Pharmacological Treatment of Adrenal and Thyroid Disease Flashcards
Zona Glomerulosa
Mineralocorticoids
Zonae Fasciculata/Reticularis
Glucocorticoids
Adrenal androgens
Glucocorticoids
carbohydrate metabolism
Major type: hydrocortisone/cortisol
Mineralocorticoids
electrolyte-water homeostasis
Major type: aldosterone
ACTH i.v. test
stimulate cortisol secretion, diagnosis of adrenocortical insufficiency
Morning ACTH level
evaluate pituitary function during the recovery from prolonged glucocorticoids exposure
Corticosteroid-binding-globulin (CBG): availability
bind greater than 80% of circulating cortisol (unavailable)
<20% cortisol is free or loosely bound to albumin (available)
Aldosterone dose not bind CBG, has short half-life
Dexamethasone dose not bind CBG, thus is 100% active
Pharmacokinetics Corticosteroids
short-acting: cortisol and cortisone - Salt-retaining
intermediate-acting: prednisone
Intermediate anti-inflammatory and salt-retaining activity
long-acting: dexamethasone and betamethasone
Maximal anti-inflammatory and minimal salt-retaining activity
Glucocorticoid Metabolic effects
Promotes gluconeogenesis in liver and inhibits glucose utilization in periphery
Increased protein and fat catabolism
Inhibits Calcium absorption, osteoblast formation and activity
Glucocorticoid Anti-inflammatory effects
Suppress activation of T cells and production of cytokines
Prevent release of inflammation mediators
Reduce circulating lymphocytes, monocytes, eosinophils, and basophils
Inhibit the function of leukocytes and macrophages
stimulate gastric acid and pepsin production
Glucocorticoids Therapeutic Uses
Primary: Addison’s disease
Acute: emergency, hydrocortisone i.v.
Chronic: replacement therapy, mimic the circadian secretion
All adrenal steroids are reduced
Secondary
Often caused by suppression of the HPA axis
Low cortisol and androgens, but normal aldosterone
Drug selection: cortisol (hydrocortisone)
Glucocorticoids Therapeutic Uses 2
Anti-inflammation and immunosuppression
Allergy: bee sting, drug reactions, contact dermatitis
Brochial asthma, infant respiratory distress
Inflammation and autoimmune disorder: arthritis,
multiple sclerosis, systemic lupus
Prevent organ rejection in transplantation
Drug selection: intermediate- and long-acting; maximal anti-inflammatory and minimal salt-retaining activity for severe cases
Glucocorticoids Therapeutic Uses 3
Evaluate the function of hypothalamus-pituitary-adrenal axis
Cushing’s Syndrome
Increased urine cortisol level
Fail in low-dose dexamethasone suppression test
For all types of Cushing’s syndrome: failure in suppression of serum cortisol to < 5 mg/dL by a low dose of dexamethasone.
Cushing Syndrome
full moon face and trunk obesity
muscle waste and thinning of skin
osteoporosis
Glucocorticoids Adverse Effects and Clinical Problems
Withdrawal of steroids
Acute adrenal insufficiency, due to suppression of HPA axis
Flare-up of underlining disease
Mineralocorticoids Pharmacological effects and therapeutic uses
Pharmacological effects:
Salt-remaining activity: promoting reabsorption of sodium, secretion of potassium.
Therapeutic uses:
Adrenal insufficiency
Fludrocortisone is the most widely used mineralocorticoid.
Adverse effects: salt-retention and hypertension
Aminoglutethimide
Inhibits the conversion of cholesterol to pregnenolone.
Therapeutic Uses: adrenal and/or pituitary adenoma
Spironolactone
Antagonist for mineralocorticoid receptor.
Uses: aldosteronism, such as adrenal adenoma
Mifepristone (RU486)
Antagonist for glucocorticoid receptor
Also acts as an antagonist for progesterone receptor
Hypothyroidisim
Causes: destruction of thyroid
Autoimmune : Hashimoto’s thyroiditis
Surgery or lithium over dose
Levothyroxine
Synthroid, L-T4
Liothyronine
L-T3
Acute Severe Hypothyroidism
Hyperthyroidisim
Grave’s disease: Autoimmune antibody binds TSH receptor and mimics hormone
Hyperfunction goiter
Clinical symptoms:
Increased metabolic rate
Irregular heart beat/rapid pulse
Increased appetite with dramatic weight loss
Protruding eyes (bug eye), and Goiter
Thioureylene
Propylthiouracil (PTU)
Methimazole (Tapazol)
Inhibits peroxidase reactions in iodination of
TG and coupling of MIT/DIT
PTU also inhibits the conversion of T4 to T3
control of symptoms prior to surgery or RIA
Iodide or KI (Lugol’s) solution/tablet: >6 mg/day
Inhibits TH formation and release
Application: thyroid storm, preoperative thyroidectomy given after thioureylene
Radioactive iodide (131I) and surgery
Mechanisms: 131I emits beta-rays that kills surrounding thyroid cells
Application: severe hyperthyroidism/thyroid tumor, combined with life-long therapy with Synthroid
Propranolol
Beta blocker to reverse tachycardia during thyroid storm.
Used in combination with thioureylene
