2 - Antiandrogens and Androgen Inhibitors Flashcards Preview

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Flashcards in 2 - Antiandrogens and Androgen Inhibitors Deck (110):
1

Androgens influence cutaneous structures such as hair follicles and sebaceous glands

True

2

Free testosterone and dihydrotestosterone are biologically active androgens that affect the pilosebaceous unit

True

3

Dihydrotestosterone is the target tissue active androgen

True

4

Testosterone and dihydrotestosterone have a central role in the pathogenesis of androgenetic alopecia, acne vulgaris and hirsutism

True

5

Antiandrogen refers to agents that block the androgen receptor I.e. Spironolactone, flutamide and cyproterone acetate

True

6

Spironolactone is an antiandrogen (blocks the androgen receptor)

True

7

Flutamide is an antiandrogen (blocks the androgen receptor)

True

8

Androgen inhibitors block androgen synthesis

True

9

Finasteride and Dutasteride are androgen inhibitors that specifically inhibit 5-alpha reductase

True (less conversion of free testosterone to dihydrotestosterone)

10

Leuprolide is a gonadotropin-releasing hormone agonist that initially increases LH and FSH production by the pituitary before sustained feedback inhibition of the secretion of these 2 gonadotropins

True

11

Progesterone and medroxyprogesterone act as both antiandrogens (block androgen receptor) and androgen inhibitors (inhibit dihydrotestosterone formation via 5-alpha reductase inhibition)

True

12

Finasteride (type II 5-alpha reductase inhibitor) is FDA approved for men with androgenetic alopecia

True (in contrast, the more potent Dutasteride is FDA approved for benign prostatic hypertrophy but not for androgenetic alopecia due to blockade of both isoenzymes I and II of 5-alpha reductase)

13

Testosterone can be formed in cutaneous sites, from the androgen precursor androstenedione derived from the adrenal cortex

True (this occurs when large amounts of androstenedione are secreted by adrenal tumours or in congenital adrenal hyperplasia)

14

The ovary and adrenal cortex are the primary sources of testosterone and other androgens in women

True

15

Androstenedione and dehydroepiandrosterone (DHEA) are produced by the ovary and adrenal gland

True

16

Androstenedione and dehydroepiandrosterone (DHEA) produced by the ovary and adrenal gland can be converted to more potent androgens I.e. Testosterone or to Oestrogens in peripheral organs including skin

True

17

The average daily rate of testosterone production in women is approx 0.25mg with half of this derived from metabolic conversion of androstenedione to testosterone at extra glandular sites including skin

True

18

PCOS is caused by increased quantities of androgens secreted by the ovary resulting in alopecia, acne and hirsutism

True

19

The 2 isoenzyme forms of 5-alpha reductase are type I and type II

True

20

Testosterone has minimal biological activity at the pilosebaceous unit and prostate until it is converted to dihydrotestosterone by 5-alpha reductase

True

21

Both testosterone and dihydrotestosterone bind to intracellular androgen receptor

True

22

Both type I and type II forms of 5-alpha reductase are located in the pilosebaceous unit

True

23

Type II isoenzyme form of 5-alpha reductase is also found in the prostate gland, epididymis and seminal vesicles (genital skin)

True

24

Type I isoenzyme form of 5-alpha reductase is found in non-genital skin

True (also includes scalp and face)

25

The hair follicles and sebaceous glands ducts on top of the scalp from frontal to vertex scalp host the Type II isoenzyme of 5-alpha reductase

True

26

The type II isoenzyme of 5-alpha reductase is absent from the occipital scalp

True

27

Spironolactone is an aldosterone antagonist which also blocks the androgen receptor

True

28

Spironolactone has no effect on 5-alpha reductase

True

29

Spironolactone is a steroid molecule which resembles mineralocorticoids

True (aldosterone antagonist with anti-mineralocorticoid activity)

30

Spironolactone may be converted to other active metabolites via progesterone 17-hydroxylase with the net result of decreased testosterone and dihydrotestosterone production

True

31

Spironolactone is 98% protein bound

True

32

Canrenone is the primary metabolite of Spironolactone contributing to the diuretic and antiandrogen activities of Spironolactone

True

33

The liver rapidly metabolised Spironolactone to its primary and active aldosterone antagonist metabolite, Canrenone

True

34

Food increases the absorption of Spironolactone

True

35

Metabolites of Spironolactone (active metabolite canrenone, and inactive canrenoate which is converted from canrenone by hydrolysis) are excreted in urine and bile

