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NAPLEX Review > Benign Prostatic Hyperplasia (BPH) > Flashcards

Benign Prostatic Hyperplasia (BPH) Flashcards

1
Q

What is the main function of the prostate?

A

The main function of the prostate is to secrete fluid that becomes part of the seminal fluid carrying sperm

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2
Q

What is the prostate dependent on?

A

The prostate is dependent on androgens (mainly testosterone) for development, maintenance of size and function

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3
Q

How is testosterone metabolized?

A

Testosterone is metabolized to dihydrortestosterone (DHT) by 5 alpha-reductase

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4
Q

What is DHT responsible for?

A

DHT is responsible for normal and hyperplastic growth (increase in the number of cells)

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5
Q

How does benign prostatic hyperplasia occur?

A

BPH results from overgrowth of the stromal and epithelial cells of the prostate gland

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6
Q

What contributes to lower urinary tract symptoms (LUTS)?

A

The layer of tissue surrounding the enlarged prostate stops it from expanding, causing the gland to press against or pinch the urethra

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7
Q

Describe the pathophysiology of LUTS.

A

Direct bladder outlet obstruction and increased smooth muscle tone and resistance leads to the bladder wall becoming thicker and irritated. It begins to contract even when it contains small amounts of urine causing frequent urination. Eventually, the bladder weakens and loses the ability to empty itself

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8
Q

What does a diagnosis of BPH require?

A

Diagnosis requires an assessment of the medical history (surgeries, trauma and current medications) and a physical exam. The physical exam should include a digital rectal exam (DRE) to determine the size of the prostate and identify any lumps or nodules

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9
Q

What medications can worsen BPH?

A

Centrally-acting anticholinergics, drugs with anticholinergic effects (e.g. antihistamines, decongestants, phenothiazines, TCAs), caffeine, diuretics, SNRIs, testosterone products

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10
Q

What tests are used to rule out BPH?

A

A urinalysis and serum prostate-specific antigen (PSA) are used to rule out conditions other than BPH

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11
Q

What can PSA indicate?

A

PSA, a protein produced by prostate cells, is frequently increased in prostate cancer. It can increase when the prostate becomes larger due to BPH, though BPH is a benign (non-cancerous) condition and does not increase prostate cancer risk

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12
Q

What are the main signs and symptoms of BPH?

A
  • Hesitancy intermittent urine flow, straining or a weak stream of urine
  • Urinary urgency and leaking or dribbling
  • Incomplete emptying of the bladder (bladder feels full)
  • Urinary frequency, especially nocturia (urination at night)
  • Bladder outlet obstruction
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13
Q

What is a rare but severe symptom of BPH?

A

BPH rarely causes more severe symptoms, but if the blockage is severe, the urine could back up into the kidneys and result in acute renal failure. UTIs can also be present but are uncommon

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14
Q

What guides the selection of treatment for BPH?

A

The severity of reported BPH symptoms guides selection of treatment

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15
Q

What are some example questionnaires that quantify symptoms?

A

American Urological Association Symptom Score (AUASS) or the International Prostate Symptom Score (I-PSS)

*The scoring systems rate how bothersome the symptoms are, with higher scores indicating more severe symptoms

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16
Q

What are some treatment options of BPH?

A

treatment options can include watchful waiting, pharmacological therapy or surgical intervention

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17
Q

How is mild BPH generally treated?

A

Mild disease is generally treated with watchful waiting and yearly reassessments

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18
Q

How is moderate/severe BPH treated?

A

Moderate/severe disease is generally treated with medications or a minimally invasive procedure or surgery, such as transurethral resection of the prostate (TURP)

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19
Q

What is the guideline recommendation about the use of natural products for the treatment of BPH?

A

The American Urological Association (AUA) guidelines do not recommend natural products for the treatment of BPH symptoms, though various natural products have been investigated

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20
Q

What are some examples of natural products that have been investigated for BPH?

A

Saw palmetto (unlikely to be effective based on contradictory and inconsistent data, Pygeum, pumpkin seed, rye pollen and Lycopene

*Lycopene is used for prostate cancer prevention but there is no good evidence for use in BPH

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21
Q

What medications can be used for the treatment of BPH?

A

Medications include alpha-blockers (selective and non-selective), used alone or in combination with a 5 alpha-reductase inhibitor

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22
Q

How do 5 alpha-reductase inhibitors work?

A

The 5 alpha-reductase inhibitors work by decreasing prostate size, but they have a delayed onset

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23
Q

Who should not used 5 alpha-reductase inhibitors?

A

They should not be used in men who have bladder outlet obstruction symptoms without prostate enlargement

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24
Q

What is the benefit and limitation of alpha blockers in comparison to 5 alpha-reductase inhibitors?

