Presentation is loading. Please wait.

Presentation is loading. Please wait.

Lísek, 2003 Corticosteroids Slíva, M.D.. Lísek, 2003 ADRENOCORTICOSTEROIDS GLUCOCORTICOIDS MINERALOCORTICOIDS SEXUAL HORMONS Lísek, 2003.

Similar presentations


Presentation on theme: "Lísek, 2003 Corticosteroids Slíva, M.D.. Lísek, 2003 ADRENOCORTICOSTEROIDS GLUCOCORTICOIDS MINERALOCORTICOIDS SEXUAL HORMONS Lísek, 2003."— Presentation transcript:

1 Lísek, 2003 Corticosteroids Slíva, M.D.

2 Lísek, 2003 ADRENOCORTICOSTEROIDS GLUCOCORTICOIDS MINERALOCORTICOIDS SEXUAL HORMONS Lísek, 2003

3 ADRENOCORTICOSTEROIDS Hypothalamus Adenohypophysis Suprarenal cortex trauma emotion diurnal rhythm corticosteroids ACTH CRF negative feedback Lísek, 2003

4 A. Clinical uses Substitutional therapy suprarenal insuficiency Non-endocrine diseases arthritis vascular disorders eye diseases gastrointestinal diseases blood disorders sarcoidosis immunosuppression infections (suppression of inflammation) mountain sickness nervous system disorders (MS) diseases of skin, kidney etc. Lísek, 2003

5 Daily production of corticosteroids: Lísek, 2003

6 1. Corticosteroids bind to glucocorticoid or mineralocorticoid receptors, the steroid-receptor complex then regulates gene transcription. 2. Example for anti-inflammatory properties: glucocorticoids increase lipocortin transcription lipocortin inhibits phospholipase A decreased arachadonic acid and eicosanoids B. Mechanism of action: Lísek, 2003

7 Mechanism of action:

8 Lísek, 2003 C. Effects of glucocorticoids  liver deposits of glykogen  gluconeogenesis  catabolism of proteins  catabolism of bones  inflammatory response  immune response Lísek, 2003

9 Fluoride CH3-methyl group (  antiinflam. úč.) (  retence sodíku) D. Structure-activity relationship: - required for activity: ketone at position 3 & double bounds at 4-5 Smaller modifications in the basic corticosteroid structure alter: sodium-retaining potency antiinflammatory potency drug half-life transcortin binding Lísek, 2003

10 E. Therapeutic potential of various corticosteroids (in comparisson to hydrocortisone): Lísek, 2003

11 Glucocorticoid potencies : very high high very low dexamethasone prednisolon fludrocortisone triamcinolone methylprednisolone betamethasone Mineralocorticoid potencies: very high low very low fludrocortisoneprednisolonedexamethasone methylprednisolonebetamethasone triamcinolone Lísek, 2003 E. Therapeutic potential of various corticosteroids (in comparisson to hydrocortisone):

12 Lísek, 2003 F. Pharmacokinetics 1. Routes of administration: - oral (systemic, long-term treatment - i.m., i.v. (emergency) - topical (eyes, skin, HEENT) - intra-articular injection - inhalation - nosespray systemic local Lísek, 2003

13 2. Metabolism of corticosteroids (liver): - reduction of double bound at 4-5 position yield to inactive forms - conjugation of inactive metabolism - excretion Liver disease affects steroid metabolis: prednisone (inactive) prednisolone (active) Lísek, 2003 F. Pharmacokinetics

14 Lísek, Half-lives of various corticosteroids : Lísek, 2003 F. Pharmacokinetics

15 Lísek, 2003 G. Adverse effects & toxicity: 1. General considerations: - route of administration - systemic x local - dose - length of therapy 2. Short-term systemic therapy: - no ADRs Lísek, 2003

16 3. Long-term systemic administration: - Cushingoid features (fat redistribution) - Sodium retetion (edema, hypertension, heart failure) - Potassium loss (muscle weakness) - Glucose intolerance - Weight gain - Loss of skin collagen => skin atrophy, stria - Osteoporosis - Peptic ulcer - HPA axis suppression - CNS effects (psychosis, insomnia, nervousness, euphoria depression) - Susceptibility to infection - triamcinolone – weight loss and sedatione - Masking of symptoms of other diseases Lísek, 2003 G. Adverse effects & toxicity:

17 Lísek, Local use: - inhaled steroids - candidal infection, dysphonia - nasal steroids – irritation, headache, nosebleed, dry nose - topical - epidermal atrophy, steroidal acne akné, teleangiectasis, hypertrichosis, pigmentation disorders, dermatitis perioralis, granuloma gluteale infantum Lísek, 2003 G. Adverse effects & toxicity:

18 Lísek, Minimizing side effects: - Smallest possible dose - Shortest possible duration - Local application - Alternate day therapy - Descendent therapy during withdrawal - Encapsulation into liposomes Lísek, 2003 G. Adverse effects & toxicity:

19 Lísek, 2003 H. Corticosteroid withdrawal: 1. General consideration - dose - duration - half-life 2. Withdrawal - administration of short or intermediating-acting steroids - gradually taper dose Lísek, 2003

20 3. Withdrawal symptoms: - acute adrenal insufficiency - dependence - exacerbation of underlying disease - re-bound phenomenon Lísek, 2003 H. Corticosteroid withdrawal:

21 Lísek, 2003 I. Drug interactions: Drugs that decrease steroid effectiveness: inductors of liver enzymes cholestyramine Drugs that increase steroid effectiveness: ATB - erythromycin oral contraceptives ketoconazole Lísek, 2003

22 Drugs affected by steroid administration: anticoagulants (dosage increase needed) antihypertensives (dosage increase needed) hypoglycemics (dosage increase needed) sympathomimetics (dosage decrease needed) Lísek, 2003 I. Drug interactions:


Download ppt "Lísek, 2003 Corticosteroids Slíva, M.D.. Lísek, 2003 ADRENOCORTICOSTEROIDS GLUCOCORTICOIDS MINERALOCORTICOIDS SEXUAL HORMONS Lísek, 2003."

Similar presentations


Ads by Google