Benign Prostate Hyperplasia (BPH) alpha blockers = alpha 1 blockers !

Where is the prostate relative to the bladder and urethra?

its right under the bladder and goes around the urethra

Where are the detrusor muscles located and what does it do when its triggered?

its the muscle that wraps around the whole bladder
- when it contracts the bladder is squeezed and urine comes out

What chemical is responsible for prostate growth?

Dihydrotestosterone (DHT) (active form of testosterone

what enzyme converts Testosterone to DHT

5 alpha reductase

** What are the OBSTRUCTIVE s/sx associated with BPH!!!!! **

Reduced Bladder emptying
- Weak pee stream
- Hesitancy to urinate
- Cant abruptly stop peeing
- Dribbling after peeing
- Feel like bladder is full/not completely empty after urinating
- Urine retention

** What are the IRRITATIVE s/sx associated with BPH!!! **

really annoying s/sx
- Increased frequency
- Increased urgency
- Nocturia
- Painful urination
- Urge incontinence

What is the IPSS grading system?

questionare about the prostate:
- international Prostate Symptom score
- higher the number = worse the symptom
- has obstruction and Irritative symptoms on here

0-7 score in IPSS means what severity of BPH sx

Mild

8-19 score in IPSS means what severity of BPH Sx

Moderate

20 to 35 on the IPSS means what severity of BPH sx

Severe sx

Mediations that Aggravate BPH

Diuretics (bc inc urine frequency)
Sympathomimetics
- OTC Decongestants: Sudafed (Alpha 2 agonist constrict blood vessels in face and bladder stuff)
Anticholinergics:
- Antihistamines
- Antidepressants
- Antipsychotics
- Gi Antispasmodics

What are complications secondary to BPH?

- Renal insufficency
- Refractory urinary retention
- Recurrent UTIs
- recurrent bladder stones
- Gross hematouria

What is the PSA and what is it used for

Prostate specific antigen blood test
- help to estimate prostate size
- 0 to 2.5 ng/mL is normal (anything above 2.5 = prostate cancer)
- PSA velocity = how quickly PSA changes
- PSA Density = PSA/size of the prostate

Definition of an enlarge prostate (lab findings)

Any of these 3:
- Volume over 30 cc on imaging
- PSA over 1.5 ng/dL
- Palpable prostate on DRE (Digital Rectal Exam)

What is the reccomended treatment regimen for Asymptomatic BPH or mildly bothersome sx (0-7 IPSS)

Watchful waiting OR
Behavioral Modifications

Behavior modifications you can do in BPH

- Fluid restriction before bed
- Avoid caffeine, alcohol and spicy food
- Pee while sitting (will help get it out)
- Scheduled voiding

Who is Pharmacological treatment the first line option along with behavioral interventions

- Moderate to severe sx (IPSS at least 8)
- Bothersome sx
- Severe sx (20+ IPSS) but refuses surgery or isnt qualified for surgery
- Severe sx and has no BPH complications/secondary causes

What patients are qualified for surgery as their first line option?

Refractory to meds/unwilling to do meds
Have complications associated with BPH:
- kidney insufficiency
- Refractory Urine retention
- Recurrent UTIs or Bladder stones
- Gross hematuria

List out all the drug classes for BPH

Alpha 1 blockers
5 Alpha reductase inhibitors
"Anticholinergic Agents" (TECHNICALLY possible, urologist would Rx)
Mirabegron
Tadalafil

** List of all the Uro Specific Alpha 1 (adrenergic) Blockers ** (- Zosin or - Losin)

- Alfuzosin (Uroxatral)
- Tamsulosin (Flomax)
- Silodosin (Rapaflo)

List of the non specific Alpha 1 (Adrenergic) Blockers (-Zosin)

- Terazosin (Hyrtin)
- Doxazosin (Cardura)
- Prazosin (Minipress) fun fact for ptsd nightmares

suffix associated with most of the alpha 1 blockers

- Zosin

List of the 5 alpha Reductase Inhibitors

- Finasteride (Proscar)
- Dutasteride (Avodart)

what suffix? is associated with the 5 alpha reductase inhibitors

- Asteride

List of the PDE5 inhibitor for BPH (and its 5 alpha reductase combo product)

Tadalafil
Combo: Finasteride + Tadalafil (Entadfi)

What is the first drug/class a pt starts on for any patient qualified for pharm treatment for BPH

Alpha 1 Blocker (-Zosin or -Losin)
- Usually Tamsulosin (Flomax)

What is the first durg used for sx relief in BPH

Alpha 1 blockers (-zosin or -losin)

MOA of Alpha 1 (-zosin or - losin) blockers

Inhibit Alpha 1 adrenergic receptors either uroselectively or systemically
- In bladder: block alpha 1 = smooth muscle relaxation in the prostate, bladder neck and urethra

