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3152 Reprod Health > Benign Prostate Hyperplasia > Flashcards

Benign Prostate Hyperplasia Flashcards

1
Q

What is BPH?
- Describe the condition and its impacts

A

BPH - non-malignant growth of some components of the prostate (e.g., transitional zone)

It is a progressive condition that results in:
- Lower urinary tract signs and symptoms (LUTS)
- Negative impact on QoL

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2
Q

Describe the physiology of the Prostate

A
  1. Epithelial (glandular) tissue
    - Androgen (DHT) stimulates its growth/enlargement
    - Testosterone secreted by testicles and adrenal gland is converted by type II 5a-reductase to DHT in the prostate
  2. Stromal (smooth muscle) tissue
    - innervated by a1 adrenergic receptors
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3
Q

PATHOPHYSIOLOGY OF BPH

Describe the pathogenesis of BPH (static and dynamic component)

*Etiology is unknown, likely due to age + hormonal factors

A
  1. Static component
    - Hormonal factors (T => DHT)
    - Enlargement of prostate tissue
  2. Dynamic component
    - Incr smooth muscle tissue and agonism of a1 receptors (contraction of the prostate smooth muscles)
    - Narrowing of urethra outlet

=> Both components contribute to urethral obstruction/signs and symptoms

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4
Q

PATHOPHYSIOLOGY OF BPH

What happens to the bladder response to obstruction in the short term?

A

Bladder/detrusor muscles able to forcefully contract to force urine through the narrowed urethra

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5
Q

PATHOPHYSIOLOGY OF BPH

What happens to the bladder response to obstruction in the long term?

A

Bladder muscle gradually thickens (hypertrophy) overtime

Once highest state of hypertrophy, muscle decompensates

Detrusor muscle becomes irritable and overly sensitive (detrusor overactivity or instability), contracts abnormally in response to small amounts of urine in the bladder

Results in increase urinary frequency

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6
Q

What are the signs and symptoms of BPH
- Organize the Lower urinary tract symptoms (LUTS) into obstructive/voiding symptoms and irritative/storage symptoms

A

Many pts remain asymptomatic initially, s/s start to occur in 1/3 men older than 65yo

Obstructive/Voiding symptoms (early in disease):
- Hesitancy
- Weak stream
- Sensation of incomplete emptying
- Dribbling
- Straining
- Intermittent flow

Irritative/Storage symptoms (occurs after several years untreated):
- Dysuria
- Frequency
- Nocturia
- Urgency
- Urinary incontinence

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7
Q

LUTS is not specific to BPH, what are some other causes of LUTS?

A

UTIs, prostate or bladder cancer, diabetes mellitus

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8
Q

What are some ways to conduct assessment of BPH? *5 ways

A
  1. Digital rectal exam
  2. Ultrasonography
  3. Maximum Urinary Flow Rate (Qmax)
  4. Prostate specific antigen (PSA)
  5. Postvoid residual (PVR)
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9
Q

What is the relevance of PSA?

A

Might be elevated in BPH, positively correlated with prostate size
Can predict progression of BPH (>1.5ng/mL)
Higher risk for prostate cancer

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10
Q

What are the PVR volumes after voiding in normal and inadequate emptying?

What is the relevance of PVR in BPH treatment?

A

PVR <100ml in normal circumstance (adequate emptying)
PVR >200ml in inadequate emptying

When use anticholinergics (for irritative/storage symptoms), PVR must be <250ml or <150ml if conservative

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11
Q

Recall the AUA-SI score for mild, moderate, and severe BPH, and describe the symptoms and signs for each severity.

A

Mild
- =<7
- Asymptomatic or mildly symptomatic

Moderate
- 8-19
- All of the above s/s + obstructive voiding symptoms + irritative voiding symptoms

Severe
- >=20
- All of the above + one or more complications of BPH
- Consider Transurethral Resection of Prostate (TURP)

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12
Q

What are some complications of BPH?

*1 or more complications = severe BPH, consider surgery

A
  • Recurrent UTI
  • Bladder stones
  • Acute urinary retention
  • Urinary incontinence (if bladder is overactive)
  • Hematuria
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13
Q

For assessment of BPH, medication history must be taken to ensure medications don’t cause development/worsening of BPH.

What are some medications that may worsen BPH?

A
  1. Anticholinergics
  2. a1 adrenergic agonist
  3. Opioid analgesic
  4. Diuretics
  5. Testosterone
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14
Q

Explain how anticholinergics may worsen BPH

A

Anticholinergics - antihistamines (all gen), TCA
- Decrease bladder muscle contractability

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15
Q

Explain how alpha-1 adrenergic agonist may worsen BPH

A

Alpha-1 adrenergic agonist (e.g., decongestants - pseudoephedrine)
- Contraction of prostate smooth muscle

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16
Q

Explain how opioid analgesics may worsen BPH

A

Opioid analgesics (e.g., morphine, tramadol)
- Increase urinary retention

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17
Q

Explain how diuretics may worsen BPH

A

Diuretics
- Increase urinary frequency

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18
Q

Explain how testosterone may worsen BPH

A

Testosterone
- Stimulate prostate growth

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19
Q

Management of BPH

Watchful waiting is recommended for which group of patients?

