Module 3: Corticosteroids (systemic) Flashcards
What are indications for systemic corticosteroids?
Inflammatory, allergic and immunological disorders. e.g. polymyalgia rheumatica, inhaled preparations in asthma, topical in atopic dermatitis. May be short or long term.
Used for immunosupression in organ transplant.
Endocrine disorders = given to establish dx and cause of Cushing syndrome. Tx of adrenal insufficiency, congenital adrenal hyperplasia.
Medical emergencies = anaphylaxis, septic shock, macrophage activation syndrome.
What are the anticipated clinical outcomes?
- Suppression of inflammation
Less often: - dx and cause of Cushing Syndrome
- hormone replacement in adrenal insufficiency and congenital adrenal hyperplasia
Describe the mechanism of action of Corticosteroids.
Primarily exert effects via up-or down regulation of gene transcription
Other proposed mechanisms:
- Interaction with glucocorticoid receptors after passive diffusion through the cell membrane - influence the activation and repression of gene expression.
- interaction with proinflammatory transcription factors - reduce transcription of proinflammatory genese
Describe the pharmacokintecs of glucocorticoids.
A: different oral glucocorticoids have the same rate of absorption and are roughly bioequivalent (60-100%). Note for inhaled, correct use of inhaler aids in abosorption.
D: Many synthetic glucocorticoids bind to transcortin (corticosteroid-binding globulin) and/or albumin.
NOTE: pt’s with lower albumin levels may see higher concentrations of free glucocorticoid thus greater adverse effects.
M: Converted to hydrophilic inactive metabolites.
E: Renally excreted. Varies with dose and time of day.
NOTE: variations exist in potency and duration of action.
What are some special prescribing considerations for glucocorticoids?
In pregnancy some glucocorticoids are used when an effect on the fetus is desired. Other glucocorticoids are inactivated by the placenta.
Lactation: excreted in small amounts in breast milk and adjustment to breastfeeding may be needed for some doses.
Pediatrics: Growth impairment, most pronounced with daily therapy. Children more susceptible to cataract cormation.
Menstruation: delayed, irregular, heavier or lighter menstruation.
What are common side effects of glucocorticoids?
Typically with high doses and cumulative steroid burden over time but can occur with lower doses:
- insomnia and sleep disturbances
- gastric irritation
- hyperglycemia
- Mood changes
- increased appetite and weight gain
- osteoperosis
- sodium and fluid retention
- adrenal suppression
- increased risk for infection
- HTN
- delayed wound healing
What are significant adverse effects of glucocorticoids?
Organ-based toxicity (from insomnia to serious infection). Accelerated reductions in bone mineral density, early cataracts.
What are some general treatment considerations and monitoring parameters for glucocorticoids?
- use lowest dose for shortest period of time
- assess for preexisting comborbid conditions
- prevention of infection (immunizations)
- prevention of osteoperosis
- monitor for adverse effects related to the specific drug
What are some significant drug interactions with systemic glucocorticoids?
Meds that strongly inhibit or induce P450 3A4 (CYP3A4) and/or P-glycoprotein transporters may alter the glucocorticoid serum concentration.
Meds that increase serum glucocorticoid levels: oral contraceptives, some antibiotics and antifungals
Meds that decrease: aluminum/ magnesium containing antacids, phenytoin, phenobarbital, rifampin.
What are contraindications/ cautions with systemic corticosteroids?
Concurrent administration of live or live-attenuated vaccines (when using immunosuppressive dosages)
Systemic fungal infection
Osteoporosis
Uncontrolled hyperglyemia
Glaucoma
