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Corticosteroids Pharmacology - drdhriti
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  1. 1. CORTICOSTEROIDS Prof. Dr. Shah Murad [email_address]
  2. 2. <ul><li>Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex . </li></ul><ul><li>Corticosteroids are involved in a wide range of physiologic systems such as </li></ul><ul><li>stress response , </li></ul><ul><li>immune response and regulation of inflammation , </li></ul><ul><li>carbohydrate metabolism , </li></ul><ul><li>protein catabolism , </li></ul><ul><li>blood electrolyte levels, and </li></ul><ul><li>behavior. </li></ul>
  3. 3. <ul><li>Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms. </li></ul><ul><li>Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney . </li></ul>
  4. 4. common natural hormones <ul><li>corticosterone (C21H30O4), </li></ul><ul><li>cortisone (C21H28O5, 17-hydroxy-11-dehydrocorticosterone) </li></ul><ul><li>aldosterone </li></ul>
  5. 5. Biosynthesis <ul><li>The corticosteroids are synthesized from cholesterol within the adrenal cortex . </li></ul><ul><li>Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor </li></ul><ul><li>Aldosterone and corticosterone share the first part of their biosynthetic pathway. </li></ul><ul><li>The last part is either mediated by the aldosterone synthase (for aldosterone ) or by the 11β-hydroxylase (for corticosterone ). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). </li></ul>
  6. 6. <ul><li>Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex ; 11β-hydroxylase is found in the zona fasciculata and reticularis. </li></ul>
  7. 7. Classes of corticosteroids <ul><li>Corticosteroids are generally grouped into four classes, based on chemical structure. </li></ul><ul><li>Allergic reactions to one member of a class typically indicate an intolerance of all members of the class. </li></ul><ul><li>&quot;Coopman classification&quot; </li></ul><ul><li>The highlighted steroids are often used in the screening of allergies to topical steroids </li></ul>
  8. 8. <ul><li>Group A </li></ul><ul><li>(short to medium acting glucocorticoids) Hydrocortisone , Hydrocortisone acetate , Cortisone acetate , Tixocortol pivalate , Prednisolone , Methylprednisolone , and Prednisone . </li></ul><ul><li>Group B </li></ul><ul><li>Triamcinolone acetonide , , Mometasone , Amcinonide , Budesonide , Desonide , Fluocinonide , Fluocinolone acetonide , and Halcinonide . </li></ul>
  9. 9. <ul><li>Group C </li></ul><ul><li>Betamethasone , Betamethasone sodium phosphate , Dexamethasone , Dexamethasone sodium phosphate , and Fluocortolone . </li></ul><ul><li>Group D </li></ul><ul><li>Hydrocortisone-17-butyrate , Betamethasone valerate , Betamethasone dipropionate , Prednicarbate , , , , , and Fluprednidene acetate </li></ul>
  10. 10. Routes of adm: of Corticosteroids <ul><li>1. Topical steroid for use topically on the skin, eye, and mucous membranes. </li></ul><ul><li>2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs. </li></ul><ul><li>3. Oral forms - such as prednisone and prednisolone. </li></ul><ul><li>4. Systemic forms - available in injectibles for use intravenously and parenteral routes </li></ul>
  11. 11. Uses <ul><li>Synthetic drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumors to skin diseases . </li></ul>
  12. 12. <ul><li>Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. </li></ul>
  13. 13. <ul><li>Fludrocortisone (Florinef) is a synthetic mineralocorticoid. </li></ul><ul><li>Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia . </li></ul>
  14. 14. <ul><li>Synthetic glucocorticoids are used in the treatment of joint pain or inflammation ( arthritis ), temporal arteritis , dermatitis , allergic reactions, asthma , hepatitis , systemic lupus erythematosus , inflammatory bowel disease ( ulcerative colitis and Crohn's disease ), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency . </li></ul>
  15. 15. <ul><li>Topical formulations are also available for the skin , eyes , lungs , nose , and bowels . </li></ul><ul><li>Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists ( e.g. ondansetron ). </li></ul>
  16. 16. <ul><li>Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome . </li></ul>
  17. 17. <ul><li>Typical mineralocorticoid side effects are hypertension (abnormally high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema , metabolic alkalosis and connective tissue weakness </li></ul>
  18. 18. <ul><li>Corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC). </li></ul><ul><li>A variety of steroid medications, from anti-allergy nasal sprays (Nasonex, Flonase) to topical skin creams, to eye drops (Tobradex), to Prednisone have been implicated in the development of CSR. </li></ul>
  19. 19. <ul><li>Cortisone, often mispelled cortizone, brand name Cortone, is a corticosteroid used to treat arthritis pain and inflammation. </li></ul><ul><li>Cortisone acetate may also be given in an intramuscular injection (cortisone shot). </li></ul>