True

36

The unmetabolised Spironolactone does not appear in the urine

True (only the metabolised metabolites of spironolactone Canrenone and Canrenoate appear in the urine)

37

Spironolactone has been used to treat hirsutism, acne and androgenetic alopecia

True

38

Flutamide is more effective than Spironolactone in improving hirsutism

True

39

Spironolactone is more effective than Finasteride in improving hirsutism

True

40

Spironolactone may commonly cause menorrhagia and other menstrual dysfunction which usually last during the first 2-3 months of therapy

True

41

Finasteride specifically inhibits the type II isoenzyme of 5-alpha reductase

True

42

Dutasteride inhibits both type I and type II isoenzymes of 5-alpha reductase

True

43

Hyperkalaemia is a potentially serious common adverse effect of Spironolactone, particularly if given to patients with severe renal insufficiency

True

44

Spironolactone may cause gynaecomastia

True

45

Spironolactone may cause mild GI symptoms

True

46

Agranulocytosis is a rare adverse effect associated with Spironolactone, particularly in those with hepatic or renal impairment

True

47

Spironolactone is contraindicated in women with a genetic predisposition to breast cancer

True (not be given to these women even though causal role is lacking)

48

Spironolactone may cross the placental barrier

True (risk of feminisation of a male fetus)

49

Spironolactone should not be given concurrently with other agents that increase the risk of hyperkalaemia

True

50

Spironolactone should not be given concurrently with ACE-inhibitors (increases the risk of hyperkalaemia)

True

51

Spironolactone should not be given concurrently with Aliskerin, a direct renin inhibitor (increases the risk of hyperkalaemia)

True

52

Spironolactone should not be given concurrently with an Angiotensin receptor blocker (increases the risk of hyperkalaemia)

True

53

Patients on Spironolactone should be cautioned against excessive dietary intake of potassium rich foods

True (risk of hyperkalaemia)

54

Drosperinone is a synthetic progestin used in OCP and a Spironolactone analogue with anti-mineralocorticoid (diuretic) activity and anti-androgenic activity

True

55

Drosperinone may cause hyperkalaemia

True (is a Spironolactone analogue)

56

Drosperinone is contraindicated in patients with hepatic dysfunction, renal dysfunction and adrenal insufficiency

True

57

Besides the progesterone receptor, Progestins may also interact with other steroid hormone receptors I.e. Androgen receptor, estrogen receptor, mineralocorticoid receptor and glucocorticoid receptor

True

58

Older progestins are derived from progesterone or 17-hydroxyprogesterone I.e. Medroxyprogesterone which are structurally similar to testosterone

True

59

Due to the structural similarity of androgen and Progesterone/other progestins, these can bind to the androgen receptor and act as a substrate for 5-alpha reductase to be converted to 5-alpha-pregnane-3, 20-dione (similar to dihydrotestosterone)

True

60

Cyproterone acetate is a progestin with antiandrogen properties

True

61

Cyproterone acetate competes with dihydrotestosterone for the androgen receptor binding site

True

62

Cyproterone acetate may also inhibit testosterone production

True

63

Cimetidine, an H2 antihistamine also has antiandrogen effects through binding with the androgen receptor

True

64

Finasteride is well absorbed

True

65

Finasteride is metabolised in the liver and excreted in urine and faeces

True

66

Finasteride is excreted in the urine and faeces

True

67

After finasteride administration, serum dihydrotestosterone decreases by 65% in 24 hours

True

68

Finasteride has no adverse consequences in female partners of men receiving finasteride who are exposed to the drug by sexual contact

True (no adverse effects despite minute quantities of finasteride is detectable in semen)

69

Minute quantities of finasteride is detectable in semen

True

70

The lack of scalp hair improvement in older men taking finasteride for prostatic hypertrophy is most likely due to the innate reduced response of scalp pilosebaceous units to finasteride in older men

True

71

Finasteride is not efficacious in female pattern alopecia

True

72

Finasteride (androgen inhibitor of 5-alpha reductase type II isoenzyme) and dutasteride (dual type I and type II 5-alpha reductase inhibitor) was associated with loss of libido, erectile and ejaculatory dysfunction in older men

True (though only decreased volume of ejaculate is likely to be causally related to finasteride due to dihydrotestosterone's central role in the pilosebaceous unit and prostate)

73

Finasteride and dutasteride may cause gynaecomastia

True

74

Finasteride may cause a 20-30% decrease in PSA in men 18-41 years old

True (finasteride reduces the size of the prostate gland and hence is also indicated in benign prostatic hypertrophy)

