Use of a New Vasodilator Agent in Management of Peripheral Arterial Insufficiency

Samuels, Saul S.; Shaftel, Herbert E.

doi:10.1097/00043764-196008000-00045

Cited by 3 publications

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“…In man, isoxsuprine has been used to treat night cramps, intermittent lameness and various vasospastic states, with con- Samuels and Shaffel (1959) reported good results in the treatment of intermittent claudication and Coffman (1968) demonstrated an increase in calf muscle blood flow after oral isoxsuprine administration. However, when used to treat patients with arteriosclerosis obliterans, controlled studies showed that there was little effect obtained from isoxsuprine administration (Strandness 1970;Coffman and Mannick 1972).…”

Section: Discussionmentioning

confidence: 99%

Studies on isoxsuprine hydrochloride for the treatment of navicular disease

Rose

Allen

Hodgson

et al. 1983

Equine Veterinary Journal

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Summary A peripheral vasodilating agent, isoxsuprine hydrochloride, administered as an oral paste, was evaluated to determine its efficacy for the treatment of navicular disease. In a clinical trial, 13 horses with navicular disease were treated at a dose rate of 0.6 mg/kg body weight (bwt) twice daily for periods of six to 14 weeks. Twelve of the horses became completely sound while being treated, although two required a 50 per cent increase in dose. Nine of the horses have remained sound two to 10 months after ceasing therapy. In a controlled randomised double blind clinical trial, 16 horses with navicular disease were assigned to treatment with either a placebo paste or isoxsuprine paste for three weeks and then re‐examined. All the horses treated with isoxsuprine showed improvement in gait, with seven of eight horses becoming sound, whereas only two horses treated with a placebo paste showed slight improvement. This difference in response was highly significant (P<0.001). To evalulate any physiological and biochemical effects of isoxsuprine, it was administered to five Standardbred geldings at dose rates of 0.6 mg/kg bwt and 1.2 mg/kg bwt. Complete blood counts, routine plasma biochemical parameters, cardinal signs and blood pressure measurements were performed up to 24 h after a single dose. No significant change in any of these parameters was found. To assess the peripheral vasodilatory action of isoxsuprine, infra‐red thermography of the lower limb was performed before and up to 8 h after administration to horses. This revealed a significant increase in distal limb temperature which occurred from 90 to 480 mins after isoxsuprine administration. The maximum mean increase in distal limb temperature was 3.1°C and this occurred 4 h after administration of the drug. Résumé On s'est efforcé d'evaluer l'efficacité dans le traitement de la maladie naviculaire d'un vasodilateur périphérique, le chlorhydrate d'isoxsuprine administré en pâte orale. Treize chevaux atteints de maladie naviculaire ont été traités lors d'une épreuve clinique à la dose de 0.6 mg/kg de poids vif, deux fois par jour durant 6 à 14 semaines. Douze de ces chevaux montrèrent une complète guérson fonctionnelle durant le traitement avec pour deux d'entre eux la nécessité d'augmenter la posologie de 50 pour cent. Neuf de ces animaux sont restés utilisables durant une période variant de 2 à 10 mois après la cessation du traitement. Lors d'une épreuve de contrôle, 16 chevaux atteints de maladie naviculaire recurent un traitement sous forme d'un placebo ou d'isoxsuprine en pâte durant 3 semaines et furent ensuite réexaminés. Tous les chevaux traités à l'isoxsuprine montrèrent une amélioration de leurs allures, 7 d'entre eux étant normaux; tandis que deux chevaux traités par placebo montrèrent une amélioration légère. La différence entre les résponses était très significative (P<0.001). Pour évaluer les effets physiologiques et biochimique de l'isoxsuprine, on l'administra à 5 chevaux hongres aux posologies de 0.6 mg et 1.2 mg/kg. Les hémogrammes comp...

