Adrenocorticosteroids and Antagonists -pg6 onwards Flashcards
(121 cards)
1
Q
What function is impaired in Congenital Adrenal Hyperplasia?
A
mostly caused by lack of P450c21 (21-B hydroxylase) function, resulting in the accumulation of 17-hydroxyprogesterone
2
Q
Lack of cortisol synthesis in Congenital Adrenal hyperplasia causes what?
A
Lack of cortisol synthesis will cause increased release of ACTH and consequently adrenocorticol hyperplasia and increased production of 17-hydroxy-progesterone (normally involved in cortisol production) which will lead to increased production of androgens.
3
Q
What will the increased production of androgens cause in Congenital Adrenal hyperplasia?
A
The production of androgens will cause virilization of the fetus (normally fine but in this case an unhealthy biological development of the fetus into a male or female sex. ex: if fetus is genetically female and virilization causes the development of male sex organs, the child will be born with testes or ambiguous sex.)
4
Q
How do you treat Congenital Adrenal hyperplasia in the mother?
A
Give Dexamethasone to the mother to prevent congenital effects
5
Q
if defect in 11-B hydroxylase what occurs?
A
accumulation of 11 deoxycorticocosterone- normally degraded to androgen- (has mineralocorticoid activity) will result in hypernatermia, hypertension, hypokalemia and hypogonadism
6
Q
how do you treat a 11-B hydroxylase defect?
A
Dexamethasone
7
Q
What are the two forms of Adrenal Corticol HYPOFUNCTION?
A
- Congenital Adrenal Hyperplasia
- 11-B hydroxylase defect
treat both with Dexamethasone
8
Q
What are symptoms due to in Cushings Syndrome?
A
due to glucocorticoid Hypersecretion (HTN, DM, poor wound healing, osteoporosis, muscle wasting, fat redistribution and facial puffiness, mental disorders)
9
Q
How do you treat Cushings Syndrome?
A
- irradiation or surgical removal of tumor or bilateral adrenolectomy
- -> after adrenolectomy pt has to be maintained on hydrocortisone and sodium sparing drug (FLUDROCORTISONE)
*any dose adjustment of corticosteroids has to be gradually tapered; abrupt change causes withdrawal.
10
Q
Lack of cortisol synthesis in Congenital Adrenal hyperplasia causes what?
A
Lack of cortisol synthesis will cause increased release of ACTH and consequently adrenocorticol hyperplasia and increased production of 17-hydroxy-progesterone which will lead to increased production of androgens.
11
Q
What will the increased production of androgens cause in Congenital Adrenal hyperplasia?
A
The production of androgens will cause virilization of the fetus (normally fine but in this case an unhealthy biological development of the fetus into a male or female sex. ex: if fetus is genetically female and virilization causes the development of male sex organs, the child will be born with testes or ambiguous sex.)
12
Q
What is Aldosteronism caused by?
A
Adrenal adenomas producing excessive aldosterone, causing Hypernatremia and hypokalemic alkalosis
-could also be due to deficiency in the biosynthetic pathway; producing excessive deoxycorticosterone, corticosterone or 18-hydroxycorticosterone, which have mineralocorticoid function.
13
Q
How do you treat Aldosteronism?
A
Patients are treated with Spirinolactone, an aldosterone receptor antagonist
14
Q
What would you use to diagnose Adrenal Corticoid dysfunction?
A
Dexamethasone used for diagnosis of Cushings Disease (not syndrome). Suppression of ACTH is caused in bonafide Cushing’s disease as opposed to ectopic tumors secreting cortisol
aka: if giving pt dexamethasone, Cortisol wont decrease if unless patient has cushings DISEASE (tumor on pituitary).
15
Q
What is Cushings Syndrome due to?
