al asadi pharmacology Department March 2023 objectives Mechanism of action Physiological effect Suppression of HPA system The main type of corticosteroids Side effects U ses of steroid ID: 1040274
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1. corticosteroidsDr. zubaidah al asadipharmacology DepartmentMarch 2023
2. objectivesMechanism of actionPhysiological effectSuppression of HPA systemThe main type of corticosteroids Side effectsUses of steroid
3. Adrenal Steroids
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5. Mechanism of steroid actionA) Actions mediated through regulation of genesB) Actions not mediated by genes (non-genomic effects)
6. Pharmacological Effects Effects on organic metabolism Carbohydrate metabolism: decreased peripheral glucose utilization resulting in hyperglycemia and sometimes glycosuria (latent diabetes becomes overt) 2. Protein metabolism: catabolism continues. - muscle wasting - osteoporosis - slow growth in children - skin atrophy - increased capillary fragility (bruising) - striae – delayed healing of peptic ulcer and of wounds
7. 3. Fat metabolism: trunkal or central obesity. 4. Inflammatory and Allergic responses are suppressed. The inflammatory consequences of antigen- antibody interaction are inhibited. Lymphoid tissue is reduced. 6. CNS: euphoria or psychotic states may occur (? CNS electrolyte changes)(confusion, irritability, delusion, suicidal thoughts, especially with high doses) 7. Anti-vitamin D action, reduced hypercalcemia and increased urinary calcium excretion
8. Suppression of HPA system(complete suppression of cortex by exogenous daily dose of hydrocortisone 40- 80mg or prednisolone 10-20mg or equivalent doses of other steroids)Suppression of HPA axis is greatest and most prolonged when corticosteroids are given at night. Dexamethasone, 1 mg at night, is sufficient to suppress corticotropin secretion for 24 hRecovery of adrenal function is quick after use of steroids for few days. It may take months after months of use, and take years after years of use
9. Circadian rhythm
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11. The main type of corticosteroids are:Tablets, syrups and liquids – such as prednisoloneInhalers or nasal sprays – such as beclometasone and fluticasone injections (given into joints, muscles or blood vessels) – such as methylprednisolonecreams, lotions and gels – such as hydrocortisone skin cream
12. Beclomethasone, Budesonide, fluticasone,… Potent, soluble steroids, more marked topical effect than when given by mouth, suitable for use by inhalation for asthma and intra-nasally for hay fever. The swallowed part of the inhaled dose is largely inactivated by hepatic first pass (less systemic side effects)
13. Pharmacokinetics of corticosteroids in general Most synthetic steroids are: - given orally - their biological effect may occur after 2-8 hours - metabolized in the liver, some pass unchanged in urine - highly protein bound If a single daily dose is to be given, it should be given in the morning to coincide with the natural activation of the HPA axis (high level in the morning and low at evening)
14. Adverse effects of steroid therapy Unwanted effects are unlikely if the daily dose is below the equivalent of hydrocortisone 50mg or prednisolone 10mg. 1. Endocrine adverse effects Features of Cushing’s syndrome - HPA suppression is dependent on: - The type of corticosteroid used, its dose, the duration of use, the time of administration(morning vs evening), more if given at night.
