Corticosteroids 2020
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Lecture class for BDS 2nd Year MMCTH
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Corticosteroids 2020
- 1. CORTICOSTEROIDS Dr. Pravin Prasad MBBS, MD Clinical Pharmacology Assistant Professor, Department of Clinical Pharmacology Maharajgunj Medical Campus, Kathmandu 13 July 2020 (29 Asar 2077), Monday
- 2. By the end of this discussion, BDS 2nd year students will be able to: ► List the hormones secreted from adrenal cortex ► Explain the mechanism of action of synthetic corticoids ► List the indications, adverse reactions, precautions and contraindications of synthetic corticoids ► List the adverse reactions, precautions and contraindications of synthetic corticoids Endocrine Pharmacology and Dental Therapeutics 2
- 3. Adrenal hormones ► Adrenal glands has two parts: Cortex Glomerulosa- aldosterone (mineralocorticoid) Fasciculata- hydrocortisone (glucocorticoids) Reticularis- testosterone (sex hormone) Medulla Adrenaline Endocrine Pharmacology and Dental Therapeutics 3
- 4. Adrenal hormones ► Precursor molecule: cholesterol ► Corticoid, Corticosteroid: Natural glucocorticoids and mineralocorticoids Synthetic analogues of glucocorticoids and mineralocorticoids ► Actions: Glucocorticoids- carbohydrate, protein and fat metabolism Mineralocorticoids- Na+, K+ and fluid balance Endocrine Pharmacology and Dental Therapeutics 4
- 5. Mechanism of action ►Penetrates the cell ►Binds to glucocorticoid receptors (cytoplasm) ►Bound complex migrates into nucleus ►Interacts with glucocorticoid response elements Interacts with co-activators: increased transcription Interacts with co-repressors: decreased transcription ►Altered cellular activities seen (30-60 mins) ►Immediate actions through alternate pathway also seen Endocrine Pharmacology and Dental Therapeutics 5
- 6. Synthetic corticosteroids Class Compound Relative activity (Biological t½) Gluco. Mineralo. Glucocorticoid Short acting (<12 hrs) Hydrocortisone (cortisol) 1 1 Intermediate (12-36 hrs) Prednisolone 4 0.8 Methylprednisolone 5 0.5 Triamcinolone 5 0 Deflazacort 3-4 0 Long acting (>36 hrs) Dexamethasone 25 0 Betamethasone 25 0 Mineraloco rticoid Desoxycorticosterone acetate (DOCA) 0 100 Fludrocortisone 10 150 Aldosterone 0.3 3000 Endocrine Pharmacology and Dental Therapeutics 6
- 7. Synthetic corticosteroids ►Inhalational corticoids: Beclomethasone dipropionate Budesonide Fluticasone Flunisolide Ciclesonide ►Topical Beclomethasone, clobetasol, flucinolone, flucortolone Mometasone, hydrocortisone Endocrine Pharmacology and Dental Therapeutics 7
- 8. Indications ► Replacement Therapy Acute adrenal insufficiency (Hydrocortisone, dexamethasone) Chronic adrenal insufficiency / Addison’s disease (Hydrocortisone +/- fludrocortisone) Congenital adrenal hyperplasia/ adrenogenital syndrome (Hydrocortisone +/- fludrocortisone) Endocrine Pharmacology and Dental Therapeutics 8
- 9. Indications ► Pharmacotherapy Arthrides- rheumatoid, osteoarthritis, rheumatic fever, gout Severe allergic reactions Anaphylaxis- adrenaline (Drug of choice) Autoimmune disease Lung disease: Bronchial asthma, COPD, Pulmonary edema, for fetal lung maturation (dexamethasone/ betamethasone) Infective diseases Endocrine Pharmacology and Dental Therapeutics 9
- 10. Indications ► Pharmacotherapy Ocular conditions- Anterior chamber- allergic, iritis, iridocyclitis, keratitis Posterior chamber- retinitis, optic neuritis, uveitis Skin disease- eczema, pemphigus, SJS-TEN Intestinal disease- IBD Neurological conditions- cerebral oedema, Bell’s palsy Nausea and vomiting Endocrine Pharmacology and Dental Therapeutics 10
- 11. Indications ► Pharmacotherapy Malignancies- Primary role in conditions involving lymphocytes Secondary role in others Organ transplant Septic shock Not responding to fluid replacement and vasopressors Thyroid storm Endocrine Pharmacology and Dental Therapeutics 11
- 12. Adverse effects ► Mineralocorticoid: Sodium and water retention Oedema Hypokalaemic alkalosis Progressive rise in BP Endocrine Pharmacology and Dental Therapeutics 12