A
It is the bilateral adrenal Hyperplasia secondary to a pituitary adenoma (Cushings Disease) or nodular carcinoma or the adrenal or ectopic tumor OVERPRODUCTION OF CORTISOL
- Cushings Disease is a kind of Cushings Syndrome. Other causes of Cushings Syndrome include
taking drugs that increase ACTH -> too much cortisol
Tumor of the adrenal gland
Tumor elsewhere in the body that produces cortisol
Tumors elsewhere in the body that produce ACTH (such as the pancreas, lung, and thyroid)
treat both with Dexamethasone
16
Q
What is Corticosteroid treatment used for in mothers?
A
Corticosteroid treatment (Betamethasone, IM) of the mother reduces respiratory distress syndrome in prematurely delivered infants by stimulating pulmonary surfactant secretion in the fetal lung.
17
Q
When are Corticosteroids used for Non-adrenal disorders?
A
- Supress inflammatory and immune responses and alter leukocyte activity.
- treatment of transplant rejection
18
Q
Corticosteroids supress inflammatory and immune responses and alter leukocyte activity, so what are they used to treat?
A
hence used for treating inflammatory and hyperimmune disorders including those due to autoimmune processes (such as pemphigus, myasthenia gravis, sarcoidosis etc), type I hypersensitivity (allergic hypersensitivity such as urticaria and bronchospasm) etc.
19
Q
How should corticosteroids be used?
A
Corticosteroids relieve symptoms but not the cause. If CHRONIC therapy is warranted, medium to intermediate acting steroids such as prednisone/prednisolone should be used preferably alternate day therapy, as well as ancillary drugs such as METHOTREXATE or AZATHIOPRINE to reduce dosage of corticosteroid.
-taper! to avoid drug withdrawal
20
Q
Because Corticosteroids cause immunosupression what should be tested in certain patients?
A
- Chest Xrays to check for dormant MYCOBACTERIUM
- presence of DM, Peptic Ulcers, Osteoporosis, and psychological disturbance are likely to be worsened by corticosteroid therapy –> assess CV functions
21
Q
Why are corticosteroids used to treat transplant rejections?
A
a) corticosteroids supress antigen expression in transplanted tissue.
b) delay revascularization
c) suppress T cell and B cell fx hence reduce acute and chronic transplant rejection
22
Q
What are Corticosteroid toxicities?
A
short term (less than 2 weeks): no serious AE’s
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-ti
23
Q
What is Aldosteronism caused by?
A
Adrenal adenomas producing excessive aldosterone, causing Hypernatremia and hypokalemic alkalosis
-could also be due to deficiency in the biosynthetic pathway; producing excessive deoxycorticosterone, corticosterone or 18-hydroxycorticosterone, which have mineralocorticoid function.
24
Q
How do you treat Aldosteronism?
A
Patients are treated with Spirinolactone, an aldosterone receptor antagonist
25
What would you use to diagnose Adrenal Corticoid dysfunction?
Dexamethasone used for diagnosis of Cushings Disease (not syndrome). Suppression of ACTH is caused in bonafide Cushing's disease as opposed to ectopic tumors secreting cortisol
aka: if giving pt dexamethasone, Cortisol wont decrease if unless patient has cushings DISEASE (tumor on pituitary).
26
What is Cushings Syndrome due to?
It is the bilateral adrenal Hyperplasia secondary to a pituitary adenoma (Cushings Disease) or nodular carcinoma or the adrenal or ectopic tumor OVERPRODUCTION OF CORTISOL
* Cushings Disease is a kind of Cushings Syndrome. Other causes of Cushings Syndrome include
taking drugs that increase ACTH -> too much cortisol
Tumor of the adrenal gland
Tumor elsewhere in the body that produces cortisol
Tumors elsewhere in the body that produce ACTH (such as the pancreas, lung, and thyroid)
treat both with Dexamethasone
27
What is Corticosteroid treatment used for in mothers?
Corticosteroid treatment (Betamethasone, IM) of the mother reduces respiratory distress syndrome in prematurely delivered infants by stimulating pulmonary surfactant secretion in the fetal lung.
28
When are Corticosteroids used for Non-adrenal disorders?
