Glucocorticoids Flashcards
Hypothalamic Pituitary Adrenal Axis (HPAA)
hypothalamus secretes corticotropin releasing hormone (CRH) which stimulates the anterior pituitary to produce adrenocorticotropic hormone (ACTH) which tells the adrenal cortex to release cortisol
Cortisol Effect on Hypothalamus and Anterior Pituitary
negative feedback loop to decrease release of CRH and ACTH
ACTH effect on Hypothalamus
negative feedback loop to decrease release of CRH
3 General Effects of Cortisol
- Physiologic
- Pharmacologic
- Adverse
When we use glucocorticoids, what effects of cortisol are we targeting?
pharmacologic
4 Systems Affected by Glucocorticoids
- Renal (Kidney)
- Cardiovascular
- Immune
- Metabolic
Renal Effects of Glucocorticoids
increase blood pressure (d/t sodium retention and volume expansion); inhibit ADH release so urine becomes less concentrated
Cardiovascular Effects of Glucocorticoids
increase blood pressure (d/t increase vasoconstriction), decreases vascular permeability
Immune Effects of Glucocorticoids
inhibits phospholipase A2 (PLA2) therefore decreasing prostaglandins, decreases cell-mediated immunity
Excess Glucocorticoid Effect on Immune System?
anti-inflammatory and immunosuppression
Metabolic Effects of Glucocorticoids
increases gluconeogenesis, glycogenolysis, and lipolysis (diabetes risk)
2 Major Endogenous Glucocorticoids
- Cortisol (majority of species)
- Corticosterone (a few species)
Are we typically administering endogenous or synthetic steroids?
synthetic!
3 Ways to Classify Pharmacologic Steroids
- Glucocorticoid Potency
- Mineralocorticoid Potency
- Duration of Action
Relationship between Prednisone and PredniSOlone?
prednisone is a prodrug of predniSOlone
We talk about glucocorticoid potency in relation to what drug?
Prednisone
Short-Acting (<12 hours) Glucocorticoids (2)
- Cortisone
- Hydrocortisone
Intermediate-Acting (12-36 hours) Glucocorticoids (4)
- Prednisone
- PredniSOlone
- Methylprednisone
- Triamcinolone
Long-Acting (>48 hours) Glucocorticoids (3)
- Flumethasone
- Dexamethasone
- Betamethasone
Which intermediate-acting glucocorticoid is not mineralocorticoid potent?
triamcinolone
Which glucocorticoids are most mineralocorticoid potent - short or long acting?
SHORT (long acting have no mineralocorticoid potency)
Glucocorticoid Esters
chemical groups that can be added to steroid base to alter onset and/or duration
Ester Effect on Onset
increases water solubility to hasten absorption, therefore a faster onset
Ester Effect on Duration
decrease solubility to allow depot formation, then bond must be hydrolyzed to be absorbed, resulting in longer duration
4 Pharmacologic Indications for Use of Glucocorticoids
- Physiologic Replacement
- Anti-inflammatory
- Anti-neoplastic
- Immunosuppressive
Dosing Range Effect on Function
we use DIFFERENT dosing ranges to have different effects, and they can be highly dependent on the individual patient
Physiologic Replacement Dosing Range
0.1 - 0.25mg/kg/day [prednisone equivalent]
Anti-Inflammatory Dosing Range
0.5 - 1 mg/kg/day [prednisone equivalent]
Anti-Neoplastic Dosing Range
1 - 2 mg/kg/day [prednisone equivalent]
Immunosuppressive Dosing Range
2 [- 4] mg/kg/day [prednisone equivalent]
Does continuing to increase does become more immunosuppressive?
no, it has a limit, and generally closer to the lower end of the range
Indications for Physiologic Replacement
Hypoadrenocorticism (Addisons) or other insufficiency; to prevent hypotension, shock, hypoglycemia, bradycardia (so essentially death, don’t die k)
Anti-Inflammatory Indications
pruritic ear/skin diseases mainly; prevents PLA2 formation, also prevents histamine release
Can you use steroids as an anti-inflammatory medication all willy-nilly?
no, please rule out primary infectious cause first as steroids can sometimes make these worse
Anti-Neoplastic Indications
lround cell tumors (such as lymphoma or MCTs); causes apoptosis of [some] lymphocytes (lympholytic effect)
Why do we use steroids with neoplasms?
more for quality of life rather than survival, best used in combination with chemotherapy
Immunosuppressive Indications
for various anemias, cytopenias, opathys, meningitis, whatever; acts by many mechanisms of action, including inhibiting macrophages, poor cell adhesion, T cell apoptosis, etc
Which indications require tapering?
mainly in immunosuppressive (but depending on practice will taper in other uses as well)
Most Common Adverse Effects (in dogs)
PU/PD, polyphagia (excessive hunger), weight gain, muscle loss, hair loss
Cardiovascular and Renal Adverse Effects
PU/PD, hypertension, proteinuria
Musculoskeletal Adverse Effects
pot-belly, muscle wasting, ligament/tendon weakness, osteoporosis; also laminitis in horses
CNS Adverse Effects
polyphagia, panting, aggression or other behavior change; also masks disease progression
Metabolic Adverse Effects
weight gain, diabetes mellitus, iatrogenic Addison’s d/t quick withdrawal
just a cool table to look at
look at it
Cutaneous Adverse Effects
hair loss, thin skin, poor wound healing
Skin Fragility Syndrome
in cats, skin tearing, yikes
Gastrointestinal Adverse Effects
gastritis and ulceration WHEN USED IN COMBINATION with other drugs like NSAIDs (generally not a problem on their own)
Calcinosis Cutis
calcium deposition in the skin, very very itchy
What glucocorticoid is ineffective in cats?
PREDNISONE (surprise, they don’t have the necessary enzyme to break it down into prednisolone)
Dosing Steroids in Cats
round UP - generally require more as they are more “resistant” than other species
If cats get diabetes mellitus from steroid administration, is it reversible?
sometimes
Iatrogenic Addison’s
d/t rapid withdrawal of steroids; signs include dullness/depression/fatigue, GI signs, and unthrifty appearance
Local Glucocorticoids
topical, OTIC, or eye preparations; can still have systemic effects d/t lipophilia (easily absorbed)
Soft Glucocorticoids
have a very high first pass effect and are rapidly absorbed by the liver, so they have very minimal systemic effects
Examples of Soft Steroids
budesonide PO (chronic enteropathy), fluticasone (asthma)
