Alpha blockers:

These are the sympatholytic agents acting on the adrenergic alpha receptors. These are primarily used in the treatment of hypertension and Benign Prostatic Hyperplasia (BPH).
The major result of interaction of these agents with other antihypertensive drugs is the enhanced hypotensive effect. 'First dose hypotension' is the chief adverse affect reported with these drugs resulting in postural hypotension, syncope and dizziness.

III. Alpha blockers and ACE inhibitors.

Synergistic hypotensive effects are seen in patients on administration of Alpha blocker with ACE inhibitors. Difference in the effect on blood pressure was observed with Terazosin under different conditions. Tamsulosin did not have any appreciable effects on blood pressure that was already in control by Enalapril. [1]

Clinical evidence:

Severe 'first dose hypertension' was reported in a patient on administration of Bunazosin who is already taking Enalapril. [2]

Retrospective analysis on Terazosin in multinational subjects revealed that-
* Terazosin affected the blood pressure of patients taking ACE inhibitors; if the blood pressure was uncontrolled.
* No significant effect was observed in healthy subjects and in patients with hypertension under control by ACE inhibitors. [3]
* No clinically significant effects were reported on administration of Tamsulosin in patients taking Enalapril. [4]

Mechanism:

First dose effect of Alpha blockers may be exaggerated by ACE inhibitors. Absence of any significant effect in conjunction with Tamsulosin can be attributed to its selectivity for Alpha receptors in the prostate gland.

Conclusions:
* Starting the treatment with an initial low dose of Alpha blocker can significantly lower the incidence of the above stated adverse effects. [1]
* When used in combination with ACE inhibitors, special attention towards reduction of dose of ACE inhibitor (to maintenance level) before giving Alpha blocker is necessary.

References:

1. Stockley's drug interactions, 7th edition; Pharmaceutical press.67-68 [access date: 8th October, 2010]
2. Baba T, Tomiyana T, Takebe K. Enchacement by an ACE inhibitor of first dose hypotension caused by an alpha blocker. N Engl Med (1990) 322,1237 [access date: 8th October, 2010]
3. Kirby RS Terazosin in benign prostatic hyperplasia: effects on blood pressure in normotensive and hepertensive men. Br J Urol (1998) 82, 373-9 [access date: 8th October, 2010]
4. Lowe FC Coadminstration of Tamsulosin and three antihypertensive agents with benign prostatic hyperplasia: pharmacodynamic effect. Clin Ther (1997) 19, 730-42 [access date: 8th October, 2010]

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