Post on 11-Jan-2016
Cairo University
Faculty of Pharmacy
Department of Pharmacology & Toxicology
Pharmacology IIIPractical Sessions
Adrenocortical
hormones
Adrenocortical
hormones
The adrenal cortex secretes 3 types of hormones:
• Mineralocorticoids (mainly aldosterone)• Glucocorticoids (mainly cortisol = hydrocortisol)• Androgens
Hormones Pharma-III Practical
- Regulation of secretion:
Hypothalamus
Anterior Pituitary
Adrenal cortex
Glucocorticoids
CRF
ACTH = Corticotropin
-
-
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Long-term administration of exogenous GCs -ve feedback on ACTH & CRH
Suppression of Adrenal cortices
Too rapid withdrawal of GCs acute adrenal insufficiency may lead to death!!!
Hence, GCs should be GRADUALLY withdrawn
Very important
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Diurnal (circadian rhythm)
• ACTH is secreted in irregular bursts through out the day
• Plasma cortisol tends to rise and fall in response to these bursts
• These bursts are most frequent in early morning and least frequent in the evening
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1- Glucocorticoids
Actions of GCs:1. Metabolism: CHO metabolism: maintains an adequate glucose
supply within a normal range. Similar to growth hormone (GH), GC has anti-insulin activity utilization of glucose
by peripheral tissues GC also gluconeogenesis hepatic glucose
output Both hyperglycemia insulin secretion
(hyperinsulinemia)
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Protein metabolism: pharmacological or therapeutic dose of GC has catabolic effect on protein.
Fat metabolism: pharmacological or therapeutic dose of GC causes peculiar redistribution of fats thin extremities & central obesity (↑ fat deposition in abdominal area & in face & back of neck & shoulders moon-face & buffalo hump)
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2. Electrolyte balance: hydrocortisone has a weak mineralocorticoid-like activity Na+& H2O reabsorption & K+ & H+ secretion.
3. CVS: blood Pressure.4. CNS: behavioral changes.5. GIT: PGs HCl & mucus formation predispose to peptic ulcer.6. Skeletal muscles: GCs are essential for normal muscle
work ( GC muscle weakness due to protein catabolism and electrolyte imbalance)
7. Anti-inflammatory effect8. Immunosuppressive effect
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Clinical disorders
Hypercorticism: Cushing`s syndrome
Hypocorticism: Addison`s disease
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Cushing’s syndrome
Clinical state of excess free GCs occurs due to:
Therapeutic administration of ACTH or GCs for long periods Endocrine disorder (Pituitary ACTH dependent ACTH secretion), Known as cushing disease (Pituitary ACTH independent adrenal tumor) Tumor outside the normal pituitary-adrenal system,
which produces ACTH (ectopic Cushing’s syndrome) (small cell lung cancer).
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The dexamethasone suppression test is designed to diagnose and differentiate among
the various types of Cushing's syndrome
Dexamethasone is given at night & plasma cortisol is measured next morning
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Cortisol Interpretation
Not suppressed Adrenal CS
Suppressed Pituitary CS
Features of Cushing`s syndrome : Hyperglycemia . Thinning of skin. Myopathy & muscle weakness Uneven fat redistribution.
• Buffalo hump.• Moon face.• abdominal fat.
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Features of Cushing`s syndrome….. contd.
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Hypertension. Poor wound healing. susceptibility to
infection. in hair growth (increase
androgens and inhibition of GNRH
FSH and LH, estrogen).Osteoporosis (decrease Ca abs,
increase Ca secretion, stimulate PTH to
increse bone resorption, inhibition of GnRH ). Euphoria, psychosis or
depression.
Features of Cushing`s syndrome…… contd.
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Purple or red stria (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage)
Features of Cushing`s syndrome …… contd.
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☺ Treatment of Cushing’s syndrome:
- or stop exogenous GC gradually (risk vs benefit)
- Surgical removal of the tumor
- Using inhibitors of biosynthesis, e.g.:Aminoglutethimide Trilostane Metyrapone
- Using GCs receptor antagonists , e.g.: Mifepristone
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Addison’s disease
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This clinical state occurs due to:1ry adrenal insufficiency:Adrenal cortex dysfunction ( GCs ACTH)2ry adrenal insufficiency:pituitary disorder ( ACTH GCs)3ry adrenal insufficiency:hypothalamic disorder ( CRF ACTH GCs)
Features of Addison`s disease :
Weakness & fatigue. Hypotension. Anorexia & , weight loss. Hyperpigmentation (bronzing of skin) Why? Due to ↑ ACTH, which has structural similarity with MSH ↑ melanin production by melanocytes also MSH is a by product of ACTH synthesis from common precursor.
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☺ Treatment of Addison’s disease:
Replacement therapy with:
• GCs as prednisolone &• Mineralocorticoids as fludrocortisone
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N.B. Immune mediated destruction of the adrenal glands often occurs in conjunction with other autoimmune endocrine diseases such as thyroiditis (hypothyroidism), diabetes mellitus or hypoparathyroidism or non endocrine disease as vitiligo (autoimmune polyendocrine syndrome )
Diagnosis: Physical examination Laboratory tests:
Laboratory tests Cushing’s syndrome
Addison’s disease
Serum cortisol(190-680 mmol/l)
↑ ↓
Serum ACTH(10-47 ng/l)
↑ or ↓ ↑
Na+ ↑ ↓K+ ↓ ↑Fasting BGL(70-120 mg/dl)
↑ ↓
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2- Mineralocorticoids
Actions: - ↑ Na+ & H2O reabsorption and ↑ K+ & H+ secretion.
- Regulation of aldosterone secretion: ↓ plasma Na+ , ↑ K+ ↑ aldosterone. ↓ Na+ , ↓ BP ↑ renin ↑ Ang II ↑ aldosterone. ACTH also stimulates secretion but to a much smaller
extent.
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• Hypertension• Hypernatremia• Hypokalemia• Alkalosis
Clinical disordersHyperfunction:
1ry hyperaldosteroni
sm(CONN`s disease)
Hypofunction:Hypoaldosteronis
m
• Hypotension•
Hyponatremia• Hyperkalemia• Acidosis
ttt: Aldosterone antagoniste.g. Spironolactone
ttt: RT with fludorocortisone
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due to overactivity of the renin-angiotensin system. As inJuxtaglomerular cell tumor.Renal artery stenosis. Hyporeabsorption of sodium from kidney tubules
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Hyperfunction:
2ry hyperaldosteronism
(hyperreninism, or hyperreninemic hyperaldosteronism)
Instructions•Students will be informed with their antibiotics (drug profile) on Monday.•Only presentations are required.•Presenting time = 10 min.•The presentations will be held on Sunday (30/11) and Tuesday (2/12), each group in their corres-ponding labs.
Chrousos syndrome
Assessment
Thank You!