Steroids

Question 1

1. If cortisol secretion in the dog is 1 mg/kg/day and prednisolone is 5X as potent as cortisol, give the doses for: a) replacement therapy b) anti‐inflammatory therapy c) immune suppression.

Answer 1

• Replacement therapy = 0.2 mg/kg/day
• Anti-inflammatory therapy = 1mg/kg/day
• Immune suppression = 3 mg/kg/day

Question 2

2. How do the glucocorticoid requirements of an Addisonian patient increase during stressful situations?

Answer 2

• Animals will need supplemental glucocorticoids beyond maintenance doses in times of stress
o Give 3x dose if boarding/groomer/company
o Because they do NOT have the Pituitary-Adrenal Axis, so you must act as that axis for them

Question 3

3. What criteria are used to make dosage adjustments in Addison’s for the
   • Mineralocorticoid
   • Glucocorticoid

Answer 3

• Mineralocorticoid = based on serum Na and K
• Glucocorticoid = based on clinical signs
o Inappetence, vomiting, diarrhea, depression = increase the dose
o Peripheral edema, PU/PD, other signs of hyperadrenocorticism dose-decrease dose

Question 4

4. Name the two drugs and their routes of administration used in Addison’s disease to supplement mineralocorticoids. (I am not asking for prednisolone.)

Answer 4

• Fludrocortisone (Flurinef) – given orally, some glucocorticoid activity
• Desoxycorticosterone pivalate (DOCP) – given SQ, devoid of glucocorticoid activity

Question 5

5. What glucocorticoid is similar in potency and duration to prednisolone, but lacks its mineralocorticoid activity?

Answer 5

• Triamcinolone

Question 6

6. Name a steroid known to induce surfactant production in the bovine fetus.

Answer 6

• Prednisolone
• Isoflupredone
• Cortisol induces surfactant production from alpha 2 receptor cells at a specific time of gestation
• Can give injection of dexamethasone 36-48 hours before c-section so surfactant is produced and lungs can expand upon birth
o Dex is more lipid soluble so crosses placenta better
• Methylprednisolone doesn’t cross placenta like dexamethasone so won’t induce surfactant production

Question 7

7. Classify injectable steroids as repository versus suitable for iv use. (Based on name of formulation. e.g., a succinate versus acetate.)

Answer 7

• IV Nonrepository:
o Water soluble, can be given IV
o Duration controlled by biological half-life
o Sodium succinate and Sodium phosphate
 E.g. prednisolone sodium succinate, dexamethasone sodium phosphate
• IM Repository (Depo)
o Water insoluble, given IM
o Duration controlled by rate of absorption (usually lasts 2-4 weeks)
o Acetate, Acetonide, Pivalate
 E.g. methylprednisolone acetate (DepoMedrol), triamcinolone acetonide (Vetalog), and flumethasone pivalate (Locorten)

Question 8

8. What effect does the ester formulation have on use of an oral steroid?

Answer 8

• NO EFFECT; Duration of an oral steroid is due to its biological half-life and not the formulation

Question 9

9. Compare and contrast the benefit of steroid therapy in acute spinal cord trauma versus acute brain trauma.

Answer 9

• Traumatic injuries to the spinal cord (but not brain) can be minimized by prompt treatment with high dose methylprednisolone
o mechanisms other than phospholipase inhibition may be involved
o though steroids can inhibit vasogenic edema, most traumatic CNS injuries develop cytotoxic
• Edema that is nonsteroid responsive.
o appears that neuroprotective mechanisms do not revolve around minimization of edema

Question 10

10. Which steroid(s) has shown the greatest utility (most evidence) in minimizing spinal cord trauma injury? Include the formulation of the steroid(s).

Answer 10

• Most work has used high dose of methylprednisolone sodium succinate.
o to be effective, the drug must be given promptly
 after 8 hours there is no benefit to giving steroids
o give 30 mg/kg IV immediately. Various regimens follow with additional doses
o neurologist dependent!!
• Methylpred has be shown to improve neurologic status and survival to discharge when administered during CPR

Question 11

11. What are the types of cerebral edema and which are steroid responsive? Indicate the most common cause of each type of brain swelling.

Answer 11

• Interstitial cerebral edema:  hydrocephalus
o Responds to steroids  help by decreasing CSF production  decreasing pressure
• Vasogenic cerebral edema:  some brain tumors and infection
o responds to steroids (slows replication and to decrease edema)
• Cytotoxic cerebral edema:  following trauma
o NOT steroid responsive (osmotic diuretics, etc instead)

Question 12

12. Explain why steroids have been hypothesized to predispose to laminitis in horses and which steroids have been most commonly implicated.

