Doxazosin

OC-Adrenoceptor Blockers. Nonselective a-adrenoceptor blockers (Table 6), such as phentolamine, which block both a - and a2 adrenoceptors, produce vasodilation by antagonizing the effects of endogenous norepinephrine. They also produce severe tachycardia and have been replaced by selective a -adrenoceptor blockers, such as prazosin, terazosin, and doxazosin, which do not usually cause severe tachycardia. 

QUINAZOLINES AND QUINAZOLINONES Doxazosin (84) is an adrenergic postsynaptic a-1 receptor antagonist with antihypertensive... 

Alpha (a)-adrenergic blocking dragp—for example, doxazosin (Cardura) and prazosin (Minipress)... 

Generally, arblockers are considered as second-line agents to be added on to most other agents when hypertension is not adequately controlled. They may have a specific role in the antihypertensive regimen for elderly males with prostatism however, their use is often curtailed by complaints of syncope, dizziness, or palpitations following the first dose and orthostatic hypotension with chronic use. The roles of doxazosin, terazosin, and prazosin in the management of patients with hypertension are limited due to the paucity of outcome data and the absence of a unique role for special populations or compelling indications from JNC 7. 

Requirement for up-titration of dose Yes (for terazosin and doxazosin immediate-release) no (for alfuzosin possibly for doxazosin extended-release and tamsulosin) No... 

Need for up-titration of daily dose. Up-titration is required for terazosin and immediate-release doxazosin. It is minimally required for extended-release doxazosin and tamsulosin. It is not required for extended-release alfuzosin. 

Dosage formulation. Immediate-release formulations of terazosin and doxazosin are quickly absorbed and produce high peak plasma levels. Modified- or extended-release formulations of doxazosin, alfuzosin, and tamsulosin produce lower peak levels, but more sustained therapeutic plasma levels, than immediate-release formulations and have less potential for producing hypotensive episodes, thereby allowing initiation of treatment with a therapeutic dose and once daily dosing.25-27... 

In patients with BPH and hypertension, it is not recommended to use an a-adrenergic antagonist alone to treat both disorders. In the ALLHAT study, where doxazosin was compared to other agents for treatment of essential hypertension, doxazosin was associated with a higher incidence of congestive heart failure. Therefore, in patients with hypertension and BPH, it is recommended that an appropriate antihypertensive be added to an a-adrenergic antagonist.11... 

McConnell JD, Roehrborn CG, Bautista OM et al. The long term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl 1 Med 2003 349 2387-2398. 

Figure 5 Doxazosin release rate versus the osmotic pressure of the core formulation. (From Ref. 20.)...

Figure 12 Release of doxazosin from asymmetrical capsule shells versus the osmotic pressure of the receptor solution (gastric buffer, 7.5 atm, and dextrose solutions, 21 and 34 atm). (From Ref. 28.)...

This system is the only osmotic system developed commercially at this time that is suitable for the oral administration of insoluble drugs to humans. It has been utilized in the development of several other drugs including isradipine, doxazosin, diltiazem, contraceptive steroids, glipizide, and verapamil [48-53], The system has also been utilized to codeliver the free bases of compounds normally administered as water-soluble salts such as pseudoephedrine and bromo-pheniramine [54], The latter system includes both a loading dose and a controlled release dose and is intended for applications in the over-the-counter market. 

---