1. Supress inflammatory and immune responses and alter leukocyte activity.
2. treatment of transplant rejection
29
Corticosteroids supress inflammatory and immune responses and alter leukocyte activity, so what are they used to treat?
hence used for treating inflammatory and hyperimmune disorders including those due to autoimmune processes (such as pemphigus, myasthenia gravis, sarcoidosis etc), type I hypersensitivity (allergic hypersensitivity such as urticaria and bronchospasm) etc.
30
How should corticosteroids be used?
Corticosteroids relieve symptoms but not the cause. If CHRONIC therapy is warranted, medium to intermediate acting steroids such as prednisone/prednisolone should be used preferably alternate day therapy, as well as ancillary drugs such as METHOTREXATE or AZATHIOPRINE to reduce dosage of corticosteroid.
-taper! to avoid drug withdrawal
31
Because Corticosteroids cause immunosupression what should be tested in certain patients?
- Chest Xrays to check for dormant MYCOBACTERIUM
- presence of DM, Peptic Ulcers, Osteoporosis, and psychological disturbance are likely to be worsened by corticosteroid therapy --> assess CV functions
32
Why are corticosteroids used to treat transplant rejections?
a) corticosteroids supress antigen expression in transplanted tissue.
b) delay revascularization
c) suppress T cell and B cell fx hence reduce acute and chronic transplant rejection
33
What are Corticosteroid toxicities?
short term (less than 2 weeks): no serious AE's
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-thinning
34
What is Aldosteronism caused by?
Adrenal adenomas producing excessive aldosterone, causing Hypernatremia and hypokalemic alkalosis
-could also be due to deficiency in the biosynthetic pathway; producing excessive deoxycorticosterone, corticosterone or 18-hydroxycorticosterone, which have mineralocorticoid function.
35
How do you treat Aldosteronism?
Patients are treated with Spirinolactone, an aldosterone receptor antagonist
36
What would you use to diagnose Adrenal Corticoid dysfunction?
Dexamethasone used for diagnosis of Cushings Disease (not syndrome). Suppression of ACTH is caused in bonafide Cushing's disease as opposed to ectopic tumors secreting cortisol
aka: if giving pt dexamethasone, Cortisol wont decrease if unless patient has cushings DISEASE (tumor on pituitary).
37
What is Cushings Syndrome due to?
It is the bilateral adrenal Hyperplasia secondary to a pituitary adenoma (Cushings Disease) or nodular carcinoma or the adrenal or ectopic tumor OVERPRODUCTION OF CORTISOL
* Cushings Disease is a kind of Cushings Syndrome. Other causes of Cushings Syndrome include
taking drugs that increase ACTH -> too much cortisol
Tumor of the adrenal gland
Tumor elsewhere in the body that produces cortisol
Tumors elsewhere in the body that produce ACTH (such as the pancreas, lung, and thyroid)
treat both with Dexamethasone
38
What is Corticosteroid treatment used for in mothers?
Corticosteroid treatment (Betamethasone, IM) of the mother reduces respiratory distress syndrome in prematurely delivered infants by stimulating pulmonary surfactant secretion in the fetal lung.
39
When are Corticosteroids used for Non-adrenal disorders?
1. Supress inflammatory and immune responses and alter leukocyte activity.
2. treatment of transplant rejection
40
Corticosteroids supress inflammatory and immune responses and alter leukocyte activity, so what are they used to treat?
hence used for treating inflammatory and hyperimmune disorders including those due to autoimmune processes (such as pemphigus, myasthenia gravis, sarcoidosis etc), type I hypersensitivity (allergic hypersensitivity such as urticaria and bronchospasm) etc.
41
How should corticosteroids be used?
Corticosteroids relieve symptoms but not the cause. If CHRONIC therapy is warranted, medium to intermediate acting steroids such as prednisone/prednisolone should be used preferably alternate day therapy, as well as ancillary drugs such as METHOTREXATE or AZATHIOPRINE to reduce dosage of corticosteroid.
