Adrenal Physiology and Pharmacology

 

Chapter 22:  Physiology and Pharmacology: Adrenocorticosteroids / Adrenocortical Antagonists

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Adrenocorticosteroids and Adrenocortical Antagonists

Glucocorticoids (naturally occurring; cortisol -- hydrocortisone)

Synthetic Adrenocorticosteroids

 

Activity
Drug Anti-inflammatory Salt-retaining Dosage Forms
Short/medium-acting glucocorticoid

hydrocortisone (cortisol)

1

1

oral, injectable, topical

cortisone (Cortone)

0.8

0.8

oral, injectable, topical

prednisone (Deltasone)

4

0.3

oral

prednisolone (Prelone)

5

0.3

oral, injectable, topical

methylprednisolone (Solu-Medrol)

5

0

oral, injectable, topical

Intermediate-acting glucocorticoid

triamcinolone (Aristocort)

5

0

oral, injectable, topical

fluprednisolone

15

0

oral

Long-acting glucocorticoid

betamethasone (Celestone)

25-40

0

oral, injectable, topical

dexamethasone (Decadron)

30

0

oral, injectable, topical

Activity
Drug Anti-inflammatory Salt-retaining Dosage Forms
Mineralocorticoids

fludrocortisone (Florinef)

10

250

oral, injectable, topical

desoxycorticosterone acetate

0

20

injectable, pellets

Adapted from Table 39-1: Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 640.

Clinical Pharmacology

Altered Adrenal Function: Diagnosis and Treatment

"Atrophic adrenal, gross, in chronic adrenocortical insufficiency "; 1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center.For more information concerning endocrine pathology http://www.kumc.edu/instruction/medicine/pathology/ed/ch_21/ch_21_f.html
 

Symptoms (frequency of symptom %)

fatigue (99%)

weakness (99%)

anorexia (90%)

nausea (90%)

vomiting (90%)

weight loss (97%)

cutaneous/mucosal pigmentation (99%, 82%)

hypotension (87%,<than 110/70 mmHg)

hypoglycemia (occasionally)

Glucocorticoid Reserve Test

  • Shortly after ACTH administration (minutes), cortisol increases in adrenal venous blood.
    • Responsiveness: an indication of functional adrenal gland cortisol production reserve
    • Maximal ACTH stimulation: cortisolsecretion may increase tenfold -- with prolonged ACTH infusion;
      • with 24 hour infusion of cosyntropin, patients with secondary or primary adrenal insufficiency will have diminished maximal plasma cortisol values
  • Screening Test-- rapid ACTH stimulation test
    • administer 0.25mg of cosyntropin by intravenous or intramuscular injection
    • measure plasma cortisol levels before and 30 and 60 minutes after:
      • minimal stimulated normal cortisol increment: > 7 ug/dL; normal response > 18 ug/dL

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Adrenocortical hyperfunction

"Hyperplastic adrenals and poorly developed ovaries, uterine tubes and uterus in a female child with congenital adrenal hyperplasia"; 1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center;For more information concerning endocrine pathology http://www.kumc.edu/instruction/medicine/pathology/ed/ch_21/ch_21_f.html

"Abdominal striae in a patient with trucal obesity in Cushing syndrome"; 1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center. For more information concerning endocrine pathology http://www.kumc.edu/instruction/medicine/pathology/ed/ch_21/ch_21_f.html

Adrenocorticosteroids in treatment of nonadrenal disorders
Disorder Some Examples

Allergic reactions

angioneurotic edema, asthma, contact dermatitis, drug reactions, allergic rhinitis, urticaria

Collagen-vascular pathology

giant cell arteritis, lupus erythematosus, polymyositis, rheumatoid arthritis, temporal arteritis
Eye diseases allergic conjunctivitis, optic neuritis
Gastrointestinal inflammatory bowel disease than
Hematologic acute allergic purpura, leukemia, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, multiple myeloma
Infections gram-negative septicemia and
Inflammatory disorders of joints/bones arthritis, bursitis,tenosynovitis
Neurologic cerebral edema, multiple sclerosis
Organ Transplantation prevention/treatment of rejection (immunosuppression)
Pulmonary bronchial asthma, prevention of infant respiratory distress,sarcoidosis, aspiration pneumonia
Renal nephrotic syndrome
Skin atopic dermatitis, dermatoses, mycoses fungoides, seborrheic dermatitis
Thyroid malignant exophthalmos, subacute thyroiditis
adapted from Table 39-2; Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 643.

 

Antagonists of Adrenocortical Agents

  1. Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 635-650.
  2. Williams, G. H and Dluhy, R. G. , Diseases of the Adrenal Cortex, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2035-2056

     

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