What are the side effects of selective alpha‑1 blockers such as prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin?

Side Effects of Selective Alpha-1 Blockers

Selective alpha-1 blockers cause ejaculatory dysfunction, orthostatic hypotension, dizziness, nasal congestion, and asthenia, with the specific side effect profile varying significantly between agents—tamsulosin and silodosin cause more ejaculatory problems but less hypotension, while doxazosin and terazosin cause more cardiovascular effects. 1, 2

Cardiovascular Side Effects

Orthostatic Hypotension and Syncope

• Postural hypotension is the most clinically significant cardiovascular adverse effect, occurring most commonly with doxazosin and terazosin, and least commonly with tamsulosin 2, 3
• Doxazosin causes postural hypotension with or without symptoms (dizziness) that may develop within hours of administration, with infrequent reports of symptomatic hypotension occurring later than a few hours after dosing 4
• Terazosin causes postural hypotension in 3.9% of patients versus 0.8% with placebo, with syncope occurring in 0.6% versus 0% with placebo 5
• Tamsulosin demonstrates the lowest probability of orthostatic hypotension among all alpha-blockers, making it the safest choice for older adults vulnerable to blood pressure-related adverse effects 2, 3
• Real-world data confirms silodosin has 2 times lower risk of orthostatic hypotension compared to alfuzosin 6

Blood Pressure Effects

• The risk of hypotensive events is greatest during the initial seven days of treatment but continues at all time intervals 5
• Terazosin significantly decreases both systolic and diastolic blood pressure in sitting position 7
• First-dose orthostatic hypotension may be minimized by initiating doxazosin at 1 mg/day 8

Palpitations

• Palpitations occur in 0.9% of terazosin-treated patients versus 1.1% with placebo 5

Sexual Dysfunction

Ejaculatory Dysfunction

• Ejaculatory dysfunction is significantly more common with tamsulosin and silodosin compared to other alpha-blockers 1, 2
• Tamsulosin has a higher probability of ejaculatory dysfunction compared to other alpha-blockers, though it has lower cardiovascular side effects 2
• Silodosin carries an 18.5 times higher risk of ejaculatory disorders (11% incidence) compared to alfuzosin 6
• Alfuzosin is the safest option regarding ejaculatory disorders 6

Impotence

• Terazosin causes impotence in 1.6% of patients versus 0.6% with placebo 5

Central Nervous System Effects

Dizziness and Somnolence

• Dizziness occurs in 9.1% of terazosin patients versus 4.2% with placebo 5
• Somnolence affects 3.6% of terazosin patients versus 1.9% with placebo 5
• Dizziness was significantly more common with terazosin compared to tamsulosin in head-to-head trials 7

Asthenia (Weakness/Fatigue)

• Asthenia occurs in 7.4% of terazosin patients versus 3.3% with placebo 5
• Tamsulosin causes asthenia in 1-2% of patients receiving 0.4 mg daily 2
• Higher rates of fatigue are observed with terazosin and doxazosin compared to uroselective agents 9

Headache

• Headache occurs in 4.9% of terazosin patients versus 5.8% with placebo 5

Vertigo

• Vertigo affects 1.4% of terazosin patients versus 0.3% with placebo 5

Respiratory Effects

Nasal Congestion/Rhinitis

• Nasal congestion occurs in 1.9% of terazosin patients versus 0% with placebo 5
• Nasal congestion and rhinitis are common side effects resulting from alpha-receptor blockade in nasal vasculature 2

Ophthalmologic Complications

Intraoperative Floppy Iris Syndrome (IFIS)

• All alpha-1 blockers are associated with IFIS during cataract surgery, characterized by flaccid iris billowing, progressive intraoperative miosis, and potential iris prolapse 1, 4
• Patients planning cataract or glaucoma surgery should inform their ophthalmologist about current or previous alpha-blocker use 2
• Initiation of alpha-blockers is not recommended in patients with scheduled eye surgery 2
• There is no benefit to stopping alpha-1 blocker therapy prior to cataract surgery 4
• Increased awareness of IFIS has resulted in year-by-year decreased complication rates 1

Other Adverse Effects

Peripheral Edema

• Peripheral edema occurs in 0.9% of terazosin patients versus 0.3% with placebo 5

Blurred Vision

• Blurred vision/amblyopia affects 1.3% of terazosin patients versus 0.6% with placebo 5

Priapism

• Alpha-1 antagonists, including doxazosin, have been associated with priapism (painful penile erection sustained for hours), which can lead to permanent impotence if not promptly treated 4

Comparative Safety Profile Between Agents

Uroselective vs Non-Selective Agents

• Alfuzosin and tamsulosin (uroselective agents) offer better tolerability than terazosin and doxazosin (non-selective agents) 9
• Higher rates of vasodilatatory cardiovascular side effects (dizziness, fatigue, hypotension) occur with terazosin and doxazosin compared to alfuzosin and tamsulosin 9
• Tamsulosin was superior to terazosin in both efficacy and adverse event profile, with significantly fewer adverse events (13 vs 50 events, p<0.01) 7

Drug-Specific Recommendations

• Choice of alpha-blocker should be based on patient age, comorbidities, and different adverse event profiles (ejaculatory dysfunction versus blood pressure changes) 1
• Tamsulosin 0.4 mg once daily requires no dose titration and provides equivalent symptom improvement with minimal cardiovascular side effects 2
• Doxazosin and terazosin require gradual uptitration to minimize orthostatic effects 2

Critical Drug Interactions

Concomitant Antihypertensive Therapy

• Alpha-blocker therapy should not be assumed to constitute optimal management of concomitant hypertension in patients with cardiac risk factors; separate management of hypertension may be required 2
• Concomitant administration with PDE-5 inhibitors can result in additive blood pressure lowering effects and symptomatic hypotension 4

Management with Beta-Blockers

• When combining with carvedilol, start with lowest effective doses and titrate slowly, monitoring blood pressure in both supine and standing positions, particularly 2-4 hours post-dose when peak effects occur 2