-taper! to avoid drug withdrawal
42
Because Corticosteroids cause immunosupression what should be tested in certain patients?
- Chest Xrays to check for dormant MYCOBACTERIUM
- presence of DM, Peptic Ulcers, Osteoporosis, and psychological disturbance are likely to be worsened by corticosteroid therapy --> assess CV functions
43
Why are corticosteroids used to treat transplant rejections?
a) corticosteroids supress antigen expression in transplanted tissue.
b) delay revascularization
c) suppress T cell and B cell fx hence reduce acute and chronic transplant rejection
44
What are short term Corticosteroid toxicities?
short term (less than 2 weeks): no serious AE's
45
What can the mineralocorticoid activity of cortisone/hydrocortisone cause?
Electrolyte imbalances (Hypernatremia, fluid retention, hypokalemia, hyperchloremic alkalosis) causing HTN
46
What do you do if a pt with Hypoproteinemia, liver disease or renal disease is being treated with corticosteroids?
EDEMA may occur in these patients, hence they must be placed on high protein and K+ enriched diet.
47
What toxicities occur in heart patients taking corticosteroids?
may cause HF in these patients. Effects can be reduced by switching to non-salt retaining steroids, sodium restriction and potassium supplements.
48
What toxicites occur in children taking corticosteroids?
may stunt growth
49
What else may corticosteroid use cause?
PU, Hypomania, acute psychosis, depression, cataracts, glaucoma
50
What are chronic corticosteroid use toxicites?
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-thinning of skin
-increased facial hair growth
-punctate (studded/ tiny holes) acne
-aseptic necrosis of the hip
51
What can the mineralocorticoid activity of cortisone/hydrocortisone cause?
Electrolyte imbalances (Hypernatremia, fluid retention, hypokalemia, hyperchloremic alkalosis) causing HTN
52
What do you do if a pt with Hypoproteinemia, liver disease or renal disease is being treated with corticosteroids?
EDEMA may occur in these patients, hence they must be placed on high protein and K+ enriched diet.
53
What toxicities occur in heart patients taking corticosteroids?
may cause HF in these patients. Effects can be reduced by switching to non-salt retaining steroids, sodium restriction and potassium supplements.
54
What toxicites occur in children taking corticosteroids?
may stunt growth
55
What else may corticosteroid use cause?
PU, Hypomania, acute psychosis, depression, cataracts, glaucoma
56
What are chronic corticosteroid use toxicites?
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-thinning of skin
-increased facial hair growth
-punctate (studded/ tiny holes) acne
-aseptic necrosis of the hip
57
What can the mineralocorticoid activity of cortisone/hydrocortisone cause?
Electrolyte imbalances (Hypernatremia, fluid retention, hypokalemia, hyperchloremic alkalosis) causing HTN
58
What do you do if a pt with Hypoproteinemia, liver disease or renal disease is being treated with corticosteroids?
EDEMA may occur in these patients, hence they must be placed on high protein and K+ enriched diet.
59
What toxicities occur in heart patients taking corticosteroids?
may cause HF in these patients. Effects can be reduced by switching to non-salt retaining steroids, sodium restriction and potassium supplements.
60
What toxicites occur in children taking corticosteroids?
may stunt growth
61
What else may corticosteroid use cause?
PU, Hypomania, acute psychosis, depression, cataracts, glaucoma
62
What are chronic corticosteroid use toxicities?
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-thinning of skin
-increased facial hair growth
-punctate (studded/ tiny holes) acne
-aseptic necrosis of the hip
63
What is chronic (>2 wks) corticosteroid administration likely to cause?
- Adrenal Suppression (Glucocorticoid-induced adrenal insufficiency)
- must gradually taper off
- if suddenly withdrawn, Glucocorticoid-induced adrenal insufficiency will cause major withdrawal effects
64
How should corticosteroids be administered?
After the initial dose required to suppress symptoms, the dose could be reduced to what is sufficient to keep symptoms down. Alternate day drug therapy is judicious.
