Glucocorticoids

Question 1

How much cortisol/day is produced?
How much is bound to circulating proteins?
How much is free and how much is bound to albumin

Answer 1

normally 10-20mg
most (90%) is bound to circulating proteins synthesized by the liver
5-10% is free and ~5% is loosely bound to albumin

Question 2

the 1/2 life of cortisol is what?
what may increase the half life?
How is it metabolized?
How is it excreted?

Answer 2

~60-90 min
exogenous hydrocortisone is given, stress, hypothyroidism, liver dz
liver
urine

Question 3

Cortisol’s effects
Influences the function of what?
Interacts with what?

Answer 3

most cells in the body
widely distributed glucocorticoid receptors & influence target genes

Question 4

Cortisol’s effects - CHO, Protein & fat metabolism
Stimulates what in a fasting state?
Increased glucose levels/stimulation of insulin release results in what?
Stimulation of lipase/lipolysis & lipogenesis with what results?

Answer 4

gluconeogenesis & glycogen synthesis
inhibits glucose uptake by muscle
increase in fat deposition, increased fatty acid & glycerol release

Question 5

Cortisol’s effects - Catabolic & anti-anabolic effects in skin, muscle fat, lymphoid, & connective tissue
Increased amounts of glucocorticoids = ?

Answer 5

decreased muscle mass, weakness, thin skin, osteoporosis

Question 6

Cortisol stimulates RNA & protein synthesis where?

Answer 6

the liver

Question 7

Cortisol’s effects - Anti-inflammatory
Affects activation, production, circulation, function & survival of what?
Increases neutrophils in peripheral circulation but decreases what cell counts?
Induction of apoptosis on what?
Decreases multiple inflammatory cytokines & interleukins (which ones?) and increases anti-inflammatory cytokines (which ones?)
Inhibits function of what cell type? limits the cells ability to do what?

Answer 7

leukocytes
monocytes, lymphocytes, (T&B cells), eosinophils, & basophils
immature & activated T cells
IL- 1, 2, 6, TNF); IL-4, 10, 13)
macrophages; phagocytose & kill microorganisms

Question 8

Cortisol regulates the expansion of what?

Answer 8

the protein responsible for the conversion of NE to epi in adrenal medulla

Question 9

Synthetic steroids are metabolized how?
however, alterations in glucocorticoid molecule alters what?

Answer 9

similarly as endogenous steroids
affinity for receptors & protein-binding affinity, stability, rate of elimination, & metabolic products

Question 10

Synthetic steroids half lives are?

Answer 10

prolonged by > 50%

Question 11

Synthetic steroids are sometimes administered as a prodrug ____ which is rapidly converted to active form ____)

Answer 11

prednisone –> prednisolone

Question 12

Indications to administer synthetic steroids includes?

Answer 12

Adrenocortical insufficiency
Allergic rxns
Collagen-vascular d/os (arteritis, SLE, connective tissue disease, PMR, RA)
GI disease (IBS)
Hematologic disease (hemolytic anemia, leukemia, ITP, myeloma)
Infections/sepsis
Inflammation of bones/joints (arthritis, bursitis)
Pulmonary dz (asthma, COPD)
Transplantation

Question 13

What is Critical Illness-Related Corticosteroid Insufficiency (CIRCI)?

Answer 13

Inadequate intracellular corticosteroid activity manifested by insufficient down regulation of pro-inflammatory transcription factors

Question 14

How do we diagnose CIRCI?

Answer 14

CST: delta (change) in baseline cortisol @ 60 MIN OF < 9 nanogram/dL after cosyntropin (250 nanogram) administration & random plasma cortisol of < 10 nanogram/dL; not widely used in practice

use total cortisol level

Question 15

What 3 major pathophysiologic events may be involved in CIRCI?

Answer 15

dysregulation of HPA axis
Altered cortisol metabolism
Tissue resistance to glucocorticoids

Question 16

Clinical features of CIRCI - General

Answer 16

fever
asthenia

Question 17

Clinical features of CIRCI - Neurologic

Answer 17

Confusion
Delirium
Coma

Question 18

Clinical features of CIRCI - Cardiovascular

Answer 18

Hypotension refractor to fluid resuscitation
Decreased sensitivity to catecholamines
High CI

Question 19

Clinical features of CIRCI - Digestive

Answer 19

Nausea
Vomiting
Intolerance to enteral nutrition

Question 20

Clinical features of CIRCI - Respiratory

Answer 20

Persistent hypoxia

Question 21

Clinical features of CIRCI - Laboratory

Answer 21

Hypoglycemia
Hyponatremia
Hyperkalemia
Metabolic Acidosis
Hypereosinophilia

Question 22

Clinical features of CIRCI - Imaging

Answer 22

Hemorrhage or necrosis in hypothalamus, pituitary gland or adrenal gland

Question 23

CIRCI occurs in severe acute conditions including?

Answer 23

Sepsis/septic shock
Severe CAP
ARDS
Cardiac Arrest
Head Injury
Trauma
Burns
Major Surgery

Question 24

Treatment for CIRCI?

