Evaluation of the risk for drug-induced postural hypotension in an experimental model: investigations with carvedilol, prazosin, labetalol, and guanethidine.
Postural hypotension is a common side effect observed in the treatment of hypertension with various drugs. Carvedilol, a vasodilating beta-blocker, was compared with prazosin, labetalol, and guanethidine for its ability to induce orthostatic hypotension. The comparison was carried out using doses of the drugs required to lower baroreceptor reflex hypertension in anesthetized rabbits by 30 mm Hg (ED -30 mm Hg). The following doses were found in independent investigations to be equipotent in this rabbit model: ED -30 mm Hg (mg/kg i.v.): prazosin = 0.03; labetalol = 1.8; guanethidine = 0.12; carvedilol = 0.12. These doses did not markedly inhibit the orthostatic reaction in rabbits after tilting stress, so 10-fold higher doses were used and clear discrimination between the drugs was found. The orthostatic index was reduced after prazosin and labetalol by about 24%, after guanethidine by about 30%, and after carvedilol by about 13%. The 50-fold dose of carvedilol (6 mg/kg i.v.) does not lead to any greater inhibition of the orthostatic index. From these results it is concluded that a relatively lower risk of postural hypotension is to be expected after carvedilol treatment than with the other drugs presented here. Furthermore, these results do not provide any indication that carvedilol exerts its vasodilator properties via alpha-blockade.
Bartsch
W
W
Department of Experimental Cardiovascular Research, Boehringer Mannheim GmbH, F.R.G.
Sponer
G
G
Strein
K
K
Böhm
E
E
Hooper
R G
RG
D000818:Animals; D001794:Blood Pressure; D002227:Carbazoles / Q000009:adverse effects*; D000077261:Carvedilol; D004195:Disease Models, Animal; D006145:Guanethidine / Q000009:adverse effects; D007024:Hypotension, Orthostatic / Q000139:chemically induced* / Q000503:physiopathology; D007741:Labetalol / Q000009:adverse effects; D011224:Prazosin / Q000009:adverse effects; D011412:Propanolamines / Q000009:adverse effects*; D011817:Rabbits; D012306:Risk; D014665:Vasodilator Agents / Q000009:adverse effects*
D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D007741:Labetalol; D011224:Prazosin; D006145:Guanethidine