prostate disease and erectile dysfunction Flashcards
the prostate
fibromuscular and glandular organ
tubuloalveolar glands arranged in lobules surrounded by stroke
3 regions of the prostate
TZ - surrounds the urethra, forms benign prostatic hyperplasia and 20% of prostate cancers
PZ - most of the prostate tissue - 70% of cancers
central zone
androgen receptor
expresses in both stromal and epithelial cells
development of prostate is driven by
5a-dihydrotestosterone
DHT
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
5a-reductase
2 types
type 2 used in the prostate
benign prostatic hyperplasia
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
symptoms of benign prostatic hyperplasia
obstructive - decreased force of urinary stream, hesitancy initiating voiding
irritative symptoms - dysuria. frequency, urgency, nocturia
dynamic obstruction
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
a1- adrenageric blockers
receive rritative and obstructive symptoms
5a-reductase inhibitor
finasteride
dutasteride
drugs used to treat BPH
alpha adrenergic blockers
5a-reductase inhibitors - finasteride and dutasteride
selective a1-adrenergic blockers
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
tamsulosin
- selective a1(A)-antagonist, selectivity for the bladder, less postural hypotension
terazosin
anger half life than prazosin
a1-adrengergic blockers in BPH side effects
usually mild
fall in blood pressure due to vasodilatation
postural hypotension - dizziness, syncope
tiredness
headache
ejaculatory dysfunction (tamsulosin)
5a-reductase nhibtors most effective in men wth
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
dutasteride
type 1 and type 2
5a-reductase inhibitor
more effective when combined wth alpha blocker (eg. tamsulosin)
prostate volume reduces after 1 month
sexual adverse effects of 5a-reductase inhibits
erectile dysfunction
ejaculatory disorders
reduced libido
gynaecomastia
sexual dysfunction with 5a-reductase inhibitors is more common when
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
finasteride
type 2 5a-reductase inhibitor
similar side effect profile as dutasteride
androgens and prostate cancer
growth and development of normal prostate and prostate cancer is androgen dependant
anti-androgen therapy induces apoptosis and reduced cell proliferation
androgen indépendant growth
inevitable n advanced prostate cancer disease
tumour recurrence and progression
called castrate resistant prostate cancer
androgen receptor antagonists
hormonal therapy used for prostate cancer
flutamide, bicalutamide, nilutamide
inhibitors of androgen production
hormonal therapy in prostate cancer
GnRH analogues
total androgen blockade
combination of GnRH agonist with androgen receptor antagonist
provide maximal blockade of androgen receptor activation
flutamide
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
enzalutamide
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
cyproterone acetate
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
GnRH agonists
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
GnRH administered by
subcutaneous injection or IM depot
abiraterone acetate
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
prostate cancer therapies for skeletal metastasis
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
erectile dysfunction
inability to develop and maintain an erecton in absence of ejaculatory disorder
erectile dysfunction is a risk marker for
future cardiovascular events
sexual arousal is activated in
higher cortical centres
phosphodiesterase inhibitors
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
phosphodiesterase 5
breaks down cGMP, the second messenger of NO
side effects of PDE 5 inhibitors
headache
facial flushing
nasal congestion
dyspepsia
side effects usually mild and transient
may increase res of nonarteritic anterior ischaemia optic neuropathy
phosphodiesterase subtype selectivity
PDE-6 - in the retina, sildenafil causes blue vision
PDE-11 - skeletal muscle, tadalafil causes muscle and back pain
sildenfail
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
tadalafil
longer duration of action
can be taken as daly medication at a reduced dose
food does not interfere with absorption
PDE-5 inhibitor contraindications
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
efficacy of PDE-5 inhibitors
does not restore erection quality to full normal extent
diabetics and post radial prostatectomy tend to have lower response rates
intracavernosal alprostadil
70-80% efficacy use limited by adverse side effects penile pain penile fibrotic changes priaprism - if erection lats longer than 60 minutes
priapism
if erection last longer than 60 minutes
psuedaephidrine can be given
transurethral alprostadil
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
testosterone replacement
only works when the individual is androgen deficient
non-pharmacological interventions
vacuum devices
penile prostheses
