B
β-Endorphin
Black Walnut
Blood tests
Blood pressure/hypertension
Body Condition Score (BCS)
Bone
P3 Bone changes - osteopenia/osteitis and ski tips
Bromocriptine
Bute - see Phenylbutazone
Black Walnut
Blood tests
Blood pressure/hypertension
Body Condition Score (BCS)
Bone
P3 Bone changes - osteopenia/osteitis and ski tips
Bromocriptine
Bute - see Phenylbutazone
β-Endorphin
β-Endorphin is a POMC-derived peptide hormone produced by the pars intermedia; it is secreted in greater than normal amounts by horses with PPID - horses with PPID were found to have 60 x the plasma β-Endorphin levels of healthy horses (Millington et al. 1988).
β-Endorphin is an endogenous opioid which reduces pain-associated inflammation, has an analgesic effect, stimulates food intake, induces a feeling of euphoria and has been found to affect behaviour, the immune system and vascular tone.
Golynski M, Krumrych W, Lutnicki K
The role of beta-endorphin in horses: a review
Veterinarni Medicina, 56, 2011 (9): 423-429
Millington WR, Dybdal NO, Dawson R Jr, Manzini C, Mueller GP
Equine Cushing's disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary
Endocrinology. 1988 Sep;123(3):1598-604 (PubMed)
"Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels of circulating glucocorticoids inhibit POMC biosynthesis in corticotrophs. Although the i beta-endorphin concentration of the tumors was not different from that in normal tissue, the posttranslational processing of beta-endorphin in the two tissues differed significantly. In controls, beta-endorphin-(1-31) was extensively processed to N-acetyl-beta-endorphin-(1-31), -(1-27), and -(1-26) and des-acetyl beta-endorphin-(1-27). N-Acetyl-beta-endorphin-(1-27) was the predominant form, constituting 57% of the total i beta-endorphin, whereas beta-endorphin-(1-31) was quantitatively minor (less than 7% of the total immunoreactivity. In adenomatous pituitaries, the processing of beta-endorphin was restricted, significantly increasing the proportions of beta-endorphin-(1-31) and N-acetyl-beta-endorphin-(1-31) and lowering the amounts of N-acetyl-beta-endorphin-(1-27) and -(1-26). These changes in peptide processing were associated with markedly reduced levels of dopamine, suggesting that the dopaminergic neurons that normally control intermediate lobe secretion no longer innervate the hyperplastic tissue. These findings are consistent with evidence that the dopaminergic innervation of the intermediate pituitary regulates the posttranslational processing and release of beta-endorphin."
There is a complex relationship between β-endorphin and alpha-MSH:
Endocrinology. 2012 Sep;153(9):4246-55 (PubMed) (Full paper)
β-Endorphin antagonizes the effects of α-MSH on food intake and body weight
Dutia R, Meece K, Dighe S, Kim AJ, Wardlaw SL
"Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake." "This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance."
β-Endorphin is involved in the regulation of pigmentation in the skin.
J Invest Dermatol. 2003 Jun;120(6):1073-80 (PubMed)
Regulation of human epidermal melanocyte biology by beta-endorphin.
Kauser S, Schallreuter KU, Thody AJ, Gummer C, Tobin DJ.
"Functional studies showed that beta-endorphin has potent melanogenic, mitogenic, and dendritogenic effects in cultured epidermal melanocytes deprived of any exogenous supply of pro-opiomelanocortin peptides. Thus, we report that human epidermal melanocytes express a fully functioning beta-endorphin/mu-opiate receptor system. In the absence of any data showing cross-talk between the mu-opiate receptor and the melanocortin-1 receptor, we conclude that the beta-endorphin/mu-opiate receptor system participates in the regulation of skin pigmentation."
Proc Natl Acad Sci U S A. 1979 October; 76(10): 5377–5381.
β-Endorphin: Analgesic and hormonal effects in humans
Foley KM, Kourides IA, Inturrisi CE, Kaiko RF, Zaroulis CG, Posner JB, Houde RW, Hao C
Vitex Agnus Castus has been found to exert a β-Endorphin-like activity.
