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Dr. K. R. Professor,
Assistant Professor.
1
Introduction
Adenal gland
Medulla Cortex
Epinephrine
Z. glomerulosa Z. fasciculata Z. reticularis
Mineralocorticoids Glucocorticods
Androgens
2
Steroid biosynthesis
3
Steroid transport in blood
 Glucocorticoids reversibly bind to transcortin.
 Transcortin is a -globulin.
 80% of plasma cortisol is bound to transcortin.
 Only 10% is bound to serum albumin.
 Remaining 10% is free hormone.
4
Mechanism of action
5
Transactivation
 Leads to transcription & translation.
 Induces enzymes - Camp dependent kinase.
 Induce formation of annexin-1 (lipocortin-1).
 Lipocortin-1 inhibits phospholipase A2.
 Induction of Annexin-1 is slow.
 Antiinflammatory response takes several hours.
6
Transrepression
 Inhibits transcription factors like- AP-1 & NF-kB.
 Inhibits transcrption of genes for-
COX-2
Cytokines
Inducible form of NO synthase.
 Biological lag of several hours is seen before effects.
 Effects are present even when steroid levels fall.
 Side effects can be minimized by alternative day
therapy
7
Mineralocorticoid receptor
 Binds to MRE.
 Expressed mainly in kidney, also in colon, salivary glands,
sweat glands & hippocampus.
 Glucocorticoids will also bind to MRs.
 MRs bind aldosterone & hydrocortisone (cortisol) with
equal affinity.
 Cortisol is inactivated by 11-β-HSD on binding to MRs.
 Aldosterone exists as hemiacetyl derivative which is
resistant to degradation by 11-β-HSD.
8
Pharmacological actions
General considerations
 Actions of corticoids are divided in to
Gluco- carbohydrate, fat & protein metabolism.
- antiinflammatory & immunosuppressant actions.
Mineralo- Na+, K+ & fluid homeostasis.
 Glucocorticoid potency α antiinflammatory effects.
 Direct and some permissive actions.
 Exogenous glucocorticoids depress secretion of CRH &
ACTH by negative feedback mechanism.
9
Glucocorticoid actions
Carbohydrate & protein metabolism
 Exert anti-insulin effects by:
1. ↓ Peripheral utilization of glucose
2. ↑ gluconeogenesis
3. Inhibit protein synthesis in muscle, connective tissue
& skin.
 Net result of glucocorticoid administration is-
↑ Blood sugar, liver glycogen & excretion of nitrogen.
 Prolonged high doses- DM like state, protein wasting.
10
Fat metabolism
 Enhance lipolytic effects of GH, Adr, Thyroxine.
 Mobilization of free fatty acids ↑.
 Insulin release → ↑ deposition of fats.
 Prolonged high doses cause redistribution of fat.
Neck & shoulders- buffalo hump
Face- moon face, abdomen- centripetal obesity.
 Cuta striae- due to stretching of skin.
 Central adipocytes are more sensitive to insulin.
11
12
Anti-inflammatory effects
 Endogenous GC prevent excessive defense response.
 Inhibit inflammation irrespective of its cause.
In macrophages, monocytes, endothelium &
fibroblasts
 Induce the production of lipocortin.
 Inhibit cytokine release & T-cell activation.
 This reduces the process of chemotaxis.
 Inhibit synthesis of adhesion molecules- ELAM-1 &
ICAM-1, promote leukocyte localization.
 Impair recruitment to the sites of inflammation.
13
Transrepression of proinflammatory transcription
factors
 Inhibit nuclear factor-kB (NF-kB) & activatory protein
(AP-1).
 These enhance transcription of genes for COX-2,
various cytokines & iNOS.
Lymphocytes
 ↓Release of cytokines (IL-1, 2,4&6) from lymphocytes.
 GC ↓ L, M, E & B in circulation
14
Miscellaneous effects
Basophils & mast cells:
 Gc ↓ IgE dependent release of histamine LT-C4 from
basophils. ↓Capillary permeability.
 Acute phase reactant production ↓.
 ↓ Production of collagenase & stromelysin , hinder
tissue damage
 Prolonged therapy ↓ production of collagen –
obstructs wound healing & repair.
15
Immune response
 Suppress CMI
 Inhibit genes for cytokines- IL-1,2,3,4,5,6,8 & INF-ɣ.
 ↓cytokines reduce T-cell proliferation.
 Also suppress humoral immunity.
 Down regulate Fc receptors on macrophages.
