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Clinical Pharmacology > Equine Endocrine > Flashcards

Equine Endocrine Flashcards

1
Q

Picture of Equine Metabolic Syndrome

A
  • Overweight
  • “Easy keeper”
  • History of laminitis
  • Regional adiposity
  • Especially “cresty” neck
  • Resting insulin and glucose levels: insulin is elevated and glucose is high
  • Oral glucose absorption test was positive
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2
Q

Treating EMD

A
  • Diet and exercise

- Can also use levothyroxine and metformin

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3
Q

Biologically active thyroid hormones

A
  • 2 biologically active hormones: thyroxine (T4) and 3,5,3-triiodothyronine (T3)
  • Plus reverse triiodothyronine rT3
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4
Q

What controls T4, T3, and Reverse T3?

A
  • Thyroid stimulating hormone or TSH

- Work via feedback system to keep metabolism in homeostasis

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5
Q

T3 and T4 metabolic effects

A
  • Increase concentrations of ATP
  • Increase metabolism
  • Increase HR
  • Increase GI motility
  • Increase sensitivity to catecholamines and increases sympathetic tone
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6
Q

Site of release of thyroid releasing hormone

A
  • Hypothalamus
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7
Q

Action of TRH

A
  • causes release of Thyroid stimulating hormone TSH
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8
Q

Things that cause negative feedback for TRH

A
  • T3, T4
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9
Q

TSH site of release

A
  • Anterior pituitary lobe
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10
Q

Action of TSH

A
  • Causes release of T3 and T4
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11
Q

Levothyroxine (for horses)

A
  • Manufactured form of T4

- Used typically to treat hypothyroidism in other species, but it’s very rare in horses

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12
Q

Mechanism of action of Levothyroxine

A
  • Synthetic form of thyroxine
  • Converted to T3
  • T3 and T4 bind to thyroid receptor proteins in the cell nucleus
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13
Q

What causes the metabolic effects of levothyroxine?

A
  • Metabolic effects caused by control of DNA transcription and protein synthesis
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14
Q

Effect of Levothyroxine for EMS horses

A
  • Accelerates weight loss with horses on a controlled diet (NEED TO BE ON A CONTROLLED DIET TOO)
  • Increases metabolic rate
  • Increases insulin sensitivity
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15
Q

Dosing of Levothyroxine

A
  • Usually once a day dosing

- Mild state of hyperthyroidism induced

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16
Q

How long should EMS horses be on levothyroxine?

A
  • 3-6 months only

- Then slowly weaned off

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17
Q

Side effects of levothyroxine

A
  • Not described at listed doses
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18
Q

Metformin use

A
  • Used in human diabetes mellitus type II

- Decreases amount of glucose produced by liver (gluconeogenesis) and reduces glucose absorption from the intestine

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19
Q

Metformin in horses

A
  • Controversial due to absorption and bioavailability
  • No real change of glucose absorption in some studies depending on dose
  • Decreased intestinal absorption of glucose and limits post prandial insulin concentrations
  • Used for EMS to help decrease weight
20
Q

Dosing frequency and dose timing of metformin

A
  • Give 30-60 minutes prior to feeding

- 2-3 times a day

21
Q

Monitoring for Metformin

A
  • Check insulin concentrations 2 hrs post-feeding before and 7 days after initiating metformin
  • Doesn’t always work
22
Q

Problems with metformin

A
  • Expensive: $2000 a year!
  • No long term studies in horse
  • No FDA approval
23
Q

Side effects of metformin (people only)

A
  • Lactic acidosis - rhabdomyolysis
  • GI pain
  • Interferes with thyroid medication
24
Q

Sodium Glucose Co- transporter 2 (SGLT2) Inhibitor Use in humans

A
  • FDA approved in humans for use with diet and exercise to lower blood glucose in adults with diabetes mellitus Type 2
  • SGLT2 inhibitors lower blood glucose by causing diuresis through the kidneys
25
Q