75

Finasteride may cause a 50% decrease in PSA in men aged 50 years old

True (the PSA needs to be doubled in all males aged 41 and above without benign prostatic hypertrophy if the PSA is ordered while taking finasteride to reflect the true PSA level)

76

Decreased libido, erectile dysfunction, or decreased volume of ejaculate have been reported in <4% of younger patients on finasteride

True (though only decreased volume of ejaculate is likely to be causally related to finasteride due to dihydrotestosterone's central role in the pilosebaceous unit and prostate)

77

Finasteride should be used with caution in men at high risk for depression

True (increased rates of depression noted after 2 months)

78

Finasteride is associated with a 26% risk reduction in prostate cancer, but a greater number of high grade Gleason score tumours

True (similar with dutasteride)

79

Finasteride may result in external genitalia abnormalities in male fetuses of pregnant women who take finasteride or handle crush or broken tablets

True (pregnancy category X)

80

The antiretroviral agent Nevirapine may reduce finasteride levels and hence efficacy

True

81

Finasteride is extensively metabolised in the liver primarily by the CYP3A4 subfamily

True (but no important interactions result given the drug's wide therapeutic index)

82

A baseline PSA is appropriate for men 50 years and older before receiving finasteride

True

83

Blood donation is contraindicated for those taking finasteride and dutasteride for at least 6 months after the last dose of medication to prevent blood donation to a pregnant female transfusion recipient as this may cause external genitalia abnormalities in male fetuses

True

84

It is contraindicated for dutasteride to be handled by women of childbearing potential

True (for the same reasons as finasteride)

85

Dutasteride has a very long half life of approximately 5 weeks

True

86

Serum concentrations of dutasteride remain detectable for up to 4-6 months after discontinuation of treatment

True

87

Dutasteride is metabolised by CYP3A4 in the liver and care should be taken in patients on chronic CYP3A4 inhibitors

True (Dutasteride has long half life in contrast to Finasteride)

88

HIV protease inhibitors (ritonavir, nelfinavir) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

89

Hep C virus protease inhibitors (telaprevir, boceprevir) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

90

Azole antifungals (ketoconazole, itraconazole) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

91

SSRI antidepressants (fluvoxamine) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

92

Macrolide antibiotics (erythromycin, clarithromycin) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

93

Fluoroquinolones (ciprofloxacin) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

94

Calcium channel blockers (verapamil, diltiazem) are CYP3A4 enzyme inhibitors that may increase the serum levels of dutasteride

True

95

Anti tuberculous agents (rifampicin, isoniazid) are CYP3A4 enzyme inducers that may decrease the serum levels of dutasteride

True

96

Cimetidine (H2 antihistamine) is a CYP3A4 enzyme inhibitor that may increase the serum levels of dutasteride

True

97

Ketoconazole may be used in the treatment of hirsutism (androgen inhibitor)

True

98

The mini pill contains progestin only

True

99

The combined OCP contains both an estrogen and progestin

True

100

The estrogen in all the combined OCP is ethinyl oestradiol

True

101

Synthetic progestin for the combined OCP are derived from 19-nortestosterone and can have androgenic, estrogenic and antiandrogenic properties

True

102

The more androgenic progestins I.e. Norgestrel, levonorgestrel, norethindrone may induce acne, androgenetic alopecia and hirsutism

True

103

The less androgenic progestins in the combined OCP I.e. Norgestimate, desogestrel, etonogestrel may be useful in women with acne and hirsutism

True (OCP is first line therapy in premenopausal women since other antiandrogens have a significant risk of teratogenecity)

104

The adverse effects of oestrogen include nausea, increased breast size and tenderness, weight gain, headaches, thromboemboli, mood swings, and vaginal bleeding

True

105

Lower dosages of oestrogen in the combined OCP result in increased rates of breakthrough bleeding

True

106

Higher dosages of oestrogen in the combined OCP result in increased risk of thromboemboli

True

107

Rifampin and griseofulvin alter hormone levels and are biologically plausible causes of OC failure

True

108

Women aged 65 years and older taking oestrogen for at least 4 years have an increased risk of dementia

True

109

Women taking Oestrogens for at least 5 years had significant increases in myocardial infarction, stroke, breast cancer, PE and VTE

True

110

Cyproterone and Drosperinone (antiandrogen progestin) confer a 2 fold risk for VTE than levonorgestrel (progestin with androgenicity)

True (the risk decreases with longer duration of use and with lower doses of oestrogen)