 Graft rejection is prevented by-
1. Reducing antigen expression from grafted tissue.
2. Delay revascularization.
3. ↓ Sensitization of cytotoxic T-lymphocytes.
16
Calcium metabolism
 Inhibit Abs & enhance renal Exc of Ca2+.
 Loss of osteoid results in loss of Ca2+ from bone.
 Produces negative calcium balance.
 Spongy bones (vertebrae, ribs etc.) are more sensitive.
Stomach
 Secretion of gastric acid and pepsin is increased—may
aggravate peptic ulcer.
17
CVS effects
 Directly stimulate cardiac output.
 Potentiates pressor effects of catecholamines & AngII.
 Predisposes to HTN & CHD.
Haematopoietic system
 ↑RBC, platelets & neutrophils in circulation.
 ↓Lymphocytes, eosinophils & basophils.
 Marked lytic effect on malignant lymphatic cells.
 Used in treating lymphomas.
18
Miscellaneous effects
 Cortisol is needed for maintaining normal GFR.
 Stimulates surfactant production in foetal lung.
 Higher doses ppt peptic ulcer.
 Increases renal excretion of uric acid.
 Depress TRH secretion
19
Mineralocorticoid actions
 Aldosterone is the most important MC.
 ↑Na+ reabsorption in DCT & CD, ↑K+ & H+ excretion.
 3 types of mechanisms operate for Na+ reabsorption.
Rapid non genomic effect by stimulation of Na+/H+
exchanger in the apical membrane.
Delayed effect by binding to MC receptor &
synthesizing aldosterone induced proteins (AIP).
↑No. of Na+/K+ ATPase molecules in basolateral
membrane.
20
21
22
USES
Replacement therapy
Acute adrenal insufficiency
 Hydrocortisone or dexamethasone are given i.v., first
as a bolus injection and then as infusion, along with
isotonic saline and glucose solution.
Chronic adrenal insufficiency (Addison’s disease)
 Hydrocortisone given orally.
 Adequate salt and water allowance.
 Patients who excrete excess Na+ need additional
mineralocorticoid: fludrocortisone is added.
23
24
Cong. adrenal hyperplasia (Adrenogenital syndrome)
 Genetic deficiency of mostly 21-hydroxylase.
 Synthesis of hydrocortisone and aldosterone ↓.
 ACTH secretion↑ leads to adrenals hypertrophy;
 Enzyme deficiency is partial in most cases,
 Excessive amounts of weak androgens → virilization
and/or precocious sexual development.
 If the deficiency is severe, salt wasting also occurs.
Treatment
 Hydrocortisone 0.6 mg/ kg daily in divided doses.
 Salt wasting persists, fludrocortisone 50–200 μg/d
25
Arthritides
Rheumatoid arthritis
 Indicated only in severe cases as adjuvants to NSAIDs.
 To suppress exacerbations, or systemic manifestations.
Osteoarthritis
 Intra-articular inj to control an acute exacerbation.
 Repeated 2–3 times a year, but have the potential to
cause joint destruction.
Rheumatic fever
 Used only in severe cases with carditis and CHF
 Aspirin is given in addition and is continued after
corticoids have been withdrawn.
26
Gout
 Corticoids (short course) should only be used in
 Acute gouty arthritis when NSAIDs have failed
Colchicine is not tolerated.
 Intra-articular inj of a soluble GC is preferred.
 Though they are uricosuric- use in chronic gout is not
recommended.
27
Immunosuppressive therapy
Collagen vascular disease
 Systemic lupus erythematosus,
 Polyarteritis nodosa,
 Dermatomyositis,
 Sarcoidosis & mixed connective tissue diseases
 Need corticosteroid therapy.
 They may be life saving in these diseases.
 Therapy is generally started with high doses which are
tapered to maintenance dose when remission occurs.
28
Skin graft & organ transplant
 High doses of GC are used .
 Other immunosuppresants e.g Azathioprine are also
used to prevent rejection.
Nephrotic syndrome
 Sec to minimal lesion nephropathy is immunological.
 Respond well to steroid therapy.
 Prednisolone 60mg/d X 6wk provides remission in
95% cases with in 3 months.
29
Autoimmune diseases
 Autoimmune hemolytic anemia, Thrombocytopenia
 Active chronic hepatitis
 Usually respond to corticosteroids.
 Long term therapy is needed as relapses are common.
Ch. Demyelinating polyneuropathies
 Suppress immune reaction but not progression.