A

Patients with mild symptoms (AUA SI score =<7)

or

Patients with moderate symptoms (AUA SI score 8-19) who are not bothered by symptoms

20
Q

Management of BPH

How often should reassessment of symptoms using the AUA SI be done

A

Annually or more frequent

21
Q

Management of BPH

What are some non-pharmacological methods?

A
  1. Limit fluid intake in the evening to reduce nocturia
  2. Minimize caffeine and alcohol intake as these can act as diuretics and increase urinary frequency
  3. Educate patients to take time to empty bladder completely and often (impt as residual urine can cause overactive bladder)
  4. Avoid medications that exacerbate symptoms
22
Q

Management of BPH

When should pharmacologic treatment be started?

A

Symptoms become bothersome or complications occur

23
Q

Management of BPH

What are the 5 key considerations in choosing BPH treatment?

A
  1. LUTS severity (AUA-SI score)
  2. Prostate size
  3. Concurrent comorbidities
  4. PSA value
  5. Presence of irritative/storage symptoms
24
Q

Management of BPH

Explain the MOA of alpha-1 adrenergic antagonist for the treatment of BPH

A

Alpha-1 adrenergic antagonist

  • MOA: decrease muscle tone, relax prostate smooth muscle, hence reduce bladder obstruction and improve urinary flow
25
Q

Management of BPH

What are the 2 types of alpha-1 adrenergic antagonist, and list examples

A
  1. Non-selective a1 adrenergic antagonist
    - Doxazosin
    - Terazosin
    - Prazosin (not recommended for use in BPH, use in HTN)

=> Antagonize both peripheral vascular and urinary a1 receptors, need to titrate slowly to therapeutic dose to reduce risk of hypotension and syncope (due to vasodilation)

  1. Selective a1 adrenergic antagonist
    - Alfuzosin
    - Silodosin
    - Tamsulosin

=> Antagonize urinary a1 receptors in the prostate and LUT only, hence lesser risk of hypotension, no dose titration needed

26
Q

Management of BPH

Which group of patient most likely to benefit from alpha-1 adrenergic antagonist?

A

a1 adrenergic antagonist effective in reducing LUTS, especially in those classified with moderate or severe LUTS, with small prostate <40g

*s/s likely recur if discontinued (therefore, require long-term therapy to maintain effect)

27
Q

Management of BPH

alpha-1 adrenergic antagonist does not have effect on _______

A

No effect on prostate size, does not reduce PSA value

Hence, does not offer prevention for progression of BPH or need for surgery

28
Q

Management of BPH

Describe the onset of alpha-1 adrenergic antagonist

A

Fast onset (days to weeks) - just dilates the prostate smooth muscle

29
Q

Management of BPH

Describe the side effect profile of alpha-1 adrenergic antagonist

A

General SEs: *think dilation

  • muscle weakness, fatigue, ejaculatory disturbance, headache, back pain etc.
  • bedtime administration to decrease orthostatic effect

Non-selective:

  • dizziness
  • first dose syncope and orthostatic hypotension

Uroselective:

  • Low to none peripheral vascular dilatation hence less hypotension or syncope
  • Ejaculatory disturbance (delayed or retrograde ejaculation)
30
Q

Management of BPH

Describe the syndrome related to cataract surgery that occurs due to the use alpha-1 adrenergic antagonist

A

Intraoperative Floppy Iris Syndrome (IFIS)

  • Condition that complicates cataract surgery
  • MOA linked to blockage of a1 receptor in iris dilator muscle, cause iris prolapse
  • Most commonly linked to TAMSULOSIN*

*Avoid initiation of a1 adrenergic antagonist until the cataract surgery has been completed OR hold 2-3 weeks before surgery

31
Q

Management of BPH

When might non-selective a1 adrenergic antagonists be useful?

A

When pt has concurrent BPH + HTN, and require additional BP lowering
BUT NOT used as monotherapy for pt with concurrent BPH + HTN as it will not be sufficient

Note that in BEERs list, a1 adrenergic antagonist is listed as a drug to avoid in patient with history of syncope

If pt does not require BP lowering effect, use selective instead

32
Q

Management of BPH

Explain the MOA of 5 alpha reductase inhibitors (5ARI) for the treatment of BPH

A

MOA; inhibits type II 5a reductase, hence decrease conversion from testosterone to DHT, reduce prostate size, and cause less urine obstruction and improve urinary flow

Finasteride, Dutasteride

33
Q

Management of BPH

Which group of patient most likely to benefit from 5ARI?

