PHARM - BP and ED Pharmacology Flashcards
What is BPH?
Benign Prostatic Hyperplasia
Prostate cells proliferate (non-cancerous)
Causes bladder outlet obstruction, as well as urethra constriction
What are the symptoms of BPH?
- Interrupted stream
- Urinary Frequency
- Urinary Hesitation
- Bladder Fullness
- Dribbling
- Urinary Urgency
- Weak Stream
What type of drugs can be used to treat BPH?
Alpha 1 Antagonists and Steroid 5-alpha Reductase Inhibitors
Which Alpha 1 Antagonists are used to treat BPH?
STAT-D
- Silodosin
- Tamsulosin
- Alfuzosin
- Terazosin
- Doxazosin
All alpha-1 Antagonists end in -osin
What effects of Alpha 1 Antagonists specificalyl helps with BPH?
Alpha 1 Antagonists:
- Reduce spasm
- Relax prostatic smooth muscle
- Relax urinary sphincter smooth muscle
- Improve urinary flow
What receptors do drugs used to treat BPH target?
Alpha-1 Antagonists in this case of treating BPH are targeting Alpha-1A and Alpha-1D receptors
Where will you find Alpha-1A and Alpha-1D receptors?
Alpha-1A receptors are found in the prostate and the bladder outlet
Alpha-1D receptors are found in the Detrusor muscles of the bladder
What is the best mono therapy for prompt relief of BPH symptoms (days)?
Alpha-1 Antagonists
Which Steroid 5-alpha Reductase Inhibitors are used to treat BPH?
- Finasteride
- Dutasteride
Why does the prostate enlarge in BPH?
- Aging
- Dihydrotestosterone, Testosterone (DHT is 10x more potent than T)
What is SAR?
SAR is just Steroid 5-alpha Reductase
There is a Type 1 SAR (SAR-1) and a Type 2 SAR (SAR-2)
SAR-1 and SAR-2 are responsible for the conversion of serum Testosterone (T) into Dihydrotestosterone (DHT) in cells
A prostate that has undergone hyperplasia (as in BPH) has excess SAR-2
What are the direct effects of SAR-Inhibitors?
Testosterone accumulation
DIhydrtestosterone depletion
What are the indirect effects of SAR-inibitors?
Androgen receptor less occupied
No gene transcription
What is ED?
Erectile Dysfunction
Consistent or recurrent inability to acquire or sustain an erection of sufficient rigidity and duration for sexual intercourse
What are some risk factors for developing ED?
Obesity
Stress
Smoking
How does an erection generally occur?
Blood flows into the corpora cavernosa and corpus spongiosum (glans penis)
Nitric Oxide facilitates smooth muscle relaxation
- Maximize blood flow
- Penile engorgement
Relaxed smooth muscle leads to blood in sinusoids and a rigid organ
What is the secondary messenger cascade responsible for maintaining an erection?
- Nitric Oxide Synthase converts L-Arginine to NO
- NO signals the production of cGMP
- cGMP normally leads to a decrease in intracellular Ca2+
- Decreased intracellular Ca2+ leads to smooth muscle relaxation
- Smooth muscle relaxation causes an erection
How does a penis return from erect to flaccid?
cGMP is required to maintain an erection
- cGMP causes a decrease in intracellular Ca2+
- Decreased intracellular Ca2+ causes smooth muscle relaxation and an erection
PDE-5 converts cGMP to 5’-GMP, stopping downstream signaling for erection maintenance
What class of drugs are used to treat ED?
Phosphodiesterase-5 (PDE-5) Inhibitors
PGE1 Agonists
How do PDE-5 Inhibitors work?
PDE-5 converts cGMP to 5’GMP
cGMP is required to maintain an erection
PDE-5 Inhibitors competitively inhibit PDE-5 thus preventing its 5’-GMP production and maintaining high levels of cGMP
What are the names of PDE-5 Inhibitor drugs?
- Sildenafil (viagra)
- Vardenafil (Levitra)
- Tadalafil (Cialis)
- Avanafil (Stendra)
How do PGE1 Agonists work?
PGE1 Agonist (Alprostadil) activates the PGE1 receptor
Activated PGE1 activates Adenylate Cyclase
Adenylate Cyclase increases intracellular cAMP production
cAMP promotes a decrease in intracellular Ca2+
Decreased intracellular Ca2+ induces smooth muscle relaxation, allowing erection to be maintained
