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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
Q

What is Ketoconazole?

A

antifungal at lower concentration (block the synthesis of ergosterol)

26
Q

Ketoconazole inhibits

A

P450scc; 17alpha-hydroxylase, and 11beta-hydroxylase

27
Q

Ketoconazole can treat

A

hyperglucocorticoid states (Cushing’s syndrome)

28
Q

Therapeutic uses of corticosteroids

A
  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
Q

What is required for GC activity in glucocorticoids?

A

4,5-double bond
C3 ketone
11-beta hydroxyl
C17 hydroxyl

30
Q

What is required for MC activity in mineralcorticoids?

A

4,5-double bond

C3 ketone

31
Q

Cortisol versus cortisone

A

Oxidation of 11 hydroxyl to ketone inactivates glucocorticoids

32
Q

Cortisone should not be used to treat patients with

A

impaired liver functions

33
Q

Short-acting systemic corticosteroids

A

Hydrocortisone and Cortisone

34
Q

Intermediate-acting systemic corticosteroids

A

Prednisone;
Prednisolone;
Methylprednisolone;
Triamcinolone

35
Q

Long-acting systemic corticosteroids

A

Dexamethasone and Betamethasone

36
Q

Fludrocortisone

A

synthetic glucocorticoid; 9alphaF; greater glucocorticoid activity; strong mineralocorticoid activity; intense Na+ retention/edema; used in mineralocorticoid replacement therapy

37
Q

Prednisone/prednisolone

A

extra double bond between C1 and C2; more potent glucocorticoid activity; reduced mineralocorticoid activity; interconvertible by 11beta-hydroxysteroid dehydrogenase

38
Q

Methylprednisolone

A

synthetic glucocorticoid; 6alpha-methyl group

39
Q

Triamcinolone

A

synthetic glucocorticoid; 9alphaF and 16alphaOH; similar to prednisone; increased hydrophilicity; low oral bioavailability

40
Q

Dexamethasone

A

16alpha-methyl group; increased lipophilicity; stronger effect; increased stability; reduced mineralocorticoid activity

41
Q

Betamethasone

A

Enantiomer of dexamethasone at 16; similar to dexamethasone

42
Q

What does changing the hydroxyl group at 21 to an acetate or butyrate do to glucocorticoids?

A

increased lipophilicity; prolonged action upon IM or intra-articular injection?

43
Q

What does changing the hydroxyl group at 21 to an succinate do to glucocorticoids?

A

makes it more soluble; slows hydrolysis

44
Q

What does changing the hydroxyl group at 21 to a phosphate group do to glucocorticoids?

A

increased solubility; rapid hydrolysis by phosphatases; IV or IM injection for emergencies

45
Q

Desired properties of topical glucocorticoids

A

high lipophilicity for fast absorption; minimal systeic effect; prolonged action

46
Q

Acetonide or ester glucocorticoids have better potency for topical applications due to

A

high lipophilicity

47
Q

Topical glucocorticoids

A

Tramcinolone acetonide
Betamethasone valerate
Fluticasone propionate
Mometasone furoate

48
Q

21-chlorocorticoids

A

Clobetasol propionate
Halobetasol propionate
Halcinonide

49
Q

Substitution of a chlorine atome for the 21-hydroxyl group does what?

A

greatly enhances topical anti-inflammatory activity

50
Q

Desired properties for inhaled glucocorticoids

A

high potency; minimal systemic effects; prolonged action

51
Q

Inhaled glucocorticoids

A 
Triamcinolone acetonide
Beclomethasone dipropionate
Flunisolide
Budesonide
Mometasone furoate
Fluticasone propionate
52
Q

Adverse effects of corticoids

A 
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
Q

What can happen upon withdrawal of corticoids?

A

Adrenal insufficiency - Addisonian crisis; due to negative feedback on hypothalamus and pituitary from prolonged doses

Pharmacology Test #5 (11 decks)

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