BPH and ED drugs Flashcards
Why are alpha blockers useful in the treatment of BPH?
Alpha 1 blockers are useful because they relax the muscles in the detrussor, trigone, prostate, and urethra.
**note: blocking some of the action of the detrussor (although its mostly M3, there is still some alpha1) is not very useful, so more specific agents have been invented**
What is the relative abundance of alpha1a, 1b, and 1d receptors in the prostate?
Prostate alpha receptors: alpha1a > alpha 1d > alpha 1b
If you want to maximize the flow of urine through relaxing muscles in urinary excretion, what alpha1 receptor subtype should you target?
Alpha 1d is
represents the greatest portion of receptors in the detrusor of the bladder while alpha 1a predominates in the Trigone, Prostate and Urethra => blocking alpha receptors leads to smooth muscle relaxation allowing for urination
What drugs act as short acting selective alpha blockers?
**Why might you run into problems with patient compliance on one of these?
Alpha Blockers
Short
Acting Selective – Prazosin, Alfuzosin
Long Acting Selective – Terazosin, Doxazosin
Partially Selective alpha 1a – Tamsulosin, Sild**osin
***Prazosin has patient compliance issues b/c activity is variable across patients and doses must be titrated****
***Alfuzosin is thought to be the superior alpha1 inhibitor among all of these currently**
What drugs act as LONG acting selective alpha blockers?
Alpha Blockers
Short
Acting Selective – Prazosin, Alfuzosin
Long Acting Selective – Terazosin, Doxazosin
Partially Selective alpha 1a – Tamsulosin, Sildosin
What drugs are alpha1a specific?
*What is the advantage and disadvantage associated with these drugs?
Partially Selective alpha 1a – Tamsulosin, Sildosin
Advantage:
- less side CV effects than most alpha blocker
Disadvantage:
- more problems with ejaculation dysfunction (reverse ejaculation b/c its a sympathetic response to tighten inner urinary sphincter)
Administration and MOA of Prazosin, Alfuzosin, Terazosin, Doxazosin, Tamsulosin, and Slidosin?
ADMINISTRATION
1x per day PO, heavy CYP metabolism
MOA
Blockage of alpha1 receptors that maintain rigid muscle tone in the bladder, urethra, and prostate. Relaxation allows for easier urination
Adverse Effects and indication of Prazosin, Alfuzosin, Terazosin, Doxazosin, Tamsulosin, and Slidosin?
ADVERSE EFFECTS
Prazosin requires dose titration due to variation in activity among patients
Commonly: Orthostatic hypotension, syncope, Xerostomia, Asthenia, N/HA, dizziness, Insomnia
Alpha 1a antagonists = less CV effects, MORE retrograde ejaculation possible (Silodosin > Tamsulosin)
INDICATION
BPH
Of the two alpha1a blockers which is more likely to cause retrograde ejaculation?
Sildosin > Tamsulosin
There are two types of 5-alpha reductase in the body, which type is found mostly in the prostate?
Type II 5 alpha reductase is found in the prostate mostly
What are the the two 5-alpha Reductase inhibitors used to treat BPH?
Finasteride and Dutasteride
Finasteride and Dutasteride
Administration
MOA (which is more specific?)
Finasteride /Dutasteride
ADMINISTRATION
PO
MOA
Inhibition of 5-alpha reductase to prevent the conversion of testosterone to DHT
Finasteride = MORE SPECIFIC => inhibition of type II (prostate only)
Dutasteride => Inhibition of type I and type II (peripheral and prostate inhibition)
Finasteride/Dutasteride
- Adverse Effects
Finasteride /Dutasteride
ADVERSE EFFECTS
BOTH are category X in pregnancy, but are NOT carried in semen
Side Effects: ED, Decreased Libido, Gynecomastia
Decreased PSA levels -> makes monitoring PSA in prostate CA difficult increased incidence of prostate CA
Finasteride/Dutasteride
Indication
Contraindication
Finasteride /Dutasteride
INDICATION
BPH, male pattern baldness (low dose)
CONTRAINDICATION
DO NOT GIVE BLOOD
DO NOT LET WOMEN HANDLE (birth defects)
Between Beta-Sitosterol and Saw Palmetto which is more effective at treating BPH?
