Drug treatment of Prostate Diseases and Erectile Dysfunction Flashcards
What kind of organ is the prostate?
Fibromuscular and glandular
What are the zones of the prostate?
Central zone
Transitional zone (20% cancers)
Peripheral zone (70% cancers)
Where in the prostate are androgen receptors located?
In both stomal and epithelial cells
What does DHT do? How is it produced?
Acts on androgen R 10x more strongly than testosterone
It is produced by 5-alpha reductase (type 2 isoenzyme in the prostate)
What kind of receptor is the androgen receptor?
It is a cytosolic receptor which goes to the nucleus and acts as a transcription factor
What part of the prostate undergoes overgrowth?
Nodular overgrowth occurs in the transitonal zone
What causes overgrowth?
Androgens
Does BPH cause cancer to develop?
No it does not predispose to cancer.
What are the symptoms of BPH?
Obstructive symptoms
Irritative symptoms: dysuria, frequency, urgency, nocturia
Why are alpha1 antagonists used?
Alpha1 receptors trigger contraction of smooth muscles in the prostate.
Thus using them relieves irritation and increases blood flow to the prostate
What are the side effects of alpha 1 antagonists?
Fall in BP
Postural hypotension
Tiredness
Headache
Ejaculatory dysfunction (tamsulosin)
What DDIs do alpha1 antagonists have?
They interact with phosphodiesterase-5 inhibitors (sildenafil or verdenafil) to potentiate hypotension.
What are the alpha1 inhibitors in use today?
Prazosin
Terazosin
Tamulosin (some selectivity for the bladder)
Alfuzosin
Which alpha1 inhibitor is most commonly associated with ejaculatory dysfunction?
Tamulosin
What are 5-alpha reductase drugs used for?
Indicated for moderate to severe BPH, reduces prostate volume, improves symptoms and flow, reduces disease progression, decreases requirement for surgery.
How are alpha1 inhibitors and 5-alpha reductase inhibitors different?
5-alpha reductase inhibitors actively stop progression of the disease and cause regression in size of the prostate. Alpha1 inhibitors only affect muscles.
What are the side effects of 5 alpha reductase inhibitors?
Sexual function reduced
Ejaculatory problems
Gynocomastia
How do androgens affect the prostate?
They increase its size (prostate growth is androgen dependent)
Prostate cancer development is also dependent on androgens
Anti-androgen therapy kills cancer cells and reduces proliferation however, eventually prostate becomes castrate resistant
What are the androgen receptor antagonists used for advanced prostate cancer?
Flutamide
Bicalutamide
Nitrutamide
Enzalutamide
Cyproterone acetate
What are the inhibitors of androgen production subclasses?
GnRH analogues: Leuprotide, goserelin
Inhibitors of CYP17A1: Abiraterone acetate