A

5ARI indicated for:

  • Moderate or severe LUTS, with large prostate >40g
  • Patients who want to avoid surgery
  • Patients who cannot tolerate SE of a1 antagonist
  • Initial PSA >1.5ng/ml
34
Q

Management of BPH

What is 5ARI effect on PSA?

A

Because it reduces prostate size, 5ARI reduces PSA levels as well, thus consider adding if initial PSA >1.5ng/ml

Hence, slows progression of disease, decrease need for surgery

*Note that PSA should be obtained BEFORE initiating therapy, as PSA levels are not easily interpretable after initiation

35
Q

Management of BPH

Describe the onset of 5ARI

A

Slow onset 6-12 months, as it takes time to reduce prostate size

36
Q

Management of BPH

Describe the side effect profile of 5ARI

A
  • Ejaculatory disorders (reduced semen during ejaculation, delayed ejaculation) (*higher risk than a1 antagonist)
  • Decreased libido (dcr testosterone)
  • Erectile dysfunction (dcr testosterone)
  • Gynecomastia and breast tenderness (dcr testosterone)
  • Less risk of hypotension
37
Q

Management of BPH

What are some contraindications to the use of 5ARI?

A

5ARI is carcinogenic and teratogenic

Not to be handled by pregnant/child bearing age females
CI in pregnant women and children

Note that Finasteride (anti-androgenic) can be used for hirsutism in women

38
Q

Management of BPH

Explain the MOA of phosphodiesterase 5 inhibitor (PDE5) for the treatment of BPH

Which PDE5 is approved for use in BPH?

A

PDE5i is used in ED

However, Tadalafil is approved for BPH, exact MOA is unknown, likely smooth muscle relaxation

39
Q

Management of BPH

Which group of patient most likely to benefit from PDE5i?

A

Usually as add-on therapy, for patients with concomittant ED
- E.g., 5ARI + PDE5i (can cancel out effect on ED)

40
Q

Management of BPH

What is PDE5i effect on PSA?

A

Does not affect prostate size, does not affect PSA

41
Q

Management of BPH

Describe the onset of PDE5i

A

Fast onset (days to weeks) - dilates

42
Q

Management of BPH

There has been increasing evidence to support the use of PDE5i as monotherapy in BPH with or w/o concomitant ED

Who might benefit from this monotherapy?

A

Postulated MOA: smooth muscle relaxation

Not yet approved as monotherapy for BPH with or w/o ED, but maybe in the future

Administration of Tadalafil 5mg daily for younger patients with low BMI and higher baseline symptoms

43
Q

Management of BPH

Which group of patient is most likely to benefit from combination therapy?

A

Individuals with moderate symptoms (AUA-SI score 8-19) and prostate size >25g

44
Q

Management of BPH

Discuss combination therapy (a1-antagonist + 5ARI) *most common combi

A

Benefits of this combi:
- Studies have shown that long-term use of this combi is safe with only mild adverse effects
- a-blocker fast onset within weeks, 5-ARI take months to shrink prostate

Combi is reserved for:
- Symptomatic patients with enlarged prostate

After 6 months of this combi,
- a1-blocker can be discontinued in moderate BPH, because prostate should be small enough and BPH management no longer require dilation of prostate smooth muscle by a1-blocker

45
Q

Management of BPH

Discuss combination therapy (5ARI + PDE5i)

A

Benefits of this combi:
- PDE5i can mitigate sexual adverse effects that may arise from 5-ARI / concomitant erectile dysfunction

However, pt with BPH and ED often have cardiac comorbidities
- If unstable angina, do not initiate PDE5i as contraindicated with concomitant use of nitrates

46
Q

Management of BPH

Discuss combination therapy (a1-antagonist + PDE5i)

A

*This combi is rarely used, if used choose uroselective a1 blocker

Downsides to this combi:
- Severe life threatening hypotension (both cause vasodilation)
- Does not shrink prostate

Dosing:
- Optimize/stabilize a1 antagonist dose first before adding PDE5i
- PDE5i should be added at lowest effective dose possible

47
Q

Management of BPH

*The above drugs all dealt with obstructive/voiding symptoms (due to narrow urethral)

What drug can be used for irritative/storage symptoms (due to overactive bladder)?

A

Antimuscarinic

  • ADD ON for pt with irritative voiding symptoms
  • MOA: block muscarinic receptors in detrusor muscle, decrease involuntary contraction of the bladder
  • Agents: Oxybutynin, Tolterodine, Solifenacin etc.
  • PVR <250ml (<150ml) to prevent bladder from bursting due to too much urine not being voided
  • Historically, anticholinergics CI in BPH due to concern for urinary retention, but studies have found minimal risk

3152 Reprod Health (7 decks)

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