This ppt discusses pharmacological actions, toxic effects and clinical applications of corticosteroids. It also mentions precations to be taken while using steroids
2. The hormones produced from three zones of adrenal cortex
Adrenal medulla : Epinephrine (adrenaline)
Zona glomerulosa (outer) : Mineralocorticoids
Zona fasciculata (middle) : Glucocorticoids
Zona reticularis (inner) : Adrenal androgens
Acute stress
Chronic stress
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5. DIAGNOSTIC USES (ACTH)
1. Adrenal insufficiency
Primary insufficiency
No increase in cortisol level
Secondary insufficiency
Increase in cortisol level
2. Cushing syndrome
ACTH injected
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6. THERAPEUTIC USES
Replacement therapy: Tumour in anterior pituitary
To stimulate the adrenal gland inactivated by steroid
therapy
Both uses are expensive & inconvenient
similar to that of steroids.
Being a foreign protein, ACTH may produce anaphylactic
reactions.
Side effects and contraindications
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8. History
1855 – Addison's disease
1856 – Adrenal glands essential for life
1930 – Cortex > medulla
1932 – Cushing’s syndrome
1949 – Hench et al (Steroids in rheumatoid arthritis)
1952 – Aldosterone
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9. CORTICOSTEROIDS
• Adrenal cortex essential for survival
• Adapt for changing environment
• Organ of par excellence -homeostasis
• Zona glomerulosa-aldosterone
• Zona fasciculata- glucocorticoids
• Zona reticulata- sex steroids
• Regulatory control from the hypothalamus
and pituitary.
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29. Pharmacological Actions
• For most clinical purposes, synthetic
glucocorticoids are used because they have a
higher affinity for the receptor, are less
activated and have little or no salt-retaining
properties.
• Hydrocortisone used for: orally for
replacement therapy, i.v. for shock and
asthma, topically for eczema (ointment) and
enemas (ulcerative colitis).
• Prednisolone the most widely used drug given
orally in inflammation and allergic diseases.04/30/19 29PATKI
30. Pharmacological Actions
• Betamethasone and dexamethasone: very
potent, w/o salt-retaining properties; thus,
very useful for high-dose therapies (e.g.,
cerebral edemas).
• Beclometasone, diproprionate, budesonide:
pass membranes poorly; more active when
applied topically (severe eczema for local anti-
inflammatory effects) than orally; used in
asthma, (aerosol).
• Triamcinolone: used for severe asthma and
for local joint inflammation (intra-articular
inj.).04/30/19 30PATKI
35. Actions: Electrolyte and water balance
• Aldosterone is more important
• Act on DT and CD of kidney
– Na+
reabsorption
– Urinary excretion of K+
and H+
• Addison’s disease ??
• Na+ loss
• Shrinkage of ECF
• Cellular hydration
• Hypodynamic state of CVS
• Circulatory collapse,
renal failure, death
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36. • Restrict capillary permeability
• Maintain tone of arterioles
• Myocardial contractility
Actions: Cardiovascular system
Mineralocorticoid induced hypertension ??
Na+
sensitize blood vessels to the action of
catecholamines & angiotensin
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37. Addison's disease: weakness and fatigue is due to
Prolonged use:
Actions: Skeletal Muscles
Needed for maintaining the normal function of Skeletal
muscle
inadequacy of circulatory system
Steroid myopathy
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39. Immunosuppressive and anti-allergic actions
• Suppresses all types of hypersensitivity and
allergic phenomenon
• At High dose: Interfere with all steps of
immunological response
• Causes greater suppression of Cell-mediated
immunity (graft rejection and delayed
hypersensitivity)
• Transplant rejection: antigen expression from
grafted tissues, delay revascularization,
sensitisation of T lymphocytes etc.
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41. • Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children
Actions: Growth and Cell division
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42. • Intestinal absorption
• Renal excretion
• Excessive loss of calcium from spongy bones
(e.g., vertebrae, ribs, etc)
Actions: Calcium metabolism
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43. • Not bronchodilators
• Most potent and most effective anti-inflammatory
• Effects not seen immediately (delay 6 or more hrs)
• Inhaled corticosteroids are used for long term control
Actions: Respiratory system
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47. Guidelines for steroid therapy
• Largely empirical neither specific nor curative except
replacement therapy
• Dose to be determined by trial & error method and
reevaluate periodically
• Careful patient assessment is mandatory
• A single large dose is virtually without harmful effects &
be reserved for life threatening conditions
• A short course therapy is unlikely to be harmful
• Abrupt withdrawal may be fatal
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60. Adverse reactions….contd
• Peptic ulcer
• Growth arrest
• Acne, hirsutism
• Topical –loss of skin collagen
• Inhalation: hoarseness of voice
• Teratogenicity: cleft palate, altered neuronal
development
• Reactivation of TB
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61. Antagonists of Adrenocortical Agents
A. Synthetic inhibitors and glucocorticoid antagonists
1. Metyrapone – inhibits 11-hydroxylation, interfering
with cortisol and corticosterone synthesis (0.25g
BID to 1g QID)
- used in tests of adrenal function (300-500mg q
4hrs. X 6doses, fed by urine collection
- treat hypercorticotism: 4 g/day
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62. 2. Aminoglutethimide – blocks the conversion of
cholesterol to pregnanelolone and causes a
reduction in the synthesis of all hormonally
active steroids; breast Ca and Cushing’s
syndrome due to adrenocortical Ca: 250 mg
every 6hrs.
- enhances metabolism of dexamethasone
3. Trilostane - inhibits 3beta hydroxysteroid
dehydrogenase
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63. 3. Ketoconazole – an antifungal imidazole
derivative; potent, non-selective inhibitor of
adrenal and gonadal steroid synthesis; tx of
Cushing’s syndrome (200-1200mg/d)
4. Mifepristone (RU 486) –
11β-aminophenyl-substituted 19-norsteroid;
has strong anti-progestin activity; blocks
glucocorticoid receptor
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64. B. Mineralocorticoid Antagonists
1. Spirinolactone – diagnosis of aldosteronism
(400-500mg/day fro 4-8 days); preparing for
surgery (300-40mg/day x 2 wks to reduce the
incidence of arrhythmias); hirsutism in women
(androgen antagonist 50-200mg/d x 2-6 mos);
diuretic
2. Eplerenone
3. Drospirenone – progestin in a new oral
contraceptive, antagonizes the effect of
aldosterone
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65. PATKI
Drug interactions
• Estrogens may decrease prednisone metabolism.
• Phenobarbital, phenytoin, and rifampicin may
increase metabolism of glucocorticoids
• May cause digitalis toxicity secondary to
hypokalemia.
• Monitor for hypokalemia with co-administration of
diuretics
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66. PATKI
Fludrocortisone
• It is the only mineralocorticoid given orally.
• It has a very great mineralocorticoid plus a significant
glucocorticoid activities.
• It has a long duration of action
Fludrocortisone is preferred in:
- Replacement therapy in Addison's disease.
- to preserve sodium and treat hypotension as in cases
of interstitial nephritis and autonomic neuropathy.
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