Corticosteriods Flashcards
Define corticosteroids
A group of natural and synthetic substances that mimic in part or wholly the actions of the adrenal hormone, cortisol
- most tx uses based on glucocorticoid actions
- broad physiological effects: anti-inflammatory mainly
- therapeutic uses and dose ranges are intertwined
- Medium doses: anti-inflammatory tx
Why do corticosteroids exhibit a delayed response?
Due to the requirement for protein synthesis
Describe tissue selectivity in corticosteroid action
- Aldosterone selectively activates MCR
- Cortisol binds with equal affinity to MCR/GCR
- Synthetic agents are designed to have GCR selectivity
What can cause hyperactivation of HPA axis?
Hyperadrenocorticism, Cushing’s syndrome - can arise from pituitary tumors or adrenal gland tumors
What is the MOA for stressors to inhibit cortisol synthesis?
Stressors inhibit 3-beta-hydroxysteroid dehydrogenase > decr cortisol synthesis (adrenal cortex)
Most physiological actions of corticosteroids are mediated what two classes of receptors?
Glucocorticoid receptors (GCR) Mineralcorticoid receptors (MCR)
What 4 paths do pharmacological doses of glucocorticoids evoke actions through?
1) genomic responses via cytotoxic GCRs - involves altered protein synth (slow-medium effects) 2) Non-Genomic Responses via cytotoxic GCRs 3) Non-Genomic Responses via membrane-bound GCRs 4) other non specific responses
Glucocorticoid actions
- Enhanced carb metabolism
- Protein catabolism
- Mobilizes FA from adipose
- Blockade of Inflammatory Cascade (robust doses)
- Altered electrolyte and water balance (MCR activation)
- CNS effects
Adverse effects of Corticosteroids
- HPAA suppression (sudden withdrawal - fatal)
- Muscle wasting, delayed wound healing, bone loss, thinning of skin (protein catabolism)
- Diabetes
- Hypothyroidism
**adverse effects correlate with DOSE and DURATION of treatment
Precautions for Glucocorticoid Therapy
- Rx does NOT cure dz
- use topical if feasible to lessen systemic imbalances
- use minimal effective dose > prevent Cushing’s
- use step-down protocols when terminating tx > prevent Addison’s
Contraindications for Glucocorticoids
- untreated pre-existing infections
- high doses in late stage pregnant animals
- diabetes mellitus
- renal dz/insufficiency
- CHF
- Young animals
- GI ulcers or hypersecretory disorders
What are some lab concerns with glucocorticoids?
- Leukopenia, neutrophilia (aka stress leukogram)
- Thrombocytosis
- Hyperglycemia
- Hypercholesterolemia
- Elevated ALP
- Dec serum K+
- Decr thyroid values
- Suppressed rxn to skin tests/systemic bacterial infxn
What are the four chemical classes of glucocorticoids?
- Group A (short-acting): hydrocortisone, prednisolone, methylprednisolone, prednisone
- Group B (intermediate-acting): triamcinolone
- Group C (long-acting): betamethasone, dexmethasone, dexamethasone sodium phosphate
- Group D
What two things are associated with the C21 hydroxyl group in glucocorticoids?
Incr GCR activity and decr MCR activity
Pharmacokinetics of Glucocorticoids
- most eliminated by hepatic metabolism
- certain side chains delay metabolism and enhance duration of action
- many synthetic agents are NOT bound to transcortin - improves speed of cellular penetration/faster action
