Glucocorticosteroids

Question 1

Ant. Pituitary Hormones

Answer 1

Hypothalamus - CRH -
ACTH (Adrenal Cortex; Diurnal variation) - Cholesterol to Pregnenolone - Cortisol (Feedback on Hypothalamus, Reduce CRH), Aldosterone, Androgens, Estrogens

Question 2

Adrenal Gland Hormones

Answer 2

Cortisol (Glucocorticoid - Zona fasciculata)
Aldosterone (Mineralocorticoid - Zona glomerulosa)
Adrenal Androgens (Androstenedione and Dehydroepiandrosterone - DHEA - Zona reticularis)
Epinephrine (Adrenaline)
Enkephalin (Both in Medulla)
Inner Medulla and Outer Cortex - Cortex from Mesoderm and Medulla from NC Cells

Question 3

Inhibited by Ketoconazole

Answer 3

17a-hydroxylase

17,20 lyase

Question 4

Adrenal Steroids Pharmacokinetics

Answer 4

Cortisol and Progesterone - Bind Corticosteroid-Binding Globulin (CBG) also called Transcortin and Albumin
CBG w/ high affinity for cortisol but low capacity
Albumin w/ low affinity for cortisol but high capacity
Unbound cortisol exterts biologic activity - Affinity and capacity of plasma proteins regulate availability and activity
Amt of transcortin in plasma elevates by female sex hormones (estrogens) and lowered by liver disease, amyloid disease or multiple myeloma
Aldosterone, dehydroepiandrosterone and androstenedione transported diff from cortisol - Bound to albumin
Liver and kidney responsible for cortisol metabolism
Cortisol reduced in liver and conjugated to glucuronic acid and excreted in kidney
Cortisol activity regulated by 11beta-hydroxysteroid dehydrogenase (Liver and adipose tissue w/Type I, Kidney collecting duct cells w/Type 2)

Question 5

11 Beta-Hydroxysteroid Dehydrogenase

Answer 5

Type I - Liver - Ketone to Hydroxygroup

Type II - Kidney - Hydroxygroup to Ketone

Question 6

Inactive Metabolites

Answer 6

Peripheral tissues and by liver
Conversion to inactive tetrahydro-derivatives
Conjugated to glucuronic or sulfuric acid and excreted in urine

Question 7

Genomic Glucocorticoids Action

Answer 7

Increase blood glucose, Gluconeogenesis, Brain activity, Stress resistance, Decrease Inflammation, Immune response

(Also increase resistance to stress, Increase WBC, Decrease water excretion;
Permissive effects - allow Epi/NE to work better)

Question 8

Nongenomic Glucocorticoids Action

Answer 8

Occur fast (<5min)
Not stopped blocking MR and GR
Effect don’t rely on protein synthesis
Effect on receptors other than MR or GR
Described in brain, lungs, liver, muscle, fat, kidney and immune system;
Behavior aggression, Memory, Risk taking, Mood (Euphoria-depression)
Alter membrane fluidity
Effect on ion channels (Ca++)
Neurotransmitter release
Intracellular but non-nuclear proteins, kinases
Glucocorticoid importers and CBG

Question 9

Cortisol

Answer 9

Glucocorticoid
Counter-regulatory to insulin
Elevates blood glucose and promotes Gluconeogenesis (Inhibits peripheral protein synthesis and stimulates breakdown of muscle protein; Amino acids then available for liver Gluconeogenesis)
Induces synthesis of gluconeogenic enzymes in liver
Increases glycogen deposition and glucose release by liver

Question 10

Physiologic Effect of Glucocorticoids - Inflammation

Answer 10

Antiinflammatory
Decrease NFkB - Decrease cytokine from immune cells
Suppress genes for IL 1-6,8, IFN-y leading to decrease Tcell proliferation
Stimulate Lipocortin (Annexin A1) production which inhibit PLA2 - Inhibit 2 products of inflammation, prostaglandins and leukotrienes - Inhibit various leukocyte inflammatory events and suppress COX expression