Answer 24

IV hydrocortisone < 400mg/day for >/= 3 days @ gfull dose in patients with septic shock not responsive to fluid & moderate- to high-dose vasopressor therapy (conditional, low quality evidence)

Question 25

Results of Annane Trial?
Patients were randomly assigned to receive either hydrocortisone (50mg IV q 6 hrs) & fludrocortisone (50 nanogram qd) or placebo x 7days

Answer 25

7-day treatment w/ low doses of hydrocortisone & fludrocortisone significantly reduced risk of death in patients with septic shock & relative AI w/o increasing adverse events

Question 26

Hydrocortisone MOA

Answer 26

decreases inflammation via suppression of migration of PMN leukocytes & reversal of increased cap permeability

Question 27

Hydrocortisone Drug interactions
Decreased effect of what drugs?
Increased effect of what drugs?

Answer 27

insulin, phenytoin, phenobarb, rifampin d/t increased metabolism of drug

may increase PT with anticoagulants, increase risk of hypokalemia with diuretics, increase risk of arrhythmias or dig toxicity d/t hypokalemia

Question 28

Hydrocortisone Pharmacokinetics
Can be given which routes?
onset of action?
Absorption?
1/2 life?
metabolism?
excretion?
Dose?

Answer 28

topical (acetate), IV (succinate), IM
acetate (slow), succinate (rapid)
rapid
8-12 hrs
hepatic
urine
varies

Question 29

Prednisone MOA

Answer 29

decreases inflammation via suppression of migration of PMN leukocytes & reversal of increased cp permeability; reduces activity & volume of lymphatic system

Question 30

Drug interactions with prednisone
Decreased effect
Increase risk of GI ulceration when used w/ what?

Answer 30

barbituates, phenytoin, rifampin

NSAIDs

Question 31

Pharmacodynamics/kinetics of Prednisone
Form?
1/2 life?
Metabolism?
Excretion?
Dose?

Answer 31

PO
18-36 hrs
hepatic
urine
varies

Question 32

Methylprednisolone Drug Interactions
Decrease what drugs effects?
Increases what?

Answer 32

insulin’s effect d/t increased glucose levels, phenytoin, phenobarb, rifampin increase metabolis of drug = decreased levels

CSA & tacrolimus levels, intraconazole increases steroid levels

Question 33

Methylprednisolone Pharmacodynamics/kinetics
forms?
Onset of action?
Duration of action?
1/2 life?
Metabolism?
Excretion?

Answer 33

PO, Intra-articular, IM, IV
PO (1-2 hrs), Intra-articular (1 wk), IM acetate (4-8days), & IV succinate (rapid)
PO (30-36 hrs), intra-articular (1-5 wks), IM (1-4 wks)
18-36hrs
hepatic
urine

Question 34

Dexamethasone MOA

Answer 34

Decreases inflammation via suppression of neutrophil migration, decreases production of inflammatory mediators, & reduces cap permeability

Question 35

Dexamethasone drug interactions
decreased effect in what drugs?
increased effect in what drugs

Answer 35

isoniazid & phenytoin levels may be decreased, may see reduction in coumadin effect

‘azoles’, CCBs, CSA, estrogens may increase levels. NSAIDs & aspirin may increase risk of adverse GI effects. +/- increased weakness if receiving anticholinergics & neuromuscular blocking agents

Question 36

Dexamethasone Pharmacodynamics/kinetics
Forms?
Onset of action?
1/2 life?
Duration of action?
Metabolism?
Excretion?

Answer 36

PO, IM, IV
prompt
36-54 hrs
72hrs
hepatic
urine & feces

Question 37

Steroid Generalities - Adverse Effects
Cushing’s Syndrome presents as?

Answer 37

Moon faces
redistribution of fat from extremities to trunk, back of neck, supraclavicular fossae
Increased hair growth to face, thighs, turnk
acne
weight gain
thinning skin, striae, bruising
hyperglycemia
osteoporosis, DM, aseptic necrosis of hip
muscle weakness/wasting

Question 38

Steroid Generalities
Other adverse effects

Answer 38

Infections
peptic ulcers
myopathy
hypomania, acute psychosis
depression
cataracts
Glaucoma
Na/H2O retention when cortisone, hydrocortisone given supraphysiologic doses
Adrenal suppression (usually not seen until after 2-3 weeks of therapy, qd dosing is less suppressive than divided doses)

Question 39

ACTH stimulation test may be used to detect adrenal insufficiency - how is it done?

Answer 39

1. measure baseline cortisol level
2. inject 250 mcg cosyntropin IM or IV
3. meausre cortisol level @ 30 & 60 min (level should be >18 mcg/dL

Question 40

Use steroids w/ caution in what conditions?

Answer 40

PUD
Heart Disease
HTN
CHF
varicella
TB
psychosis
DM
osteoporosis
glaucoma

Question 41

Avoid administering what while on steroids?

Answer 41

live vaccinations

Question 42

In elderly what precautions should be made with steroids?

Answer 42

use the smallest effective dose for shortest amount of time