 Guillian Barre syndrome- reduce inflammation &
improves final outcome.
30
Bronchial Asthma
 Inhaled/systemic steroids are preferred for mod/severe
 Inhaled steroids:
Beclomethasone
Budesonide
Flunisolide
Fluticasone
Mometasone
Triamcinolone
 Concomitant β–agonists or theophylline ↓dose of
steroids
31
Other lung diseases
 Benefit aspiration pneumonia and pulmonary edema
from drowning.
 To Prevent respiratory distress syndrome in premature
infants.
 Two doses of betamethasone 12 mg i.m. at 24 hour
interval may be administered to the mother if
premature delivery is contemplated.
32
Infective diseases
 Tuberculosis (miliary, meningeal, renal, etc.),
 Severe lepra reaction,
 Bacterial meningitis
 Pneumocystis carinii pneumonia with hypoxia in AIDS
patients.
Skin diseases
 Topical corticosteroids are highly effective in many
eczematous skin diseases.
 Systemic therapy is needed (may be life-saving) in
pemphigus vulgaris, exfoliative dermatitis, Stevens-
Johnson syndrome and other severe afflictions.
33
Intestinal diseases
 Ulcerative colitis, Crohn’s disease, coeliac disease are
inflammatorybowel diseases with exacerbations and
remissions.
 Corticoids are indicated during acute phases.
Malignancies
 Useful in haematopoietic malignancies, Hodgkin’s &
other lymphomas.
 Secondary role in hormone responsive breast
carcinoma, act probably by causing HPA suppression
34
Cerebral edema
 Due to tumours, tubercular meningitis, etc., respond.
 Dexa-or betamethasone are preferred.
 Reduce neurological sequelae after spinal injury.
 Bell’s palsy- oral prednisolone X 2–4 weeks.
 Multiple sclerosis- methyl prednisolone 1 g i.v. daily for
2–3 days may be given in the beginning.
35
Septic shock
 Recent studies have documented beneficial effects of
low-dose (hydrocortisone 100 mg 8 hourly i.v. infusion
for 5–7 days) therapy in patients who are adrenal
deficient and do not respond adequately to fluid
replacement and vasopressors.
Thyroid storm
 Many patients in thyroid storm have concomitant
adrenal insufficiency.
 Corticosteroids reduce peripheral T4 to T3 conversion.
36
To test pituitary-adrenal axis function
 Dexamethasone suppression test is used for diagnosis
of cushings syndrome.
 Normal suppression of cortisol- HPA axis intact.
 Failure- hypersecretion of ACTH by pitutary tumor or
cortisol by adrenal tumor.
 Dexamethasone 1mg orally at 11PM, sample obtained at
8AM.
 Normal- cortisol levels <3mg/dl.
 Cushing’s- >5mg/dl.
37
Adverse effects
 Altered distribution of fat.
 Oedema, hypokalemia & hypertension
 Suppression of HPA axis
 Osteoporosis & osteonecrosis
 Hyperglycemia & glycosuria
 Peptic ulcer
 Ocular effects- cataract & glaucoma
38
 Myopathy & muscle wasting
 Susceptibility to infections
 CNS side effects- euphoria, insomnia & nervousness
 Delayed healing: of wounds and surgical incisions.
 Growth retardation: in children
 IUGR can occur after prolonged therapy.
 Pregnancy- increases the risk of gestational diabetes,
pregnancy induced hypertension and preeclampsia.
39
Contraindications
1. Peptic ulcer
2. Diabetes mellitus
3. Hypertension
4. Viral and fungal infections
5. Tuberculosis and other infections
6. Osteoporosis
7. Herpes simplex keratitis
8. Psychosis
9. Epilepsy
10. CHF
11. Renal failure
40
Metyrapone
 Inhibits 11-β hydroxylase in adrenal cortex
 Prevents synthesis of hydrocortisone.
 Level falls → increased ACTH release → increased
synthesis, release and excretion of 11-desoxycortisol in
urine
 Used to test the responsiveness of pituitary and its
ACTH producing capacity.
41
 Aminoglutethimide,
 Trilostane and
 High doses of Ketoconazole also
 Inhibit steroidogenic enzymes—can be used to treat
Cushing’s disease when surgery or other measures are
not an option.
 Ketoconazole reduces gonadal steroid synthesis as
well.
42
 Mifepristone
 Glucocorticoid antagonist & antiprogestin
 May be used in Cushing’s syndrome
 Indicated only for inoperable cases of adrenal ca and
in patients with ectopic ACTH secretion.