- 13. Adverse effects ►Glucocorticoid: Cushing’s habitus Fragile skin, purple striae Hyperglycaemia, glycosuria, precipitation of diabetes Muscular weakness Myopathy- STOP drug Susceptibility to infection Endocrine Pharmacology and Dental Therapeutics 13
- 14. Adverse effects ► Glucocorticoid: Delayed healing of wounds and surgical incisions. Peptic ulceration Osteoporosis Eye: Posterior subcapsular cataract, glaucoma Growth retardation in children Psychiatric disturbances: mild euphoria, depression Suppression of HPA axis Endocrine Pharmacology and Dental Therapeutics 14
- 15. Precautions and Contraindications ► Peptic ulcer ► Diabetes mellitus ► Hypertension ► Viral and fungal infections ► Tuberculosis and other infections ► Osteoporosis ► Herpes simplex keratitis ► Psychosis ► Epilepsy ► CHF ► Renal failure Endocrine Pharmacology and Dental Therapeutics 15
- 16. Conclusion: Classwork!! ► List the hormones secreted from adrenal cortex ► Explain the mechanism of action of synthetic corticoids ► List the indications, adverse reactions, precautions and contraindications of synthetic corticoids ► List the adverse reactions, precautions and contraindications of synthetic corticoids Endocrine Pharmacology and Dental Therapeutics 16
- 17. Questions?? ► Thank you! Endocrine Pharmacology and Dental Therapeutics 17
Editor's Notes
- Cushing’s habitus: characteristic appearance with rounded face, narrow mouth, supraclavicular hump, obesity of trunk with relatively thin limbs Fragile skin, purple striae—typically on thighs and lower abdomen, easy bruising, telangiectasis, hirsutism. Cutaneous atrophy localized to the site occurs with topical application as well Muscular weakness: proximal (shoulder, arm, pelvis, thigh) muscles are primarily affected. Myopathy occurs occasionally, warrants withdrawal of the corticoids. Susceptibility to infection: this is nonspecific for all types of pathogenic organisms. Latent tuberculosis may flare; opportunistic infections with low grade pathogens (Candida, etc.) set in.
- Delayed healing: of wounds and surgical incisions. Peptic ulceration: risk is doubled; bleeding and silent perforation of ulcers may occur. Dyspeptic symptoms are frequent with high dose therapy. Osteoporosis: especially involving vertebrae and other flat spongy bones. Compression fractures of vertebrae and spontaneous fracture of long bones can occur, especially in the elderly. Radiological evidence of osteoporosis is an indication for withdrawal of corticoid therapy. Corticosteroid induced osteoporosis can be prevented/arrested by calcium supplements + vit D, and by estrogen/raloxifene or androgen replacement therapy in females and males respectively. However, bisphosphonates are the most effective drugs in this regard. Growth retardation: in children occurs even with small doses if given for long periods. Large doses do inhibit GH secretion, but growth retardation may, in addition, be a direct cellular effect of corticoids. Recombinant GH given concurrently can prevent growth retardation, but risk/benefit of such use is not known. Foetal abnormalities: Cleft palate and other defects are produced in animals, but have not been encountered on clinical use in pregnant women. The risk of abortion, stillbirth or neonatal death is not increased, but intrauterine growth retardation can occur after prolonged therapy, and neurological/behavioral disturbances in the offspring are feared. Prednisolone appears safer than dexa/beta methasone, because it is metabolized by placenta, reducing foetal exposure. There Psychiatric disturbances: mild euphoria frequently accompanies high dose steroid treatment. This may rarely progress to manic psychosis. Nervousness, decreased sleep and mood changes occur in some patients. Rarely a depressive illness may be induced after long-term use. Suppression of hypothalamo-pituitary-adrenal (HPA) axis: occurs depending both on dose and duration of therapy. In time, adrenal cortex atrophies and stoppage of exogenous steroid precipitates withdrawal syndrome consisting of malaise, fever, anorexia, nausea, postural hypotension, electrolyte imbalance, weakness, pain in muscles and joints and reactivation of the disease for which they were used. Subjected to stress, these patients may go into acute adrenal insufficiency leading to cardiovascular collapse.