For large dose therapy, medium/intermediate- acting steroids with no mineralocorticoid activity are preferred
** caution in pts with PU, heart disease, HTN w/ HF, inf with Varicella, TB, DM, Osteoporosis or glaucoma
65
which patients should you be cautious administering corticosteroids to?
pts with PU, heart disease, HTN w/ HF, inf with Varicella, TB, DM, Osteoporosis or glaucoma
(because they would excerbate these conditions. most of these are AE's of corticosteroid use..)
66
What dosage forms are available to minimize corticosteroid toxicity?
1. Topical preparations for skin disease, opthalmic forms for eye disease
2. Intra-articular injections for joint disease
3. Inhaled steroids for asthma
4. Hydrocortisone enemas for Ulcerative Collitis etc are ways of administering the drugs to the affected region minimizing systemic effects.
67
What are the corticosteroids used for Asthma?
```
Aerosols
1. Beclomethasone (QVAR)
2. Triamcinolone (Azmacort)
3. Budesonide (Pulmicort)
4. Flunisolide (Aerobid)
5. Fluticasone (Flovent)
6. Fluticasone/salmeterol (Advair Diskus)
7. Mometasone furoate (Asmanex, Twisthaler)
Nasal Sprays for allergic rhinitis
1. Mometasone (Nasonex)
2. Fluticasone (Flovent)
```
68
What are the dermatological corticosteroid preparations?
Creams and ointments containing corticosteroids applied directly on affected area.
69
What is Aldosterone?
main mineralocorticoid, secreted by zona glomerulosa of adrenal cortex
70
What does Aldosterone do?
retains Na+ in the distal part of the distal convuluted tubule and cortical collecting duct
71
What is Fludrocortisone?
the main (potent) synthetic steroid with significant mineralocorticoid activity used clinically
given in case of adrenal insufficiency (addison's disease)
doses not sufficient to cause antiinflamm/ antigrowth effects
72
What can the mineralocorticoid activity of cortisone/hydrocortisone cause?
Electrolyte imbalances (Hypernatremia, fluid retention, hypokalemia, hyperchloremic alkalosis) causing HTN
73
What do you do if a pt with Hypoproteinemia, liver disease or renal disease is being treated with corticosteroids?
EDEMA may occur in these patients, hence they must be placed on high protein and K+ enriched diet.
74
What toxicities occur in heart patients taking corticosteroids?
may cause HF in these patients. Effects can be reduced by switching to non-salt retaining steroids, sodium restriction and potassium supplements.
75
What toxicites occur in children taking corticosteroids?
may stunt growth
76
What else may corticosteroid use cause?
PU, Hypomania, acute psychosis, depression, cataracts, glaucoma
77
What are chronic corticosteroid use toxicities?
chronic treatment: leads to iatrogenic (symptoms due to illness) Cushings Syndrome.
-changes in appearance due to fat redistribution (steatosis)
(facial puffiness, trunk obesity, fat in neck, back an supraclavicular fosse)
-Osteoporosis
-DM
-Muscle wasting,
-thinning of skin
-increased facial hair growth
-punctate (studded/ tiny holes) acne
-aseptic necrosis of the hip
78
What is chronic (>2 wks) corticosteroid administration likely to cause?
- Adrenal Suppression (Glucocorticoid-induced adrenal insufficiency)
- must gradually taper off
- if suddenly withdrawn, Glucocorticoid-induced adrenal insufficiency will cause major withdrawal effects
79
How should corticosteroids be administered?
After the initial dose required to suppress symptoms, the dose could be reduced to what is sufficient to keep symptoms down. Alternate day drug therapy is judicious.
For large dose therapy, medium/intermediate- acting steroids with no mineralocorticoid activity are preferred
** caution in pts with PU, heart disease, HTN w/ HF, inf with Varicella, TB, DM, Osteoporosis or glaucoma
80
which patients should you be cautious administering corticosteroids to?
pts with PU, heart disease, HTN w/ HF, inf with Varicella, TB, DM, Osteoporosis or glaucoma
(because they would excerbate these conditions. most of these are AE's of corticosteroid use..)