Answer 12

• Glucocorticoids may not cause it on its own, but they might only increase the risk of developing laminitis when other causative factors are present or may exacerbate existing laminitis
• If it occurs, the mechanism is unknown but may be due to sensitization of alpha receptors in the hoof wall
• Steroids:
o Triamcinolone
o Dexamethasone (and related flumethasone, betamethasone)

Question 13

13. Name two steroids with the lowest risk of inducing parturition in the cow in late pregnancy.

Answer 13

• Prone to abortion/induction of parturition from certain steroids in the last half of gestation and especially in the last month of gestation
o Prednisolone & isoflupredone

Question 14

14. Which steroid is most commonly used to induce partition/abortion in cows?

Answer 14

• C16-methylated Dexamethasone (betamethasone, flumethasone)

Question 15

15. At one time dexamethasone was a commonly used inhaled steroid. Why has it been largely replaced by fluticasone?

Answer 15

• Fluticasone is VERY water insoluble, it undergoes the first pass effect and never reaches systemically
o Not absorbed into the central circulation and therefore have few if any systemic side-effects
• Dexamethasone is more soluble, meaning that it would impart systemic effects.

Question 16

16. Not including reproductive effects or Cushing’s syndrome, name the six contraindications one should consider before administering a glucocorticoid.

Answer 16

• Gastrointestinal ulceration
o Steroids may result in ulcer development or aggravate an existing ulcer
o May want to add an acid suppressor to the regimen
• Systemic mycoses
o Diseases are held in check by cell mediated immunity which are inhibited by steroids (mycobacterial infections inhbited as well)
o Consider using steroids if animal is on an antifungal agent first
• Situations where rapid healing is desired (slow wound healing)
o Intestinal resectin and anastomosis
o Steroids delay wound healing and should be avoided because dehiscence may result
o Short-acting water soluble steroid if steroid must be used
• Abortion and birth defects (not in horses or sheep, dogs are also difficult 10days)
o Gives a high risk for retained placenta
o Will decrease milk production (important for dairy cattle)
o Birth defects may result if steroids are sed in the first trimester
o High dose steroids in the pregnant bitch can cause fetal death and reabsorption in the first half of gestation or abortion thereafter
o Catlle are most prone to steroid-induced abortion (prone from mid-gestation on but especially during last month of gestation)
• Procoagulant effects
o Higher risk for thromboembolism  pulmonary thromboembolism
o Animals with hyperadrenocorticism are predisposed to sudden death from thromboembolism  occurs with exogenous steroid administration (steroids should be avoided)
o Immune mediated hemolytic anemia patients commonly die from thromboembolism since immune disease requires the use of steroids (combine with an anticoagulant drug)
• Pancreatitis
o Animals may develop pancreatitis while using steroids (risk factor)
o Association is week so still use in immunosuppressed patients if needed (avoid in animals with history of pancreatitis or prone to it)
• Diabetes mellitus
o Anti-insulin effect (difficult regulation of the diabetic insulin regulation but not impossible)
o Cats treated with Depo-Medrol repeatedly are at high risk for developing diabetes (can get into remission, consider oral pred for repeat kitty allergy offenders)

Question 17

17. Classify the common steroids as to whether they are appropriate for alternate‐day use.

Answer 17

• Only short acting or intermediate acting steroids (prednisolone, methylprednisolone, and triamcinolone) can be given as alt-day doses. Dexamethasone is NOT ideal because it is long-acting.
o Prednisolone = most commonly used
o Methylprednisolone = used to minimize sodium and water retention
o Hydrocortisone = rarely used systemically in vet med
o Triamcinolone = used to minimize sodium and water retention

Question 18

18. What advantages does alternate‐day steroid use provide over daily use?

Answer 18

• Less immunosuppression

* Less pituitary-adrenal axis suppression

Question 19

19. If dogs are given once daily steroids, all other considerations being equal, what time of day should the dose be given and why? What about the cat?

Answer 19

• Dogs: Morning – cortisol surge naturally in the morning (Diurnal rhythm), trying to mimic this
• Cats: No diurnal rhythm (perhaps nocturnal)  time of administration not important so can give at any time point during day

Question 20

20. What effect do glucocorticoids have on excretion of calcium?

Answer 20

• Enhance renal elimination of calcium (effective in tx of hypercalcemia)

Question 21

21. In which species is prednisone a poor choice for a glucocorticoid and why?

Answer 21

Cats and Horses  Do NOT absorb/convert prednisone well

Question 22

22. How do cats differ from dogs relative to:
    • The risk of causing iatrogenic Cushing’s. • The usual dose required to achieve an equivalent effect.  • Risk of induced diabetes mellitus 

Answer 22

• The risk of causing iatrogenic Cushing’s.  Very low risk, dogs at higher risk for iatrogenic Cushing’s
• The usual dose required to achieve an equivalent effect.  Cats require 2x dose as a dog for same anti-inflammatory effect
• Risk of induced diabetes mellitus  Cats at greater risk

Question 23

23. Identify the glucocorticoids discussed that also have significant mineralocorticoid effects.

Answer 23

• Hydrocortisone

* Prednisolone

Question 24

24. What branch of immunity is most severely impaired by steroid use? What group of infectious agents does this immunosuppression have the greatest clinical impact on?

Answer 24

• Cell-mediated immunity (systemic mycoses and mycobacteria)

Fungal