13. BPH and Erectile Dysfunction Pharmacology Flashcards
Benign prostatic hyperplasia BPH is caused by enlarged prostate. What are the common lower urinary tract symptoms LUTS?
frequency interrupted steam hesitation dribbling fullness urgency weak stream
The following are what? Terzosin doxazosin tamsulosin sildosin alfuzosin
alpha 1 adrenergic receptor antagonists
The -osins a1 receptor antagonists relax muscle tone and provide rapid releif of symptoms in days. What does a1A receptors + NE result in? 2
muscle contraction
bladder outlet obstruction
What does alpha1D receptors + NE result in? 1
Detrusor instability
With alpha1 antagonists to compete with NE, what are the positive results? 3
reduce spasm
promote muscle relaxation
improve urine flow
terazosin and doxazosin
have alpha1 specificity
adverse effects of postural hypotension, dizziness and fatigue
are they uroselective?
no
Tamsulosin and silodosin Are uroselective for alpha1A/D have alpha1A/D specifcity and increases concentration of CYP3a4 substrates What are the two adverse effects?
Reduced ejaculation
IFIS
Alfuzosin is a nonspecific alpha1 selective it is uroselective inc. conc. of CYP3A4 substrates adverse effects?
QT prolongation
What do all the a1 adrenergic receptor antagonists have a drug interaction with?
PDE5 inhibitors (sildenafil/vardenafil)
Alfuzosin has function uroselectivity meaning it distributes into the prostate more than serum. Why is this good?
to avoid hepatic impairment
What are the two 5alpha reductase inhibitors that prevent enlargement and shrinks prostate in 3-6 months?
Finasteride
Dutasteride
Androgenic steroids, testosterone and dihydrotestosterone DHT enable prostate epi to grow. DHT is 10x more potent than T. What does steroid 5a reductase do?
types 1 and 2, convert serum T to DHT
hypertrophic prostate has excess SAR2
SAR inhibitors bind SAR2 and inhibit T to DHT, resulting in?
Excess T, lack of DHT, and no gene transcription for the prostate
What is the enzyme selectivity for finasteride?
FInasteride
speciFIc inhibitor of only SAR2
What is the enzyme selectivity for DUtasteride?
DUtasteride
DUal inhibitor of both SAR1/2
Why is there a difference in the serum DHT when comparing finasterid and dutasteride’s effects?
because dutasteride inhibits both SARs = has a great decrease in the serum DHT than finsteride
When can one use a combination therapy of a1 receptor antagonist and 5a reductase inhibitor? 3
when there are severe symptoms of BPH
known to have large prostate
**no response to monotherapy
What are 3 risk factors of erectile dysfunction ED?
obesity
smoking
stress
Larginine from sexual stimulation causes increase in NO leading to inc cGMP, releasing Ca2+ causing smooth muscle relaxation leading to?
erection
What is used by the body to rid a erection?
PDE-5 takes cGMP and makes 5’GMP, ending the erection
What allows for a sustained erection?
Increase NO
sustained levels of cGMP
(dec Ca2+?)
What are the 4 different types of PDE5 inhibitors for ED? and how are they cleared through the body?
Sildenafil Vardenafil Tadalafil Avanafil Hepatic CYP3A4
What are the two things that makes tadalafil (Cialis) different from the rest?
lasts for 36 hours
half life of 18 (much longer than other PDE5 inhibitors)
What is unique about avanafil PDE5 inhib?
it has a high dose and a normal dose
What are some side effects of PDE5 inhibs?
Headache
dyspepsia
nasal congestion
(back pain, myalgia, limb pain tadalafil)
What is an extremely important contraindictation to remember with PDE5 inhibitors?
DONT combine with organic nitrates (NO) can cause extreme and dangerous hypotension
A few secondline ED therapies include vacuum erection devices, and penile injections with?
(caverject) alprostadil, a prostaglandin E1 agonist leading to increase in cAMP
Adverse effects of alprostadil include prolonged erection (priapism) which is a medical emergency that can result in?
permanent corporal fibrosis and ED
NOTE: what is special about tadalafil?
It is a PDE5 inhibitor that can treat both BPH AND ED
