Tiodazosin, a new antihypertensive, resembles prazosin in structure and alpha-adrenergic-blocking activity, and it also exerts a direct vasodilator effect. We evaluated its long-term hemodynamic and systemic effects in patients with essential hypertension. Our data show that after 10 wk of therapy with tiodazosin, 7 of our 10 patients had significant reduction in intra-arterial mean blood pressure as a result of a fall in systemic vascular resistance. Heart rate, cardiac output, and plasma volume did not change. Systemic effects were minor and included a gain in weight and a reduction in hemoglobin, hematocrit, platelet count, serum protein, albumin, bilirubin, and specific gravity of urine. No patient initially developed orthostatic symptoms after the first dose, but there were transient episodes of light-headedness in three patients, palpitations in two, increased urinary frequency in one, and drooping of eyelid in another during the trial period. One patient developed profound orthostatic hypotension, which could be attributed to the drug. Because of such side effects and the failure to lower blood pressure in 30% of patients with essential hypertension, tiodazosin appears to have several important drawbacks and little advantage over currently available antihypertensives.
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http://dx.doi.org/10.1038/clpt.1983.170 | DOI Listing |
J Pharm Pharmacol
August 1991
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
The pharmacological activity of three alpha 1-adrenergic antagonists, prazosin, tiodazosin and WB4101 has been studied in the presence and absence of 20 microM alpha 1-acid glycoprotein (AAG) in rabbit aortic strips, and measured as the ability to increase the EC50 value of the alpha 1-adrenergic agonist phenylephrine. For all three drugs, the presence of AAG diminished the pharmacological activity when compared with equivalent unbound concentrations in the absence of AAG. In the presence of AAG the EC50 value of phenylephrine at 5.
View Article and Find Full Text PDFProg Clin Biol Res
October 1989
Department of Pharmacy, University of California, San Francisco 94143-0446.
Prior reports by Dr. Bond [1] have described the occurrence of an initial compensatory vasoconstriction followed by a decompensatory vasodilation response in animals that progress to irreversible shock induced by blood loss. Further analysis suggests that the secondary vascular decompensation is the result of sympathetic inhibition of adrenergic neurotransmission.
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