Question 11

Physiologic Effect of Glucocorticoids - Development

Answer 11

Promote maturation of lung and production of surfactant necessary for extra-uterine lung function

Question 12

Physiologic Effect of Glucocorticoids - Brain Function

Answer 12

Form memories w/emotion
Arousal and alertness
Adrenal insufficiency w/ depression
Increase initial cause euphoria and insomnia then depression
ACTH treat infantile spasms w/hypsarrythmia

Question 13

Physiologic Effect of Glucocorticoids - Bone

Answer 13

Inhibit bone formation (Reduce osteoblasts)
Increase RANK - Increase osteoclasts
Decrease osteoblast function directly and indirect through modulation of growth factor expression, receptor binding or binding protein levels
GIOP treat w/bisphosphonates, anabolic hormones and PTH

Question 14

Adverse Effects of Glucocorticoids

Answer 14

Endocrine - Decrease GH, Decrease TSH, LH, FSH
GI - Peptic ulcers
Brain - CNS depression, Psychosis
Bone - Decrease bone formation, Decrease bone mass, Osteoporosis
Skeletal m./CT - Protein catabolism, Muscle atrophy, Collagen breakdown, Skin thicken
Eye - Cataract, Glaucoma
Carb - Increase Gluconeogenesis, Free FA production, Increase insulin resistance, Increase hepatic glycogen deposition, Visceral fat
Cardio/Renal - Increase BP, Salt and water retention
Growth - Decrease linear growth
Immune system - Immunosuppressive, Antiinflammatory

Question 15

Adrenal Androgens

Answer 15

Anabolic
Increase protein synthesis in peripheral tissues
Opposite of cortisol
Pubertal growth spurt in F
Masculinization if excessive (Adrenal tumor)
Androstenedione - Substrate for estrogen synthesis in adipose tissue and estrogen-secreting endocrine glands

Question 16

Steroids

Answer 16

(Memorize chart)

Question 17

Slight Soluble in Water

Answer 17

Cortisol (Hydrocortisone) (Cortef)
Prednisolone (Hydeltra)
Triamcinolone (Kenacort)
Oral, Topical

Question 18

Insoluble in Water

Answer 18

Hydrocortisone Acetate (Cortef Acetate)
Prednisolone Bytylacetate (Hydeltra-T,B,A)
Triamcinolone Acetonide (Kenalog)
Intra-articular, Topical,

Question 19

Very Soluble in Water

Answer 19

Hydrocortisone Sodium Succinate (Solu-Cortef)
Prednisolone Sodium Phosphate (Hydeltrasol)
IM, IV, Topical

Question 20

Medrol Dosepak

Answer 20

Reduce interference with HPA control axis - Provided in descending dosage regimen for six day anti-inflammatory treatment
Prolong inhibition of HPA leads to prolonged loss of natural corticosteroid release

Question 21

TMJ Arthritis Treatment

Answer 21

Steroid Injection
Prednisolone Acetate (Meticortelone Acetate), 10-15mg (25mg/mL in 5mL vials), 3-4days

Question 22

Oral Lesion Treatment

Answer 22

Steroid Topical
Triamcinolone Acetonide (Kenalog) - 0.1% paste in Orabase, Apply thing film 2-3Xd for 5d

Question 23

Fludrocortisone

Answer 23

Florinef
Glucocorticoid and Mineralocorticoid activity (Widely used Mineralocorticoid)
Adrenocortical insufficiency
Aldosterone insufficiency

Question 24

Deoxycorticosterone (DOC)

Answer 24

Precursor of Aldosterone

Secretion under control of ACTH

Question 25

Cushing Syndrome Cause

Answer 25

Endogenous Cause: Bilateral adrenal hyperplasia, Secondary to ACTH-secreting pituitary adenoma; Due to adrenal tumors or production of ACTH from ectopic lung tumors Exogenous Cause: Large doses of steroids given for management - asthma, rheumatoid arthritis, lupus or chronic skin conditions can increase cortisol levels in blood