J Ethnopharmacol. 2006 Jun 30;106(2):216-21. Epub 2006 Jan 24 (PubMed)
Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS
Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ
"VAC acted as an agonist at the mu-opiate receptor"
Phytomedicine. 2000 Oct;7(5):373-81 (PubMed)
Pharmacological activities of Vitex agnus-castus extracts in vitro
Meier B, Berger D, Hoberg E, Sticher O, Schaffner W
"A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL." "While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction."
B-Endorphin edited by Choh Hao Li (1981)
β-Endorphin is an endogenous opioid which reduces pain-associated inflammation, has an analgesic effect, stimulates food intake, induces a feeling of euphoria and has been found to affect behaviour, the immune system and vascular tone.
Golynski M, Krumrych W, Lutnicki K
The role of beta-endorphin in horses: a review
Veterinarni Medicina, 56, 2011 (9): 423-429
Millington WR, Dybdal NO, Dawson R Jr, Manzini C, Mueller GP
Equine Cushing's disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary
Endocrinology. 1988 Sep;123(3):1598-604 (PubMed)
"Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels of circulating glucocorticoids inhibit POMC biosynthesis in corticotrophs. Although the i beta-endorphin concentration of the tumors was not different from that in normal tissue, the posttranslational processing of beta-endorphin in the two tissues differed significantly. In controls, beta-endorphin-(1-31) was extensively processed to N-acetyl-beta-endorphin-(1-31), -(1-27), and -(1-26) and des-acetyl beta-endorphin-(1-27). N-Acetyl-beta-endorphin-(1-27) was the predominant form, constituting 57% of the total i beta-endorphin, whereas beta-endorphin-(1-31) was quantitatively minor (less than 7% of the total immunoreactivity. In adenomatous pituitaries, the processing of beta-endorphin was restricted, significantly increasing the proportions of beta-endorphin-(1-31) and N-acetyl-beta-endorphin-(1-31) and lowering the amounts of N-acetyl-beta-endorphin-(1-27) and -(1-26). These changes in peptide processing were associated with markedly reduced levels of dopamine, suggesting that the dopaminergic neurons that normally control intermediate lobe secretion no longer innervate the hyperplastic tissue. These findings are consistent with evidence that the dopaminergic innervation of the intermediate pituitary regulates the posttranslational processing and release of beta-endorphin."
There is a complex relationship between β-endorphin and alpha-MSH:
Endocrinology. 2012 Sep;153(9):4246-55 (PubMed) (Full paper)
β-Endorphin antagonizes the effects of α-MSH on food intake and body weight
Dutia R, Meece K, Dighe S, Kim AJ, Wardlaw SL
"Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake." "This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance."
β-Endorphin is involved in the regulation of pigmentation in the skin.
J Invest Dermatol. 2003 Jun;120(6):1073-80 (PubMed)
Regulation of human epidermal melanocyte biology by beta-endorphin.
Kauser S, Schallreuter KU, Thody AJ, Gummer C, Tobin DJ.
"Functional studies showed that beta-endorphin has potent melanogenic, mitogenic, and dendritogenic effects in cultured epidermal melanocytes deprived of any exogenous supply of pro-opiomelanocortin peptides. Thus, we report that human epidermal melanocytes express a fully functioning beta-endorphin/mu-opiate receptor system. In the absence of any data showing cross-talk between the mu-opiate receptor and the melanocortin-1 receptor, we conclude that the beta-endorphin/mu-opiate receptor system participates in the regulation of skin pigmentation."
Proc Natl Acad Sci U S A. 1979 October; 76(10): 5377–5381.
β-Endorphin: Analgesic and hormonal effects in humans
Foley KM, Kourides IA, Inturrisi CE, Kaiko RF, Zaroulis CG, Posner JB, Houde RW, Hao C
Vitex Agnus Castus has been found to exert a β-Endorphin-like activity.
J Ethnopharmacol. 2006 Jun 30;106(2):216-21. Epub 2006 Jan 24 (PubMed)
Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS
Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ
"VAC acted as an agonist at the mu-opiate receptor"
Phytomedicine. 2000 Oct;7(5):373-81 (PubMed)
Pharmacological activities of Vitex agnus-castus extracts in vitro
Meier B, Berger D, Hoberg E, Sticher O, Schaffner W
"A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL." "While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction."
