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Comparative effects of phenylbutazone, naproxen and flunixin meglumine on equine platelet aggregation and platelet factor 3 availability in vitro.

Abstract: Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10(-6) M significantly depressed the maximum degree of adenosine diphosphate-induced (10(-6)M) aggregation while much higher concentrations of phenylbutazone and naproxen (5 X 10(5)M) were required to produce similar effects. None of the non-steriodal anti-inflammatory drugs significantly affected the duration of the lag phase or the initial velocity of adenosine diphosphate-induced aggregation within the range of drug concentrations used (10(-6)-10(-3)M). The lag phase and initial velocity of acid-soluble collagen-induced aggregation were significantly affected by 10(-6) M flunixin and 10(-4) M phenylbutazone or naproxen was required to produce equivalent effects. Concentrations of 5 X 10(-6) M flunixin and 5 X 10(-4) M phenylbutazone or naproxen were required to significantly depress the degree of collaen-induced aggregation of horse platelets. Although the effects of the nonsteroidal anti-inflammatory drugs were qualitatively similar, flunixin was a much more potent inhibitor of platelet aggregation than either of the other two drugs (which were equipotent). At very high drug concentrations (5 X 10(-4) M and greater), all three drugs produced the same degree of inhibition of equine platelet aggregation. Platelet factor 3 activity was made available by exposing horse platelets to 10(-5) M adenosine diphosphate or 1:800 acid-soluble collagen; but not by exposure to a suspension of kaolin particles. Only a small portion of the total platelet factor 3 activity was made available on stimulation with either adenosine diphosphate or collagen. Pretreatment of horse platelets with any of the nonsteroidal anti-inflammatory drugs (10(-4) M concentration) had no significant effect on adenosine diphosphate or collagen-induced platelet factor 3 availability.
Publication Date: 1983-04-01 PubMed ID: 6883184PubMed Central: PMC1235914
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates the effects of three different nonsteroidal anti-inflammatory drugs (NSAIDs)- phenylbutazone, naproxen, and flunixin meglumine, on horse platelet functionality, particularly their ability to aggregate and activate platelet factor 3, a procoagulant activity. Flunixin demonstrated a higher potency than the other two drugs, although high concentrations of all three showed similar inhibition of platelet aggregation. No significant effect was found on platelet factor 3 activity after pretreatment with any of these NSAIDs.

Understanding the Research

  • The study revolves around the comparative analysis of three nonsteroidal anti-inflammatory drugs (NSAIDs) namely phenylbutazone, naproxen (equiproxen) and flunixin meglumine(banamine) and their influence on the functions of equine (horse) platelets. The NSAIDs were tested for effects on two main responses of horse platelets: their ability to join together forming a cluster (aggregating) and their capacity to release platelet factor 3 procoagulant activity (a factor involved in blood clotting).
  • In the experiments performed, flunixin showcased significantly greater efficacy in depressing the maximum degree of platelet aggregation induced by adenosine diphosphate at a concentration of 10(-6) M whereas comparatively higher concentrations (5 x 10(5) M )of phenylbutazone and naproxen were required for similar outcomes.
  • The three NSAIDs displayed no significant impact on the duration of the lag phase or the initial velocity of adenosine diphosphate-induced aggregation. However, the lag phase and initial velocity of collagen-induced aggregation were significantly affected by flunixin at 10(-6) M, while phenylbutazone and naproxen required a much higher concentration of 10(-4) M to achieve the same, indicating that flunixin was noticeably more potent in comparison.
  • At extremely high drug concentrations (5 X 10(-4) M and greater), all three drugs i.e., phenylbutazone, naproxen and flunixin, exhibited an equivalent degree of inhibition of equine platelet aggregation.

The Activity of Platelet Factor 3

  • This research also discussed platelet factor 3, a phospholipid that aids in forming blood clots or coagulation. This activity presented when exposed to adenosine diphosphate or collagen but not kaolin particles. However, only a minor portion of total platelet factor 3 activity was available in these cases.
  • The application of the NSAIDs in question (at 10(-4) M concentration) followed by exposing to adenosine diphosphate or collagen didn’t significantly affect the platelet factor 3 availability, indicating that these NSAIDs had minimal influence on modulating the platelet factor 3 procoagulant activity in the horse platelets.

Cite This Article

APA
Johnstone IB. (1983). Comparative effects of phenylbutazone, naproxen and flunixin meglumine on equine platelet aggregation and platelet factor 3 availability in vitro. Can J Comp Med, 47(2), 172-179.

Publication

ISSN: 0008-4050
NlmUniqueID: 0151747
Country: Canada
Language: English
Volume: 47
Issue: 2
Pages: 172-179

Researcher Affiliations

Johnstone, I B

    MeSH Terms

    • Adenosine Diphosphate / physiology
    • Animals
    • Blood Coagulation Factors / physiology
    • Blood Platelets / analysis
    • Blood Platelets / physiology
    • Clonixin / analogs & derivatives
    • Clonixin / pharmacology
    • Collagen / physiology
    • Horses / blood
    • Humans
    • In Vitro Techniques
    • Naproxen / pharmacology
    • Nicotinic Acids / pharmacology
    • Phenylbutazone / pharmacology
    • Platelet Aggregation / drug effects
    • Platelet Factor 3 / analysis
    • Platelet Factor 3 / physiology

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