43

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corticosteroids

  • 1. Dr. K. R. Professor, Assistant Professor. 1
  • 2. Introduction Adenal gland Medulla Cortex Epinephrine Z. glomerulosa Z. fasciculata Z. reticularis Mineralocorticoids Glucocorticods Androgens 2
  • 4. Steroid transport in blood  Glucocorticoids reversibly bind to transcortin.  Transcortin is a -globulin.  80% of plasma cortisol is bound to transcortin.  Only 10% is bound to serum albumin.  Remaining 10% is free hormone. 4
  • 6. Transactivation  Leads to transcription & translation.  Induces enzymes - Camp dependent kinase.  Induce formation of annexin-1 (lipocortin-1).  Lipocortin-1 inhibits phospholipase A2.  Induction of Annexin-1 is slow.  Antiinflammatory response takes several hours. 6
  • 7. Transrepression  Inhibits transcription factors like- AP-1 & NF-kB.  Inhibits transcrption of genes for- COX-2 Cytokines Inducible form of NO synthase.  Biological lag of several hours is seen before effects.  Effects are present even when steroid levels fall.  Side effects can be minimized by alternative day therapy 7
  • 8. Mineralocorticoid receptor  Binds to MRE.  Expressed mainly in kidney, also in colon, salivary glands, sweat glands & hippocampus.  Glucocorticoids will also bind to MRs.  MRs bind aldosterone & hydrocortisone (cortisol) with equal affinity.  Cortisol is inactivated by 11-β-HSD on binding to MRs.  Aldosterone exists as hemiacetyl derivative which is resistant to degradation by 11-β-HSD. 8
  • 9. Pharmacological actions General considerations  Actions of corticoids are divided in to Gluco- carbohydrate, fat & protein metabolism. - antiinflammatory & immunosuppressant actions. Mineralo- Na+, K+ & fluid homeostasis.  Glucocorticoid potency α antiinflammatory effects.  Direct and some permissive actions.  Exogenous glucocorticoids depress secretion of CRH & ACTH by negative feedback mechanism. 9
  • 10. Glucocorticoid actions Carbohydrate & protein metabolism  Exert anti-insulin effects by: 1. ↓ Peripheral utilization of glucose 2. ↑ gluconeogenesis 3. Inhibit protein synthesis in muscle, connective tissue & skin.  Net result of glucocorticoid administration is- ↑ Blood sugar, liver glycogen & excretion of nitrogen.  Prolonged high doses- DM like state, protein wasting. 10
  • 11. Fat metabolism  Enhance lipolytic effects of GH, Adr, Thyroxine.  Mobilization of free fatty acids ↑.  Insulin release → ↑ deposition of fats.  Prolonged high doses cause redistribution of fat. Neck & shoulders- buffalo hump Face- moon face, abdomen- centripetal obesity.  Cuta striae- due to stretching of skin.  Central adipocytes are more sensitive to insulin. 11
  • 12. 12
  • 13. Anti-inflammatory effects  Endogenous GC prevent excessive defense response.  Inhibit inflammation irrespective of its cause. In macrophages, monocytes, endothelium & fibroblasts  Induce the production of lipocortin.  Inhibit cytokine release & T-cell activation.  This reduces the process of chemotaxis.  Inhibit synthesis of adhesion molecules- ELAM-1 & ICAM-1, promote leukocyte localization.  Impair recruitment to the sites of inflammation. 13
  • 14. Transrepression of proinflammatory transcription factors  Inhibit nuclear factor-kB (NF-kB) & activatory protein (AP-1).  These enhance transcription of genes for COX-2, various cytokines & iNOS. Lymphocytes  ↓Release of cytokines (IL-1, 2,4&6) from lymphocytes.  GC ↓ L, M, E & B in circulation 14
  • 15. Miscellaneous effects Basophils & mast cells:  Gc ↓ IgE dependent release of histamine LT-C4 from basophils. ↓Capillary permeability.  Acute phase reactant production ↓.  ↓ Production of collagenase & stromelysin , hinder tissue damage  Prolonged therapy ↓ production of collagen – obstructs wound healing & repair. 15
  • 16. Immune response  Suppress CMI  Inhibit genes for cytokines- IL-1,2,3,4,5,6,8 & INF-ɣ.  ↓cytokines reduce T-cell proliferation.  Also suppress humoral immunity.  Down regulate Fc receptors on macrophages.  Graft rejection is prevented by- 1. Reducing antigen expression from grafted tissue. 2. Delay revascularization. 3. ↓ Sensitization of cytotoxic T-lymphocytes. 16