Question 26

Cushing Syndrome Signs and Symptoms

Answer 26

Emotional disturbance, Enlarged sella turcica, Truncal adiposity (abdomen, neck, face), Round face (moon like), Osteoporosis, Hypertension, Obesity, Adrenal tumor/Hyperplasia, Loss of subcutaneous adipose tissue, Thin and wrinkled skin, Abdominal striae, Amenorrhea, Bruising, Striae, Hyperglycemia, Muscle wasting, Poor wound healing, Mental disorders, Purpura, Skin ulcers

Question 27

Cushing Syndrome Treatment

Answer 27

Surgery, Radiation, Medication Mifepristone (GR receptor antagonist) approved to control hyperglycemia in adult patients who are not good surgical candidates

Question 28

Cushing Syndrome Dental Alerts

Answer 28

Increase risk for systemic diseases - Modify management Monitor BP routinely, Aspirin and NSAIDs should be avoided bc of high incidence of peptic ulcer Increased risk of periodontitis, oral candidiasis and bleeding gums Excess steroids in system lower immune system activity - Increase risk of infections and poor wound healing Adequate antibiotic coverage for 7days following major surgery Assess and treat oral cavity for oral and esophageal candidiasis when present General osteoporosis also affect mandible and patients w/dentures need readjustment

Question 29

Addison Disease

Answer 29

Adrenal insufficiency mostly autoimmune Bronze pigmentation of skin, Weight loss, GI disturbance, Change in body hair distribution, Hypoglycemia, Hypotension, Hyperkalemia, Fatigue, Muscle weakness, Pigmented mucous memrane patches and pigmentation around mouth (due to ACTH binding to MSH receptors or MSH from POMC)

Question 30

Congenital Adrenal Hyperplasia

Answer 30

Defects in cortisol synthesis Lack of 21beta-hydroxylase activity - Decrease cortisol, Increase ACTH, gland is hyper plastic and increase precursors like 17-hydroxyprogesterone that make androgens to cause virilzation (adrenal androgens) Metabolite pregnanetriol in urine is diagnostic

Question 31

Addisons Disease Dental Alerts

Answer 31

Steroids to fight stress w/infection, inflammation, bleeding, post procedure starvation, preop and postop pain and trauma Consult w/physician and provide steroid coverage to compensate stress Fail to provide coverage precipitates acute adrenal insufficiency and cardiovascular collapse Steroids for more than 2wks w/adrenal insufficiency and could need coverage for 2yrs for HPA to recover Treat oral infections aggressively to prevent hypoadrenal crisis or acute adrenal insufficiency Best to treat in first appointment of day Night shift workers may have circadian rhythm reversal - Max release in evening Patient on steroids - Best to take steroid 2hrs before appt Minor procedure - No steroid supplement Avoid barbiturates (Decrease cortisol)

Question 32

Mild Stress Steroid Dose

Answer 32

(1-4 extractions/1 quad flap) Double steroid dose Patient not currently on steroids - Use 1/3 1h before surgery: 1. 6mg Prednisone PO 2. 25mg Hydrocortisone PO/IV 3. 5mg Prednisone PO

Question 33

Moderate Stress Steroid Dose

Answer 33

(5-16 extractions/2quad flap) Use 1/2 1h before surgery: 1. 15-20mg Prednisone PO 2. 50-75mg Hydrocortisone PO/IV

Question 34

Severe Stress Steroid Dose

Answer 34

(17> extractions/3quad flap) Use 1/2 1h before surgery: 1. 25-40mg Prednisone PO 2. 100-150mg Hydrocortisone PO/IV

Question 35

Commonly Used Steroids

Answer 35

Cortisol and Cortisone - Replacement in adrenal insufficiency, Small doses Addisons disease patients Abrupt withdrawal after long-term therapy glucocorticoid induces deficiency Most freq use is treatment of allergic condition, inflammation (ex. rheumatoid arthritis, dermatitis, seasonal rhinitis, bronchial asthma, stomatitis, gingivitis, TMJ dysfunction) Pharm (large, anti-inflammatory) doses used Exudation inhibited Cell proliferation inhibited Phagocytosis suppression