Page 534 - Adams and Stashak's Lameness in Horses, 7th Edition

500 Chapter 4

In the animal demonstrating renal compromise or Therapy Regarding Matrix Metalloprotease Inhibition
clinical signs of GI ulceration, ketoprofen is indicated Although many practitioners have used tetracyclines
VetBooks.ir toxin effects and lameness 4,57 and a markedly increased in laminitis cases based on the drugs’ reported MMP
due to its reported efficacy in ameliorating both endo-
inhibitory properties, preliminary data from an equine
margin of safety when compared with flunixin or
49
PBZ. Due to the poor response when the drug is only study indicate that doxycycline is a poor inhibitor of
equine MMPs of interest (MMP‐2 and MMP‐9) and
administered BID and the incredible safety of the drug, oxytetracycline inhibits MMPs in vitro but was ineffec-
the BID dosage of ketoprofen can be administered QID tive in treating the disease in a model of laminitis.
33
(2.2 mg/kg IV QID). Since a “peak and trough” analge- Additionally, further studies have decreased the interest
sic effect between ketoprofen dosages has been observed in MMPs as a therapeutic target including (1) a study
in some animals, it may be prudent to administer demonstrating that MMP‐2 and MMP‐9 were neither in
2.2 mg/kg PBZ SID in order to have a more consistent an active state in lamellar extracts from clinical cases of
NSAID effect. laminitis and (2) the inability to block lamellar pathol-
48
Analgesia in the chronic case most commonly con-
sists of PBZ therapy, with long‐term doses usually in ogy with marimastat—a potent broad‐spectrum MMP
inhibitor—in using an experimental model of laminitis
the range of 2.2–4.4 mg/kg/day to avoid complica- (Underwood and Pollitt, personal communication).
tions. An important reason for PBZ’s higher incidence
of toxicity when compared with the other NSAIDs
(almost every reported case of NSAID‐related right Drugs Affecting Blood Flow
dorsal colon ulceration has been due to PBZ) is that
the drug has a longer half‐life and accumulates in the The majority of drugs that have been introduced
tissues to a much greater degree than either flunixin for treatment of possible decreased lamellar blood
or ketoprofen. One way to avoid toxicity in animals flow have been demonstrated to be ineffective in
on long‐term PBZ therapy is to cease administration increasing lamellar blood flow in the horse (i.e. isox-
of the drug for 24 hours once every 5–7 days to allow suprine, pentoxifylline, and nitroglycerin paste). The
clearance of PBZ from the system. If the animals are only drug demonstrated to increase digital blood
too painful to be without an NSAID for 24 hours, flow is the phenothiazine tranquilizer acepromazine,
either ketoprofen or flunixin may be given without which only increases flow for a short period of time
interfering with the clearance of PBZ. Firocoxib has (approximately 30 minutes) when administered
the advantage of once‐a‐day treatment and is much intramuscularly. 45
more protective against GI concerns than PBZ; how-
ever, in the authors’ opinion, it commonly does not Anticoagulant Therapy
provide an adequate amount of analgesia in many
laminitis cases. Although there are data supporting the role of plate-
2
Pentoxifylline is reported to be anti‐inflammatory lets in SRL, there is no consensus on the use of any
3
due to its “anti‐TNF” effect ; preliminary results from a therapies to address this area. There are confounding
study using the carbohydrate model indicate a decreased data from retrospective clinical studies on the efficacy of
incidence of lamellar failure in animals with pentoxifyl- heparin as a prophylaxis in horses at risk of laminitis. 8,13
line therapy initiated at the time of intragastric adminis- Furthermore, experimental treatment with heparin 24
tration of carbohydrate. It is unknown whether the hours after carbohydrate overload (CHO) administra-
17
efficacy is due to inhibition of inflammatory signaling, tion did not ameliorate signs of laminitis or lamellar
50
inhibition of matrix metalloproteases, or any hemor- lesions. One problem with previous heparin studies is
rheologic effect (not likely as requires prolonged therapy that unfractionated heparin was used, which induces
to achieve this effect in other species). Although digital autoagglutination of equine red blood cells and becomes
hypothermia (“cryotherapy”) has been demonstrated to lodged in capillaries (including lamellar capillaries); this
protect the lamellae from structural failure when insti- event may further compromise affected lamellar capil-
tuted at multiple time point in models of SRL (discussed laries in laminitis. Low molecular weight heaparin
below), 18,20,24,25 it has a variable effect on inhibition of (LMWH) may be a valuable alternative because it
inflammatory signaling depending on when it has been does not cause equine RBC autoagglutination and
instituted. 15,16,20 Hypothermia has an inhibitory effect on has recently been reported to reduce the incidence
61
a broad array of inflammatory molecules (multiple and severity of laminitis in postoperative colic cases.
cytokines and chemokines, adhesion molecules, COX‐2) Unfortunately, no further studies have been published
if initiated prior to the administration of a carbohydrate on LMWH in laminitis in the past decade.
24
overload, but a much more focused effect (primarily
IL‐6 and COX‐2) when initiated later in the disease process Analgesic Therapy
(onset of sepsis), and, when instituted at the onset of lame-
16
ness, no consistent anti-inflammatory effect (although still The mainstay of analgesic therapy in laminitis cases is
protective against lamellar failure). Although intrave- still the use of NSAIDs. Whereas PBZ is still the NSAID
15
nous lidocaine infusion, similar to that used for treat- providing the greatest analgesia in the laminitic horse exhib-
ment of ileus in the equine patient, has been proposed as iting digital pain, flunixin meglumine or COX‐2 selective
a treatment to decrease inflammatory signaling in lami- NSAIDs (e.g. firocoxib) may be used if there are ongoing
nitis, no anti‐inflammatory and actually some proin- systemic concerns in which the other NSAIDs may either be
flammatory properties of constant rate intravenous more effective or less harmful (i.e. concomitant renal disease

lidocaine infusion were reported in a laminitis model. 72 or GI ulceration, ongoing endotoxemia).