  • 17. Calcium metabolism  Inhibit Abs & enhance renal Exc of Ca2+.  Loss of osteoid results in loss of Ca2+ from bone.  Produces negative calcium balance.  Spongy bones (vertebrae, ribs etc.) are more sensitive. Stomach  Secretion of gastric acid and pepsin is increased—may aggravate peptic ulcer. 17
  • 18. CVS effects  Directly stimulate cardiac output.  Potentiates pressor effects of catecholamines & AngII.  Predisposes to HTN & CHD. Haematopoietic system  ↑RBC, platelets & neutrophils in circulation.  ↓Lymphocytes, eosinophils & basophils.  Marked lytic effect on malignant lymphatic cells.  Used in treating lymphomas. 18
  • 19. Miscellaneous effects  Cortisol is needed for maintaining normal GFR.  Stimulates surfactant production in foetal lung.  Higher doses ppt peptic ulcer.  Increases renal excretion of uric acid.  Depress TRH secretion 19
  • 20. Mineralocorticoid actions  Aldosterone is the most important MC.  ↑Na+ reabsorption in DCT & CD, ↑K+ & H+ excretion.  3 types of mechanisms operate for Na+ reabsorption. Rapid non genomic effect by stimulation of Na+/H+ exchanger in the apical membrane. Delayed effect by binding to MC receptor & synthesizing aldosterone induced proteins (AIP). ↑No. of Na+/K+ ATPase molecules in basolateral membrane. 20
  • 21. 21
  • 22. 22
  • 23. USES Replacement therapy Acute adrenal insufficiency  Hydrocortisone or dexamethasone are given i.v., first as a bolus injection and then as infusion, along with isotonic saline and glucose solution. Chronic adrenal insufficiency (Addison’s disease)  Hydrocortisone given orally.  Adequate salt and water allowance.  Patients who excrete excess Na+ need additional mineralocorticoid: fludrocortisone is added. 23
  • 24. 24
  • 25. Cong. adrenal hyperplasia (Adrenogenital syndrome)  Genetic deficiency of mostly 21-hydroxylase.  Synthesis of hydrocortisone and aldosterone ↓.  ACTH secretion↑ leads to adrenals hypertrophy;  Enzyme deficiency is partial in most cases,  Excessive amounts of weak androgens → virilization and/or precocious sexual development.  If the deficiency is severe, salt wasting also occurs. Treatment  Hydrocortisone 0.6 mg/ kg daily in divided doses.  Salt wasting persists, fludrocortisone 50–200 μg/d 25
  • 26. Arthritides Rheumatoid arthritis  Indicated only in severe cases as adjuvants to NSAIDs.  To suppress exacerbations, or systemic manifestations. Osteoarthritis  Intra-articular inj to control an acute exacerbation.  Repeated 2–3 times a year, but have the potential to cause joint destruction. Rheumatic fever  Used only in severe cases with carditis and CHF  Aspirin is given in addition and is continued after corticoids have been withdrawn. 26
  • 27. Gout  Corticoids (short course) should only be used in  Acute gouty arthritis when NSAIDs have failed Colchicine is not tolerated.  Intra-articular inj of a soluble GC is preferred.  Though they are uricosuric- use in chronic gout is not recommended. 27
  • 28. Immunosuppressive therapy Collagen vascular disease  Systemic lupus erythematosus,  Polyarteritis nodosa,  Dermatomyositis,  Sarcoidosis & mixed connective tissue diseases  Need corticosteroid therapy.  They may be life saving in these diseases.  Therapy is generally started with high doses which are tapered to maintenance dose when remission occurs. 28
  • 29. Skin graft & organ transplant  High doses of GC are used .  Other immunosuppresants e.g Azathioprine are also used to prevent rejection. Nephrotic syndrome  Sec to minimal lesion nephropathy is immunological.  Respond well to steroid therapy.  Prednisolone 60mg/d X 6wk provides remission in 95% cases with in 3 months. 29
  • 30. Autoimmune diseases  Autoimmune hemolytic anemia, Thrombocytopenia  Active chronic hepatitis  Usually respond to corticosteroids.  Long term therapy is needed as relapses are common. Ch. Demyelinating polyneuropathies  Suppress immune reaction but not progression.  Guillian Barre syndrome- reduce inflammation & improves final outcome. 30
