Presentation on theme: "Adrenocortical hormones"— Presentation transcript:
1 Adrenocortical hormones Cairo UniversityFaculty of PharmacyDepartment of Pharmacology & ToxicologyPharmacology IIIPractical SessionsAdrenocortical hormones
2 Mineralocorticoids The adrenal cortex secretes 3 types of hormones: Pharma-III PracticalThe adrenal cortex secretes 3 types of hormones:Mineralocorticoids(mainly aldosterone)Glucocorticoids(mainly cortisol = hydrocortisol)Androgens
3 - Regulation of secretion: HormonesPharma-III Practical- Regulation of secretion:-HypothalamusCRFAnterior PituitaryACTH = CorticotropinAdrenal cortexGlucocorticoids
4 Very important Hormones Pharma-III PracticalVery importantLong-term administration of exogenous GCs -ve feedback on ACTH & CRH Suppression of Adrenal corticesToo rapid withdrawal of GCs acute adrenal insufficiency may lead to death!!!Hence, GCs should be GRADUALLY withdrawn
5 1- Glucocorticoids Diurnal (circadian rhythm) Hormones Pharma-III Practical1- GlucocorticoidsDiurnal (circadian rhythm)ACTH is secreted in irregular bursts through out the dayPlasma cortisol tends to rise and fall in response to these burstsThese bursts are most frequent in early morning and least frequent in the evening
6 Actions of GCs: Hormones 1. Metabolism: Pharma-III PracticalActions 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 outputBoth hyperglycemia insulin secretion (hyperinsulinemia)
7 HormonesPharma-III PracticalProtein 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)
8 HormonesPharma-III Practical2. Electrolyte balance: hydrocortisone has a weak mineralocorticoid-like activity Na+& H2O reabsorption & K+ & H+ secretion.3. CVS: blood Pressure.4. CNS: behavioral changes.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
10 Clinical state of excess free GCs occurs due to: HormonesPharma-III PracticalCushing’s syndromeClinical state of excess free GCs occurs due to:Therapeutic administration of ACTH orGCs for long periodsEndocrine 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).
11 The dexamethasone suppression test HormonesPharma-III PracticalThe 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 morningCortisolInterpretationNot suppressedAdrenal CSSuppressedPituitary CS
12 Features of Cushing`s syndrome : HormonesPharma-III PracticalFeatures of Cushing`s syndrome :Hyperglycemia .Thinning of skin.Myopathy & muscle weaknessUneven fat redistribution.Buffalo hump.Moon face. abdominal fat.
13 Features of Cushing`s syndrome….. contd. HormonesPharma-III PracticalFeatures of Cushing`s syndrome….. contd.
14 Hormones Pharma-III Practical Hypertension. Poor wound healing. Features of Cushing`s syndrome…… contd.Hypertension.Poor wound healing. susceptibility to infection. in hair growth (increase androgens and inhibition of GNRHFSH and LH, estrogen).Osteoporosis (decrease Ca abs, increase Ca secretion, stimulate PTH to increse bone resorption, inhibition of GnRH ).Euphoria, psychosis or depression.
15 HormonesPharma-III PracticalFeatures of Cushing`s syndrome …… contd.Purple or red stria (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage)
16 ☺ Treatment of Cushing’s syndrome: HormonesPharma-III Practical☺ Treatment of Cushing’s syndrome: or stop exogenous GC gradually(risk vs benefit)Surgical removal of the tumorUsing inhibitors of biosynthesis, e.g.:AminoglutethimideTrilostaneMetyraponeUsing GCs receptor antagonists , e.g.:Mifepristone
17 Addison’s disease Hormones This clinical state occurs due to: Pharma-III PracticalAddison’s diseaseThis 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)
18 Features of Addison`s disease : HormonesPharma-III PracticalFeatures 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.
19 ☺ Treatment of Addison’s disease: HormonesPharma-III Practical☺ Treatment of Addison’s disease:Replacement therapy with:GCs as prednisolone &Mineralocorticoids as fludrocortisoneN.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 )
23 2ry hyperaldosteronism HormonesPharma-III PracticalHyperfunction:2ry hyperaldosteronism(hyperreninism, or hyperreninemic hyperaldosteronism)due to overactivity of the renin-angiotensin system. As in Juxtaglomerular cell tumor. Renal artery stenosis. Hyporeabsorption of sodium from kidney tubules
24 InstructionsStudents 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.