General Pros of Alpha 1 blockers (-zosin or -losin)

- Quick sx relief (initial within a week, full effects 2 to 3 months)

General Cons of Alpha 1 blockers (- zosin or -losin)

Does not effect prostate size (no shrink it)
Does not delay disease progression

A warning associated with alpha 1 blockers (-zosin) and a procedure (Hint: IFIS)

IFIS Intraoperative Floppy Iris Syndrome
- tell optometrist if you are getting cataract surgery that you are on an alpha 1 blocker
- dc drug does not always dec risk w/ surgery
- Delay initiation of alpha 1 blockers until after surgery

Which Alpha 1 blocker (-zosin or -losin) has the highest risk of IFIS

Tamsulosin (Flomax)

Are co administration btwn alpha 1 blockers (-zosin -losin) CI and why?

Nope now its just a caution
- Both will vasodilate and have additive dec BP (esp if not uroselective)

Does the efficacy of sx relief differ amongst the Alpha 1 (-zosin -losin) blockers?

Nope all the alpha 1 blockers have similar efficacy, only their SE profiles and tolerability differ

What are the AEs for all the non selective Alpha 1 (-zosin) blockers

- Orthostasis
- Nasal Congestion
- Asthenia (tired/lack of energy)
- Dizziness

What is a noted DDI with all the Alpha 1 (-zosin -losin) blockers (no longer a CI)

- PDE5 inhibitors for Hypotension/orthostasis? risk

Which Alpha 1 blockers (-zosin and -losin) have a first dose effect of Dec BP (almost orthostasis warning)

- Terazosin (Hytrin)
- Doxazosin (Cardura)
- Prazosin (Minipress)

Which alpha 1 blockers (-zosin) non selective have titrations and why?

- Terazosin (Hytrin) to tolerate Orthostasis
- Doxazosin (Cardura) to tolerate orthostasis
- Prazosin (Minipress) im assuming same reason

Brand name and class/selectivity of Terazosin

Hytrin
- Non uroselective Alpha 1 blocker

Generic of Hytrin and class/selectivity

Terazosin
- non uroselective Alpha 1 blocker

Why would someone do a Terazosin (Hytrin) Slow Taper?

- More at risk for orthostasis ex. on multiple bp meds

Terazosin (Hytrin) Dosing Taper (Same for Slow and Quick Taper)

Days 1 to 3: 1 mg at bedtime
Days 4 to 14: 2 mg at bedtime
Weeks 2 to 3: 5 mg at bedtime

Terazosin (Hytrin) slow dosing taper weeks 4-6

5 mg at bedtime

Terazosin (Hytrin) slow dosing taper week 7

10 mg at bedtime

Terazosin (Hytrin) Quick taper weeks 4 to 6

10 mg at bedtime

Warning associated with Terazosin (Hytrin)

orthostasis warning! so tell pt about that

Is Terazosin (Hytrin) uroselective alpha 1 (-zosin -losin) blocker?

it blocks all alpha receptors

Doxazosin brand and class/selectivity

Cardura
Alpha 1 blockers Non uroselective

Cardura generic and class/selectivity

Doxazosin
Alpha 1 blocker Non uroselective

What is the dosing/taper of Doxazosin (Cardura) and why

0.5 to 2 mg at bedtime
to help avoid orthostasis

What is the target dose for Doxazosin (Cardura)

8 mg at bedtime

is Doxazosin (Cardura) a uroselective Alpha 1 (-zosin -losin) blocker or not?

its NOT Uroselective

Brand name for Prazosin and what drug class/selectivity

Minipress
Alpha 1 blocker and non uroselective

Generic name for Minipress and what drug class/selectivity

Prazosin
Alpha 1 blocker and non uroselective

why is Prazosin (Minipress) NOT used in BPH?

Bc of CNS side effects! so they suck at BPH (too cns active)
often used for PTSD nightmares

Starting dose and target dose for Prazosin (Minipress)

1 mg BID
and target is 2 mg BID

is Prazosin (Minipress) a uroselective Alpha 1 (-zosin -losin) blocker or not?

NO its is not uroselective it binds to any alpha 1 blocker

Brand of Alfuzosin and what class/selectivity

Uroxatral
Alpha 1 blocker and UROSELECTIVE for prostate!

Uroxatral generic and what class/selectivity

Alfuzosin
Alpha 1 blocker and UROSELECTIVE for prostate!

AEs for Alfuzosin (Uroxatral)

- Dizziness, Headache, Fatugue
- not really orthostasis bc UROSELECTIVE
- Abnormal/retrograde ejaculation (cloudy urine right after ejaculation)

Warnings associated with Alfuzosin (Uroxatral) specifically

Prolongs the QT interval!

