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sx
- LUTS (lower urinary tract symptoms)
- - Hesitancy, intermittency, straining, or weak stream of urine
- - Urinary urgency and leaking
- - Incomplete emptying of bladder (bladder feels full)
- - Urinary frequency, especially nocturia
- - Bladder outlet obstruction
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Pathophysiology
- Testosterone converts to dihydrotestosterone (DHT) by 5 alpha-reductase enzyme
- - DHT is responsible for hyperplastic growth
- - As prostate enlarges, the gland presses against urethra
- - Causes more frequent urination
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Dx
- Physical exam
- Digital rectal exam (DRE)
- Urinalysis
- Serum prostate specific antigen (PSA)
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Natural products
- None currently recommended for tx of BPH sx
- Saw palmetto, pygeum, beta-sitosterol, rye pollen
- RPH don't recommend natural products --> must see MD, possible prostate cancer
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Treatment
- 1. Alpha blockers (selective, non-selective)
- 2. 5 alpha-reductase inhibitors
- 3. Phosphodiesterase 5 inhibitors
- 4. Anticholinergics
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5 alpha-reductase inhibitors
- Decrease prostate size
- - should not use in men with BPH without prostatic enlargement
-
1st line treatment of BPH
- Alpha blockers
- - 1st line treatment in patients with moderate-severe sx
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Alpha blockers MOA
- Inhibit alpha-1 adrenergic receptors and relax smooth muscles of bladder neck
- - Reduces bladder outlet obstruction, improves urinary flow
- - 3 types of alpha receptors: 1A, 1B, 1D
- - 1A more common in the prostate
-
Alpha blocker drugs
- 1. Non-selective: terazosin, doxazosin
- - Causes more side effects: orthostasis, dizziness, fatigue, HA
- 2. Selective: tamsulosin, alfuzosin, silodosin (Major 3A4 substrates)
- *Used for bladder outlet obstruction in women (off-label)
- - Does not shrink prostate or change PSA levels
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Terazosin
- - Brand: N/A
- - Start 1 mg at bedtime; titrate slowly
- - 10 mg at bedtime is effective, max: 20 mg at bedtime
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Doxazosin
- - Brand: Cardura, Cardura XL
- - IR: start 1 mg; titrate slowly up to 4-8 mg at bedtime
- - XL: start 4 mg with breakfast, titrate to max 8 mg
- *OROS formulation: ghost tablet
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Tamsulosin
- - Brand: Flomax
- - + dutasteride (Jalyn)
- - 0.4 mg daily, 30 minutes after the same meal each day, max: 0.8 mg daily
- *Abnormal ejaculation, rhinitis
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Alfuzosin
- - Brand: Uroxatral
- - 10 mg daly, immediately after same meal each day
- - CrCl < 30 ml/min: use with caution
- *QT prolongation
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Silodosin
- - Brand: Repaflo
- - 8 mg daily with a meal
- - CrCl 30-50 ml/min: 4 mg daily
- - CrCl < 30 ml/min: don't use
- *Retrograde ejaculation
- *Do not use with strong P-gp inhibitors (cyclosporine)
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Alpha blockers SE
- - Dizziness, fatigue, HA, fluid retention
- - Rhinitis (tamsulosin)
- - Abnormal ejaculation (tamsulosin, silodosin)
- - Orthostatic hypotension/syncope: with 1st dose, if therapy interrupted for several days, dosage increased to rapidly, started taking with other anti-HTN or PDE-5 inhibitor
- - Intraoperative floppy iris syndrome: in cataract surgery patients on alpha-1 blocker
- - Priapism: seek medical attention if > 4 hours
- - Angina: d/c if angina begins or worsens
- - Alcohol makes dizziness worse
- - Taking cold/allergy med (decongestants/antihistamines) make BPH sx worse
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Drugs that worsen BPH
- Anticholinergics (benztropine)
- Antihistamines (diphenhydramine, chlorpheniramine)
- Caffeine
- Decongestants (pesudoephedrine)
- SNRIs
- TCAs (phenothiazines and other drugs with anticholinergic properties)
- Testosterone products
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Alpha blocker contraindications
- Use of silodosin and alfuzosin with strong 3A4 inhibitors
- hepatic impairment (Child-Pugh class C for silodosin, B/C for alfuzosin)
- severe renal impairment (alfuzosin)
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5 alpha-reductase inhibitors MOA
- Block conversion of testosterone to DHT
- Shrinks prostate and decrease PSA
- Indicated for tx of symptomatic BPH in men with an enlarged prostate to improve sx, decrease risk of acute urinary retention
- Do not use in BPH without prostatic enlargement Tx 6 months or longer for maximal efficacy
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5 alpha-reductase inhibitor drugs
- Finasteride (Proscar)
- Dutasteride (Avodart)
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Finasteride
- - Brand: Proscar
- - 5 mg daily
- - Affects 5 alpha receptors type 2
- - Propecia 1 mg daily for hair loss
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Dutasteride
- - Brand: Avodart
- - + Tamsulosin: Jalyn; take 30 min after same meal
- - 0.5 mg daily
- - Affects both types of 5 alpha receptors (1 and 2)
- *Swallow whole. Do not chew or crush, can cause oropharyngeal irritation
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5 alpha reductase inhibitor SE
- Impotence, decreased libido, ejaculation disturbances
- Breast enlargement, tenderness
- Rash
- Sexual SE decrease with time by 1 year
- Make take several months or longer to reduce BPH sx
- Taking cold/allergy med (decongestants/antihistamines) make BPH sx worse
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5 alpha reductase inhibitor contraindications
- Women of child-bearing potential
- Pregnancy
- Children
- * Pregnant women, do not handle, can cause detrimental effects to fetus
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Phosphodiesterase-5 inhibitors MOA
- MOA not well known
- Likely decrease smooth muscle and endothelial cell proliferation, decrease nerve activity, increase smooth muscle relaxation and tissue perfusion of prostate and bladder
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Phosphodiesterase-5 inhibitors drugs
- Tadalafil (Cialis)
- Only PDE-5 inhibitor FDA approved for tx of BPH
- Used alone or in combo with Finasteride (Proscar)
- Used in combo with alpha blocker (esp non-selective) can increase hypotension, orthostasis
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Tadalafil
- - Brand: Cialis
- - 5 mg daily, same time each day
- - 3A4 inhibitor: 2.5 mg
- - CrCl 30-50 ml/min: 2.5 mg initially, max 5 mg daily
- - CrCl <30: do not use
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Phosphodiesterase-5 inhibitors SE
- HA, flushing, dizziness, dyspepsia
- Blurred vision, vision lost, increased sensitivity to light, epistaxis (nosebleeds), diarrhea, myalgia, muscle/back pain
- Hearing loss
- Impaired color discrimination
- Hypotension
- Priapism
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