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16. 2. Mineralocorticoid side effects ..??3. Musculoskeletal - Proximal myopathy - Tendon rupture - Osteoporosis (leading to fractures) Growth in children is impaired - Avascular necrosis of bone (particularly femoral heads) – a serious complication occurs at higher doses due to restriction of blood flow through bone capillaries
17. 4. Immune and anti-inflammatory adverse effects Results: - Atypical signs and symptoms of inflammation - Increased susceptibility to infection Spread of infection – more severe, clinical presentation may be atypical - Candidiasis occurs; especially in GIT - Dormant Tb may become active - Live vaccines become dangerous
18. 5. GIT adverse effects -increase incidence of peptic ulcers and hemorrhage (perforation may be silent because of inhibition of signs and symptoms of inflammation) 6. CNS adverse effects - Depression and psychosis (during the first few days of high-dose administration) - Euphoria, insomnia, suicidal thoughts,.. - Aggravation of schizophrenia and epilepsy - Increased intracranial pressure with papilledema
19. 7. Ophthalmic effects cataract Glaucoma (with prolonged use of eye drops) - Corneal and scleral thinning - Spread of viral (e.g. herpetic) infection with perforation of corneal ulcers 8. Others e.g. - Menstrual disorders - Delayed tissue healing
20. During pregnancy - Steroids are teratogenic in animals. No convincing evidence in human. - Fluorinated steroids are more teratogenic; betamethasone and dexamethasone cross the placenta readily while 88% of prednisolone is inactivated as it crosses the placenta. - Adrenal insufficiency can occur in the newly-borne if the mother is treated with high doses, resolves spontaneously and is rarely important. - Labour is managed as for a major stress (75-150 mg hydrocortisone i.v. daily in divided doses for 2-3 days)
21. Clinical uses of corticosteroids 1- For replacement therapy in acute and chronic adrenocortical insufficiency 2- For suppression of adrenocortical function in congenital adrenal hyperplasia 3- As anti-inflammatory, anti-allergic and for immuno-suppression (prednisolone is preferred for prolonged use) e.g. - connective tissue diseases such as SLE - severe asthma
22. Severe allergic reactions e.g. serum sickness, angioneurotic edema... etc.Diseases of allergic origin; bronchial asthma, rhinitis, conjunctivitis, eczema & many other atopic & proliferative skin diseasesAutoimmune disorders; rheumatoid arthritis, inflammatory bowel disease systemic lupus erythrematosus, nephrotic syndrome,…Organ transplantation; kidney, cardiac, bone marrow (rejection)Blood problems; hemolytic anemia, thrombocytopenic purpura, etc.Acute gout (resistant) to other drugs
23. OTHER USES:1-Raised intracranial pressure andPry or 2ndry neoplasms in the brain & postoperative to brain surgery. Why??2- In antiemetic regimens : prevent / cure emesis of chemotherapy
24. Withdrawal of steroid therapy “The longer the duration of treatment, the slower must be the withdrawal” - If treatment for less than one week, withdrawal can be rapid - Treatment for 2 weeks, dose is reduced by 50% every day
25. - Longer, particularly if repeated doses given in the evening or in high doses (>40 mg prednisolone); withdrawal should be very slowly (e.g. 2.5-5mg prednisolone or equivalent every 3-7 days) - Full recovery (response to stress) may take up to 2 years after the initial recovery.
26. Stopping suddenly can cause your adrenal gland to stop working. This is known as adrenal insufficiency.Symptoms of adrenal insufficiency include:feeling extremely tiredfeeling nauseadizzinessloss of appetite and weight lossThe original symptoms may also come back suddenly.
27. Mitotane selectively inhibits the activity od adrenal cortex,Used for symptomatic treatment of advanced or inoperable adrenocortical carcinoma. Please remember …SPIRONOLACTONEIs a competitive aldosterone antagonist Is a K+ sparing diuretic (weak, slow onset & prolonged effect)Used in hypertension (alternation with others), in heart failureHyperaldosteronism (Conn’s)
28. Clinical Points to be further discussed in practical sessionsmissing a steroid dose.Coping with side effects of steroid tabletsSide effects of steroid nasal sprays .Side effects of topical corticosteroids.Adrenal Insffciency .Cushing syndrome vs disease.Addisonian crisis.
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30. 1-Corticosteroids are: Anti-diabetic drugs Antihypertensive drugs Anti-inflammatory drugs Anti-obesity drugs
31. The typical appearance of a person who has taken corticosteroids over a long duration is described as Cushing's habitus Adenoid habitus Addison's habitus None of the above
32. TRUE OR FALSE:1-Corticosteroids can prevent a reaction following organ transplantation. (True) 2-Corticosteroids cannot be stopped suddenly if they are used continuously for 2 to 3 weeks.( True)3-Corticosteroids should not be given in patients with stomach ulcer(TRUE)
33. References1-D. R. Laurence, P. N. Bennett and M. J. Brown, “Clinical Pharmacology,”2-BNF 83 (MARCH_ SEPTEMBER 2022)3-NHS website, available at https://www.nhs.uk/conditions/steroids/
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