Character and duration of pharmacological effects of intravenous isoxsuprine

Abstract

Summary Isoxsuprine is a therapeutic medication used to treat navicular disease and other lower limb problems in horses and is one of the more frequently detected therapeutic agents in racing horses. In a crossover study, horses were administered isoxsuprine i.v. to determine the character and duration of its pharmacological effects. Isoxsuprine significantly increased heart rate 5–150 min following injection. Unrestrained activity following isoxsuprine treatment was significantly greater than control activity for 105 min after treatment. There was an apparent, although statistically nonsignificant, increased cutaneous blood flow resulting in visible water vapour and sweat production 5–60 min after administration. Initially, there was no difference in skin temperature between control and isoxsuprine treatment values; however, skin temperature decreased below control values 45–120 min after injection. Concurrently, there was a significant decrease in rectal temperature reflecting a decrease in body core temperature. Using infrared thermography, a significant decrease in superficial skin temperature of the front legs occurred 30–240 min after treatment. Isoxsuprine also reduced smooth muscle tone, which was apparent by decreased tone of the internal anal sphincter 10–180 min after treatment. It was concluded that the measurable pharmacological effects of i.v. isoxsuprine are short lived, since none of the above responses were apparent 4 h or more after i.v. administration.

An Analgesic Evaluation of Isoxsuprine in Horses

“…It was beyond the scope of this trial to evaluate these parameters, but they most certainly would have been in between to those reported by Matthews et al. (1986) and Harkins et al. (1996).…”

“…The biological activity of the resulting metabolites – isoxsuprine‐glucuronide and isoxsuprine‐glucuronide‐dipotassium (Bosken et al., 2000) – has not been evaluated, but it is highly likely that their effects might be insignificant, at least cardiovascularly. This is because intravenous, but not oral, administration of isoxsuprine produces a transient decrease in systemic blood pressure, systemic vascular resistance and stroke volume, as well as a transit increase in heart rate and cardiac output (Matthews et al., 1986; Harkins et al., 1996, 1998). It was beyond the scope of this trial to evaluate these parameters, but they most certainly would have been in between to those reported by Matthews et al.…”

“…However, oral and intravenous administration of isoxsuprine did not modify digital or laminar blood flow in healthy horses (Adair et al., 1997; Ingle‐Fehr and Baxter, 1999). Harkins et al. (1996) reported diminished thermographic temperature of the forelimbs with a tendency, but with no significant difference, to increase cutaneous blood flow in the pastern of horses given isoxsuprine intravenously.…”

Equine sweating and anhidrosis Part 1 – equine sweating

“…Isoxsuprine is predominantly a β 2 agonist but has also been described as an α‐receptor antagonist, thereby explaining its peripheral vasodilatatory effect 111 . However, this is in contrast to the findings of Harkins and Tobin, 110 who demonstrated that isoxsuprine given orally had little effect on heart rate, sweat output, or vascular tone, whereas intravenous administration caused an increase in heart rate, cutaneous blood flow, sweat output and vascular tone, but that these effects were short lived. This finding is supported by another study, which showed that isoxsuprine given orally had no effect on sweating 112 …”

“…The onset of sweating correlates with cutaneous blood flow. Intravenous injection of isoxsuprine, a vasodilator drug used in horses for lower limb problems, produces an increase in sweat production and cutaneous blood flow to the pastern, whereas controls produce neither 110 . Isoxsuprine is predominantly a β 2 agonist but has also been described as an α‐receptor antagonist, thereby explaining its peripheral vasodilatatory effect 111 .…”