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STEROIDS PowerPoint Presentation

STEROIDS

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STEROIDS

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  1. STEROIDS Pharmacology Study Group February 2013 – Lorna Roden

  2. Naturally occurring steroids do the same things as synthetic steroids and therefore if you understand the normally physiology you can understand the mechanism of action of steroids we give to patients. 1. Physiology

  3. What is a steroid? • A type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other.

  4. Types of steroid – Major classes Biosynthesis note: Progestogens serve as precursors to all other human steroids • Progestogens • Progesterone • Corticosteroids • Aldosterone (Mineralocorticoids) • Cortisol/Hydrocortisone (Glucocorticoids) • Androgens • Testosterone • Oestrogens • Oestrogen Mnemonic ALdosterone is a minerALocorticoid Sodium is a Mineral

  5. Where are they produced? ACTH + Corticosteroids Glucocorticoids Mineralocorticoids Oestrogen + Angiotensin II, low plasma Na+, high plasma K+ Testosterone

  6. Biosynthesis • Steroidogenesis • “The biological process by which steroids are generated from cholesterol and transformed into other steroids” • Metabolism • Oxidised by CYP450 enzymes • Form bile acids

  7. Action of Glucocorticoids • Cortisol • Bind to the glucocorticoid receptor (GR) • MANY effects Main effects: • Immunological • Up-regulate expression of anti-inflammatory proteins (COX-2, NO, IL’s) • Down-regulate the expression of pro-inflammatory proteins (NF-ƙB) • Decrease the function and numbers of lymphocytes (B and T cells) • Metabolic – in the fasted state… • Stimulate gluconeogenesis (liver) • Mobilisation of amino acids from extra-hepatic tissue • Inhibition of glucose uptake in muscle and adipose tissue • Stimulation of fat breakdown in adipose tissue

  8. Action of Glucocorticoids • Anti-inflammatory • Lipocortin-1 • Arousal and cognition • Hippocampus, amygdala and frontal lobes • Vigilance and cognitive performance • Blood fluid homeostasis • ANP • Transactivation of genes involved in metabolic control • Mineralocorticoid activity

  9. Action of mineralocorticoids • Aldosterone • AT1 receptor induces release • ↑ number of Na+ channels • Stimulates Na+/K+ATPase pump • Results in active reabsorption of Na+ and loss of K+ • Blood pressure ↑

  10. The drugs we give, for what and what effects these might have on patients – mainly focusing on the glucocorticoids 2. pharmacology

  11. Names of synthetic glucocorticoids • Beclomethasone • Betamethasone • Dexamethasone • Hydrocortisone • Prednisolone • Prednisone

  12. Indications for glucocorticoids • Use it’s synthetic function • Replacement in deficiency • Suppress the immune system • Rheumatoid arthritis • SLE • Psoriasis • Asthma • Eczema • Ulcerative Colitis • Crohn’s • Haemorrhoids • Congenital adrenal hyperplasia • Raised ICP/cerebral oedema due to malignancy – should NOT be used for stroke or head injury (harmful) • Acute hypersensitivity • Autoimmune hepatitis • Sarcoidosis • TTP • Polyarteritisnodosa

  13. Medical use of glucocorticoids • Benefits vs. side-effects – lifesaving use? • Administration • Orally – prednisolone, betamethasone, dexamethasone • Inhaled – beclomethasone • Intramuscular • Intravenous (usually in the acute setting) • Topical – hydrocortisone (↑ anti-inflammatory component) • Information for patients – ISCE • Increase dose when ill • Inform anaesthetists and surgeon of therapy • Regular monitoring for adverse effects • Withdrawal of glucocorticoids • GRADUAL (tapered) • Suppression of normal CRH-ACTH-corticosteroid axis • Susceptibility to stress – infection, injury

  14. Cautions • Hepatic and renal impairment – ‘use with caution’ • Pregnancy and breast-feeding – ‘safe’ • Children and adolescents – growth restriction • Elderly – because they’re old • History of TB – CXR • HTN/MI – rupture reported • Congestive Cardiac Failure • DM (inc. FHx) • Osteoporosis • Ocular Herpes Simplex – corneal perforation • Severe affective disorders – psychosis • Steroid myopathy • UC • Diverticulitis • Thromboembolic disorders

  15. Interactions Either reduce or increase the metabolism of corticosteroid or interacting drug – BNF! • Antibacterials • Antiepileptics • Antifungals • Antivirals

  16. Skin/soft tissue Cushingoid appearance Abdominal striae Acne Hirsutism Oedema Psychiatric Sleep disturbance/activation Mood disturbance Psychosis Neurologic Neuropathy Pseudomotorcerebri MSK Osteoporosis Asceptic necrosis of bone Myopathy Endocrine Diabetes mellitus Adrenal cortex suppression Immunologic Lymphocytopenia Immunosuppression False-negative skin test CV Hypertension Opthalmic Cataract Narrow-angle glaucoma Developmental Growth retardation Adverse effects • Occur with prolonged use of high doses • Cushing’s disease MSK • Osteoporosis • Asceptic necrosis of bone • Myopathy Endocrine • Diabetes mellitus • Adrenal cortex suppression Immunologic • Lymphocytopenia • Immunosuppression • False-negative skin test Opthalmic • Cataract • Narrow-angle glaucoma Developmental • Growth retardation Psychiatric • Sleep disturbance/activation • Mood disturbance • Psychosis Skin/soft tissue • Cushingoid appearance • Abdominal striae • Acne • Hirsutism • Oedema Neurologic • Neuropathy • Pseudomotorcerebri Cardiovascular • Hypertension

  17. Adverse effects “CUSHINGS BAD MD” Cataracts Up all night (sleep disturbance) Suppression of HPA axis Hypertension/buffalo Hump Infections Necrosis (avascular, of femoral head) Gain weight Striae Bone loss (osteoporosis) Acne Diabetes Myopathy/Moonface Depression and emotional changes

  18. Adverse effects Steroid-induced psychosis Infections Atypical presentations Late presentations (septicaemia and tuberculosis) At risk of severe chickenpox Pneumonia, hepatitis, DIC – NO rash Measles Avoid exposure ?Ig immunisation • Prescribe with care in those with previous psychiatric history • Mild: euphoria, nightmares, insomnia, irritability, mood lability, psychotic reactions, behavioural disturbances. • Severe: suicidal thoughts/severe depression • Rx: reduce dose/withdraw

  19. Medical use of mineralocorticoids • Fludrocortisone • Mineralocorticoid replacement in adrenocorticalinsufficienct

  20. Re-cap!

  21. Interesting things for bedtime reading! • Liquorice and steroids