  20. 20. <ul><li>Prednisone is a potent medication which is used to treat many inflammatory conditions including rheumatoid arthritis. </li></ul><ul><li>It is important to know the proper use of the drug and be aware of the potential serious side effects. </li></ul>
  21. 21. <ul><li>Steroid withdrawal symptoms can occur if corticosteroid drugs are not discontinued gradually. </li></ul><ul><li>Tapering the dose of steroids minimizes corticosteroid withdrawal symptoms. </li></ul>
  22. 22. <ul><li>Glucocorticoid-induced osteoporosis is both preventable and treatable. </li></ul><ul><li>Glucocorticoids (steroids) are the most common cause of drug-induced osteoporosis. </li></ul>
  23. 23. <ul><li>The term steroids is often misunderstood. </li></ul><ul><li>Corticosteroids (a class of drugs used to treat arthritis and many other conditions) are often just called &quot;steroids&quot;. </li></ul><ul><li>So what's in a name? Confusion results when they are mistaken for anabolic steroids (drugs used by athletes to boost strength and enhance physical performance). </li></ul><ul><li>What is the difference between anabolic steroids and corticosteroids? </li></ul>
  24. 24. <ul><li>According to the National Institute of General Medical Sciences, the term &quot;steroid&quot; is a chemical name for any substance that has a characteristic chemical structure consisting of multiple chemical rings of connected atoms. Some common examples of steroids are: </li></ul><ul><li>Vitamin D </li></ul><ul><li>cholestrol </li></ul><ul><li>estrogen </li></ul><ul><li>cortisone </li></ul>
  25. 25. <ul><li>Steroids are critical for keeping the body running smoothly. </li></ul><ul><li>Various steroids have important roles in the body's reproductive system and both the structure and function of membranes </li></ul>
  26. 26. anabolic steroids <ul><li>According to the National Institute on Drug Abuse, anabolic steroids are synthetic substances related to the male sex hormones (androgens). </li></ul><ul><li>They promote growth of skeletal muscle (anabolic effect) and the development of male sexual characteristics (androgenic effects). </li></ul>
  27. 27. <ul><li>The proper term for these compounds actually is &quot;anabolic / androgenic&quot; steroids: </li></ul><ul><li>“ anabolic” refers to muscle-building </li></ul><ul><li>“ androgenic” refers to increased masculine characteristics </li></ul><ul><li>“ steroids” refers to the class of drugs </li></ul>
  28. 28. <ul><li>Anabolic steroids are available legally only by prescription, to treat conditions that occur when the body produces abnormally low amounts of testosterone, such as delayed puberty and some types of impotence. </li></ul>
  29. 29. Anabolic steroids <ul><li>They are also prescribed to treat body wasting in patients with AIDS and other diseases that result in loss of lean muscle mass. </li></ul>
  30. 30. Abuse <ul><li>Anabolic steroids are being abused by some athletes and others to enhance performance or improve physical appearance. Abuse of anabolic steroids can lead to serious health problems, some of which are irreversible. Major side effects can include: </li></ul><ul><li>liver tumors </li></ul><ul><li>cancer </li></ul><ul><li>jaundice </li></ul><ul><li>high blood pressure </li></ul><ul><li>kidney tumors </li></ul><ul><li>severe acne </li></ul><ul><li>trembling </li></ul>
  31. 31. <ul><li>In males, side effects may include shrinking of the testicles and breast development. </li></ul><ul><li>In females, side effects may include growth of facial hair, menstrual changes, and deepened voice. In teenagers, growth may be halted prematurely and permanently. </li></ul>
  32. 32. <ul><li>Corticosteroids or glucocorticoids, often just called &quot;steroids&quot;, are drugs closely related to cortisol, a hormone which is naturally produced in the adrenal cortex (the outer layer of the adrenal gland). </li></ul>
  33. 33. <ul><li>Corticosteroids act on the immune system by blocking the production of substances that trigger allergic and inflammatory actions, such as prostaglandins. </li></ul>
  34. 34. Corticosteroids <ul><li>Betamethasone (Celestone) </li></ul><ul><li>Budesonide (Entocort EC) </li></ul><ul><li>Cortisone (Cortone) </li></ul><ul><li>Dexamethasone (Decadron) </li></ul><ul><li>Hydrocortisone (Cortef) </li></ul><ul><li>Methylprednisolone (Medrol) </li></ul><ul><li>Prednisolone (Prelone) </li></ul><ul><li>Prednisone (Deltasone) </li></ul><ul><li>Triamcinolone (Kenacort, Kenalog) </li></ul>
  35. 35. Corticosteroids (Steroids): Benefits vs. Risks <ul><li>Corticosteroids are powerful drugs which can quickly reduce swelling and inflammation, greatly improve symptoms and provoke incredible results. </li></ul><ul><li>However, there are potential consequences and side effects. </li></ul><ul><li>The power of corticosteroids should not be feared, but must be respected. </li></ul>