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Section: Discussionmentioning

confidence: 99%

Studies on isoxsuprine hydrochloride for the treatment of navicular disease

Rose

Allen

Hodgson

et al. 1983

Equine Veterinary Journal

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“…This has been stated to decrease the total peripheral resistance without a significant drop in blood pressure in therapeutic doses (18). There is an increase in peripheral blood flow (19) which prevents stasis and occluding thrombosis; thus explaining better tissue survival in cold injury with isoxsuprine hydrochloride therapy.…”

Section: Discussionmentioning

confidence: 99%

Isoxsuprine Hydrochloride in Cold Injury

1967

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“…A dosage of 0.25 mg/kg administered orally every 12 h for 3 days, then increased to 0.6 mg/kg on the fourth day yielded maximum plasma isoxsuprine concentrations of about 5 ng/mL 15 min after the last dose. Concentration of the isoxsuprine metabolite increased rapidly to a maximum of around 500 ng/mL in 2 h. Oral bioavailability in horses was determined to be only 2.2% (Joujou‐Sisic et al ., 1996), whereas, oral isoxsuprine is rapidly and completely absorbed from the gastrointestinal tract in humans (Samuels & Shaftel, 1959). Rapid conjugation of isoxsuprine to its conjugated metabolite by the liver may explain the low bioavailability.…”

Section: Pharmacokinetics/pharmacodynamicsmentioning

confidence: 99%

“…It is a member of the β ‐phenylethylamine group of epinephrine‐like compounds with structural similarities to epinephrine (Moed & van Dijk, 1956) and papaverine, a spasmolytic drug (Menard, 1984). Isoxsuprine is vasodilatory (Samuels & Shaftel, 1959; Baxter et al ., 1989; Galey et al ., 1989; Belloli et al ., 2000), decreases blood viscosity (DiPerri et al ., 1978; Weber et al ., 1980; Suda et al ., 1981; Aarts et al ., 1986) and inhibits platelet aggregation (Weber et al ., 1980; Aarts et al ., 1984). It has been used for the treatment of peripheral arterial (Samuels & Shaftel, 1959; DiPerri et al ., 1978; Weber et al ., 1980; Aarts et al ., 1986) and cerebral vascular insufficiency (Cook & James, 1981) in humans, and as a tocolytic agent for the inhibition of premature labor in both humans and animals (Menard, 1984; Hendricks et al ., 1961).…”

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confidence: 99%

Isoxsuprine hydrochloride in the horse: a review

Erkert

MacAllister

2002

Vet Pharm & Therapeutics

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Isoxsuprine hydrochloride has been suggested for use in horses for treatment of navicular syndrome and laminitis. The drug has been shown to be a beta-adrenoreceptor antagonist with beta-adrenoreceptor agonistic properties, with both characteristics contributing to vasodilation and uterine relaxation. In addition, the drug is capable of decreasing blood viscosity and platelet aggregation. Studies have shown i.v. isoxsuprine to have a plasma half-life of <3 h with a large apparent volume of distribution. Cardiovascular effects resolve rapidly following i.v. administration, but are absent with oral dosing. Oral bioavailability is 2.2% with a high first pass effect. Isoxsuprine has an apparent affinity for melanin that may contribute to extended renal excretion. Clinical trials appear to support the use of isoxsuprine for treatment of navicular disease. However, poor bioavailability, lack of cardiovascular effects following oral administration, superficial support in clinical trials, and new evidence regarding the pathogenesis of navicular syndrome indicate that the use of isoxsuprine for treatment of navicular syndrome or laminitis is questionable at best.

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Use of a New Vasodilator Agent in Management of Peripheral Arterial Insufficiency

Cited by 3 publications

References 0 publications

Studies on isoxsuprine hydrochloride for the treatment of navicular disease

Studies on isoxsuprine hydrochloride for the treatment of navicular disease

Isoxsuprine Hydrochloride in Cold Injury

Isoxsuprine hydrochloride in the horse: a review

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