Corticosteroids are ___ with receptors ____ throughtout the body. Example?
anti-inflammatory
widely distributed
glucocorticoids (cortisol)
Secretion of endogenous cortisol increases in response to ___. What is baseline episodic secretion?
stress
~20 mg/day
What are the anti-insulin effects of corticosteroids?
gluconeogenesis
inhibition of glucose utilization
hyperglycemia
Corticosteroid interaction with catecholamines?
vascular smooth muscle response
Corticosteroids have some sodium ___ and potassium
retention
excretion (mineral corticoid effect)
Exogenous glucocorticoids are primarily used to replace
glucocorticoid deficiency (Addison’s disease)
25-37.5 mg daily replacement
Inhaled exogenous glucocorticoids are used for
asthma
Inhaled steroids have a ___ effect and little
local effect
systemic absorption
Examples of inhaled steroids?
Azmacort - triamcinolone Beclovet - beclomethasone Flovent - fluticasone Pulmicort - budesonide Advair - flutocasone + salmetrol
Inhaled steroids can cause significant ____ deposition leading to
pharyngeal
dysphonia, candidiasis
Exogenous systemic steroids are typically used for ___ of asthma given ___ hours before anesthesia
acute exacerbations
1-2 hours
Exogenous glucocorticoid given as an antiemetic? It has similar efficacy to ____. Is there data to support giving more?
4 mg IV dexamethasone
odansetron or droperidol
no
Dexamethasone is best if given near the
beginning of surgery
Dexamethasone prevents surgery-induced ____ and increases release of
inflammation
endorphins?
Why is dexamethasone used in caution with diabetics?
consider the risks of hyperglycemia vs benefits of therapy
Given for cerebral edema?
dexamethasone
larger doses required (10-20 mg)
Dexamethasone is effective for ____ due to global ischemic injury by decreasing ____ for intracranial surgery
elevated ICP
cerebral volume
What are the other uses of exogenous glucocorticoids?
anti-inflammatory - postop pain, lumbar disc disease, collagen diseases, arthritis, skin disorders, ulcerative colitis, acute spinal cord injury
immunosuppressiob (transplant) - respiratory distress syndrome, leukemia, myasthenia gravis
All patients you want to administer exogenous glucocorticoids to should be evaluated for
past/current steroid use
Many people give ____ for post-intubation laryngeal edema but there is no evidence of efficacy
dexamethasone
Side effects of glucocorticoid therapy
suppression of hypothalamic-putitary-adrenal (HPA) axis
electrolyte/metabolic changes
osteoporosis
peptic ulcer disease
CNS: psychosis (steroid rage), depression; cataracts
immunosupression: bacterial/fungal infection
Suppression of the HPA axis can occur only ___ after taking 20 mg/day ___ and take ___ to fully recover
5 days
prednisone
9-12 months
When corticosteroid therapy suppresses the HPA axis, the ____ no longer secrets ____ in response to stress (illness, injury) which causes risk of ____ with stress
adrenal gland, cortisol
acute adrenal insufficiency (cardiovascular collapse)
Risk of HPA axis suppression increases with
dose and duration of therapy
every other day therapy is better than daily
topical/inhaled/local treatment is better than systemic
How is “stress-dose” corticosteroid administered?
- Continue daily basal maintenance dosing
- Supplementation with hydrocortisone
It is a subject of much debate
What is the low and high dose for stress-dose corticosteroid?
25 mg Q12h
100 mgQ6h
Stress doses vary based on ____ of the surgical procedure as well as the perceived rush of this patient developing
magnitude
acute renal insufficiency
Is tapering needed when giving a steroid for colonoscopy?
No, 25 mg bolus
What is the dosing of steroids for a moderate surgery such as hysterectomy?
50-75 mg
25 mg q8h x3 doses
Dose of steroids for a major surgery (cardiac)?
100-150 mg
50 mg q8h x3, 50 mg q12h x2, 25 mg q12h x 2
Glucocorticoid therapy can cause a ____ effect that leads to hypokalemic metabolic acidosis (think ____)
mineralcorticoid
aldosterone
binds at renal tubules “save sodium, pee potassium”
edema, weight gain, HTN
Electrolyte/metabolic changes associated with glucocorticoid therapy?
mineralcorticoid effect
hyperglycemia
buffalo hump, moon facies, abdominal striae, tissue-paper skin
Which steroid causes the most sodium retention?