81
What dosage forms are available to minimize corticosteroid toxicity?
1. Topical preparations for skin disease, opthalmic forms for eye disease
2. Intra-articular injections for joint disease
3. Inhaled steroids for asthma
4. Hydrocortisone enemas for Ulcerative Collitis etc are ways of administering the drugs to the affected region minimizing systemic effects.
82
What are the corticosteroids used for Asthma?
```
Aerosols
1. Beclomethasone (QVAR)
2. Triamcinolone (Azmacort)
3. Budesonide (Pulmicort)
4. Flunisolide (Aerobid)
5. Fluticasone (Flovent)
6. Fluticasone/salmeterol (Advair Diskus)
7. Mometasone furoate (Asmanex, Twisthaler)
Nasal Sprays for allergic rhinitis
1. Mometasone (Nasonex)
2. Fluticasone (Flovent)
```
83
What are the dermatological corticosteroid preparations?
Creams and ointments containing corticosteroids applied directly on affected area.
84
What is Aldosterone?
main mineralocorticoid, secreted by zona glomerulosa of adrenal cortex
85
What does Aldosterone do?
retains Na+ in the distal part of the distal convuluted tubule and cortical collecting duct
86
What is Fludrocortisone?
the main (potent) synthetic steroid with significant mineralocorticoid activity used clinically.
given in case of adrenal insufficiency associated with mineralocorticoid deficiency
doses not sufficient to cause antiinflammatory/antigrowth effects
87
What do adrenal tumors/mineralocorticoid overdoses cause?
- Hypokalemia
- Hypernatremia (aldosterone (a mineralocorticoid) retains Na+.
- fluid retention (")
- HTN (maybe due to high Na+ and fluid?)
- metabolic alkalosis (loss of K in blood-- keeps acidic. remember when a lot of K leaves cells and enters blood we got acidosis? Also, retention of Na means that K leaves (NA+/K+ ATPase pump) just to tie it all in...)
88
How does Aldosterone affect Na/K
aldosterone stimulates gene expression of Na/K ATPase pumps and epithelial Na channels to cause increased Na uptake and concurrent loss of K.
89
What is Deoxycorticocosterone (DOC)
Deoxycorticocosterone is the precursor of aldosterone, has mineralocorticoid activity.
Unlike aldosterone, its secretion is mainly controlled by ACTH. Secretion may be increased due to adrenal tumors/congenital adrenal hyperplasia due to biosynthetic enzyme deficiency
90
What is an Adrenal Androgen?
Dehydroepiandrosterone (DHEA). large amounts of DHEA and small amounts of androstenodione and testosterone are secreted by the adrenal cortex.
-No clear clinical benefit
91
What are the Antagonists of adrenocortical Agents?
Biosynthetic Inhibitors
| 1.
92
What do adrenal tumors/mineralocorticoid overdoses cause?
- Hypokalemia
- Hypernatremia (aldosterone (a mineralocorticoid) retains Na+.
- fluid retention (")
- HTN (maybe due to high Na+ and fluid?)
- metabolic alkalosis (loss of K in blood-- keeps acidic. remember when a lot of K leaves cells and enters blood we got acidosis? Also, retention of Na means that K leaves (NA+/K+ ATPase pump) just to tie it all in...)
93
How does Aldosterone affect Na/K
aldosterone stimulates gene expression of Na/K ATPase pumps and epithelial Na channels to cause increased Na uptake and concurrent loss of K.
94
What is Deoxycorticocosterone (DOC)
Deoxycorticocosterone is the precursor of aldosterone, has mineralocorticoid activity.
Unlike aldosterone, its secretion is mainly controlled by ACTH. Secretion may be increased due to adrenal tumors/congenital adrenal hyperplasia due to biosynthetic enzyme deficiency
95
What is an Adrenal Androgen?
Dehydroepiandrosterone (DHEA). large amounts of DHEA and small amounts of androstenodione and testosterone are secreted by the adrenal cortex.