How is Alfuzosin (Uroxatral) metabolized?

3A4 substrate

CIs with Alfuzosin (Uroxatral)

poten 3A4 inhibitors
Renal/Hepatic failure

What population should you be concerned about using Alfuzosin (Uroxatral) in?

renal/hepatic issues
people with already prolonged QT intervals

Typical dosing with Alfuzosin (Uroxatral)

10 mg of the XR tab daily after the same meal

Brand name for Tamsulosin and class/selectivity

Flomax
Alpha 1 blocker (-zosin or -losin) and UROSELECTIVE

Generic name for Flomax and class/selectivity

Tamsulosin
Alpha 1 blocker (-zosin and -losin) and UROSELECTIVE

AEs of Tamsulosin (Flomax)

- Dizziness
- Lack of Energy
- Decreased libido
- Insomnia
- Rhinitis
- Abnormal Ejaculation

Tamsulosin (Flomax) DDIs

3A4 and 2D6

Dosing regimen for Tamsulosin (Flomax)

0.4 mg daily 30 min after the same meal usually at bedtime

Possible taper for Tamsulosin (Flomax)

can inc to 0.8 mg after 2-4 weeks usually at bedtime

Brand for Silodosin and class/selectivity

Rapaflo
Alpha 1 blocker and UROSELECTIVE

Generic for Rapaflo and class/selectivity

Silodosin
Alpha 1 blocker and UROSELECTIVE

Normal Silodosin (Rapaflo) dosing

8 mg once daily with a meal

Does Silodosin (Rapaflo) need to be renally dose adjusted and if so how/when?

- Clcr less than 50 ml/min
- dec dose to 4 mg/day

What patient population should you avoid the use of alpha 1 blockers in?

HTN patients

What alpha 1 blockers (- zosin or -losin) have the highest discontinuation rates because of CV events?

- Alfuzosin (Uroxatral) relatively lower
- Doxazosin (Cardura)
- Terazosin (Hytrin)

What alpha 1 blockers (- zosin or - losin) have the lowest dc rates bc of cv events

- Tamsulosin (Flomax)

MOA of 5 Alpha reductase inhibitors

- Inhibit converting Testosterone to its more active form DHT

Pros of 5 alpha reductase inhibitors (from summary slides)

- Reduces the enlarged Prostate's size!
- Delays disease progression

Cons of 5 alpha reductase inhibitors (from summary slides)

- Really long onset of action to actually see its effects

When is 5 Alpha reductase inhibitors typically used in therapy

When a patient has an enlarged prostate

What is the pregnancy category of the 5 alpha reductase inhibitors

Pregnancy Category X!
- even if are working in a pharmacy and are pregnant or trying to become pregnant you CANNOT touch this product

Warning with 5 alpha reductase inhibitors and blood donations

Avoid blood donations for 6 months after discontinuing these drugs

DDIs with 5 alpha reductase inhibitors

3A4 substrate

What is a warning/thing to keep in mind with PSA readings and 5 alpha reductase inhibitors

PSA levels cut in half (usually relevant for prostate cancer monitoring)

What is the concern with Prostate cancer and 5 alpha reductase inhibitors

- Chronic therapy dec overall risk of prostate cancer BUT
- chronic therapy may inc the risk of aggressive or high grade prostate tumors

What are 5 alpha reductase inhibitors often co administered with in initial treatment and why?

Alpha 1 blockers
because the alpha 1 blockers will offer immediate sx relief (this is ofc if the pt has BPH sx besides just an enlarged prostate)

What is the Brand for finasteride and the class

Proscar
its a 5 alpha reductase inhibitor

What is the generic of Proscar and what class

Finasteride
its a 5 alpha reductase inhibitor

AEs with Finaseteride (Proscar)

ED
Nausea
Abdominial pain
Asthenia
Dizziness
Gynecomastia

Dosing for Finasteride (Proscar)

5 mg Daily

Duutasteride brand and class

Avodart
5 alpha reductase inhibitor

Avodart generic and class

Dutasteriide
5 alpha reductase inhibitors

AEs of Dutasteride (Avodart)

ED
Dec libido
Ejaculation disorder
Breast tenderness and enlargement

Dosing For Dutaseride (Avodart)

0.5 mg daily

Which PDE5 Inhibitor is approved for BPH Tx

Tadalafil

When is Finasteride + Tadalafil (Entadfi) typically used in treatment

When the patient has an enlarged prostate and ED

Dosing for Finasteride + Tadalafil (Entadfi)

Finasteride 5 mg + Tadalafil 5 mg daily for up to 26 weeks

Is Finasteride + Tadalafil (Entadfi) reccomended for renally impaired population and why? (specific ClCr)

NOt reccomend for Clcr under 50 or hemodialysis
bc tadalafil is shown to be less effective