Tamsolin Mechanism of Action

Pharmacology: Mechanism of Action: Tamsulosin binds selectively and competitively to postsynaptic α₁-adrenoceptors, in particular to subtypes α_1A and α_1D. It brings about relaxation of prostatic and urethral smooth muscle resulting in an increase in urinary flow rate and a reduction in symptoms of benign prostatic hyperplasia (BPH). It also improves the irritative symptoms in which bladder instability plays an important role.
Pharmacokinetics: Absorption: Absorption of tamsulosin HCl is essentially complete (>90%) following oral administration under fasting conditions. The time to maximum concentration (T_max) is reached by 4-5 hrs under fasting conditions and by 6-7 hrs when tamsulosin HCl capsules are administered with food. Taking tamsulosin HCl capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and 40-70% increase in peak concentrations (C_max) compared to fed conditions.
Distribution: Tamsulosin HCl is extensively bound to human plasma proteins (94-99%), primarily α₁-acid glycoprotein (AAG), with linear binding over a wide concentration range. There is a minimal distribution to the brain, spinal cord and testes.
Metabolism: Tamsulosin HCl has a low first-pass effect, being metabolized slowly. It is extensively metabolized by cytochrome P-450 enzymes in the liver. Most tamsulosin HCl is present in the plasma in the unchanged form.
Excretion: Tamsulosin HCl and its metabolites are mainly excreted in the urine with <10% of a dose being present in the unchanged form. After a single dose of tamsulosin HCl in the fed state and in the steady state in patients, elimination half-lives of about 10 hrs and 13 hrs, respectively, have been measured.
Special Populations: Geriatrics: Intrinsic clearance is independent of tamsulosin HCl binding to AAG, but diminishes with age, resulting in a 40% overall higher exposure (AUC) in subjects 55-75 years compared to subjects 20-32 years.
Renal Impairment: Patients with renal impairment [mild to moderate (CrCl 30-70 mL/min/1.73 m²) or moderate to severe (CrCl ≤10-30 mL/min/1.73 m²)] do not require dose adjustment.