-No clear clinical benefit
96
What are the Antagonists of adrenocortical Agents?
Biosynthetic Inhibitors
1. Metyrapone *
2. Aminoglutethimide (Cytadren)
3. Ketoconazole (Nizoral)
4. Mifepristone (RU486) (Mifeprex)
5. Mitotane (Lysodren) *
6. Trilostane
Mineralocorticoid Antogonists
1. Spironolactone
2. Eplerenone (Inspra)
3. Drospirenone
*withdrawn in US
97
What is Metyrapone?
A Biosynthetic inh.
specific inh. of 11 hydroxylation and inh. synthesis of cortisol and corticosterone biosynthesis. There is consequent increase in ACTH release (because it seems as though there isn't enough cortisol) and 11- deoxycortisol secretion.
Useful diagnostic test for assessing capacity of anterior pituitary for releasing ACTH. Drug withdrawn from US market.
98
What is Aminoglutethimide (Cytraden)?
A Biosynthetic inh.
blocks conversion of cholesterol --> pregnenolone (cannot make cortisol)
used for treatment of Cushings Syndrome
Also an Aromatase inhibitor. Its use to prevent estrogen production in women with breast cancer has been supplanted by TAMOXIFEN
99
What is Ketoconazole?
A Biosynthetic inh.
Antifungal imidazole derivative that also inh. biosynthesis of steroidal hormones. Inh. side chain cleavage of cholesterol (....a bunch of shit idwanna type)
This effect is not seen at low doses req for antifungal activity
Used in pts with Cushings Syndrome
Causes HEPATOTOXICITY
100
What is Mifepristone?
A Biosynthetic inh.
Progesterone receptor antagonist, has strong antiprogestin activity.
Also inh. glucocorticoid receptor, acts as a competitive antagonist and blocks receptor activation. highly protein bound
Used to treat Cushings Syndrome in inoperable pts with ECTOPIC TUMORS who have failed other means of treatment
Main use as an ABORTIFACIENT in combination with misoprostol
101
What is Mitotane?
A Biosynthetic inh.
| Used to treat adrenal tumors. Drug withdrawn from US market due to toxicity.
102
What is Trilostane?
A Biosynthetic inh.
3B-17 hydroxy steroid dehydrogenase inh. Hence block adrenal and gonadal hormones like aminoglutethemide.
Used for treatment of Cushings Syndrome, including DOGS
GI AE's in about 50% of pts.
103
What corticosteroids are used to treat Cushings Syndrome?
TRilostane (also in dogs)
Mifepristone (due to ectopic tumors)
Aminoglutethemide
Ketoconazole (~meh)
104
What is Sprinolactone?
A Mineralocorticoid antagonist
- competitive aldosterone receptor antagonist. Used to treat PRIMARY ALDOSTERONISM
- also used as a K+ sparing diuretic
- also a competitive antagonist at the androgen receptor, and could be used to treat hirsutism in women.
105
What are the AE's of spironolactone?
```
Hyperkalemia
Cardiac Arrhythmia (due to hyperkalemia)
Menstrual abnormalities
gynecomastia
sedation
H/A
GI disturbances
skin rashes
```
106
What do adrenal tumors/mineralocorticoid overdoses cause?
- Hypokalemia
- Hypernatremia (aldosterone (a mineralocorticoid) retains Na+.
- fluid retention (")
- HTN (maybe due to high Na+ and fluid?)
- metabolic alkalosis (loss of K in blood-- keeps acidic. remember when a lot of K leaves cells and enters blood we got acidosis? Also, retention of Na means that K leaves (NA+/K+ ATPase pump) just to tie it all in...)
107
How does Aldosterone affect Na/K
aldosterone stimulates gene expression of Na/K ATPase pumps and epithelial Na channels to cause increased Na uptake and concurrent loss of K.
108
What is Deoxycorticocosterone (DOC)
Deoxycorticocosterone is the precursor of aldosterone, has mineralocorticoid activity.