A

Alpha-blockers work quickly but do not shrink the prostate

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25
Q

What other class of medications are reasonable for treatment of BPH?

A

Peripherally-acting anticholinergic drugs used for overactive bladder (such as tolterodine) are sometimes a reasonable option for men without an elevated post void residual (PVR) urine and when LUTS predominantly irritative

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26
Q

If anticholinergics are used what should the PVR be?

A

<250-300 mL

27
Q

What is a final treatment option for BPH that doesn’t include 5 alpha-reductase inhibitors, alpha-blockers or anticholinergics?

A

Another treatment option is the phosphodiesterase-5 inhibitor (PDE-5) inhibitor tadalafil with or without finasteride. This can be used in men with BPH alone and can be an attractive option for men with both BPH and erectile dysfunction (ED)

28
Q

What is considered first-line treatment for BPH and what is its MOA?

A

Alpha-1 blockers are first-line treatment for moderate-to-severe symptoms. They inhibit alpha-1 adrenergic receptors, causing relaxation of smooth muscle in the prostate and bladder neck which reduces bladder outlet obstruction and improves urinary flow

29
Q

What are the three types of alpha receptors and where are they located?

A

Alpha-1A receptors are primarily found in the prostate. Alpha-1B and alpha-1D receptors are dominant in the heart and arteries

30
Q

What is the disadvantage of non-selective alpha-1 blockers over selective alpha-1A blockers?

A

The non-selective alpha-1 blockers (terazosin, doxazosin) have more side effects (e.g. orthostasis, dizziness, headache) than the selective alpha-1A blockers (tamsulosin, alfuzosin, silodosin

31
Q

What is a risk of using alpha-1 blockers?

A

Patients using alpha-blockers are at risk of developing intraoperative floppy iris syndrome during cataract surgery

*The same receptors present on the smooth muscle of the prostate are also present on the iris dilator muscle in the eye

32
Q

What is the mechanism by which alpha-1 blockers cause intraoperative floppy iris syndrome and what is the recommendation if the patient is getting cataract surgery?

A

With alpha-1 blockade, the iris becomes floppy, has a risk of prolapse and the pupils do not dilate well, complicating the procedure. If cataract surgery is planned, alpha-blocker treatment should be delayed until the surgery is completed

33
Q

What are examples of non-selective alpha-1 blockers?

A

Doxazosin and Terazosin

34
Q

What are examples of selective alpha-1A blockers?

A

Tamsulosin, Alfuzosin, Silodosin

35
Q

What are some contraindications of alpha blockers?

A

Concurrent use of silodosin or alfuzosin with strong CYP3A4 inhibitors; hepatic impairment (Child Pugh class C for silodosin, class b/c for alfuzosin); severe renal impairment (silodosin)

36
Q

What are some warnings associated with alpha blockers?

A
  • Orthostatic hypotension/syncope, typically with the first dose, if therapy is interrupted for several days, if the dosage is increased too rapidly, or if another antihypertensive drug or PDE-5 inhibitor is started
  • Intraoperative floppy iris syndrome (IFIS) can occur in cataract surgery if currently on or previously treated with an alpha-1 blocker
  • Priapism (seek medical attention if an erection lasts > 4 hours)
  • Angina (discontinue if symptoms begin or worsen)
37
Q

What are some side effects of alpha blockers?

A

Dizziness, fatigue, headache, abnormal ejaculation (especially with tamsulosin and silodosin), fluid retention, rhinitis (tamsulosin)

38
Q

What are monitoring parameters of alpha blockers?

A

BP, PSA, urinary symptoms

39
Q

What are some notes about alpha-blockers in general?

A
  • The non-selective drugs are often given at bedtime to help minimize the initial “first-dose” effect of orthostasis/dizziness. This requires careful counseling as nocturia is common, and getting up at night to use the bathroom can be dangerous if dizziness and orthostasis occur
  • Alpha-blockers work right away, but 4-6 weeks may be required to assess whether beneficial effects have been achieved; they do not shrink the prostate and do not change PSA levels
40
Q

What is a counseling point about Cardura XL?

A

Cardura XL is an OROS formulation and can leave a ghost tablet (empty shell) in the stool

41
Q

What is a counseling point about Silodosin?

A

Silodosin can cause retrograde ejaculation in about ~30% of patients and is reversible upon drug discontinuation

42
Q

What is a warning about Alfuzosin?

A

Do not use alfuzosin if at risk for QT prolongation

43
Q

What is an off-label use for alpha-blockers?

A

Bladder outlet obstruction in women

44
Q

What are some general alpha-blocker drug interactions?