Beta-Sitosterol vs. Saw Palmetto for BPH
Beta-Sitosterol can reduce urinary symptoms of BPH, but does not affect prostate size
Saw Palmetto is pointless in the use of BPH
What drug should you choose for someone that has both BPH and Erectile Dysfunction?
* why does this drug work for both of these conditions?
- *Tadalifil (Cialis)**
- *PDE5 inhibitor** would be a good option for this patient as long as he isn’t taking nitrates
This works for BPH because the extra NO causes smooth muscle relaxation. Smooth muscle relaxation is also important in the penis to maintain erection.
Alprostadil
- Administration (including onset and duration of action)
- MOA
ADMINISTRATION
Intra-urethral Suppository or Intra-cavernosal injection
**Very rapid onset and last 0.5 to several hours**
MOA
PGE1 analog that activates Adenylyl Cyclase which activates PKA and leads to Ca2+ EFFLUX from the CELL leading to smooth muscle RELAXATION
Alprostadil
- Adverse Effects
- Indication
ADVERSE EFFECTS
Penile, urethral, and testicular pain (from injections, and suppository)
Rarely CV effects are reported (monitor and titrate dose in people with CV disorders)
INDICATION
Erectile Dysfunction, Good Option for people taking NITRATES
- think about pts with angina etc.
What PDE5 inhibitors are used in the treatment of Erectile Dysfunction?
PDE5 inhibitors
**Vardenafil, Avanafil, Sildenafil, Tadalafil
(VAST, like the VAS(T) - Deferens)**
PDE5 inhibitors
- name them
- Administration
- MOA
- *PDE5 inhibitors**
- *Avanafil, Sildenafil, Tadalafil, Vardenafil**
ADMINISTRATION
Oral
MOA
increased cGMP with inhibition of PDE5 leading to smooth muscle relaxation
Avanafil, Sildenafil, Tadalafil, Vardenafil
- Adverse effects (differences in AEs among them?)
-
- *PDE5 inhibitors**
- *Avanafil, Sildenafil, Tadalafil, Vardenafil**
ADVERSE EFFECTS
Hypotensive effects (from vasodilation) increased with EtOH and Alpha-blockers
Nasopharyngitis/URTIs, VISION AND HEARING LOSS
VARDENAFIL – interacts with tons of shit and cause QT PROLONGATION/Arrhythmias
Indication and Contraindications for Avanafil, Sildenafil, Tadalafil, and Vardenafil?
*how do indications differ among these drugs?
- *PDE5 inhibitors**
- *Avanafil, Sildenafil, Tadalafil, Vardenafil**
INDICATION
Erectile Dysfunction, Sildenafil and Tadalafil => BPH too
CONTRAINDICATION
NITRATES
Testosterone Replacement Therapy in the use of ED?
- is it necessary?
- What ED drugs does Testosterone improve the efficacy of?
- Who benefits the most?
TESTOSTERONE REPLACEMENT THERAPY
not a whole lot of testosterone is needed for an erection, however replacement therapy is thought to increase the effect of PDE-5 inhibitors }
- 65% of HypOgonadal men benefit from this therapy
Yohimbine
- MOA
Yohimbine
MOA
Alpha-2 adrenergic antagonist
Smooth Muscle Cells (post-junctional) to inhibit E/NE-activated phosphorylation of Myosin light Chain
NANC (non-adrenergic, non-chonlinergic nerves) blocks inhibitory action of pre-junctional HETERO-receceptors leading to increased NO production
Yohimbine
- Administration
- Adverse Effects
Yohimbine
ADMINISTRATION
PO
ADVERSE EFFECTS
- *Easily crosses BBB**: Anxienty, Antidiuresis, Vertigo, Flushing, headach, HTN, Hyperactivity, Tachycardia, Termor
- *MAOI action** at supra-clinical doses
- *Worsening of Renal Dysfunction**
Who are you most likely to see using Yohimbine?
Most likely you’ll encounter this with patients interested in:
- Taking Supplements to Improve Sexual Performance
- Promote Weight Loss
- Curb Appetite
