Drugs in Prostate Disease and Erectile Dysfunction Flashcards
Three regions of the prostate and which are most affected by benign and malignant disease?
Transition zone: surrounds the urethra
- Benign prostatic hyperplasia, 20% of prostate cacner
Peripheral zone: Most of prostate:
- 70% of cancers
Central zone
What drives development of the prostate?
5-alpha-dihydrotestosterone (DHT)
What is benign prostate hyperplasia?
What type of tissue does it involve?
Androgen dependent overgrowth of BOTH epithelial and fibromuscular tissue of the prostate.
Does benign prostatic hyperplasia pre-dispose to prostate cancer?
No
True or false: 10% of men will develop benign prostatic hyperplasia by age 60.
False - 50% of men will have BPH by age 60.
Symptoms of benign prostate hyperplasia
Obstructive symptoms:
- Decrease force of urinary stream
- Hesistancy in initiation of urination
- Dribbling post-voiding
Irritative symptoms:
- Dysuria
- Frequency
- Urgency
- Nocturia
What are the two mechanisms of symptoms of BPH?
- Obstructive symptoms from pressure of enlarged prostate against urethra
- Dynamic obstruction - tension of smooth muscle mediated by α1-adrenergic receptors contribute to both obstructive and irritative symptoms
What adrenergic drugs help to relieve irritative and obstructive symptoms?
α1-adrenergic receptor blockers
Give two examples of alpha adrenergic blockers used in treatment of BPH
Selective α1-adrenergic blockers:
- Terazosin
- Tamsulosin (best)
Besides α1-adrenergic blocking, what else is done to treat BPH?
Give two examples
5α-reductase inhibition:
- Finasteride
- Dutasteride
Side effects of α1-adrenergic blockers?
- Postural hypotension
- Headache
- Ejaculatory dysfunction
What indicates which treatment to use on BPH?
Severity of symptoms
Use α1-adrenergic blockers if prostate volume is <30mL
Use 5α-reductase inhibitors in moderate to severe symptoms.
What benefits do 5α-reductase inhibitors have?
- More effective in larger prostates
- Reduce prostate volume
- Improve symptoms
- Reduce disease progression
Which drug is more effective in combination with tamsulosin?
Dutasteride
Adverse sexual effects of 5α-reductase inhibitors
- Erectile dysfunction
- REduced libido
- Gynaecomastia
Two strategies in hormonal therapy in prostate cancer.
Example for each
- Androgen receptor antagonist (Flutamide)
- Androgen production inhibition (GnRH AGONIST - Goserelin)
What is the concept of ‘total androgen blockade’
Combination of a GnRH agonist with an androgen receptor antagonist.
Provides maximal blockade of androgen receptor activation
Side effects of androgen receptor antagonism?
Similar to 5α-reductase inhibiton S/E:
- Gynaecomastia
- Reduced libida
- Reduced facial and body hair
What is the action of cyproterone acetate?
Dual action:
- Competes with DHT for androgen receptor (partial agonist)
- Suppresses GnRH secretion
What do phosphodiesterase (PDE-5) inhibitors do?
Give two examples.
PDE-5 breaks down cGMP, the messenger of NO.
Prevention of cGMP breakdown → increase smooth muscle relaxation → increased vascular engorgement
Exmaples:
- Sildenafil (Viagra)
- Vardenafil (Levitra)
S/E of PDE-5 inhibitors
- Headache
- Nasal congestion
- Facial flushing
Contraindications for PDE-5 inhibitor use
- Men on nitrate drugs for heart disease - severe hypotension risk
- Severe postural hypotension