SGLT2 effect in horses

A
  • Glucose loss through kidneys
  • Weight decrease
  • Blood pressure decrease
  • Used for EMS in conjunction with diet changes
26
Q

Side effects of SGLT2 in humans

A
  • Ketoacidosis

- Mild genital infections

27
Q

Canagliflozin and Velagliflozin

A
  • Experimentally used in horses with EMS

- Decreased insulin concentrations

28
Q

Canagliflozin and velagliflozin adverse effects

A
  • None reported so far, but more research should be done
29
Q

Drugs used to aid EMS therapy

A
  • Levothyroxine
  • Metformin
  • SGLT2 inhibitor
  • Canagliflozin and Velagliflozin
30
Q

PPID characteristics

A
  • mild nasal discharge
  • Hair coat still long and patchy
  • Digital pulses within normal limits and TPR WNL
31
Q

Pituitary Pars Intermedia Dysfunction Overview

A
  • Dysfunction of the intermediate lobe of the pituitary causes the disease
  • Typically in horses <14 years of age
  • Problem is lack of dopamine
32
Q

PPID Dopamine

A
  • Dopamine normally decreases/regulates hormones release from the intermediate lobe of the pituitary
  • If not enough dopamine, hormones released without check and balance
33
Q

Hormones that get out of whack in PPID due to lack of dopamine

A
  • Proopiomelanicortin –> ACTH –> ACTH, alphaMSH, Corticotropin-like intermediate peptide (CLIP), endorphins
34
Q

Diagnosis of PPID

A
  • Endogenous ACTH concentrations

- Thyrotropin releasing hormone stimulation test

35
Q

Endogenous ACTH

A
  • works well in horses with clinical PPID
  • Not always accurate in early stages
  • ACTH and Cortisol are pulsatile all day
  • Also increase in late summer/fall inreparation for winter
36
Q

Thyrotropin Releasing Hormone Stimulation Test

A
  • TRH causes intermediate lobe of the pituitary to increase production of ACTH
  • Especially useful in horses in the early stage of disease
  • PPID horses will have a major increase
  • If you get an increase greater than 100-110 then it definitely has PPID
37
Q

Primary treatment for PPID

A
  • Prascend (AKA Pergolide)
38
Q

Prascend MOA

A
  • Synthetic ergot derivative
  • Long acting dopamine receptor agonist
  • Doesn’t affect norepinephrine, epinephrine, or serotonin pathways
  • Inhibits release of prolactin
  • Stimulates dopamine receptors
  • Inhibits production of POMC, ACTH, MSH
39
Q

Prascend precautions

A
  • Use caution in breeding animals
  • pregnant or lactating mares
  • May interfere with reproductive functions
40
Q

Side effects of Prascend

A
  • Sweating
  • Inappetence
  • Transient anorexia
  • Lethargy
  • Mild CNS signs (possible, not often)
  • Colic
  • Diarrhea
41
Q

Monitoring for Prascend

A
  • Recheck ACTH concentrations in 4-6 weeks
  • Much depends upon improvement of clinical signs
  • If improvement, don’t increase dose
  • If no improvement, increase dose
42
Q

Cyproheptadine Indication

A
  • Use for horses with PPID
43
Q

Cyproheptadine MOA

A
  • Serotonin (5-HT) receptor block agent
  • Serotonin stimulates intermediate lobe of the pituitary
  • Exactly why it works is unclear
  • Serotonin not primary stimulator of PID
44
Q

Cyproheptadine Use

A
  • Used with pergolide to help with clinical signs of PPID

- Typically used when you reach a maximum dose for Prascend

45
Q

Route for cyproheptadine

A
  • Oral medication
46
Q

Side effects of cyproheptadine

A
  • sedation
  • Dry mucous membranes
  • Tachycardia

Clinical Pharmacology (7 decks)

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