B-Endorphin edited by Choh Hao Li (1981)
Black Walnut
Black walnut (Juglans nigra) causes laminitis in horses. The usual cause of laminitis is when shavings or sawdust from black walnut is used for bedding, but pollen and eating the hulls of black walnuts have also been suggested to cause laminitis. Clinical signs of laminitis are usually seen within 1-2 days of exposure to black walnut. Never allow horses access to sawdust or shavings from black walnut wood, or any part of the tree or fruit.
Black Walnut and Butternut Poisoning of Horses - Dr Bob Wright, Todd Leuty, Dr Dan Kenney, www.omafra.gov.on.ca, Dec 2005
Black walnut laminitis cases reported by Illinois Vet School - University of Illinois College of Agriculture, www.thehorse.com, Dec 2007
Black walnut toxicosis in horses: fact or fiction - KER March 2014
Laminitis Caused by Black Walnut Wood Residues - DL Cassens & SB Hooser Purdue University - includes photos of black walnut in shavings.
Inflammation and Apoptosis within the Colon from Horses with Black Walnut Extract-Induced Laminitis
Ludovica Chiavaccini - MSc Thesis 2010
published as:Chiavaccini L, Hassel DM, Shoemaker ML, Charles JB, Belknap JK, Ehrhart EJ
Detection of calprotectin and apoptotic activity within the equine colon from horses with black walnut extract-induced laminitis
Vet Immunol Immunopathol. 2011 Dec 15;144(3-4):366-73
Belknap JK
Black walnut extract: an inflammatory model
Vet Clin North Am Equine Pract. 2010 Apr;26(1):95-101
Thomsen ME, Davis EG, Rush BR
Black walnut induced laminitis
Vet Hum Toxicol. 2000 Feb;42(1):8-11
Blood tests
See
How is PPID diagnosed?
How is Insulin Resistance/EMS diagnosed?
ACTH testing
Glucose
Insulin testing
Leptin
TRH stimulation test
Insulin resistance/Equine Metabolic Syndrome is diagnosed by resting insulin, glucose and leptin blood tests, and/or by dynamic tests e.g. CGIT, OGT/OST.
PPID/Cushing's Disease is diagnosed by resting ACTH (plus insulin and glucose) blood tests. DST is used by some vets but not recommended by The Laminitis Site. The TRH stimulation test measuring ACTH may be useful for borderline/equivocal cases.
Horses with PPID may show a chronic stress white blood cell profile:
Lymphopaenia (normal to decreased absolute lymphocyte count, decreased relative lymphocyte count)
Neutrophilia (increased absolute and relative neutrophil count)
How is PPID diagnosed?
How is Insulin Resistance/EMS diagnosed?
ACTH testing
Glucose
Insulin testing
Leptin
TRH stimulation test
Insulin resistance/Equine Metabolic Syndrome is diagnosed by resting insulin, glucose and leptin blood tests, and/or by dynamic tests e.g. CGIT, OGT/OST.
PPID/Cushing's Disease is diagnosed by resting ACTH (plus insulin and glucose) blood tests. DST is used by some vets but not recommended by The Laminitis Site. The TRH stimulation test measuring ACTH may be useful for borderline/equivocal cases.
Horses with PPID may show a chronic stress white blood cell profile:
Lymphopaenia (normal to decreased absolute lymphocyte count, decreased relative lymphocyte count)
Neutrophilia (increased absolute and relative neutrophil count)
Blood Pressure/Hypertension
Nostell KEA, Lindåse SS, Bröjer JT
Blood pressure in Warmblood horses before and during a euglycemic-hyperinsulinemic clamp
Acta Veterinaria Scandinavica. 2016;58(Suppl 1):65. doi:10.1186/s13028-016-0247-y
Söder J, Bröjer JT, Nostell KEA
Interday variation and effect of transportation on indirect blood pressure measurements, plasma endothelin-1 and serum cortisol in Standardbred and Icelandic horses
Acta Veterinaria Scandinavica 2012, 54:37 (Full)
Body Condition Scoring (BCS)
Body Condition Scoring or Fat Scoring is a method of assessing a horse's fat deposits using your hands and eyes, and is something every owner should carry out on a regular basis, in addition to weighing a horse, to monitor changes in their horse's condition.
