BPH and ED drugs

Question 1

Why are alpha blockers useful in the treatment of BPH?

Answer 1

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**

Question 2

What is the relative abundance of alpha1a, 1b, and 1d receptors in the prostate?

Answer 2

Prostate alpha receptors: alpha1a > alpha 1d > alpha 1b

Question 3

If you want to maximize the flow of urine through relaxing muscles in urinary excretion, what alpha1 receptor subtype should you target?

Answer 3

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

Question 4

What drugs act as short acting selective alpha blockers?
**Why might you run into problems with patient compliance on one of these?

Answer 4

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**

Question 5

What drugs act as LONG acting selective alpha blockers?

Answer 5

Alpha Blockers
Short

Acting Selective – Prazosin, Alfuzosin
Long Acting Selective – Terazosin, Doxazosin
Partially Selective alpha 1a – Tamsulosin, Sildosin

Question 6

What drugs are alpha1a specific?
*What is the advantage and disadvantage associated with these drugs?

Answer 6

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)

Question 7

Administration and MOA of Prazosin, Alfuzosin, Terazosin, Doxazosin, Tamsulosin, and Slidosin?

Answer 7

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

Question 8

Adverse Effects and indication of Prazosin, Alfuzosin, Terazosin, Doxazosin, Tamsulosin, and Slidosin?

Answer 8

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

Question 9

Of the two alpha1a blockers which is more likely to cause retrograde ejaculation?

Answer 9

Sildosin > Tamsulosin

Question 10

There are two types of 5-alpha reductase in the body, which type is found mostly in the prostate?

Answer 10

Type II 5 alpha reductase is found in the prostate mostly

Question 11

What are the the two 5-alpha Reductase inhibitors used to treat BPH?

Answer 11

Finasteride and Dutasteride

Question 12

Finasteride and Dutasteride
Administration
MOA (which is more specific?)

Answer 12

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)

Question 13

Finasteride/Dutasteride
- Adverse Effects

Answer 13

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

Question 14

Finasteride/Dutasteride
Indication
Contraindication

Answer 14

Finasteride /Dutasteride

INDICATION
BPH, male pattern baldness (low dose)

CONTRAINDICATION
DO NOT GIVE BLOOD
DO NOT LET WOMEN HANDLE (birth defects)

Question 15

Between Beta-Sitosterol and Saw Palmetto which is more effective at treating BPH?

Answer 15

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

Question 16

What drug should you choose for someone that has both BPH and Erectile Dysfunction?
* why does this drug work for both of these conditions?

Answer 16

• *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.

Question 17

Alprostadil

• Administration (including onset and duration of action)
• MOA

Answer 17

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

Question 18

Alprostadil

• Adverse Effects
• Indication

Answer 18

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.

Question 19

What PDE5 inhibitors are used in the treatment of Erectile Dysfunction?

Answer 19

PDE5 inhibitors

**Vardenafil, Avanafil, Sildenafil, Tadalafil

(VAST, like the VAS(T) - Deferens)**

Question 20

PDE5 inhibitors

• name them
• Administration
• MOA

Answer 20

• *PDE5 inhibitors**
• *Avanafil, Sildenafil, Tadalafil, Vardenafil**

ADMINISTRATION
Oral

MOA
increased cGMP with inhibition of PDE5 leading to smooth muscle relaxation

Question 21

Avanafil, Sildenafil, Tadalafil, Vardenafil
- Adverse effects (differences in AEs among them?)
-

Answer 21

• *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

Question 22

Indication and Contraindications for Avanafil, Sildenafil, Tadalafil, and Vardenafil?
*how do indications differ among these drugs?

Answer 22

• *PDE5 inhibitors**
• *Avanafil, Sildenafil, Tadalafil, Vardenafil**

INDICATION
Erectile Dysfunction, Sildenafil and Tadalafil => BPH too

CONTRAINDICATION
NITRATES

Question 23

Testosterone Replacement Therapy in the use of ED?

• is it necessary?
• What ED drugs does Testosterone improve the efficacy of?
• Who benefits the most?

Answer 23

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

Question 24

Yohimbine
- MOA

Answer 24

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

Question 25

Yohimbine

• Administration
• Adverse Effects

Answer 25

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**

Question 26

Who are you most likely to see using Yohimbine?

Answer 26

Most likely you’ll encounter this with patients interested in:

1. Taking Supplements to Improve Sexual Performance
2. Promote Weight Loss
3. Curb Appetite