Drugs Used in Urinary Retention

See also: Chronic retention of urine, catheterising bladders, urinary tract obstruction, voiding difficulties, lower urinary tract symptoms in men, lower urinary tract symptoms in women.

• Acute urinary retention with a painful, distended bladder should never be treated with medication, but with catheterisation and drainage of the retained urine, followed by further investigations to ascertain its cause.
• Further therapy after episodes of acute retention will involve discontinuing or reducing the dose of any precipitating medications, treating with medications to improve urinary outflow, as below, ± definitive surgical intervention such as trans-urethral resection of prostate (TURP) to reduce any anatomical obstruction to urinary flow.
• Chronic retention of urine is usually painless and does not require urgent catheterisation unless there is biochemical, imaging or clinical evidence of renal impairment due to back pressure.
• After chronic urinary retention has been assessed and a cause found, this should be treated using medication as below ± surgical intervention, depending on urological advice; some patients who cannot tolerate surgery or who do not respond to medication may be treated by long-term catheterisation or clean, intermittent self-catheterisation.¹
• The classes of drugs used to treat bladder outflow obstruction caused by benign prostatic hyperplasia in men are:
  1. Alpha-blockers (selective alpha-adrenergic receptor antagonists)
  2. The anti-androgenic agents classified as 5-α-reductase inhibitors
  3. Phytotherapies derived from South African star grass (beta-sitosterols); Saw palmetto (Serenoa repens); Rye grass pollen (cernilton); African prune tree (Pygeum Africanum)

1. Alpha-blockers reduce smooth muscle tone at the bladder neck through diminution of the sympathetic tone inducing its contraction, leading to improved urinary flow rates and symptoms of urinary obstruction.
   Examples: Alfuzosin, Doxazosin, Indoramin, Prazosin, Tamsulosin,Terazosin.
2. 5-α-reductase inhibitors block the conversion of the male sex hormone testosterone to its more bioactive form dihydrotestosterone; in the long-term this reduces prostatic volume and improves symptoms of bladder outflow obstruction.
   Examples: Dutasteride, Finasteride.
3. Phytotherapeutic agents mode(s) of action are less well understood and currently under evaluation. None currently licensed for prescription but are available as 'alternative' remedies for purchase in healthfood stores/some pharmacies etc.

1. Benign prostatic hyperplasia causing bladder outflow obstruction.
2. Alpha-blockers may also be used to treat hypertension; see cautions listed below due to this coincidental effect.

Alpha-blockers

• Patients already taking antihypertensive medication/other medicines with a tendency to reduce blood pressure (e.g. diuretics for heart failure, vasodilators such as dihydropyridines for indications other than hypertension like Raynaud's phenomenon)
• Older patients
• Patients with hepatic disease.

5-α-reductase inhibitors

• May increase serum levels of potential neoplastic marker, Prostate Specific Antigen (PSA) – may need to interpret results of this test with different reference values – contact local laboratory service for advice if unsure.
• These agents are secreted in semen – condoms should be used where there is a risk of conception.
• Women of childbearing age should not handle damaged/crushed or broken tablets/capsules of these agents due to the risk of systemic absorption and potential harmful effects on any fetus in case of early, undetected pregnancy (mainly of relevance to those working in pharmaceutical industry/pharmacies).

Phytotherapeutic agents

• Very little is known about the long-term effectiveness, safety and ability to prevent the complications of benign prostatic hyperplasia for the phytotherapeutic agents.
• Their ability to interact with other medicines is largely unknown.
• However, they do have variable amounts of evidence to support their efficacy and appear to be well tolerated, at least on the basis of initial studies.^2,3,4,5
• They are becoming increasingly popular agents for self-treatment of lower urinary tract symptoms in men, so practitioners should be aware of their characteristics and use among the population at risk of benign prostatic hyperplasia.
• Serenoa repens appears to be the most extensively researched agent and has been shown in a comparative trial to be as effective as tamsulosin and very well tolerated.⁶
• There appears to be no beneficial effect from the combined use of an alpha-blocker and Serenoa repens.⁶

Alpha-blockers

• History of postural hypotension
• History of micturition syncope.
• Alfluzosin and tamsulosin should not be prescibed for patients with severe hepatic impairment.

5-α-reductase inhibitors

• Must not be given to women, children or adolescents.
• Dutasteride should be avoided in patients with hepatic impairment.

Phytotherapeutic agents

There are no agreed contraindications to the use of these agents as yet.

Alpha-blockers

• Alfluzosin – 2.5 mg 3 times daily, building to maximum 10 mg daily; older patients start at 2.5 mg twice daily.
• Doxazosin – Start at 1 mg daily; double dose at intervals of 1–2 weeks, depending on response; Maximum 8 mg daily; usual maintenance dose is 2–4 mg daily.
• Indoramin – Start at 20 mg twice daily; increase dose as necessary by 20 mg every 2 weeks to maximum 100 mg daily in divided doses; older patients should start at 20 mg at night which may be adequate.
• Prazosin – Start at 500 μg twice daily for 3–7 days, then adjust according to response; usual maintenance (and maximum dose) is 2 mg twice daily; start older patients with lowest possible dose that is effective.
• Tamsulosin – 400 μg daily as a single dose, if no response then discontinue as no dose gradations available.
• Terazosin – Start at 1 mg on retiring to bed; if needed, dose may be doubled every 1–2 weeks according to response; maximum 10 mg once daily; usual maintenance dose is 5–10 mg daily.

5-α-reductase inhibitors

• Dutasteride – 500 μg daily; may require 6 months therapy before any benefit is seen.
• Finasteride – 5 mg daily, may require several months therapy before benefit is obtained.

Phytotherapeutic agents

Currently no agreed standard formulations and dosing schedules. Should be taken according to manufacturer's instructions.

Alpha-blockers

Monitor BP after initiation and advise patient to report any side effects potentially attributable to hypotension such as dizziness, sweating, lightheadedness, weakness, syncope etc.

5-α-reductase inhibitors

Be aware that serum PSA values may be affected by these drugs. If patients have this investigation for screening or follow-up of confirmed prostatic malignancy and are taking these agents, this should
be taken into account. Liaise with local chemical pathology service if you are uncertain.

Phytotherapeutic agents

As these agents are relatively newly introduced and not licensed medications, any problems caused by their use in terms of toxicity or drug interactions should be reported, ideally to the Medicines and Healthcare products Regulatory Agency, via their pharmacovigilance mechanisms. See internet section below.

Alpha-blockers

• Drowsiness
• Hypotension (particularly postural hypotension)
• Syncopal episodes
• Generalised weakness
• Low mood
• Headache
• Erectile dysfunction (including priapism)
• Dry mouth
• Gastrointestinal disturbance (including nausea, vomiting, diarrhoea and constipation)
• Peripheral oedema
• Rhinitis
• Blurred vision
• Tachycardia/palpitations
• Hypersensitivity reactions including rash, pruritus and angioedema have been reported.

5-α-reductase inhibitors

• Erectile dysfunction
• Impaired libido
• Ejaculatory dysfunction
• Breast tenderness
• Gynaecomastia.

Phytotherapeutic agents

As yet no consensus on potential complications of their use. Refer to any literature supplied by the manufacturer.

There is good evidence that combining alpha-blockers and 5-α-reductase inhibitors can slow the progression of BPH in the long-term with similar improvements in symptom scores compared to monotherapy with either drug alone, but reduction in secondary endpoint markers for progression of the disease, such as the need for surgical intervention.^7,8,9