There are 2 main methods:
1. The 1- 9 point scale based on the method developed by Henneke et al. (1993), which gives 6 points of fat accumulation on the body a score between 1 and 9.
What is Body Condition Scoring - Spillers Help & Advice
Body Condition Scores - The Henneke System - www.gerlltd.org
Equine Body Condition Score - www.thehorse.com
2. The 0-5 point scale based on the method developed by Carroll and Huntingdon (1988), which divides the horse into 3 sections - neck & shoulders, back and belly, and pelvis to tail and gives each section a score between 0 and 5.
Body condition scoring and cresty neck scoring - Care About Laminitis Project - page 6/7
Body Condition Scoring or Fat Scoring is a method of assessing a horse's fat deposits using your hands and eyes, and is something every owner should carry out on a regular basis, in addition to weighing a horse, to monitor changes in their horse's condition.
There are 2 main methods:
1. The 1- 9 point scale based on the method developed by Henneke et al. (1993), which gives 6 points of fat accumulation on the body a score between 1 and 9.
What is Body Condition Scoring - Spillers Help & Advice
Body Condition Scores - The Henneke System - www.gerlltd.org
Equine Body Condition Score - www.thehorse.com
2. The 0-5 point scale based on the method developed by Carroll and Huntingdon (1988), which divides the horse into 3 sections - neck & shoulders, back and belly, and pelvis to tail and gives each section a score between 0 and 5.
Body condition scoring and cresty neck scoring - Care About Laminitis Project - page 6/7
The Redwings video below shows how to body condition score your horse, using the modified 0-5 point scoring system, by Dr Teresa Hollands - as shown in the October 2013 The Laminitis Revolution 2 webinar. Horses that are too thin, too fat and just right are used to demonstrate how to assess BCS, including a typical underweight PPID horse and a typical overweight EMS/PPID pony.
The body should be divided into 3 sections: neck, middle and bottom, and each section scored separately by feeling for fat over the skeleton. 3 is the perfect score. Body condition scoring should be carried out ideally every 2 weeks on all horses, and the results recorded.
Neck - there shouldn't be any fat or crest above the nuchal ligament - there is no muscle above the nuchal ligament, anything felt here is fat, not top line. A large crest will score 4 or more, bulges and corregation in the crest will probably score 5.
The shoulder blade should be well defined - if you run your hand down the side of the neck, it should come to a stop at the shoulder blade.
Middle - you should be able to feel the ribs, like feeling stair banisters through a velvet curtain, but hardly see them. If you can neither see nor feel the ribs, that scores 4 or more.
If you place your hand over the backbone, it should form a nice curve - a triangle is too thin, flat is too fat.
Bottom - you should be able to feel just feel the top of the pelvis, the hip bone and the tail bone. If you can't see or feel these bones, that scores 4 or more.
In summary, if you can feel AND see bones, the horse is too thin.
If you can neither feel nor see bones, the horse is too fat.
The body should be divided into 3 sections: neck, middle and bottom, and each section scored separately by feeling for fat over the skeleton. 3 is the perfect score. Body condition scoring should be carried out ideally every 2 weeks on all horses, and the results recorded.
Neck - there shouldn't be any fat or crest above the nuchal ligament - there is no muscle above the nuchal ligament, anything felt here is fat, not top line. A large crest will score 4 or more, bulges and corregation in the crest will probably score 5.
The shoulder blade should be well defined - if you run your hand down the side of the neck, it should come to a stop at the shoulder blade.
Middle - you should be able to feel the ribs, like feeling stair banisters through a velvet curtain, but hardly see them. If you can neither see nor feel the ribs, that scores 4 or more.
If you place your hand over the backbone, it should form a nice curve - a triangle is too thin, flat is too fat.
Bottom - you should be able to feel just feel the top of the pelvis, the hip bone and the tail bone. If you can't see or feel these bones, that scores 4 or more.
In summary, if you can feel AND see bones, the horse is too thin.
If you can neither feel nor see bones, the horse is too fat.
Bone
In humans, osteopenia/osteoporosis are associated with Cushing's disease and hypercortisolism, and osteoporosis is a major side effect of glucocorticoid therapy and is attributable to inhibition of bone formation.
