Classification and Main Representatives
All drugs in this class are selective $\alpha_1$-adrenergic receptor antagonists. Depending on the duration of their clinical effect and receptor selectivity, they are divided into several subgroups:
- Short-acting: prazosin (effect lasts 6–8 hours).
- Long-acting: terazosin (duration of action is about 24 hours) and doxazosin (effect persists up to 36 hours).
- Uroselective agents: tamsulosin and alfuzosin. These act specifically on the genitourinary system.
Mechanism of Action and Main Effects
The primary target of these drugs is postsynaptic $\alpha_1$-adrenergic receptors. By blocking them, the medications prevent norepinephrine and circulating epinephrine from exerting their stimulatory effects on cells.
Effects on Vessels and Hemodynamics These drugs cause dilation of both arterial and venous beds. This leads to a decrease in total peripheral resistance (TPR) and a reduction in venous return to the heart. The predictable result is a drop in both arterial and venous blood pressure.
Effects on the Prostate Gland In benign prostatic hyperplasia (BPH), enlarged tissue compresses the prostatic urethra, causing urinary retention. $\alpha_{1A}$-receptor blockers relax the smooth muscle of the prostate itself, the bladder neck, and the urethra. The urethral lumen widens, improving urine outflow.
Metabolic Effects This drug class exhibits anti-atherogenic properties: treatment decreases levels of low-density lipoproteins (LDL) and increases concentrations of high-density lipoproteins (HDL).
Clinical Application
Due to their pharmacological effects, selective $\alpha_1$-blockers are used in the following conditions:
- Hypertension. Used for maintenance blood pressure control (long-acting forms such as doxazosin and terazosin are preferred).
- Benign Prostatic Hyperplasia. First-line agents include long-acting medications (doxazosin, terazosin) and specialized uroselective agents (tamsulosin, alfuzosin).
- Peripheral Vascular Disorders. Prazosin is effective for vascular spasms, notably in Raynaud's phenomenon.
Side Effects
Adverse reactions are directly related to systemic vasodilation and the relaxation of visceral smooth muscle:
- Orthostatic Hypotension. A sharp drop in blood pressure upon changing body position (standing up). This is particularly evident as the "first-dose effect," which is most characteristic of prazosin. Clinical strategy: patients are advised to take the first dose at bedtime.
- Reflex Tachycardia. A compensatory cardiac response to the drop in blood pressure (more common with prazosin). Important advantage: because these drugs do not block presynaptic $\alpha_2$-receptors, negative feedback remains intact. Excessive norepinephrine release does not occur, so tachycardia is only moderately expressed (unlike with non-selective blockers), and vascular tone is not excessively restored.
- Peripheral Edema.
- Increased Urinary Frequency. Caused by drug-induced reduction in urethral sphincter and bladder neck tone.
- Nasal Congestion. Resulting from vasodilation of the blood vessels in the nasal mucosa.
Characteristics of Uroselective Agents
Tamsulosin and alfuzosin possess important pharmacological properties. Tamsulosin selectively binds only to the $\alpha_{1A}$-receptor subtype, which is localized predominantly in the smooth muscle of the prostate and bladder neck.
Due to this narrow specificity, the drug does not significantly affect blood vessel tone or systemic blood pressure. Side effects typical of non-selective agents (such as prazosin) are markedly weaker here. These medications are taken orally, with a standard dosing regimen in the morning after a meal.