Classification and main drugs
All drugs in this group belong to selective $\alpha_1$-adrenergic receptor blockers. Depending on the duration of the clinical effect and the selectivity of action, they are divided into several subgroups:
- Short-acting: prazosin (effect lasts 6–8 hours).
- Long-acting: terazosin (synonyms: Kornam, Setegis — acts for about 24 hours) and doxazosin (synonyms: Artesin, Cardura, Tonocardin — effect persists for up to 36 hours).
- Uroselective drugs: tamsulosin (synonym: Omnic) and alfuzosin (synonym: Uroxatral). They act specifically on the urogenital system.
Mechanism of action and main effects
The main target of these drugs is postsynaptic $\alpha_1$-adrenergic receptors. By blocking them, the drugs prevent the neurotransmitter norepinephrine and circulating epinephrine from exerting their stimulating effect on cells.
Effect on vessels and hemodynamics The drugs cause dilation of both arterial and venous beds. This leads to a decrease in total peripheral vascular resistance (TPVR) and a reduction in venous blood return to the heart. The logical outcome is a drop in arterial and venous pressure.
Effect 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 muscles of the prostate itself, the bladder neck, and the urethra. The lumen of the urethra widens, and urine outflow improves.
Metabolic effects The group exhibits anti-atherogenic properties: treatment reduces the level of atherogenic low-density lipoproteins (LDL) and increases the concentration of anti-atherogenic high-density lipoproteins (HDL).
Clinical application
Due to their pharmacological effects, selective $\alpha_1$-blockers are used in the following cases:
- Arterial hypertension. Used for scheduled blood pressure reduction (long-acting forms such as doxazosin and terazosin are prescribed more frequently).
- Benign prostatic hyperplasia. Drugs of choice are long-acting agents (doxazosin, terazosin) and specialized uroselective drugs (tamsulosin, alfuzosin).
- Peripheral circulatory disorders. Prazosin is effective for vascular spasms, in particular, Raynaud's syndrome.
Side effects
Adverse reactions are directly related to the mechanism of systemic vasodilation and relaxation of the smooth muscles of internal organs:
- Orthostatic hypotension. A sharp drop in blood pressure when changing body position (standing up). The "first-dose phenomenon" is particularly prominent, which is most characteristic of prazosin. Clinical tactic: it is recommended to take the first pill before bedtime.
- Reflex tachycardia. A compensatory response of the heart to a drop in blood pressure (more common with prazosin). Important advantage: since the drugs do not block presynaptic $\alpha_2$-receptors, negative feedback is not disrupted. Excessive release of norepinephrine does not occur, so tachycardia is moderately expressed (unlike non-selective blockers), and vascular tone is not restored.
- Peripheral edema.
- Frequent urination. Occurs due to drug-induced reduction in the tone of the urethral sphincters and bladder neck.
- Nasal congestion. Is a consequence of the dilation of blood vessels in the nasal mucosa.
Features of uroselective drugs
Tamsulosin and alfuzosin have important pharmacological features. Tamsulosin selectively binds only to the $\alpha_{1A}$ receptor subtype, which are located predominantly in the smooth muscle of the prostate gland and the bladder neck.
Due to such narrow specialization, the drug does not have a significant effect on blood vessel tone and systemic blood pressure. Side effects characteristic of non-selective agents (such as prazosin) are significantly less pronounced here. These drugs are taken orally, with the standard dosing regimen being in the morning after a meal.
Briefly: answers to topical questions
What is the pharmacokinetics of doxazosin (bioavailability, half-life, elimination routes)?
The pharmacokinetics of doxazosin is characterized by incomplete bioavailability, prolonged persistence in the body, and an intestinal route of elimination.
- Bioavailability — is 60–70%, because after good systemic absorption, the drug undergoes presystemic metabolism.
- Half-life — is 19–22 hours, which determines the frequency of administration.
- Elimination routes — after intensive metabolism in the liver, excretion of metabolites occurs primarily through the intestines.
Maximum plasma concentration is reached in 3 hours with daytime administration and in 5 hours with evening administration, while concomitant food intake delays absorption by 1 hour.
All main drugs of this group can be easily recognized by the characteristic ending -zosin (prazosin, doxazosin, terazosin, tamsulosin, alfuzosin).
Class and exam questions
Why is tachycardia less pronounced with these drugs compared to non-selective alpha-blockers?
They do not block presynaptic $\alpha_2$-adrenergic receptors. Due to this, the negative feedback mechanism is preserved: there is no excessive release of norepinephrine that could overly stimulate cardiac $\beta_1$-receptors.
What is the "first-dose phenomenon" and how to avoid it?
This is a sharp drop in blood pressure (orthostatic hypotension) upon the first dose of the drug. It is most characteristic of prazosin; to prevent fainting, the first dose is prescribed immediately before bedtime.
What is the main advantage of tamsulosin in the treatment of BPH?
Tamsulosin selectively blocks $\alpha_{1A}$-receptors in the prostate gland and urethra, improving urine outflow, while having virtually no effect on blood vessels and not lowering systemic blood pressure.
What else to study on this topic
- Comparative pharmacokinetics: from short-acting prazosin to ultra-long-acting doxazosin.
- Pathogenesis of benign prostatic hyperplasia (BPH) and the role of $\alpha_{1A}$-receptors.
- Mechanism of reflex tachycardia development in response to vasodilation.
- Effect of $\alpha_1$-blockers on the lipid profile: decrease in LDL and increase in HDL.
- Raynaud's syndrome: why prazosin helps with peripheral vascular spasms.
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