What is the mechanism of action of terazosin?

Mechanism of Action of Terazosin

Terazosin works primarily by selectively blocking alpha-1 adrenoceptors, causing relaxation of smooth muscle in the prostate, prostatic capsule, proximal urethra, and bladder neck, which reduces urethral pressure and bladder outlet resistance. 1

Pharmacodynamic Effects

Alpha-1 Adrenoceptor Blockade

• Terazosin selectively antagonizes alpha-1 adrenoceptors, which are abundant in the prostate, prostatic capsule, and bladder neck 1
• This blockade prevents sympathetic nervous stimulation of these receptors, leading to:
  • Relaxation of smooth muscle in the urinary tract
  • Reduction in bladder outlet obstruction
  • Decreased urethral resistance 2

Effects on Urinary Symptoms

• By blocking alpha-1 adrenoceptors, terazosin addresses the dynamic component of BPH (increased smooth muscle tone) rather than the static component (prostate enlargement) 1
• This results in:
  • Improved urinary flow rates
  • Reduced obstructive symptoms (hesitancy, intermittency, terminal dribbling, impaired stream)
  • Reduced irritative symptoms (nocturia, frequency, urgency) 1
  • Decreased post-void residual volume 2

Vascular Effects

• Alpha-1 adrenoceptor blockade also causes vasodilation in the peripheral vasculature
• This leads to decreased total peripheral vascular resistance and reduction in blood pressure 1
• Blood pressure reduction occurs gradually within 15 minutes following oral administration 1

Clinical Applications

Benign Prostatic Hyperplasia (BPH)

• Terazosin is indicated for symptomatic BPH, with improvements typically seen within 2 weeks of starting treatment 2
• Clinical studies show statistically significant improvements in:
  • Symptom scores (45% improvement vs. 24% with placebo)
  • Peak urine flow rates (34% improvement vs. 10% with placebo) 1
  • Both obstructive and irritative symptoms 3

Hypertension

• Terazosin's vasodilatory effect makes it effective for treating mild to moderate hypertension 1
• The blood pressure-lowering effect persists throughout the 24-hour dosing interval 1
• In patients with normal blood pressure and BPH, terazosin does not cause clinically significant blood pressure reduction 1

Pharmacokinetic Considerations

• Terazosin has a relatively long duration of action, allowing for once-daily dosing 2
• Peak plasma concentrations occur within the first few hours after dosing 1
• The blood pressure effect is more pronounced at peak plasma concentrations and somewhat attenuated at 24 hours 1

Potential Side Effects Related to Mechanism

• First-dose phenomenon: Due to its alpha-blocking mechanism, terazosin can cause significant orthostatic hypotension after the first dose or dose increases 1
• Common side effects related to its mechanism include:
  • Dizziness (14.6-20%)
  • Peripheral edema (2.1-6%)
  • Postural hypotension
  • Asthenia 4

Clinical Implications of Mechanism

• Initial low dosing (1 mg) is recommended to minimize first-dose hypotension 1
• Gradual dose titration allows for adaptation to the vasodilatory effects 1
• Evening dosing is often recommended to minimize orthostatic symptoms 3
• Terazosin can be effectively used to treat both BPH and hypertension simultaneously in patients with both conditions 3

Terazosin's mechanism of action as an alpha-1 adrenoceptor antagonist makes it effective for both BPH and hypertension, with its therapeutic effect primarily derived from smooth muscle relaxation in the lower urinary tract and peripheral vasculature.