Unlike aldosterone, its secretion is mainly controlled by ACTH. Secretion may be increased due to adrenal tumors/congenital adrenal hyperplasia due to biosynthetic enzyme deficiency
109
What is an Adrenal Androgen?
Dehydroepiandrosterone (DHEA). large amounts of DHEA and small amounts of androstenodione and testosterone are secreted by the adrenal cortex.
-No clear clinical benefit
110
What are the Antagonists of adrenocortical Agents?
Biosynthetic Inhibitors
1. Metyrapone *
2. Aminoglutethimide (Cytadren)
3. Ketoconazole (Nizoral)
4. Mifepristone (RU486) (Mifeprex)
5. Mitotane (Lysodren) *
6. Trilostane
Mineralocorticoid Antogonists
1. Spironolactone
2. Eplerenone (Inspra)
3. Drospirenone
*withdrawn in US
111
What is Metyrapone?
A Biosynthetic inh.
specific inh. of 11 hydroxylation and inh. synthesis of cortisol and corticosterone biosynthesis. There is consequent increase in ACTH release (because it seems as though there isn't enough cortisol) and 11- deoxycortisol secretion.
Useful diagnostic test for assessing capacity of anterior pituitary for releasing ACTH. Drug withdrawn from US market.
112
What is Aminoglutethimide (Cytraden)?
A Biosynthetic inh.
blocks conversion of cholesterol --> pregnenolone (cannot make cortisol)
used for treatment of Cushings Syndrome
Also an Aromatase inhibitor. Its use to prevent estrogen production in women with breast cancer has been supplanted by TAMOXIFEN
113
What is Ketoconazole?
A Biosynthetic inh.
Antifungal imidazole derivative that also inh. biosynthesis of steroidal hormones. Inh. side chain cleavage of cholesterol (....a bunch of shit idwanna type)
This effect is not seen at low doses req for antifungal activity
Used in pts with Cushings Syndrome
Causes HEPATOTOXICITY
114
What is Mifepristone?
A Biosynthetic inh.
Progesterone receptor antagonist, has strong antiprogestin activity.
Also inh. glucocorticoid receptor, acts as a competitive antagonist and blocks receptor activation. highly protein bound
Used to treat Cushings Syndrome in inoperable pts with ECTOPIC TUMORS who have failed other means of treatment
Main use as an ABORTIFACIENT in combination with misoprostol
115
What is Mitotane?
A Biosynthetic inh.
| Used to treat adrenal tumors. Drug withdrawn from US market due to toxicity.
116
What is Trilostane?
A Biosynthetic inh.
3B-17 hydroxy steroid dehydrogenase inh. Hence block adrenal and gonadal hormones like aminoglutethemide.
Used for treatment of Cushings Syndrome, including DOGS
GI AE's in about 50% of pts.
117
What corticosteroids are used to treat Cushings Syndrome?
TRilostane (also in dogs)
Mifepristone (due to ectopic tumors)
Aminoglutethemide
Ketoconazole (~meh)
118
What is Sprinolactone?
A Mineralocorticoid antagonist
- competitive aldosterone receptor antagonist. Used to treat PRIMARY ALDOSTERONISM
- also used as a K+ sparing diuretic
- also a competitive antagonist at the androgen receptor, and could be used to treat hirsutism in women.
119
What are the AE's of spironolactone?
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Hyperkalemia
Cardiac Arrhythmia (due to hyperkalemia)
Menstrual abnormalities
gynecomastia
sedation
H/A
GI disturbances
skin rashes
```
120
What is Eplerenone?
A Mineralocorticoid antagonist
Aldosterone receptor antagonist used for treatment of HTN
more selective than spironolactone, no effect on androgen receptor
May cause Hyperkalemia
121
What is Drospirenone?
A Mineralocorticoid antagonist
Aldoserone receptor antagonist; a progestin used in oral contraceptives in combo with estrogens (Yasmin -drospirenone +ethinyl estradiol) that also antagonizes aldosterone