  • 31. Bronchial Asthma  Inhaled/systemic steroids are preferred for mod/severe  Inhaled steroids: Beclomethasone Budesonide Flunisolide Fluticasone Mometasone Triamcinolone  Concomitant β–agonists or theophylline ↓dose of steroids 31
  • 32. Other lung diseases  Benefit aspiration pneumonia and pulmonary edema from drowning.  To Prevent respiratory distress syndrome in premature infants.  Two doses of betamethasone 12 mg i.m. at 24 hour interval may be administered to the mother if premature delivery is contemplated. 32
  • 33. Infective diseases  Tuberculosis (miliary, meningeal, renal, etc.),  Severe lepra reaction,  Bacterial meningitis  Pneumocystis carinii pneumonia with hypoxia in AIDS patients. Skin diseases  Topical corticosteroids are highly effective in many eczematous skin diseases.  Systemic therapy is needed (may be life-saving) in pemphigus vulgaris, exfoliative dermatitis, Stevens- Johnson syndrome and other severe afflictions. 33
  • 34. Intestinal diseases  Ulcerative colitis, Crohn’s disease, coeliac disease are inflammatorybowel diseases with exacerbations and remissions.  Corticoids are indicated during acute phases. Malignancies  Useful in haematopoietic malignancies, Hodgkin’s & other lymphomas.  Secondary role in hormone responsive breast carcinoma, act probably by causing HPA suppression 34
  • 35. Cerebral edema  Due to tumours, tubercular meningitis, etc., respond.  Dexa-or betamethasone are preferred.  Reduce neurological sequelae after spinal injury.  Bell’s palsy- oral prednisolone X 2–4 weeks.  Multiple sclerosis- methyl prednisolone 1 g i.v. daily for 2–3 days may be given in the beginning. 35
  • 36. Septic shock  Recent studies have documented beneficial effects of low-dose (hydrocortisone 100 mg 8 hourly i.v. infusion for 5–7 days) therapy in patients who are adrenal deficient and do not respond adequately to fluid replacement and vasopressors. Thyroid storm  Many patients in thyroid storm have concomitant adrenal insufficiency.  Corticosteroids reduce peripheral T4 to T3 conversion. 36
  • 37. To test pituitary-adrenal axis function  Dexamethasone suppression test is used for diagnosis of cushings syndrome.  Normal suppression of cortisol- HPA axis intact.  Failure- hypersecretion of ACTH by pitutary tumor or cortisol by adrenal tumor.  Dexamethasone 1mg orally at 11PM, sample obtained at 8AM.  Normal- cortisol levels <3mg/dl.  Cushing’s- >5mg/dl. 37
  • 38. Adverse effects  Altered distribution of fat.  Oedema, hypokalemia & hypertension  Suppression of HPA axis  Osteoporosis & osteonecrosis  Hyperglycemia & glycosuria  Peptic ulcer  Ocular effects- cataract & glaucoma 38
  • 39.  Myopathy & muscle wasting  Susceptibility to infections  CNS side effects- euphoria, insomnia & nervousness  Delayed healing: of wounds and surgical incisions.  Growth retardation: in children  IUGR can occur after prolonged therapy.  Pregnancy- increases the risk of gestational diabetes, pregnancy induced hypertension and preeclampsia. 39
  • 40. Contraindications 1. Peptic ulcer 2. Diabetes mellitus 3. Hypertension 4. Viral and fungal infections 5. Tuberculosis and other infections 6. Osteoporosis 7. Herpes simplex keratitis 8. Psychosis 9. Epilepsy 10. CHF 11. Renal failure 40
  • 41. Metyrapone  Inhibits 11-β hydroxylase in adrenal cortex  Prevents synthesis of hydrocortisone.  Level falls → increased ACTH release → increased synthesis, release and excretion of 11-desoxycortisol in urine  Used to test the responsiveness of pituitary and its ACTH producing capacity. 41
  • 42.  Aminoglutethimide,  Trilostane and  High doses of Ketoconazole also  Inhibit steroidogenic enzymes—can be used to treat Cushing’s disease when surgery or other measures are not an option.  Ketoconazole reduces gonadal steroid synthesis as well. 42
  • 43.  Mifepristone  Glucocorticoid antagonist & antiprogestin  May be used in Cushing’s syndrome  Indicated only for inoperable cases of adrenal ca and in patients with ectopic ACTH secretion. 43