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pharmacology 2 > prostate disease and erectile dysfunction > Flashcards

prostate disease and erectile dysfunction Flashcards

1
Q

the prostate

A

fibromuscular and glandular organ

tubuloalveolar glands arranged in lobules surrounded by stroke

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2
Q

3 regions of the prostate

A

TZ - surrounds the urethra, forms benign prostatic hyperplasia and 20% of prostate cancers
PZ - most of the prostate tissue - 70% of cancers
central zone

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3
Q

androgen receptor

A

expresses in both stromal and epithelial cells

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4
Q

development of prostate is driven by

A

5a-dihydrotestosterone

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5
Q

DHT

A

dihydrotestosterone
metabolite of testosterone, converted in the prostate by 5a-reductase type 2
more potent than testosterone due to higher affinity for the androgen receptor

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6
Q

5a-reductase

A

2 types

type 2 used in the prostate

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7
Q

benign prostatic hyperplasia

A

nodular overgrowth of both epithelial and fibromuscular components of the periurethral and transition zone of the prostate
androgen dependant and does not predispose to prostate cancer

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8
Q

symptoms of benign prostatic hyperplasia

A

obstructive - decreased force of urinary stream, hesitancy initiating voiding
irritative symptoms - dysuria. frequency, urgency, nocturia

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9
Q

dynamic obstruction

A

prostate, prostate capsule and bladder neck have rash a1-adrengeric sympathetic innervation
tension of smooth muscle mediated by these receptors contributes to both obstructive and irritative symptoms

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10
Q

a1- adrenageric blockers

A

receive rritative and obstructive symptoms

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11
Q

5a-reductase inhibitor

A

finasteride

dutasteride

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12
Q

drugs used to treat BPH

A

alpha adrenergic blockers

5a-reductase inhibitors - finasteride and dutasteride

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13
Q

selective a1-adrenergic blockers

A

prazosin - oldest, short half life, more side effects
terazosn - longer half life
alfuzosin
tamsulosin - selective a1(A)-antagonist, selectivity for the bladder, less postural hypotension

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14
Q

tamsulosin

A
  • selective a1(A)-antagonist, selectivity for the bladder, less postural hypotension
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15
Q

terazosin

A

anger half life than prazosin

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16
Q

a1-adrengergic blockers in BPH side effects

A

usually mild
fall in blood pressure due to vasodilatation
postural hypotension - dizziness, syncope
tiredness
headache
ejaculatory dysfunction (tamsulosin)

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17
Q

5a-reductase nhibtors most effective in men wth

A 
men with larger prostate 
reduce prostate volume 
reduce rate of disease progression  
improve symptoms and urine flow 
decrease incidence of acute urinary retention and requirement for prostate surgery
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18
Q

dutasteride

A

type 1 and type 2
5a-reductase inhibitor
more effective when combined wth alpha blocker (eg. tamsulosin)
prostate volume reduces after 1 month

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19
Q

sexual adverse effects of 5a-reductase inhibits

A

erectile dysfunction
ejaculatory disorders
reduced libido
gynaecomastia

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20
Q

sexual dysfunction with 5a-reductase inhibitors is more common when

A

used in combination with tamsulosin
when used as a mono therapy most side effects resolve spontaneously with ongoing therapy by 2 years but she effects more likely to be ongoing when used in combination with tamsulosin

21
Q

finasteride

A

type 2 5a-reductase inhibitor

similar side effect profile as dutasteride

22
Q

androgens and prostate cancer

A

growth and development of normal prostate and prostate cancer is androgen dependant
anti-androgen therapy induces apoptosis and reduced cell proliferation

23
Q

androgen indépendant growth

A

inevitable n advanced prostate cancer disease
tumour recurrence and progression
called castrate resistant prostate cancer

24
Q

androgen receptor antagonists

A

hormonal therapy used for prostate cancer

flutamide, bicalutamide, nilutamide

25
Q

inhibitors of androgen production

A

hormonal therapy in prostate cancer

GnRH analogues

26
Q

total androgen blockade

A

combination of GnRH agonist with androgen receptor antagonist
provide maximal blockade of androgen receptor activation

