adrenocorticoids Flashcards
what medulla adrenal gland produce?
catecholamines eg: adrenaline
the outer zona glomerulosa (cortex of adrenal) produce
aldosterone
the middle zona fascicula (cortex of adrenal) produce
cortisol
the inner zona reticularis (cortex of adrenal) produce
sex hormone
function of cortisol
- restore homeostasis following stress
- cortisol is controlled by negative feedback to CRH (cortisol releasing hormone in hypothalamus)
- inhibit prostaglandin production (repress the trc of COX-2)
- blockade of transcription activity of NF-kB
- activation of endothelial nitric oxide synthase
explain hydrocortisone (cortisol)
- major glucocorticoids
- produced in zona fasciculata
- ~20mg/day secreted
- short half life 60-180 mins
- water soluble
- 95% globulin binding
- secreted in circadian rhythm
- readily diffuse through cell membrane
explain aldosterone
- major mineralocorticoids
- produced in zona glomerulosa but main production is in renin-angiotensin pathway
- 50% bound with low affinity to albumin
- salt-retaining activity
- for electrolytes and water balance
- efflux of K+ and H+
effects of too much aldosterone production
- hypernatremia
- hypokalemia
- alkalosis
cortisol function
- effect on metabolism
- carbohydrates- prevent utilise glucose, anti-insulin effect, promote glucose synthesis
- proteins- catabolic hormone
- lipids- excessive lipid moonface, ‘buffalo hump’, lipid in the trunk - as anti-inflammatory function
what glucocorticoid do in direct genomic action?
increase transcription of ANTI-inflammatory genes
what glucocorticoid do in indirect genomic action?
dampen the transcription of PRO-inflammatory genes
what causes glucocorticoid resistance?
- familial glucocorticoid resistance
- glucocorticoid receptor modification
eg: phosphorylation, nitrosylation, ubiquitination - increased pro-inflammatory trc factors
- defective histone acetylation
- increased P-Gp (efflux of steroids)
clinical uses for glucocorticoids
- opthalmic diseases
- endocrine disorders
- rheumatic disorders
- collagen disorders
- allergic eg: asthma
- dermatological diseases
- respiratory diseases
- neoplastic disease
- haematological disorders
- UC, TB, meningitis
clinical uses for mineralocorticoids
- as replacement therapy for Addison’s disease
- treatment of salt-losing adrenogenital syndrome
drug for asthma inhalation
beclomethasone
- have to rinse mouth
- might cause fungal infection
- immunosupressive drug
drug for asthma orally
prednisolone (glucocorticoids)
drug for asthma IV
hydrocortisone
effects of toxicity of glucocorticoids
- hypothalamic-pituitary-adrenal supression
- euphoria to depression in withdrawal of drug
- hyperglycemia
- loss of muscle bulk (increase proteolysis, decrease protein synthesis)
- redistribution of body fat
- growth retardation in children
- immunosuppression
- cause osteoporosis
- decrease Ca absorption in GIT
- decrease gonadotrophin secretion, hypogonadism
- congenital malformations
- dyslipidemia
- hypertension
- thrombosis
- vasculitis
- cataracts
- glaucoma
- increase Na+ retention and K+ excretion
commonly used anti-inflammatory STEROIDS
- cortisol
- fludrocortisone
- prednisone
- prednisolone
- dexamethasone
causes of cushing’s disease
- adrenal hyper-activity by eg: adrenal tumour
- excessive exposure to glucocorticoids
treatment for cushing’s disease
reduce glucocorticoids dosage and surgery
what is Addison’s disease
- adrenal insufficient
- auto-immune disorders
- both CORTISOL and ALDOSTERONE lacking
clinical sign and symptoms of Addison’s disease
- fatigue
- wasting
- dizziness
- pigmentation
- nausea
- diarrhoea
- low bp
treatment for Addison’s disease
cortisol with fludrocortisone
what is conn’s syndrome?
- hyper production of aldosterone
- aldosterone producing adenoma
- aldosterone secreting carcinoma
- inability of adrenal cortex to carry out 17a-hydroxylation
clinical signs and symptoms of conn’s syndrome
- muscle weakness
- hypertension
- hypokalemia
- cardiac arrhythmia
treatment of conn’s syndrome
- surgery removal of adenoma
- spironolactone (aldosterone receptor agonist)
