lectures 31-32 (corticosteroids) Flashcards
exam 3
principles of glucocorticoid administration
- immunosuppressant and anti-inflammatory effects
- use if palliative (except replacement therapy)
- must always carefully consider relative risks vs. benefits
- require frequent re-evaluation as underlying disease changes or complications arise (remission or exacerbation of diseases and stress)
- dose selection by trial and error
- dose should be individualized based on diagnosis, severity, prognosis, duration of disease
- incidence of side effects is time and dose related (single dose: no harm; few day therapy: unlikely harmful)
- abrupt cessation of prolonged high doses leads to adrenal insufficiency (contraindicated)
- do not administer unless absolutely indicated or more conservative measures have failed
- prescribe the lowest dose to achieve the desired effects for the shortest duration possible
implications for corticosteroids in clinical practice
to relieve pain/distressing symptoms:
- start with lower dose
- may gradually reduce dose until worsening symptoms –> lowest acceptable dose
- substitute with other medications (ex. NSAIDs)
to treat life threatening condition:
- initial dose must be high
- no benefits observed quickly –> double/triple dose
- reserve high dose, long therapy for life threatening diseases
dosage conversions of commonly used GC
physiologic dose (replacement):
- hydrocortisone: 20mg
- prednisone: 5-7.5mg
- dexamethasone: 0.75mg
- methylprednisolone: 4mg
pharmacologic dose:
- maintenance or low: prednisone 5-15mg
- moderate: prednisone 0.5mg/kg/daily
- high: prednisone 1-3mg/kg/daily
- massive: prednisone 15-30mg/kg/daily
dosing principles
dosing in the morning (before 9am)
- mimic natural circadian rhythm
- pituitary less sensitive to steroid during this time
topical dosing of steroid
- localized high concentration
- decreased systemic levels
IV and IM dosing
- typically reserved for those unable to take oral
intra-articular dosing
- slow absorption and long duration of action
selection of corticosteroids
selection is based on the primary indication
anti-inflammatory
- select steroids with minimal mineralocorticoid
- anti-inflammatory action lasts longer than negative feedback
- use intermediate acting glucocorticoid (longer acting steroids improve adherence, avoid symptoms recurrence)
- betamethasone and dexamethasone have too long of a half life
complications for prolonged corticosteroid therapy/excess cortisol
infections
myopathy
osteonecrosis
osteoporosis
psychiatric symptoms
fluid and salt retention
metabolic changes
gastric ulcers
cataracts
CV risks
*patients on high dose GC (>20mg prednisone/day) should not receive live vaccines
drug-induced cushing’s syndrome
prescription glucocorticoid preparations
- all forms of steroids with GC activity are capable (dose and duration dependent)
- every mode of delivery has been implicated (oral most common)
nonprescription and herbal products
other drugs with GC activity include megestrol acetate and medroxyprogesterone
treatment goals of cushing’s syndrome
reverse hypersortisolism
reduce exogenous GC administration
manage associated co-morbidities
- 4x increase in mortality in CV disease
minimize long-term complications
- ex. cardiac hypertrophy, osteoporosis
clinical presentation of patients with Cushing’s syndrome
hypercortisolism
supraphysiologic cortisol concentration (endogenous)
pharmacological doses (exogenous)
- redistribution of body fat (central obesity)
- moon face (buffalo hump and supraclavicular fat accumulation)
- muscle wasting and weakness (steroid myopathy)
- easy bruising
indications for GC withdrawal/monitoring parameters
- maximum desired therapeutic benefit has been obtained
- inadequate therapeutic benefit has been obtained
- side effects become serious or uncontrollable with medication (hypotension, osteoporosis, cushing’s syndrome, acute psychosis, corneal ulceration)
prevention of Cushing’s syndrome associated with exogenous glucocorticoid administration