Fludrocortisone - 250
Which steroid causes the least amount of sodium retention?
Dexamethasone - 0
Cyclooxygenase (COX) enzymes convert ____ to
arachidonic acid
prostaglandins
COX-1 activity is constitutive or at a ____ level
constant
COX-1 is involved in maintenance and protection of
gastric mucosa
platelet aggregation (depends on generation of thromboxane A2)
renal blood flow
COX-2 activity is ___, expressed at the site of injury
inducible
COX-2 up regulates sensitivity of peripheral ____ to cause ___ mediated by PGE2
nociceptors
pain, inflammation
fever
Which COX crosses the BBB to facilitate spinal nociception?
COX-2
Desirable features of NSAIDs
9 features
Aspirin is a ____ COX inhibitor that causes anti platelet function due to ____ acetylation of platelet COX-1
nonselective
irreversible
Used for the prevention of thrombosis in coronary stents?
aspirin
How long should invasive procedures be avoided for a patient taking aspirin?
7-10 days
life of the platelet
Which patients are especially sensitive to aspirin?
uremic patients
Common side effects of aspirin?
bleeding
GI irritation/ulceration
Aspirin causes ____ in 8-20% of all ____ adults
bronchoconstriction/asthma
asthmatic
Aspirin is no longer used in children, especially due to
Reyes Syndrome
Overdose on aspirin causes CNS stimulation (hyperventilation, seizures) leading to
respiratory alkalosis + metabolic acidosis
When taken orally, ibuprofen has
first pass effect
consider IV use - does not accumulate over time, use Q6h
Side effects of ibuprofen
GI irritation/ulceration
some platelet dysfunction
Ibuprofen that is twice daily dosing
Naproxen
Ketorolac is a ____ analgesic that can be used as a ___ drug or to supplement
post-operative
sole, opiates
30 mg IM ketolorac =
10 mg morphine
Ketorolac causes ____ inhibition of platelet aggregation
reversible
Why should ketorolac be used with caution in renal patients?
Decreases renal blood flow on compromised patients (CHF, hypovolemia)
NSAIDs are not recommended in
pregnancy and children
especially during third trimester, linked the premature birth and miscarriage
OK in children >6 months
NSAIDs may cause premature closure of fetal ___ and limit renal blood flow
ductus arteriosus
COX-2 inhibitor used for pain/inflammation of arthritis, surgery
Celecoxib (Celebrex)
Celebrex is well absorbed from ___ with little
GI tract
first pass effect
Safer NSAID for patient with gastritis/gastric ulcers
Celebrex
NSAID with lack of antiplatelet effects
Celebrex
NSAID that is better tolerated by patients with asthma
Celebrex
Rofecoxib (vioxx) and valdecoxib (bextra) are COX-2 inhibitors that seems to cause ____ events and were ____ due to risk of MI and CVA
pro-thrombic
withdrawn from market
Acetaminophen is not a true NSAID because it is not
anti inflammatory
The mechanism of acetaminophen is ____ but some COX-2 or ____ inhibition
Not completely understood
COX-3?
Provides excellent synergy with opioids
Acetaminophen
T or F. Acetaminophen causes gastric irritation and affects platelets
False
Hepatic metabolism of acetaminophen produces ___ metabolites that are scavenged by
Inactive
Glutathione
High doses of acetaminophen leads to the formation of ___ which are nephrotoxic
P-aminophenol
N-acetyl-p-benzoquinone
Overdose of acetaminophen can cause ____ which is increased in people who are
Hepatic necrosis
Chronic alcoholics - increased P450 activity and decreased glutathione stores
With large alcohol consumption, a single dose of acetaminophen ___ is probably OK
The next day
Antioxidant used to prevent hepatic damage if given within 8 hours of acetaminophen overdose
Acetylcysteine
IV acetaminophen causes a rapid spike in plasma concentration without
First pass effect
Use q6h scheduled to maintain plasma concentration