Prozelax Mechanism of Action

Pharmacotherapeutic Group: Alpha₁-Adrenoceptor Antagonist.
Pharmacology: Pharmacodynamics: Tamsulosin HCl is a sulfamoylphenethylamine derivative alpha₁-adrenergic blocking agent (alpha₁-adrenoceptor antagonist). It binds selectively and competitively to postsynaptic alpha₁-adrenoceptors, in particular to subtypes alpha_1A and alpha_1D. About 70% of alpha₁-receptors in human prostate are of the alpha_1A subtype. Tamsulosin brings about relaxation of prostatic and urethral smooth muscles resulting in improved 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.
Tamsulosin's ability to decrease intra-ureteral pressure and increase fluid passage has also been shown to be effective in medical expulsive therapy in increasing the rate of spontaneous stone passage.
Alpha₁-blockers can reduce blood pressure by lowering peripheral resistance. Selectivity of tamsulosin for alpha_1A-receptors which are mainly located in nonvascular smooth muscle (e.g., prostate) may result in a reduced incidence of adverse cardiovascular effects (e.g., syncope, dizziness, hypotension).
Pharmacokinetics: The plasma levels of tamsulosin HCl gradually increases reaching peak concentrations (Cmax) at a median time of 6 hours after a single dose of tamsulosin 400 mcg extended release in the fasted state. At steady state (reached by day 4 of multiple dosing), plasma concentrations of tamsulosin peak at 4 to 6 hours under fasting and fed conditions. An increase in peak plasma concentrations is observed from approximately 6 ng/mL after the first dose to 11 ng/mL in steady state. The plasma concentration decreases after the Cmax is reached; however, at approximately 16 to 24 hours post-dose, a small increase or second plateau is observed. The absolute bioavailability of tamsulosin is estimated to be 55 to 59%. Absorption of tamsulosin is reduced by a recent meal.
Tamsulosin's mean steady-state apparent volume of distribution after intravenous (IV) administration is 16 L, which suggests distribution into extracellular fluids.
Tamsulosin is 94 to 99% bound to plasma proteins primarily alpha₁ acid glycoproteins. It is extensively metabolized by cytochrome P450 enzymes (CYP3A4 and CYP2D6 isoenzymes) in the liver; less than 10% of the dose is excreted in the urine unchanged. The metabolites of tamsulosin undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. Tamsulosin's pharmacokinetic profile in humans has not been fully established, thus, possible interactions with other cytochrome P450 metabolized compounds cannot be predicted.
Tamsulosin is primarily excreted through the urine with approximately 9% of the dose excreted as unchanged drug. Because of the absorption rate-controlled pharmacokinetics of tamsulosin capsule, the apparent half-life of tamsulosin increases to about 12 to 15 hours in healthy volunteers.