A
  • Use caution when co-administered with PDE-5 inhibitors used for erectile dysfunction due to additive hypotensive effects (if tadalafil is being used to treat BPH, do not use in combination with alpha-1 blockers)
  • Use caution with other drugs that lower BP
45
Q

What are some drug interactions of tamsulosin, alfuzosin and silodosin?

A
  • Tamsulosin, alfuzosin and silodosin are major CYP3A4 substrates; do not use with strong CYP3A4 inhibitors
  • Silodosin cannot be used with strong P-gp inhibitors, such as cyclosporine
  • Alfuzosin can cause QT prolongation (do not use with other QT-prolonging drugs (use with caution in patients with CV disease)
46
Q

What is the MOA of 5 alpha-reductase inhibitors?

A

These medications inhibit 5 alpha-reductase enzyme, which blocks the conversion of testosterone to dihydrotestosterone (DHT)

47
Q

What are some examples of 5 alpha-reductase inhibitors?

A

Finasteride and Dutasteride

48
Q

What is the difference with Finasteride and Dutasteride?

A

Finasteride is selective for the 5 alpha-reductase type II enzyme (the more prevalent type within the prostate), while dutasteride inhibits both type I and type II

49
Q

What are some contraindications of 5 alpha-reductase inhibitors?

A

Women of child-bearing potential, pregnancy, children

50
Q

What are some warnings associated with 5 alpha-reductase inhibitors?

A

May increase risk of high-grade prostate cancer

51
Q

What are some side effects of 5 alpha-reductase inhibitors?

A

Impotence, decreased libido, ejaculation disturbances, breast enlargement and tenderness, rash; sexual SEs decrease with time and return to baseline at one year of use in some men

52
Q

What are some monitoring parameters of 5 alpha reductase inhibitors?

A

PSA, urinary symptoms

53
Q

What are some notes associated with 5 alpha-reductase inhibitors?

A
  • Pregnant women should not take or handle these medications as they can be absorbed through the skin and can be detrimental to the fetus (on the NIOSH list of hazardous drugs)
  • Delayed onset, treatment for 6 months (or longer) may be required for maximal efficacy
  • 5 alpha-reductase inhibitors shrink the prostate and decrease PSA levels
  • Swallow dutasteride whole. Do not chew or open as contents can cause oropharyngeal irritation
54
Q

What are some 5 alpha-reductase inhibitors?

A
  • Finasteride and dutasteride are minor CYP3A4 substrates
  • Do not use Proscar if using Propecia for hair loss
  • Strong CYP3A4 inhibitors can increase levels
55
Q

What is the MOA of PDE-5 inhibitors in treating BPH?

A

The MOA of PDE-5 inhibitors in treating BPH symptoms is not well know. They likely decrease smooth muscle and endothelial cell proliferation, decrease nerve activity, increase smooth muscle relaxation and tissue perfusion of the prostate and bladder

56
Q

What is the only PDE-5 inhibitor that is FDA approved for the treatment of BPH?

A

Tadalafil

57
Q

What are contraindications of Tadalafil?

A

Do not use with nitrates or riociguat

58
Q

What are some warnings associated with Tadalafil?

A
  • Impaired color discrimination (dose-related), higher risk with retinitis pigmentosa
  • Hearing loss ,with or without tinnitus/dizziness
  • Vision loss, rare can be due to nonarteritic anterior ischemic option neuropathy (NAION); risk factors are low cup-to-disc ratio, CAD, vascular conditions, age > 50 yrs, Caucasian ethnicity; avoid with retinal disorders
  • hypotension, due to vasodilation; higher risk with resting BP <90/50 mmHg, fluid depletion or autonomic dysfunction
  • CVD, caution with low or very high BP or recent CV events; seek immediate medical help for chest pain
  • Priapism, seek emergency medical care if an erection last > 4 hrs
59
Q

What are some side effects of Tadalafil?

A

Headache, flushing, dizziness, dyspepsia, muscle/back pain, myalgia, blurred vision, increased sensitivity to light, epistaxis, diarrhea

60
Q

What are monitoring parameters of Tadalafil?

A

BP, PSA, urinary symptoms

61
Q

What are key counseling points of alpha-blockers?

A
  • Can cause orthostasis

- Tell your healthcare provider about the sue of this medication if having cataract surgery

62
Q

What are some counseling points of Doxazosin and Terazosin?

A
  • Take at bedtime

- Ghost tablet in stool (Cardura XL)

63
Q

What are some counseling points of Silodosin?

A

Can cause sexual dysfunction (retrograde ejaculation)

64
Q

What are some counseling points of 5 alpha-reductase inhibitors?

A

Can cause sexual dysfunction (decreased libido, ejaculation disturbances and erectile dysfunction)

NAPLEX Review (45 decks)

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