  36. 36. <ul><li>To maximize benefits, but minimize potential side effects, steroids are usually prescribed in low doses or for short durations. </li></ul><ul><li>The potent effect of corticosteroids can result in serious side effects which mimic Cushing's disease , a malfunction of the adrenal glands resulting in an overproduction of cortisol </li></ul>
  37. 37. The list of potential side effects is long and can include: <ul><li>increased appetite and weight gain </li></ul><ul><li>deposits of fat in chest, face, upper back , and stomach </li></ul><ul><li>water and salt retention leading to swelling and edema </li></ul><ul><li>high blood pressure </li></ul><ul><li>diabetes </li></ul><ul><li>osteoporosis </li></ul><ul><li>cataracts </li></ul><ul><li>acne </li></ul><ul><li>muscle weakness </li></ul><ul><li>thinning of the skin </li></ul><ul><li>increased susceptibility to infection </li></ul><ul><li>stomach ulcers </li></ul><ul><li>psychological problems such as depression </li></ul><ul><li>adrenal suppression and crisis </li></ul>
  38. 38. Tappering off the dose of steroids <ul><li>Side effects are minimized by taking the lowest doses possible (that still yields positive results) and following doctor's orders. </li></ul><ul><li>It is important to avoid self regulation of the dosage, either by adding more or stopping the drug without a schedule. </li></ul>
  39. 39. <ul><li>Steroids must be gradually reduced to permit the adrenal glands to resume natural cortisol production. </li></ul><ul><li>Eliminating doses too quickly can result in adrenal crisis (a life-threatening state caused by insufficient levels of cortisol). </li></ul><ul><li>Another possible complication to coming off steroids is withdrawal syndrome, or rebound effect, which is the body's exaggerated response to removal of the drug. </li></ul>
  40. 40. Prednisone <ul><li>Prednisone is a synthetic drug closely related to cortisol, a hormone which is naturally produced in the adrenal cortex. </li></ul><ul><li>Prednisone is used to treat rheumatoid arthritis , systemic lupus erythematosus , polymyositis , polymyalgia rheumatica , giant cell arteritis , vasculitis , and other inflammatory conditions </li></ul>
  41. 41. <ul><li>The use of oral corticosteroids is associated with an increased risk of fracture, but there is limited information on the relationship between corticosteroid dose, bone mineral density (BMD), and fracture </li></ul>
  42. 42. <ul><li>Oral corticosteroid treatment is associated with osteoporosis and an increased risk of fracture </li></ul>
  43. 43. <ul><li>fracture risk doubles with each standard deviation reduction in bone mineral density (BMD) </li></ul>
  44. 44. <ul><li>It is not known whether the same is true for corticosteroid-induced osteoporosis. </li></ul><ul><li>There is some evidence that fractures associated with the use of corticosteroid occur at a higher BMD (bone mineral density ) than those caused by involutional osteoporosis, although this has been disputed </li></ul>
  45. 45. PERMISSIVE EFFECTS <ul><li>Besides therapeutic effects, glucocorticoids also possess some effects which are called “permissive” effects. </li></ul><ul><li>It means that in the absence of glucocorticoids, many normal functions become deficient. </li></ul><ul><li>For example, in the absence of glucocorticoids, the lipolytic responses of fat cells to catecholamines, ACTH and growth hormone are diminished. </li></ul>
  46. 46. EFFECTS ON METABOLISM <ul><li>Glucocorticoids promote glycogen deposition in liver by inducing glycogen synthetase and promoting Gluconeogenesis. </li></ul>
  47. 47. <ul><li>They inhibit glucose utilization by peripheral tissues. </li></ul><ul><li>They cause increased release of glucose from liver. </li></ul><ul><li>They cause hyperglycemia and thus stimulate insulin release. </li></ul>
  48. 48. <ul><li>They stimulate lipase and cause lipolysis. </li></ul><ul><li>They also promote lipolysis due to glucagon, growth hormone, adrenaline and thyroxine. </li></ul><ul><li>The cAMP induced breakdown of triglycerides is enhanced and fatty acids and glycerol are released into the circulation. </li></ul>
  49. 49. <ul><li>The increased insulin release stimulates lipogenesis and to a lesser degree inhibit lipolysis, leading to a net increase in fat deposition </li></ul>
  50. 50. <ul><li>Glucocorticoids cause breakdown of proteins and mobilization of aminoacids from peripheral tissues. </li></ul><ul><li>This protein breakdown is manifested as --- muscle wasting, lipolysis, loss of osteiod from bone and thinning of skin </li></ul>
  51. 51. <ul><li>Thus glucocorticoids are catabolic . </li></ul><ul><li>They try to maintain glucose supply to brain, during starvation, by exerting following effects. </li></ul><ul><li>Gluconeogenesis. </li></ul><ul><li>Inhibition of peripheral glucose uptake. </li></ul><ul><li>Release of aminoacids from muscle catabolism. </li></ul><ul><li>Stimulation of lipolysis. </li></ul>
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