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PT4023 CA2 > L13 Male Reproduction > Flashcards

L13 Male Reproduction Flashcards

1
Q

What enzyme converts testosterone to dihydrotestosterone (DHT)?

A

5α-reductase

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2
Q

Effects of DHT binding to androgen receptor

A

External genitalia: differentiation during gestation, maturation during puberty, adulthood prostatic diseases
Hair follicles: increased growth during puberty

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3
Q

Effects of testosterone binding to androgen receptor

A

Internal genitalia: Wolffian development during gestation
Skeletal muscle: increase mass & strength during puberty
Erythropoiesis
Bone

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4
Q

What enzyme converts testosterone to estradiol?

A

aromatase

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5
Q

Effects of estradiol binding oestrogen receptor

A

Bone: epiphyseal closure, increased density
Libido

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6
Q

What guidelines are followed for the treatment of male LUTS?

A

European Association of Urology

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7
Q

By the age of 80, what percentage of men will suffer from benign prostatic hyperplasia?

A

~90%

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8
Q

BPH is the most common cause of __.

A

Bladder outlet obstruction (BOO)

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9
Q

2 distinct mechanisms that cause BOO

A
  1. Static - prostate bulk encroaching on urethra (restrictive)
  2. Dynamic - tension of prostate smooth muscle (increased stromal smooth muscle tone)
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10
Q

What is used to determine the severity of LUTS?

A

International Prostate Symptom Score (IPSS)

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11
Q

Examples of lower urinary tract symptoms

A

incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia

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12
Q

Pharmacological treatment of BPH

A

α1-adrenoceptor antagonists (dynamic component and irritative symptoms)
5α-reductase inhibitors (static component and obstructive symptoms)

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13
Q

Examples of α1-adrenoceptor antagonists

A

terazosin, doxazosin, tamsulosin, alfuzosin, silodosin

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14
Q

How do α1-adrenoceptor antagonists treat BPH?

A
  • target α1A, α1B and α1D subtypes
  • reduce prostatic smooth muscle tone
  • relieve bladder outlet tension
  • increase urinary flow
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15
Q

Side effects of α1-adrenoceptor antagonists

A

dizziness, postural hypotension, rhinitis, sexual dysfunction

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16
Q

Examples of 5α-reductase inhibitors

A

finasteride, dutasteride

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17
Q

How do 5α-reductase inhibitors treat BPH?

A
  • 70-90% reduction in DHT
  • 20-30% reduction in prostate size
  • ~50% reduction in PSA
  • control the static obstructive component of LUTS
  • improvement in peak flow rate within 3-6 months
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18
Q

Adverse effects of 5α-reductase inhibitors

A

reduction in spermatogenesis, decreased libido

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19
Q

What is prostatic artery embolisation?

A

catheter insertion to cut off blood supply to prostate (microspheres cause calcification and inflammation) - prostate dies in situ and symptomology reversed

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20
Q

Symptoms of overactive bladder

A

urinary urgency, with or without urinary incontinence, increased frequency and nocturia

21
Q

During storage phase, __ release is suppressed.

A

parasympathetic (ACh)

22
Q

How is overactive bladder and detrusor overactivity treated?

A

Anti-muscarinic treatment strategy - detrusor M3 receptor antagonists

23
Q

Examples of anti-muscarinic drugs

A

oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin, trospium

24
Q

How do anti-muscarinics treat OAB?

A
  • reduce spontaneous myocyte activity
  • decrease frequency and intensity of detrusor activity
  • suppress cholinergic signalling and prolong storage phase (reduced contraction of detrusor)
25
Q

Side effects of anti-muscarinic treatment

A
  • dry mouth (parotid glands)
  • constipation (intestinal smooth muscle)
  • headache
  • blurred vision (ciliary muscle)
  • non-selectivity of antagonists for M3 receptors (also targets other receptor subtypes) - systemic blockade
  • blockade of vagal inhibitory input, cardiac arrhythmia
26
Q

Example of a B3 receptor agonist and how it can treat OAB

A

Mirabegron
- enhances noradrenaline release - relaxes detrusor
- improves bladder filling
- reduces irritative OAB symptoms of urgency, frequency & nocturia

27
Q

Side effect of Mirabegron use

A

increased blood pressure

28
Q

Pharmacological treatment of erectile dysfunction

A

α1-adrenoceptor antagonists
phosphodiesterase type 5 inhibitors

29
Q

How do α1-adrenoceptor antagonists treat ED?

A

They relax smooth muscle in penile arteries or corpus cavernosum, resulting in increased blood flow, causing erection

30
Q

Common adverse effect of α1-adrenoceptor blockade to treat ED

A

retrograde ejaculation, due to relaxation of the bladder neck (reduced smooth muscle tone)

31
Q

Example of a PDE5 inhibitor and how it can treat ED

A

Sildenafil (Viagra)
- vascular smooth muscle relaxation - increased blood flow to penis, causing erection

32
Q

Why take caution when using a combination of PDE5 inhibitors and α1-adrenoceptor antagonists?

A

can cause significant hypotension

33
Q

Rationale for endocrine treatment for prostate cancer

A

deprive cancerous cells of androgens, apoptotic regression

34
Q

How is testosterone production eliminated in endocrine treatment for prostate cancer?

A

GnRH agonists and GnRH antagonists

35
Q

Examples of GnRH agonists used to treat prostate cancer

A

Goserelin, buserelin, leuprolin, nafarelin

36
Q

What does high concentration of GnRH agonist result in?

A

GnRH receptor desensitisation and subsequent testosterone suppression (in 95% of patients)

37
Q

How are GnRH agonists administered in prostate cancer patients?

A

subcutaneous administration at 1-3 month intervals

38
Q

Adverse effects of GnRH agonists?

A

tumour flare (lasts 1-2 weeks), bone pain due to bone metastases

39
Q

Example of a GnRH antagonist

A

Abarelix

40
Q

Why are GnRH antagonists usually preferred to GnRH agonists?

A

They avoid the ‘tumour flare’ response as they are associated with a more rapid reduction in testosterone levels (<1 day)

41
Q

Why are anti-androgens used in prostate cancer endocrine treatment?

A

intermittent androgen deprivation; inhibition of androgenic-independent tumour cell development - improved quality of life. PSA monitored closely

42
Q

Example of a steroidal anti-androgen

A

Cyproterone acetate
- androgenic and progestogenic actions
- suppresses LH release

43
Q

Adverse effects of cyproterone acetate

A

Castration syndrome, hepatotoxicity

44
Q

Examples of non-steroidal anti-androgens

A

Bicalutamide, flutamide
- androgenic effects
- LH release maintained

45
Q

Adverse effects of non-steroidal anti-androgens

A

nausea, diarrhoea, hepatotoxicity

46
Q

Symptoms associated with Castration syndrome

A

loss of libido and erectile function, hot flushes, anaemia, obesity, decrease in muscular strength, fatigue, decrease in physical activity, mood changes, depression

47
Q

How is anaemia associated with Castration syndrome treated?

A

with recombinant human erythropoietin to help increase levels of RBCs

48
Q

What is carried out to identify osteoporosis high-risk individuals before initiating treatment?

A

bone densitometry

49
Q

How are men with Castration syndrome treated for osteoporosis?

A
  • calcium supplementation
  • oestrogen and bisphosphonates
  • intermittent androgen deprivation treatment protocol

PT4023 CA2 (6 decks)

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