8. steroidal anti-inflammatories

how do glucocorticoids decrease inflammation?

• inhibit NF-κB DNA binding activity (transcription factor with central role in inflammation)

  • IκB inhibits activation of NF-κB

• lipocortin inhibits phospholipase A₂ activity: block conversion of phospholipids → arachidonic acid

effects of glucocorticoids on inflammation/immune response

• anti-inflammatory activities (NF-κB)

  • decrease prostaglandin synthesis

• inhibit IgE-mediated histamine release

• impair leukocyte phagocytosis

• inhibit fibroblast proliferation

• inhibit lymphocytes

  • proliferation

  • induce apoptosis

adverse GI effects of glucocorticoids

• GI ulceration via PLA₂ inhibition

  • inhibit COX-1 & COX-2

  • ↑ gastric acid secretion (parietal cells)

  • ↓ gastric mucosal turnover

• ↑ risk with concurrent NSAID use

adverse endocrine effects of glucocorticoids (dogs)

iatrogenic hyperadrenocorticism

• hepatomegaly

  • deposition of hepatic glycogen

  • elevated SAP & GGT

• polyuria/polydipsia

  • inhibition of vasopressin (ADH)

• increased lipolysis & visceral adipogenesis

  • potbelly, altered fat distribution

• muscle atrophy

  • ↓ protein synthesis

• alopecia

  • ↓ collagen synthesis

  • impaired fibroblast proliferation

  • skin thins & easily stretches

  • impaired wound healing

adverse endocrine effects of glucocorticoids (cats)

diabetes mellitus

• hyperglycemia

  • increased gluconeogenesis

  • increased glycogenolysis

  • insulin resistance

    • via free fatty acid mobilization & lipolysis

other adverse endocrine effects of glucocorticoids

HPA axis suppression

• increased exogenous corticosteroids

• adrenal gland atrophy

• requires tapering of steroids to avoid hypoadrenocorticism crisis

what is a potential adverse consequence of immunosuppression by glucocorticoids?

• opportunistic infections

  • bacterial

  • fungal

• more common with

  • chronic use

  • high doses

adverse cardiovascular effects of glucocorticoids

• hypertension

• congestive heart failure

  • steroid formulations with mineralocorticoid activity

  • sodium & water retention → volume overload

  • decreased production of vasodilatory PGs → increased vasoconstriction

hydrocortisone (receptor activity, duration, onset, formulations)

• least potent GC

• mineralocorticoid receptor (MR) activity

• rapid onset; short acting

• formulations: IV, topical (OTC), oral

what is the difference between prednisone & prednisolone? which species is prednisolone used in?

• prednisone is a prodrug

• prednisolone = active drug

  • GC & MR activity

• poor liver conversion to prednisolone

  • cats: prednisolone preferred to prednisone

  • horses: prednisolone required

dexamethasone receptor activity

• GC

• no mineralocorticoid activity → no salt + water retention

budensonide uses

• oral enteric-coated formulation with high first pass metabolism (liver)

• potential for less steroid-related side effects

  • ↓ induction of steroid ALP (dogs)

  • ↓ PU/PD, polyphagia, panting

  • documented HPA suppression (dogs)

• alternative treatment for inflammatory diseases

  • gastrointestinal

  • liver

fluticasone uses

• causes bronchodilation

  • allergic bronchitis (dogs)

  • feline asthma

• high topical (inhalant) potency; low systemic absorption

• side effects: HPA axis suppression can occur

triamcinolone formulation

topical glucocorticoid

DOCP (desoxycorticosterone pivalate) receptor activity, uses

• long-acting injectable mineralocorticoid

  • dosed ~q 25-28d

  • dose & dosing interval adjusted based on serum electrolytes

• NO GR activity

  • requires adjunct use of GCs for full treatment of hypoadrenocorticism

• indications

  • hypoadrenocorticism (dogs)

    • hyponatremia & hyperkalemia

fludrocortisone receptor activity, use, side effects

• short-acting mineralocorticoid

  • daily administration

• glucocorticoid activity

  • PU/PD at doses required to normalize Na⁺ & K⁺ levels

• side effects:

  • PU/PD

  • increased risk of infections

  • muscle wasting

  • insulin resistance