Term
| How are corticosteroids synthesised? |
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Definition
| Synthesised by CYP450 enzymes in the liver from cholesterol |
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Term
| What is the MOA of corticosteroids? |
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Definition
•Corticosteroids penetrate cells and bind to a cytoplasmic receptor
•Drug-Receptor complex enters nucleus, bind to Glucocorticoid Response Elements (GRE) on gene, regulates the transcription leading to altered mRNA and protein synthesis.
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Term
| What are the actions of Mineralocorticoid? |
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Definition
Increases Na+ reabsorption from the DCT and CD
Increases K+ and H+ excretion in urine
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Term
| What are the actions of Glucocorticoid during a fasting state? |
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Definition
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1. Carbohydrate: Promotes gluconeogenesis, and
glycogenesis in fasting state - Causes
hyperglycemia by inhibiting peripheral
utilisation & stimulating release of glucose from
liver
2. Proteins: Catabolic action—increased
breakdown- bone, muscle, fat, skin
Mobilization of amino acids for glucose production
Negative nitrogen balance
3. Fat: Promotes Lipolysis- fatty acids
Redistribution of body fat occurs
Net result - In fasting state- Supply of glucose from gluconeogenesis, release of aminoacids from muscle catabolism, inhibition of peripheral glucose uptake, stimulation of lipolysis = manintain adequate glucose supply to brain
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Term
| What are the other effects of Glucocorticoids? |
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Definition
4. Inflammation:
•decrease the circulating lymphocytes, monocytes, eosinophils, basophils, increase neutrophils
•inhibit PLA2 , reduce the expression of COXII- reducing production of PGs, LTs
5.Immunity: Suppresses Cell mediated immune response
•inhibit the functions of macrophages and APCs.
•Macrophages and lymphocytes produce less IL-2, IFN-g- inducers of TH1 activity and cellular immunity
•Antibody production is reduced by large doses of steroids.
6. Calcium metabolism: Negative Ca balance
•Inhibit intestinal absorption of Ca
•Enhance renal excretion of Ca
•Loss of bone from bone due to loss of osteoids
7. Other effects:
•Antagonise effect of vitamin D on calcium absorption
•Development of fetal lung and production of surfactant
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Term
| Name the short acting glucocorticoids & their effects? |
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Definition
•Hydrocortisone (cortisol) -- short and rapid acting with equal gluco and mineralocorticoid activity
•Prednisolone—more potent, more glucocorticoid activity
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Term
| Name the intermediate acting Glucocorticoids and their action? |
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Definition
Intermediate acting: t ½ 12-36 hours
•Triamcinolone – no mineralocorticoid activity
•Fluprednisolone
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Term
| Name the long acting glucocorticoids & their action |
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Definition
Long acting: t ½ around 36 hours
•Betamethasone
•Dexamethasone
Most potent, no mineralocorticoid activity
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Term
| Name the Mineralocorticoids |
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Definition
Mineralocorticoids:
•Aldosterone
•Fludrocortisone - No glucocorticoid activity
•Desoxycorticosterone
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Term
| Name the inhaled steroidal preparations |
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Definition
•Beclomethasone
•Budesonide
•Fluticasone
•Triamcinolone
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Term
What is addisons disease?
What is used to treat it? |
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Definition
Chronic adrenal insufficiency
Hydrocortisone & Fludrocortisone |
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Term
| How is Cushings syndrome diagnosed? |
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Definition
| Dexamethasone suppression test |
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Term
| What are the non adrenal disorders where Glucocorticoids can be used? |
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Definition
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•Allergic reactions: Anaphylaxis, Angioneurotic edema, Urticaria and drug reactions, bee sting, asthma
•Inflammatory conditions: Rheumatoid arthritis, Osteoarthritis, Gout
•Collagen vascular diseases: Systemic lupus Erythematousus, giant cell arteritis, Polyarteritis nodosa
•GI disorders: Ulcerative colitis, Crohn’s disease
•Haematological disorders: Leukaemia, Lymphomas, multiple myeloma
•Organ transplantation : prevention and treatment of rejection
•Pulmonary diseases: Asthma, aspiration pneumonia
•Skin diseases: atopic dermatitis, dermatoses
•Thyroid diseases: thyroiditis
•Stimulation of lung maturation in fetus:
–Lung maturation in fetus is regulated by fetal secretion of cortisol.
–Betamethsone administration to mother reduces incidence of respiratory distress syndrome in infants delivered prematurely
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Term
| What are the ADR's associated with corticosteroids? |
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Definition
•Peptic ulcers
•Osteoporosis
•Precipitation of diabetes
•Oedema
•Muscle wasting, fragile skin,purple striae
•Precipitates infection-Tuberculosis, candidiasis
•Cataract (posterior subcapsular type)***
•Cushing’s habitus
•Delayed wound healing
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Term
What are the withdrawl symtoms of Glucocorticoids?
Why do they occur? |
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Definition
malaise, fever, weakness, joint pain, reactivation of disease - due to abrupt termination of treatment |
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Term
What could cause Hypothalamus-Pituitary-axis (HPA) suppression?
How can these effects be reduced? |
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Definition
Long term use of corticosteroids.. ie inhaler for asthma (over 2 weeks)
Alternate day therapy. |
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Term
Metyrapone
MOA?
Use?
ADR? |
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Definition
Glucocorticoid antagonist - Inhibits 11-hydroxylation and thus the synthesis of cortisol
Used:
Cushing's syndrome, specially in pregnant women, since this is the only safe antagonist.
Also used in tests of adrenal function
ADR
Hirsutism, edema are the adverse effects
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Term
Ketoconazole
MOA?
Use?
ADR? |
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Definition
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Ketoconazole
Glucocorticoid antagonist - An antifungal imidazole - Inhibit the enzymes required for steroids synthesis
Use: Cushing’s syndrome
ADR: Hepatotoxicity
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Term
Mifepristone (RU486)
MOA?
Use?
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Definition
Glucocorticoid antagonist - Has strong antiprogestinactivity- High doses blockglucocorticoid receptors
Mainly used as contraceptive,abortifacient
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Term
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Definition
Mineralocorticoid antagonist
•Primary hyperaldosteronism
•Hirsutism
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Term
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Definition
Mineralocorticoid antagonist
approved for HTN |
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