Tamulsin Mechanism of Action

Pharmacology: Pharmacodynamics: Alpha-adrenoceptor antagonist.
Preparations for the exclusive treatment of prostatic disease.
Mechanism of action: Tamsulosin binds selectively and competitively to postsynaptic alpha1-receptors, in particular to the subtype alpha1A, resulting in relaxation of the smooth muscle of the prostate, whereby tension is reduced.
Pharmacodynamic effects: Tamsulosin increases maximum urinary flow rate by reducing smooth muscle tension in the prostate and urethra, thereby relieving obstruction.
It also improves the complex of irritative and obstructive symptoms in which bladder instability and tension of the smooth muscles of the lower urinary tract play an important role. Alpha1-blockers can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with Tamsulosin.
Paediatric population: A double-blind, randomized, placebo-controlled, dose ranging study was performed in children with neuropathic bladder. A total of 161 children (with an age of 2 to 16 years) were randomized and treated at 1 of 3 dose levels of Tamsulosin (low [0.001 to 0.002 mg/kg], medium [0.002 to 0.004 mg/kg], and high [0.004 to 0.008 mg/kg]), or placebo. The primary endpoint was number of patients who decreased their detrusor leak point pressure (LPP) to <40 cm H2O based upon two evaluations on the same day. Secondary endpoints were: actual and percent change from baseline in detrusor leak point pressure, improvement or stabilization of hydronephrosis and hydroureter and change in urine volumes obtained by catheterisation and number of wet times at time of catheterisation as recorded in catheterisation diaries. No statistically significant difference was found between the placebo group and any of the 3 Tamsulosin dose groups for either the primary or any secondary endpoints. No dose response was observed for any dose level.
Pharmacokinetics: Absorption: Tamsulosin administered as a prolonged-release tablet is absorbed from the intestine and its bioavailability is approximately 55-59%. A consistent slow release of Tamsulosin is maintained over the whole pH range encountered in the gastrointestinal tract with little fluctuation over 24 hours. The rate and extent of absorption of Tamsulosin administered as a prolonged release-tablet is not affected by food intake.
Tamsulosin shows linear kinetics.
Following administration of a single dose of Tamsulosin in fasting state, plasma levels of Tamsulosin peak at a median time of 6 hours. At steady state, which is reached by day 4 of multiple dosing, plasma levels of Tamsulosin peak at 4 to 6 hours in fasting and fed state. Peak plasma levels increase from approximately 6 ng/mL after the first dose to 11 ng/mL at steady state.
As a result of the prolonged release characteristics of the tablet the trough concentration of Tamsulosin in plasma amounts to 40% of the peak plasma concentration under fasting and fed conditions. There is a considerable inter-patient variation in plasma levels, both after single and multiple dosing.
Distribution: In male patients, Tamsulosin is about 99% bound to plasma proteins and the volume of distribution is small (about 0.2l/kg).
Biotransformation: Tamsulosin has a low first pass effect, being metabolised slowly. Most Tamsulosin is present in plasma in the form of unchanged drug. It is metabolised in the liver.
In rats, hardly any induction of microsomal liver enzymes was seen to be caused by Tamsulosin.
None of the metabolites are more active than the original compound.
Elimination: Tamsulosin and its metabolites are mainly excreted in the urine. The urinary recovery of unchanged drug is estimated to be about 4-6% of the dose, administered as a prolonged release tablet.
After a single dose of Tamsulosin, and at steady state, elimination half-life of about 19 and 15 hours, respectively, has been measured.