisol > 20-20mg/dl, CBG is saturated so concentration of free cortisol rises
- t ½ =60-90 mins.; > in hypothyroidism, stress, liver disease or if administered in large
amounts
- liver
- (glucoronic acid or sulfates)
- 1/3 excreted as dihydroxyketone (17-hydroxysteroids ) while 1% is unchanged
- excretion: 1% unchanged (free cortisol)
20% is converted to cortisone by 11-hydroxysteroid dehydrogenase
CBG (transcortin) – α 2 globulin (liver)
• Electrolyte :
- ↑Ca excretion by the kidneys (antagonize vit.D effect on Ca
absorption)
Physiologic effects (cont.):
• Formed elements of blood:
- minor effects on hgb and erythrocyte production
- affect circulating WBC
(Addison’s: lymphocytosis, ↑ mass of lymphoid tissue)
C. Non-Adrenal Diseases
1. Rheumatic disorders – suppress the disease
and minimize resultant tissue damage
mgt: oral prednisone 10 mg/kg/day (taper
thereafter by decreasing 1mg/kg/day every
2-3 wks)
- intraarticular injection: triamcinolone acetonide:
minimize complications (3-4x/year)
C. Non-Adrenal Diseases (cont.)
–
To r/o depression, anxiety, concurrent illness,
Cushing’s
Liddle’s test:
1. Get urine sample and measure urinary ketosteroids
2. If elevated, proceed to #3
3. Dexamethasone 0.5mg every 6hrs x 48 hrs. – measure
urinary steroids ( if ↑, (+) Cushing’s; then proceed to #4
4. Dexamethasone 2 mg every 6 hrs. x 48 hrs.- measure
urinary steroids (if ↑, due to an adrenal tumor; if ↓, due to
a pituitary tumor)
• Skin atrophy
• Striae (groin and axillae)
• Slowed healing
• Telangiectasia
• Purpura
• Rosacea
• Acne
• Perioral dermatitis
• Hypertrichosis
Dosage regimen
• Consider seriousness of the disease
• Consider amount of drug required to obtain
desired effect
• Consider duration of therapy
• Use lowest dose possible
• Consider amount required for maintenance of
the desired therapeutic effect
• Use alternate day administration
Summary of adrenocortical agonists
and antagonists……
• Review briefly the anatomy and physiology adrenal gland
• Name the different adrenocorticotropic hormones
• Identify adrenocorticotropic hormones and discuss their
pharmacokinetics and pharmacodynamics
• Classify adrenocorticoids according to their action and
potency
• Enumerate the clinical applications of adrenocortocotropic
hormones
• Discuss adrenocortical antagonists and their clinical
applications
Thank You