27
Q

flutamide

A

androgen receptor blocker
binds competitively with androgen receptor
anti androgen side effects - gynaecomastia, hot flashes, libido reduction, reduction in muscle mass and crease in bodily fat

28
Q

enzalutamide

A

androgen receptor inhibitor
binds to receptor with greater affinity than bicalitamide
reduces efficiency of androgen receptor nuclear translocation
used in more advanced disease - even in castrate resistant prostate cancer

29
Q

cyproterone acetate

A

a derivative of progesterone
competes with DHT for androgen receptor (partial agonist)
supplies hypothalamic GnRH secretion
may be used in combination with GnRH agonists
ant androgen side effects

30
Q

GnRH agonists

A

endogenous GnRH secretion from hypothalamus is pulsatile
continuous GnRH agonist inhibits pituitary LH and FSH secretion, thereby decreasing testosterone
may cause an initial flare of disease due to a transient rise in testosterone levels

31
Q

GnRH administered by

A

subcutaneous injection or IM depot

32
Q

abiraterone acetate

A

inhibits cytochrome P450 (CYP)17A1 which its an essential enzyme in the biosynthesis of testosterone
inhibits androgen production in the testis and adrenal
used to treat metastatic castration resistant prostate cancer
hypertension and hypokalaemia, abnormal LFTs

33
Q

prostate cancer therapies for skeletal metastasis

A

zoledronic acid - an intravenous biphopshate
denosumab - a monoclonal antibody directed against RANK ligand

both are osteoporosis therapies wth reduce skeletal related events
hypocalcaemia, osteonecrosis of the jaw

34
Q

erectile dysfunction

A

inability to develop and maintain an erecton in absence of ejaculatory disorder

35
Q

erectile dysfunction is a risk marker for

A

future cardiovascular events

36
Q

sexual arousal is activated in

A

higher cortical centres

37
Q

phosphodiesterase inhibitors

A

drug therapy for erectile dysfunction
sildenafil, vardenafil, tadalafil
increased cGMP in response to ntrol oxide release resulting in increased smooth muscle relaxation and vascular engorgement
only acts in the presence of sexual stimulation

38
Q

phosphodiesterase 5

A

breaks down cGMP, the second messenger of NO

39
Q

side effects of PDE 5 inhibitors

A

headache
facial flushing
nasal congestion
dyspepsia

side effects usually mild and transient
may increase res of nonarteritic anterior ischaemia optic neuropathy

40
Q

phosphodiesterase subtype selectivity

A

PDE-6 - in the retina, sildenafil causes blue vision

PDE-11 - skeletal muscle, tadalafil causes muscle and back pain

41
Q

sildenfail

A

plasma concentration maximal at 30-120 minutes
terminal half life 4 hours
taken 1 hour prior to sexual activity
ingestion after or with a meal slows one of action

42
Q

tadalafil

A

longer duration of action
can be taken as daly medication at a reduced dose
food does not interfere with absorption

43
Q

PDE-5 inhibitor contraindications

A 
men taking nitrate drugs for heart disease - risk of severe hypotension 
caution in men with severe CVD 
severe postural hypotension 
severe aortic stenosis 
retinitis pigmentosa

introduce with caution in men using alpha blockers

44
Q

efficacy of PDE-5 inhibitors

A

does not restore erection quality to full normal extent

diabetics and post radial prostatectomy tend to have lower response rates

45
Q

intracavernosal alprostadil

A 
70-80% efficacy 
use limited by adverse side effects 
penile pain 
penile fibrotic changes 
priaprism - if erection lats longer than 60 minutes
46
Q

priapism

A

if erection last longer than 60 minutes

psuedaephidrine can be given

47
Q

transurethral alprostadil

A

administered as an intraurethral suppository with the aid of an applicator
less effective than intracavernosal injections
systemic absorption can result in hypotension
side effects - penile pain, bleeding, dizziness, female partner may report vaginal burning or itching

48
Q

testosterone replacement

A

only works when the individual is androgen deficient

49
Q

non-pharmacological interventions

A

vacuum devices

penile prostheses

pharmacology 2 (19 decks)

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