HPA axis may take up to 1 year to recover
- supplement with extra dose of steroid during period of physiologic stress
evaluate patients at risk for adrenal insufficiency
initiate steroid and mineralocorticoid replacement therapy; as appropriate
avoid concurrent administration of drugs that can induce steroid metabolism (decrease drug levels)
- CYP3A4 inducers: phenytoin, rifampin, barbiturates, carbamazepine
- management: increase dose of GC
give lowest possible dose for shortest possible duration
minimize systemic absorption
avoid concurrent administration of drugs that inhibit GC metabolism (increase drug levels)
- CYP3A4 inhibitors: protease inhibitors, antifungals
- management: decrease dose of GC
patients requiring tapering corticosteroids
- receive GC dose equivalent to prednisone >7.5mg/day for >3weeks
- receive evening dose of prednisone >5mg >few weeks
- patients with cushingoid appearance
- cautious in frail or dangerously ill patients, evaluate HPA function, monitor signs and symptoms
tapering parameters
- assess patient’s risk for adrenal insufficiency
- taper 10-20% of total daily dose (2-10% every 1-4 weeks)
- gradually taper dose to prednisone ~20mg (or eq.) daily, given in AM, then:
- change steroid to every other day administration, given in AM
- stop steroid when equivalent physiologic dose is reached (low risk for adrenal insufficiency)
clinical presentation of patients with adrenal insufficiency
bronze pigmentation of skin
changes in distribution of body hair
GI disturbances
weakness
hypoglycemia
postural hypotension
weight loss
adrenal insufficiency treatment goals
mimic endogenous secretion of GC with exogenous GC replacement
replace and correct both GC and MC deficiencies
manage symptoms
prevent development of adrenal crisis
chronic adrenal insufficiency treatment strategies
hydrocortisone 15-25mg/day
cortisone 20-35mg/day
prednisone 3-5mg/day
- give 2/3 of dose in the morning (6-8AM) and 1/3 of dose in early afternoon (2h after lunch, 2pm)
addison’s disease/primary adrenal insufficiency
hydrocortisone 10-15mg in AM, 5-10mg in afternoon
fludrocortisone 0.05-0.1mg in AM
- mineralocorticoid is required)
maintain adequate sodium intake
decrease hydrocortisone dose during stress, double for mild illness, triple for more sever illness
provide patient with injectible GC for emergency use
treatment of acute adrenal crisis
administer hydrocortisone 100mg IV bolus and 200mg/day as continuous IV infusion for 24 hours
reduce to 100mg/day when patient is stable
taper to maintenance therapy by day 4-5, add mineralocorticoid therapy as needed
maintain or increase dose to 200mg/day if complications persist or occur
correct volume depletion, dehydration, hypoglycemia, with IV saline and glucose
evaluate and correct infection and other precipitating factors
patient education
take with meals/milk
do not stop therapy without seeking healthcare provider’s advice
increase GC dose during excessive physiologic stress
how to administer parenteral GC if unable to immediately access medical care during an emergency
wear/carry medical ID
major drug interactions with the use of systemic glucocorticoids and its management
avoid drugs that can induce steroid metabolism:
- CYP3A4 inducers: phenytoin, rifampin, barbiturates
- management by increasing dose of steroid
avoid drugs that can inhibit steroid metabolism:
- CYP3A4 inhibitors: protease inhibitors, antifungals
- management by decreasing dose of steroid in presence of inhibitors
monitoring parameters
subjective well-being of the patient
resolution of hypotension, dizziness, dehydration, hyponatremia, hyperkalemia
monitor for adverse reactions of steroid
maintenance of normal weight
blood pressure
electrolytes with regression of clinical features
adjust dose accordingly as needed
signs of under-replacement:
- weight-loss, fatigue, nausea, myalgia (lack of energy)
signs of over-replacement (Cushing’s):
- weight gain, central obesity, stretch marks, osteopenia/osteoporosis, impaired glucose tolerance, high blood pressure
