| Indication |
Used in the treatment of signs and symptoms of benign prostatic
hyperplasia (reduction in urinary obstruction and relief of associated
manifestations such as hesitancy, terminal dribbling of urine,
interrupted or weak stream...etc.) |
| Pharmacodynamics |
Tamsulosin, a sulfamoylphenethylamine-derivative
alpha-adrenoceptor blocker with enhanced specificity for the
alpha-adrenoceptors of the prostate, is commonly used to treat benign
prostatic hyperplasia (BPH). The drug is commercially available in a
racemic mixture of 2 isomers, and is pharmacologically related to
doxazocin, prazosin, and terazosin. However, unlike these drugs,
tamsulosin has a higher affinity for the alpha-1A- adrenergic receptors,
which are located in vascular smooth muscle. Studies show that
tamsulosin has about 12 times greater affinity for alpha-1 adrenergic
receptors in the prostate than those in the aorta, which may result in a
reduced incidence of adverse cardiovascular effects. |
| Mechanism of action |
Tamsulosin is a selective antagonist at alpha-1A and
alpha-1B-adrenoceptors in the prostate, prostatic capsule, prostatic
urethra, and bladder neck. At least three discrete alpha1-adrenoceptor
subtypes have been identified: alpha-1A, alpha-1B and alpha-1D; their
distribution differs between human organs and tissue. Approximately 70%
of the alpha1-receptors in human prostate are of the alpha-1A subtype.
Blockage of these receptors causes relaxation of smooth muscles in the
bladder neck and prostate, and thus decreases urinary outflow resistance
in men. |
| Absorption |
Absorption of tamsulosin HCI from capsules 0.4 mg is essentially
complete (>90%) following oral administration under fasting
conditions. |
| Volume of distribution |
- 16 L [intravenous administration to ten healthy male adults]
|
| Protein binding |
94%-99% |
| Metabolism |
Tamsulosin HCI is extensively metabolized by cytochrome P450
enzymes in the liver, however, the pharmacokinetic profile of the
metabolites in humans has not been established. |
| Route of elimination |
Tamsulosin hydrochloride is extensively metabolized by cytochrome
P450 enzymes in the liver and less than 10% of the dose is excreted in
urine unchanged. The metabolites of tamsulosin hydrochloride undergo
extensive conjugation to glucuronide or sulfate prior to renal
excretion. On administration of the radiolabeled dose of tamsulosin
hydrochloride to four healthy volunteers, 97% of the administered
radioactivity was recovered, with urine (76%) representing the primary
route of excretion compared to feces (21%) over 168 hours. |
| Half life |
5-7 hours |
| Clearance |
|
| Toxicity |
LD50 = 650 mg/kg (in rats) |