According to Harold Schott (Pathogenesis and diagnosis of equine Cushing's disease (Proceedings) Apr 1, 2010), osteoporosis hasn't been specifically investigated in horses with PPID, but horses with PPID have reportedly been euthanized due to pelvic, P3, mandibular and rib fractures.
Is there a link between bone health and PPID and/or hyperinsulinaemia in horses?
If you have or have had a horse with PPID and/or hyperinsulinaemia/Insulin Resistance that has suffered from a fracture or bone problem, please comment on our forum or contact us with details.
Abra Wright MSc Thesis 2009 (page 9)
Pharmacokinetics of Pergolide in normal mares
Studies in other species:J Clin Invest. 2012 Oct 24. pii: 66180. doi: 10.1172/JCI66180. [Epub ahead of print] (PubMed)
New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it
Ferris HA, Kahn CR
"Glucocorticoids are a powerful tool used to treat a range of human illnesses, including autoimmune diseases and cancer, and to prevent rejection following organ transplantation. While lifesaving for many, they come with a steep price, often leading to obesity, insulin resistance, diabetes, and osteoporosis. In this issue of the JCI, Brennan-Speranza and colleagues provide evidence that the osteoblast-derived peptide osteocalcin is one of the drivers of the metabolic derangements associated with glucocorticoid therapy."
J Clin Densitom. 2012 Feb 8. [Epub ahead of print] (PubMed)
Insulin Resistance in Type 2 Diabetes Mellitus May Be Related to Bone Mineral Density.
Arikan S, Tuzcu A, Bahceci M, Ozmen S, Gokalp D.
"Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD."
According to Harold Schott (Pathogenesis and diagnosis of equine Cushing's disease (Proceedings) Apr 1, 2010), osteoporosis hasn't been specifically investigated in horses with PPID, but horses with PPID have reportedly been euthanized due to pelvic, P3, mandibular and rib fractures.
Is there a link between bone health and PPID and/or hyperinsulinaemia in horses?
If you have or have had a horse with PPID and/or hyperinsulinaemia/Insulin Resistance that has suffered from a fracture or bone problem, please comment on our forum or contact us with details.
Abra Wright MSc Thesis 2009 (page 9)
Pharmacokinetics of Pergolide in normal mares
Studies in other species:J Clin Invest. 2012 Oct 24. pii: 66180. doi: 10.1172/JCI66180. [Epub ahead of print] (PubMed)
New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it
Ferris HA, Kahn CR
"Glucocorticoids are a powerful tool used to treat a range of human illnesses, including autoimmune diseases and cancer, and to prevent rejection following organ transplantation. While lifesaving for many, they come with a steep price, often leading to obesity, insulin resistance, diabetes, and osteoporosis. In this issue of the JCI, Brennan-Speranza and colleagues provide evidence that the osteoblast-derived peptide osteocalcin is one of the drivers of the metabolic derangements associated with glucocorticoid therapy."
J Clin Densitom. 2012 Feb 8. [Epub ahead of print] (PubMed)
Insulin Resistance in Type 2 Diabetes Mellitus May Be Related to Bone Mineral Density.
Arikan S, Tuzcu A, Bahceci M, Ozmen S, Gokalp D.
"Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD."
P3 Bone changes - osteopenia/osteitis and ski tips
Bone loss or osteopenia commonly follows uncorrected rotation of P3. As the bone is resorbed, the area available for dermal laminae is reduced, leading to an increasing weakened laminar connection.
Osteopenia can be caused by too little use/chronic non-weightbearing, corticosteroids, vitamin D and calcium deficiencies.
Laminitis Radiology - Chris Pollitt - www.laminitisresearch.org
Pressure between the tip of P3 and the sole/ground causes the tip of the bone to slowly disappear (lyse). Radiographs may show bone remodelling, fractures of the distal margin, osteolysis and osteomyelitis, changes which take several weeks to develop after the onset of laminitis. Chronic laminitis with a mildly increased palmar angle can cause the tip of P3 to remodel and appear ski-tipped on a LM radiograph, with the distal margin appearing ragged due to lysis on a 65 degree DPPD view. With more severe palmar rotation there can be rapid and extensive decalcification of P3. (TLS comment: please note horses frequently recover from 30 degrees of rotation - rotation should be realigned at the earliest opportunity, bone remodelling should then be avoided).
