First dose phenomenon

Prazosin, an alpha₁ selective adrenoceptor blocking drug (also known as alpha₁ adrenergic antagonist) is used to lower high blood pressure, but in some patients, it can cause a sudden and severe fall in blood pressure when changing from a lying to a standing position the first time the drug is used. ^[1], or reuse it after not taking it for months.^[2] However, long term use of this alpha blocker causes relatively little postural hypotension. This usually happens shortly after the first dose is absorbed into blood. The incidence of such syncope is approximately 1% in patients given an initial dose of 2mg or greater. This adverse effect is self-limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration.^[3]

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The cause of this phenomenon is not clear. It occurs more commonly in patients who are salt and fluid volume depleted (as happens due to the use of diuretics), or were using beta blockers.^[4] Diuretics and beta blockers are frequently used to control hypertension. For this reason, treatment with prazosin (Minipress) should always be initiated with a low dose and should be taken at bedtime to avoid standing position.

Other drugs of the same family, doxazosin (Cardura) and terazosin (Hytrin), can also cause this phenomenon, though less frequently.

References

1. ^ Prazosin: the first-dose phenomenon. Graham RM, Thornell IR, Gain JM, Bagnoli C, Oates HF, Stokes GS. Br Med J. 1976 Nov 27;2(6047):1293-4. PMID 793676
2. ^ http://www.rxlist.com/cgi/generic/teraz_wcp.htm
3. ^ http://www.rxlist.com/cgi/generic/prazosin_wcp.htm#W
4. ^ Immediate cardiovascular responses to oral prazosin--effects of concurrent beta-blockers. Elliott HL, McLean K, Sumner DJ, Meredith PA, Reid JL. Clin Pharmacol Ther. 1981 Mar;29(3):303-9. PMID 6110503