First dose phenomenon

The first dose phenomenon is a sudden and severe fall in blood pressure that can occur when changing from a lying to a standing position the first time that an alpha blocker drug is used [ 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] or when resuming the drug after many months off. [ [http://www.rxlist.com/cgi/generic/teraz_wcp.htm Hytrin (Terazosin Hcl) drug warnings and precautions - prescription drugs and medications at RxList ] ] This postural hypotension usually happens shortly after the first dose is absorbed into the blood and can result in syncope (fainting). Syncope occurs in approximately 1% of 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. [ [http://www.rxlist.com/cgi/generic/prazosin_wcp.htm#W Minipress (Prazosin HCl) drug warnings and precautions - prescription drugs and medications at RxList ] ]

The alpha blocker prazosin is most notorious for producing a first dose phenomenon. Other drugs of the same family, doxazosin (Cardura) and terazosin (Hytrin), can also cause this phenomenon, though less frequently. The cause 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. [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] 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.

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