Non-septic Pedal Osteitis
AAEP Vol. 45 1999
Non-septic Pedal Osteitis - A Case of Lameness and a Diagnosis?
Moyer W, O'Brien TR, Walker M
Septic Osteitis
Septic Osteitis - One Laminitis Complication - Christy M West - www.thehorse.com
Distal phalanx: pedal osteitis - septic - Vetstream
Osteopenia can be caused by too little use/chronic non-weightbearing, corticosteroids, vitamin D and calcium deficiencies.
Laminitis Radiology - Chris Pollitt - www.laminitisresearch.org
Pressure between the tip of P3 and the sole/ground causes the tip of the bone to slowly disappear (lyse). Radiographs may show bone remodelling, fractures of the distal margin, osteolysis and osteomyelitis, changes which take several weeks to develop after the onset of laminitis. Chronic laminitis with a mildly increased palmar angle can cause the tip of P3 to remodel and appear ski-tipped on a LM radiograph, with the distal margin appearing ragged due to lysis on a 65 degree DPPD view. With more severe palmar rotation there can be rapid and extensive decalcification of P3. (TLS comment: please note horses frequently recover from 30 degrees of rotation - rotation should be realigned at the earliest opportunity, bone remodelling should then be avoided).
Non-septic Pedal Osteitis
AAEP Vol. 45 1999
Non-septic Pedal Osteitis - A Case of Lameness and a Diagnosis?
Moyer W, O'Brien TR, Walker M
Septic Osteitis
Septic Osteitis - One Laminitis Complication - Christy M West - www.thehorse.com
Distal phalanx: pedal osteitis - septic - Vetstream
Bromocriptine
Bromocriptine is a dopamine agonist, as is pergolide. Research by Beck in 1992 showed it to be effective at treating a pituitary ademona in one 21 year old pony. It has been given orally, intravenously and by subcutaneous injection, at doses ranging from 0.03 to 0.09 mg/kg every 12 hours. Bromocriptine is not readily available commercially, is not well absorbed when given orally and is expensive, therefore pergolide has become the dopamine agonist of choice for treating PPID.
Pergolide (licensed as Prascend) is currently (2017) the only drug licensed to treat PPID in horses. In the UK and the EU, when a veterinary medicine is licensed in that country for that disease in that animal, the licensed medicine must be used - see Cascade Guide for veterinarians if NO authorised medicinal product is available (FVE 2013).
Durham AE
Therapeutics for Equine Endocrine Disorders
Vet Clin North Am Equine Pract. 2017 Apr;33(1):127-139. doi: 10.1016/j.cveq.2016.11.003. Epub 2017 Feb 9
ECIRhorse.org Treatment of PPID:
"The first drug tried in horses with PPID was bromocriptine. Like pergolide, bromocriptine mimics theinhibitory effects of dopamine on the pituitary. It worked, but the problem was it had to be given subcutaneouslyseveral times a day. Oral absorption wasn't reliable."
Pituitary pars intermedia dysfunction: its diagnosis and treatment in horses - Nicola Menzies-Gow www.vettimes.co.uk Jan 2012
See page 17:
Abra Wright MSc Thesis 2009
Pharmacokinetics of Pergolide in normal mares
"Utilizing the theory that replacement of dopamine would suppress POMC peptide production, pergolide and bromocriptine have both been evaluated for the treatment of PPID in horses. Bromocriptine has been administered orally, intravenously, or by subcutaneous injection at a dose of 0.03 to 0.09 mg/kg every 12 hours.38,41 It has been shown to be an effective treatment of PPID; however it is not readily available commercially and appears to have a low bioavailability in the horses.38 For these reasons, pergolide is the most common dopamine agonist used to treat PPID in horses."
