Lecture 33/34 Flashcards
Therapeutics of Corticosteroids
relieve pain/distressing symptoms principles
start with lower dose
gradually reduce dose until worsening symptoms
substitute with other medications (like NSAIDs)
implications of glucocorticoid administration
do not administer unless absolutely indicated or more conservative measures have failed
prescribe the lowest dose to achieve the desired effects for shortest duration possible
symptoms gets worse when reducing dose
go back to the lowest acceptable dose to try and find a happy medium
try and reduce later
treat life threatening conditions principles
initial dose must be high
no benefits observed quickly, double or triple the dose
reserve high dose, long therapy for life threatening doses
physiologic dose
replacement dose, once a day
hydrocortisone - 20mg
prednisone - 5 to 7.5mg
methylprednisolone - 4 mg
dexamethasone - 0.75mg
pharmacologic dose
any dose greater than physiologic dose
maintenance or low pharmacologic dose
prednisone 5 to 15 mg per day
moderate pharmacologic dose
prednisone 0.5 mg per kg per day
high pharmacologic dose
prednisone 1-3 mg per kg per day
massive pharmacologic dose
prednisone 15-30 mg per kg per day
20mg of hydrocortisone is equal to
cortisone - 25 mg
prednisone - 5 mg
methylprednisolone - 4mg
dexamethasone - 0.75mg
clinical presentation of Cushing’s syndrome
redistribution of body fat (central obesity - 80%)
moon faces (80%)
thick neck (buffalo hump and supraclavicular fat accumulation - 80%)
muscle wasting and weakness (steroid myopathy - 70%)
easy bruising (50%)
cyp450 3a4 inhibitors
protease inhibitors
antifungals
split dose of glucocorticoid in half if necessary concurrent admin
cyp450 3a4 inducer
phenytoin
rifampin
barbiturates
carbamazepine
double dose of glucocorticoids if necessary concurrent admin
treatment strategy to prevent Cushing’s syndrome
give lowest glucocorticoid dose and shortest possible duration
use admin routes that minimize systemic absorption (like inhalation or topical)
avoid concurrent administrations of drugs that inhibit/induce steroid metabolism
gradually taper the dose
supplement with extra dose of steroid during periods of physiologic stress
gradually taper the dose
prednisone 20mg (or equivalent) daily given in the morning –> every other day in the morning –> reach equivalent physiologic dose –> stop
recovery period
up to a year for HPA axis recovering after steroid discontinuation
may need extra dose of steroid during periods of physiologic stress - surgery or emergency treatment
adrenal insufficiency
inability of the adrenal gland to produce adequate amount of cortisol to regulate normal body functions in time of stress
long term usage of steroids make adrenal glands get lazy
signs of adrenal insufficiency (addison’s disease)
bronze pigmentation of skin
changes in distribution of body hair
weakness
weight loss
key monitoring parameters
subjective well-being of the patient in primary and secondary disease
resolution of hypotension, dizziness, dehydrations, hyponatremia, and hyperkalemia
monitor for adverse reactions of steroid (under-replacement and over-replacement)
maintenance of normal weight
blood pressure
electrolytes 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
weight gain
central obesity
stretch marks
osteopenia/osteoporosis
impaired glucose tolerance
high blood pressure
appropriate education for adrenal insufficiency
take with meals or milk
do not stop therapy without seeking healthcare provider’s advice
increase the dose of glucocorticoid during excessive physiologic stress
how to administer parenteral glucocorticoid if unable to immediately access medical care during an emergency
need to wear or carry identification
cause of adrenal insufficiency, including drug-induced etiologies
how to recognize the clinical manifestations
how to prevent an acute adrenal crisis
physiologic stress
presence of fever
invasive dental procedure
invasive diagnostic procedures
surgery
traditional replacement for adults
15 to 25 mg of hydrocortisone per day OR 20 to 35 mg of cortisone per day
alternative replacement for adults
prednisone 3 to 5 mg per day
may be given to patients with reduced adherence
treatment strategies
traditional replacement for adults
dosing regimen for short-acting steroids
glucocorticoid replacement for acute adrenal crisis
TID dosing
give 2/3 of dosing in the morning between 6-8am
give 1/3 of dosing in the early afternoon roughly 2 hours after lunch
can decrease adherence
delivering at night causes insomnia
glucocorticoid replacement for acute adrenal crisis
1) administer 100mg of HC IV
2) administer 200mg per day of HC as continuous infusion for 24 hours
3) when stable, reduce dose to 100mg per day of HC the following day
4) taper to maintenance therapy by day 4 or 5
5) add mineralocorticoid therapy as required
6) maintain or increase the dose to 200-400mg per day if complications persist or occur
systemic glucocorticoid interactions
undergo metabolism by cyp450 3A4, cyp340, and other transformations in the liver
substrates of p-glycoprotein membrane efflux transporters
meds may alter serum concentration
