Generality
Indications
Doxazosin is a type 1 alpha blocker, a competitive and selective adrenergic receptor antagonist used to treat symptoms of benign prostatic hyperplasia.
In 2000 some studies showed that doxazosin was not very effective in the treatment of arterial hypertension, like other alpha blockers of the same family, and that a simple diuretic could have the same effect as regards the lowering of blood pressure. For this reason there has been a decline in interest in this application, although more recent studies have attributed renewed importance to this drug in the treatment of symptoms of benign prostatic hyperplasia and erectile dysfunction.
Mechanism of action
The way of acting of doxazosin consists in binding to the postsynaptic alpha1A adrenergic receptors (which innervate almost all the smooth muscles), in a selective and competitive way; the result is a relaxation of the smooth muscles, both that of the prostate and that of the urethra.
The relaxation of the smooth muscles of the prostate and urethra results in an increase in the maximum speed of the urinary flow and in a significant reduction of the obstruction.
Side effects
However, the relaxation of smooth muscles by doxazosin also involves a fairly frequent undesirable effect, which is the lowering of blood pressure, due to the excessive relaxation of the blood vessels with the reduction of peripheral resistance. This side effect can be a problem in patients who already suffer from hypotension, in which the hypotensive effect of doxazosin can cause dizziness and fainting. If the patient faints after administration of the drug, it is recommended to lay him down, in order to promote blood circulation, and if necessary to seek medical assistance. Administration of doxazosin causes a clinically significant reduction in blood pressure in all individuals, which continues for 24 hours following the time of intake; the manifestation of symptoms related to the lowering of blood pressure depends on the patient's individual response and blood pressure. habitual; orthostatic side effects can occur at the start of treatment in many individuals.
History and registered specialties
Doxazosin was developed by the US pharmaceutical company Pfizer and marketed under the registered names of Cardura and Carduran. In February 2005, the Food and Drug Administration (FDA) approved the market launch of extended-release doxazosin under the registered name of Cardura XL.
In Italy, doxazosin is marketed under the registered name of Cardura or as a generic drug under different names, such as Benur and Doxazosin. In other countries it can be found under other names, such as Dosin or Duracin, which depend on the pharmaceutical company that makes the drug.
Minor Shares
Unlike other non-selective alpha inhibitors of alpha-adrenergic receptors, which can cause tolerance in long-term treatment, doxazosin does not cause any phenomenon of tolerance in long-term treatment; the use of doxazosin only rarely can cause a mild tachycardia. Other clinical studies have shown that long-term treatment with doxazosin can cause a slight reduction in plasma concentrations of total cholesterol and LDL fraction, but the clinical relevance of these results remains. In the same clinical study it was shown that treatment with doxazosin can increase the sensitivity of patients to insulin, thus causing alterations in glucose metabolism.
Pharmacokinetics and Pharmacodynamics
Doxazosin has a fairly long half-life, which varies from 16 to 30 hours, and this interval of action makes the drug suitable for a single daily administration. The maximum plasma concentration of doxazosin is reached 2 hours after administration. The bioavailability of the drug in the bloodstream is about 63%.
Doxazosin is transported in the bloodstream bound to plasma proteins; in fact, the drug bound to plasma proteins reaches about 98% of the total concentration. Doxazosin is mainly metabolised by the liver and eliminated predominantly, approximately 65%, by excretion in the faeces.
Dosage and method of use
The recommended dose of doxazosin in the treatment of arterial hypertension is 1 mg / day, as a starting dose, to be taken in a single dose. The maintenance dose, on the other hand, varies from 1 to 16 mg / day, depending on the patient's needs and the severity of the disease.
In the treatment of symptoms of benign prostatic hyperplasia, the recommended starting dose of doxazosin is 1 mg / day, to be taken in a single daily administration, if using normal tablets, and 4 mg / day, always to be taken in a single dose. "Once daily administration, if prolonged-release tablets are used. The recommended dose of doxazosin for maintenance of therapy ranges from 1 to 8 mg / day, once daily, for normal tablets; for prolonged-release tablets, instead , the recommended dose ranges from 4 to 8 mg / day, once daily.Dose adjustment depends on the severity of the patient's symptoms and on the individual sensitivity to its action. Should it be necessary to switch from the use of normal tablets to the use of prolonged-release tablets, it is recommended to start with the lowest dose (ie 4 mg / day of doxazosin), regardless of the dose in use with normal tablets. Always in case of change of doxazosin tablets, it is recommended not to take the last evening dose in normal tablets. In the event of discontinuity for several days of treatment with prolonged-release tablets, it is recommended to restart therapy with the lowest dose, i.e. that of 4 mg / day.
In case of patients with hepatic insufficiency an adjustment of the dose of doxazosin is necessary; if hepatic insufficiency is severe enough, prolonged-release tablets are not recommended.
The dose adjustment must be made on the basis of the individual response to doxazosin; consequently the patient's blood pressure values must be measured in an upright position, based on three different measurements: the first after 2 hours from the administration of doxazosin, the second 6 hours after drug administration, and the third after 24 hours Postural side effects such as dizziness and syncope (fainting) usually occur between two and six hours after administration of the first dose of doxazosin.
Doxazosin: contraindications and side effects "