Clinical Endocrinology of Companion Animals - Jacquie Rand 2012
Schott HC 2nd
Pituitary pars intermedia dysfunction: equine Cushing's disease
Vet Clin North Am Equine Pract. 2002 Aug;18(2):237-70
Beck DJ
Effective long-term treatment of a suspected pituitary adenoma with bromocriptine mesylate in a pony
Equine Veterinary Education Volume 4, Issue 3, pages 119–122, June 1992
In December [at the end of the seasonal rise] 1985 a 21 year old 160 kg pony presented with chronic laminitis in the front feet, increased breathing rate, a long curly haircoat that hadn't shed the previous summer, PU/PD, hyperhydrosis, it was thin, and had hyperglycaemia (13.32 mmol/L) and glucosuria (27.75 mmol/L). A diagnosis of a pituitary adenoma was made.
5 mg Bromocriptine was injected intra-muscularly twice a day (10 mg/day) for 6 weeks, starting (we deduce) in April and ending mid-May 1986 [the time of year when PPID hormones are at their lowest]. The haircoat started shedding after 10 days' treatment. Laminitic pain and PU/PD subsided. Within 30 days blood and urinary glucose returned to normal levels.
2 months after the treatment ended - mid-July [the start of the seasonal rise] - the feet became painful again and hyperglycaemia and glucosuria returned.
In July/August bromocriptine was given orally as Parlodel, 5 mg twice a day (so 10 mg/day) for 2 weeks. No clinical response was seen [but the seasonal rise may have caused symptoms to worsen despite treatment].
The dose of oral Parlodel was increased to 15 mg twice a day (so 30 mg/day) and the pony kept on this dose from August 1986 until March 1988 - at this oral dose of 30 mg/day [inside and outside of the seasonal rise], clinical response was similar to that seen with 10 mg IM [outside of the seasonal rise]. If attempts were made to decrease the dose, an increase in glucosuria, hyperglycaemia and laminitic pain were seen.
In March 1988 [outside of the seasonal rise] the pony refused to eat oral bromocriptine and treatment returned to intramuscular injections (previous IM injections had led to lymphadenopathy so were discontinued). At 5 mg twice a day IM (so 10 mg/day) the pony responded well with normal blood glucose and urine. Attempts were made to reduce the dose of bromocriptine, but at any dose below 0.875 mg bromocriptine by intra-muscular injection twice a day (so 1.75 mg/day) clinical signs returned.
In Spring 1988 the pony shed more hair than in the previous 2 years, and with additional light therapy started to shed his winter coat in January 1989 at an increased rate to the previous year. At the start of 1989 he was continuing to improve, with his feet realigned, able to trot and canter with no noticeable lameness and graze with his companions. In March 1989 the pony developed a non-weight bearing lameness in his right hind and died. A post mortem was not carried out.
TLS comment: This research is from 1992 and the case study covered the period 1985 to 1989. Our understanding of PPID and its treatment has increased considerably since then.
The pony would appear to have had what we today would consider advanced PPID. It is impossible to say what dose of pergolide treatment might have brought the same effect. Nonetheless, 30 mg of Parlodel for oral treatment might cost ~16 euros or more per day at today's prices, making this an expensive treatment when compared to Prascend (pergolide), costing around 1.10 euros per 1 mg tablet (prices in France).
Bromocriptine is a dopamine agonist, as is pergolide. Research by Beck in 1992 showed it to be effective at treating a pituitary ademona in one 21 year old pony. It has been given orally, intravenously and by subcutaneous injection, at doses ranging from 0.03 to 0.09 mg/kg every 12 hours. Bromocriptine is not readily available commercially, is not well absorbed when given orally and is expensive, therefore pergolide has become the dopamine agonist of choice for treating PPID.
Pergolide (licensed as Prascend) is currently (2017) the only drug licensed to treat PPID in horses. In the UK and the EU, when a veterinary medicine is licensed in that country for that disease in that animal, the licensed medicine must be used - see Cascade Guide for veterinarians if NO authorised medicinal product is available (FVE 2013).
Durham AE
Therapeutics for Equine Endocrine Disorders
Vet Clin North Am Equine Pract. 2017 Apr;33(1):127-139. doi: 10.1016/j.cveq.2016.11.003. Epub 2017 Feb 9
ECIRhorse.org Treatment of PPID:
"The first drug tried in horses with PPID was bromocriptine. Like pergolide, bromocriptine mimics theinhibitory effects of dopamine on the pituitary. It worked, but the problem was it had to be given subcutaneouslyseveral times a day. Oral absorption wasn't reliable."
