Unit 1.1 - Glucocorticoids

inflammation

response to vascular tissues to harmful stimuli

purpose of inflammation

• containment of injury

• elimination of offending agent

• repair of damaged tissue

cardinal signs of inflammation

• redness, heat, swelling, pain, loss of function

  • redness, heat due to vasodilation and loss of function due to severity of inflammation

• mediators

  • WBCs, Prostaglandins, histamine, leukotrienes, cytokines

When the inflammatory pathway is initiated…

• phospholipids in the cell are broken down by phospholipase (enzyme) causing the formation of arachidonic acid

  • where glucocorticoids block

_______ and ________ breaks down the acid into prostaglandins and leukotrienes = inflammation

cyclooxygenase and lipoxygenase

Vascular and cellular changes from inflammation

• increased blood flow to area

• plasma proteins such as fibrin and immunogloblins flood the damaged area (increase in the amount of fluid in the area causes edema)

• vasodilation causes the redness and heat

corticosteroids

• hormones produced by the adrenal cortex

• drugs are synthetic replications of naturally occurring hormones

uses of corticosteroids

• inflammatory reactions

• allergies and skin irritation

• immune mediated disease

• adrenal conditions

• shock

two classifications of corticosteroids

• glucocorticoid

• mineralocorticoid

minderalocorticoids

aldosterone » maintain the balance of fluids and electrolytes

glucocorticoids

• occur naturally in the body in the form cortisone

• responsible for anti-inflammatory and immunosuppressive reactions

• affects blood glucose

• carbohydrate, fat, and protein metabolism

Most steroids used in veterinary medicine are classified as glucocorticoids

cortisol

• is the natural glucocorticoid released by the adrenal cortex when stimulated by the ACTH

• when sufficient cortisol is produced » neg feedback shuts down release of ACTH

glucocorticoid drug administration (exogenous source)

• same neg feedback suppression as ACTH

• decreases adrenal activity and the natural cortisol production

• longer duration of action of a glucocorticoid drug, the longer the neg feedback suppression and longer there is decreased adrenal gland production of natural cortisol

• always taper dose over duration of time never stop cold turkey

common uses and benefits of corticosteroids

• reduction of inflammation

• relief of allergic responses

• reduction of tissue damage

• treatment of autoimmune disorders

• treatment of addison’s disease

• termination of late stage pregnancy

acute side effects of glucocorticoids

• delayed wound healing

  • especially corneal ulcers

• polyuria (PU), polydipsia (PD), polyphagia

• stress response on CBC with WBCs

• abortion

chronic (>2wks) or high dosing side effects

• thinning of skin and muscle atrophy

• hyperadrenocorticism (Cushing’s Disease)

• Diabetes mellitus (felines)

• decreased immune response

• GI ulcers and bleeding

corticosteroid » Betamethasone

Betasone

• Forms: inj, topical, oral

corticosteroid » Budesonide

Entocort, Entocort-EC

• Forms: oral, inhalation

corticosteroid » Desoxycorticosterone pivalate

Percorten-V

• Forms: inj

corticosteroid » Dexamethasone

Azium

• Forms: inj, oral

corticosteroid » Dexamethasone sodium phosphate

DSP, Dexafort

• Forms: inj, topical

corticosteroid » Flumethasone

Flucort

• Forms: inj

corticosteroid » Hydrocortisone

Cortef, Solu-cortef

• Forms: tablet, inj, topical

• Short duration of action (<12hrs)

corticosteroid » Isoflupredone acetate

Predef 2x, Triop

• Forms: inj, topical

corticosteroid » Prednisolone

Temaril-P

• Forms: tablet

• Intermediate duration of action (12-36hrs)

corticosteroid » Prednisolone acetate

Pred Forte, Econopred Plus

• Forms: inj, topical

corticosteroid » Triamcinolone acetonide

Vetalog, Triacet Triamtabs, Cortalone

• Forms: Inj, oral, topical

corticosteroid » Short Duration of Action

Hydrocortisone

corticosteroid » Intermediate Duration of Action (12-36 hrs)

• Prednisone

• Prednisolone

• Methylprednisolone

• Triamcinolone

corticosteroid » Long Duration of Action (>48 hrs)

• Betamethasone

• Dexamethasone

• Flumethasone

• Mometasone

Physiological dosage

dose that replaces amount of natural endogenous cortisol in a 24hr period used for treatment of Hypoadrenocorticism (Addison’s Disease)

Anti-inflammatory dosage

dose that is used to control allergies, hives, injury inflammation

Immunosuppressive dosage

dose that is used to suppress the immune system and to treat autoimmune diseases like immune mediated hemolytic anemia, pemphigus

Shock dosage

very high doses - generally not recommended any more for treatment of shock, spinal trauma, etc

Rules for Safe Use of Glucocorticoid (GC) Drugs

• if another anti-inflammatory will do the job, consider using it (e.g NDSAIDs)

• avoid continuous use; select shorter acting GC if given the choice

• use smallest dose needed to control clinical signs; decrease dose when possible

• if patient has been dosed for weeks, taper off drug

• do not mix NSAIDs and GC drugs together

• if ever changing types or switching from GC drugs to NSAIDs or vice versa - always do a washout period between drugs