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Pharmacology Test #5 > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

Cortex of the adrenal glands secretes

A

glucocorticoids, mineralcorticoids, and androgens

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2
Q

Medulla of the adrenal gland secretes

A

Epinephrine and Norepinephrine

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3
Q

Glucocorticoids

A

stress hormones; increase circulating glucose concentrations; potent anti-inflammatory effects

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4
Q

Mineralocorticoids

A

Na+ retention; increase blood volume; increase blood pressure

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5
Q

What controls the synthesis of mineralocorticoids

A

Renin-angiotensin-aldosterone system

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6
Q

Transport of steroids

A

transported in plasma by plasma transport proteins

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7
Q

Corticoid-binding globulin (transcortin) transports

A

glucocorticoids and progesterone

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8
Q

Sex hormone binding globulin (SHBG) transports

A

testosterone and estradiol

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9
Q

Metabolism of steroids

A

metabolized in the liver (oxidation, sulfation, and glucuronidation)

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10
Q

Excretion of steroids

A

excreted in bile (estrogen) or in the urine (progesterone, androge, and glucocorticoids)

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11
Q

Glucocorticoids up-regulate enzymes for

A

gluconeogenesis and anti-inflammatory proteins

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12
Q

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes

A

the rate-limiting step in gluconeogenesis

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13
Q

Lipocortin I suppresses

A

phospholipase A2, which has a critical role in eicosanoid synthesis

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14
Q

Mechanism of immunosuppression by glucocorticoids

A

activated glucocorticoid receptor (GR) binds to NFkB and prevents binding of NFkB to its response element; transcription of cytokine genes are repressed

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15
Q

Physiologic effects of glucocorticoids on the liver

A

Increase gluconeogenesis and glycogen storage

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16
Q

Physiologic effects of glucocorticoids on the muscle

A

Promote protein degradation; decrease protein synthesis and decrease sensitivity to insulin

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17
Q

Physiologic effects of glucocorticoids on adipose tissue

A

promote lipolysis and decrease sensitivity to insulin

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18
Q

Physiologic effects of glucocorticoids on the immune system

A

Block the synthesis of cytokines and inhibits the production of eicosanoids

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19
Q

Addison’s disease

A

hypoadrenalism; decreased secretion of steroid hormones by the adrenal cortex

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20
Q

Causes of Addison’s disease

A
  1. destruction of the cortex by TB or atropy

2. decreased secretion of ACTH due to disease of anterior pituitary

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21
Q

Symptoms of Addison’s disease

A

Extreme weakness, anorexia, anemia, nausea, vomiting, low blood pressure, hyperpigmentation, mental depression

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22
Q

Cushing’s disease

A

Hyperadrenalism

23
Q

Causes of Cushing’s disease

A
  1. tumors in the adrenal cortex
  2. increased production of ACTH due to pituitary carcinoma
  3. ectopic production of ACTH due to non-pituitary carcinoma
24
Q

Symptoms of Cushing’s disease

A

Increased protein catabolism (easy bruising, delayed wound healing, muscle wasting), increased glucose levels, osteoporosis and opportunistic infections

25
What is Ketoconazole?
antifungal at lower concentration (block the synthesis of ergosterol)
26
Ketoconazole inhibits
P450scc; 17alpha-hydroxylase, and 11beta-hydroxylase
27
Ketoconazole can treat
hyperglucocorticoid states (Cushing's syndrome)
28
Therapeutic uses of corticosteroids
1. Primary adrenal insufficiency caused by atrophy of adrenal cortex 2. Allergic reactions 3. Inflammation and autoimmune diseases 4. Asthma 5. Immunosuppressive 6. Anti-cancer
29
What is required for GC activity in glucocorticoids?
4,5-double bond C3 ketone 11-beta hydroxyl C17 hydroxyl
30
What is required for MC activity in mineralcorticoids?
4,5-double bond | C3 ketone
31
Cortisol versus cortisone
Oxidation of 11 hydroxyl to ketone inactivates glucocorticoids
32
Cortisone should not be used to treat patients with
impaired liver functions
33
Short-acting systemic corticosteroids
Hydrocortisone and Cortisone
34
Intermediate-acting systemic corticosteroids
Prednisone; Prednisolone; Methylprednisolone; Triamcinolone
35
Long-acting systemic corticosteroids
Dexamethasone and Betamethasone
36
Fludrocortisone
synthetic glucocorticoid; 9alphaF; greater glucocorticoid activity; strong mineralocorticoid activity; intense Na+ retention/edema; used in mineralocorticoid replacement therapy
37
Prednisone/prednisolone
extra double bond between C1 and C2; more potent glucocorticoid activity; reduced mineralocorticoid activity; interconvertible by 11beta-hydroxysteroid dehydrogenase
38
Methylprednisolone
synthetic glucocorticoid; 6alpha-methyl group
39
Triamcinolone
synthetic glucocorticoid; 9alphaF and 16alphaOH; similar to prednisone; increased hydrophilicity; low oral bioavailability
40
Dexamethasone
16alpha-methyl group; increased lipophilicity; stronger effect; increased stability; reduced mineralocorticoid activity
41
Betamethasone
Enantiomer of dexamethasone at 16; similar to dexamethasone
42
What does changing the hydroxyl group at 21 to an acetate or butyrate do to glucocorticoids?
increased lipophilicity; prolonged action upon IM or intra-articular injection?
43
What does changing the hydroxyl group at 21 to an succinate do to glucocorticoids?
makes it more soluble; slows hydrolysis
44
What does changing the hydroxyl group at 21 to a phosphate group do to glucocorticoids?
increased solubility; rapid hydrolysis by phosphatases; IV or IM injection for emergencies
45
Desired properties of topical glucocorticoids
high lipophilicity for fast absorption; minimal systeic effect; prolonged action
46
Acetonide or ester glucocorticoids have better potency for topical applications due to
high lipophilicity
47
Topical glucocorticoids
Tramcinolone acetonide Betamethasone valerate Fluticasone propionate Mometasone furoate
48
21-chlorocorticoids
Clobetasol propionate Halobetasol propionate Halcinonide
49
Substitution of a chlorine atome for the 21-hydroxyl group does what?
greatly enhances topical anti-inflammatory activity
50
Desired properties for inhaled glucocorticoids
high potency; minimal systemic effects; prolonged action
51
Inhaled glucocorticoids
``` Triamcinolone acetonide Beclomethasone dipropionate Flunisolide Budesonide Mometasone furoate Fluticasone propionate ```
52
Adverse effects of corticoids
``` Crossover mineralocorticoid activity Steroid myopathy Reduced long bone growth in children Osteoporosis Cushing's like effects Impaired glucose tolerance Suppression of immune system GI/CNS Cataracts ```
53
What can happen upon withdrawal of corticoids?
Adrenal insufficiency - Addisonian crisis; due to negative feedback on hypothalamus and pituitary from prolonged doses

Pharmacology Test #5 (11 decks)

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