Drugs of Choice
None.
Precautions/Interactions
Protection for the head and limbs may be necessary due to headshaking, increased locomotion, and anti‐nociception.
Client Education
LC‐MS/MS may be useful in legal cases.
Prevention/Avoidance
Education trainers and owners about potential issues.
Possible Complications
Musculoskeletal injury due to antinociception.
Sudden death reported in humans.
Expected Course and Prognosis
No reported fatal toxicosis in horses. Effects generally subside after 1 hour.
Abbreviations
See Appendix 1 for a complete list.
Suggested Reading
1 Melchiorri P, Negri L. The dermorphin peptide family. Gen Pharm 1996; 27(7):1099–1107.
2 Negri L, Espamer GF, Severini C, et al. Dermorphin‐related peptides from the skin of Phyllomedusa bicolor and their amidated analogs activate two μ opioid receptor subtypes that modulate antinociception and catalepsy in the rat. Proc Natl Acad Sci 1992; 89: 7203–7207.
3 Negri L, Improta G. Distribution and metabolism of dermorphin in rats. Pharmacol Res Commun 1984; 16(12):1183–1191.
4 Robinson MA, Guan F, McDonnell S., et al., Pharmacokinetics and pharmacodynamics of dermorphin in the horse. J Vet Pharmacol Ther 2015; 38(4):321–329.
Author: Petra Hartmann‐Fischbach, MS, FAORC
Consulting Editor: Dionne Benson, DVM, JD
Chapter 9 Growth Hormone and Secretagogues
Growth hormone (GH) is a protein hormone that is produced in the pituitary gland and is essential to normal growth, development, and overall health of animals.
Recombinant GH, growth hormone‐releasing peptides, or small molecule drugs capable of stimulating the release of GH have been developed or approved as pharmaceutical agents.
Cases may be a result of accidental or illicit use in performance horses.
There are no FDA‐approved GH formulations approved for use in the horse. There are no peptide or small molecule mimetics of GH approved by the FDA for use in the horse.
There are many compounds that are currently undergoing pre‐clinical development or clinical trials.
Illicit formulations of GH and its mimetics are readily available on the internet, primarily directed towards body builders and other performance athletes.
The prevalence of use is unknown, and administrations may be unreported to practitioners due to illicit use.
Mechanism of Action
Natural production:Hormone produced in the anterior pituitary gland which is under the control of either GH stimulatory hormone (+) or somatostatin (–) produced in the hypothalamus.Following release into systemic circulation, GH binds to GH receptors found on target cells.GH has several effects, both directly acting on target tissues and via downstream mediators such as insulin‐like growth factor 1 (IGF‐1).GH increases muscle, bone, and organ growth and increased cellular protein synthesis and intracellular lipolysis.
Recombinant GH:Synthetically produced to mimic the effects of naturally produced GH.FDA has approved recombinant GHs for both human and bovine versions.Equine recombinant GH was developed in the late 1990s and marketed in Australia.
GH‐releasing peptides:Synthetically produced to mimic the effects of GH‐releasing hormone binding to either the GH‐releasing hormone receptor or the GH secretagogue receptor.These may also act as mimetics to the natural hormone ghrelin.Examples include hexarelin, sermorelin, hexarelin, tesamorelin, GHRP 2, GHRP 6, CJC‐1295, CJC‐1295‐DAC.
Small molecule mimetics:Small molecule drugs synthesized to mimic the effects of GH‐releasing peptides.Examples include Ibutamorelin and Anamorelin.
Toxicokinetics
Little is known about onset of action or duration of toxicity for GH.
Recombinant GH:Typical routes of administration are SC or IM injection (8 μg/kg daily) as oral bioavailability is minimal.Variable pharmacokinetics depending on dose/route with Cmax ~ 4 hours post‐dose, ~2 hours terminal half‐life. Cleared by proteolytic digestion and urinary excretion.
GH‐releasing peptides – limited pharmacokinetic information in the horse:Typically dosed via SC or IM administration as oral bioavailability is < 1% for most compounds.Rapid half‐lives < 1 hour except for CJC‐1295‐DAC due to the presence of the drug affinity complex which increases binding to free thiols in blood.Cleared by proteolytic digestion and urinary excretion.
Small molecule mimetics – limited pharmacokinetic information in the horse:Oral bioavailability is good (> 50%), distribution, metabolism and excretion are not well characterized.
Toxicity
Acute – injection site reaction and muscle stiffness. Potential pyrexia. Overdose can result in hypoglycemia followed by hyperglycemia and fluid retention. Acute effects are not fully understood in the horse.
Chronic – acromegaly and gigantism noted in humans and other species. Chronic effects are unknown in the horse.
Systems