Pituitary pars intermedia dysfunction: its diagnosis and treatment in horses - Nicola Menzies-Gow www.vettimes.co.uk Jan 2012
See page 17:
Abra Wright MSc Thesis 2009
Pharmacokinetics of Pergolide in normal mares
"Utilizing the theory that replacement of dopamine would suppress POMC peptide production, pergolide and bromocriptine have both been evaluated for the treatment of PPID in horses. Bromocriptine has been administered orally, intravenously, or by subcutaneous injection at a dose of 0.03 to 0.09 mg/kg every 12 hours.38,41 It has been shown to be an effective treatment of PPID; however it is not readily available commercially and appears to have a low bioavailability in the horses.38 For these reasons, pergolide is the most common dopamine agonist used to treat PPID in horses."
Clinical Endocrinology of Companion Animals - Jacquie Rand 2012
Schott HC 2nd
Pituitary pars intermedia dysfunction: equine Cushing's disease
Vet Clin North Am Equine Pract. 2002 Aug;18(2):237-70
Beck DJ
Effective long-term treatment of a suspected pituitary adenoma with bromocriptine mesylate in a pony
Equine Veterinary Education Volume 4, Issue 3, pages 119–122, June 1992
In December [at the end of the seasonal rise] 1985 a 21 year old 160 kg pony presented with chronic laminitis in the front feet, increased breathing rate, a long curly haircoat that hadn't shed the previous summer, PU/PD, hyperhydrosis, it was thin, and had hyperglycaemia (13.32 mmol/L) and glucosuria (27.75 mmol/L). A diagnosis of a pituitary adenoma was made.
5 mg Bromocriptine was injected intra-muscularly twice a day (10 mg/day) for 6 weeks, starting (we deduce) in April and ending mid-May 1986 [the time of year when PPID hormones are at their lowest]. The haircoat started shedding after 10 days' treatment. Laminitic pain and PU/PD subsided. Within 30 days blood and urinary glucose returned to normal levels.
2 months after the treatment ended - mid-July [the start of the seasonal rise] - the feet became painful again and hyperglycaemia and glucosuria returned.
In July/August bromocriptine was given orally as Parlodel, 5 mg twice a day (so 10 mg/day) for 2 weeks. No clinical response was seen [but the seasonal rise may have caused symptoms to worsen despite treatment].
The dose of oral Parlodel was increased to 15 mg twice a day (so 30 mg/day) and the pony kept on this dose from August 1986 until March 1988 - at this oral dose of 30 mg/day [inside and outside of the seasonal rise], clinical response was similar to that seen with 10 mg IM [outside of the seasonal rise]. If attempts were made to decrease the dose, an increase in glucosuria, hyperglycaemia and laminitic pain were seen.
In March 1988 [outside of the seasonal rise] the pony refused to eat oral bromocriptine and treatment returned to intramuscular injections (previous IM injections had led to lymphadenopathy so were discontinued). At 5 mg twice a day IM (so 10 mg/day) the pony responded well with normal blood glucose and urine. Attempts were made to reduce the dose of bromocriptine, but at any dose below 0.875 mg bromocriptine by intra-muscular injection twice a day (so 1.75 mg/day) clinical signs returned.
In Spring 1988 the pony shed more hair than in the previous 2 years, and with additional light therapy started to shed his winter coat in January 1989 at an increased rate to the previous year. At the start of 1989 he was continuing to improve, with his feet realigned, able to trot and canter with no noticeable lameness and graze with his companions. In March 1989 the pony developed a non-weight bearing lameness in his right hind and died. A post mortem was not carried out.
TLS comment: This research is from 1992 and the case study covered the period 1985 to 1989. Our understanding of PPID and its treatment has increased considerably since then.
The pony would appear to have had what we today would consider advanced PPID. It is impossible to say what dose of pergolide treatment might have brought the same effect. Nonetheless, 30 mg of Parlodel for oral treatment might cost ~16 euros or more per day at today's prices, making this an expensive treatment when compared to Prascend (pergolide), costing around 1.10 euros per 1 mg tablet (prices in France).