4 Glucocorticoids

Question 1

What is the one mineralocorticoid?

Answer 1

Fludrocortisone

Mimics aldosterone - has mineralocorticoid and SOME glucocortiocoid activity

Question 2

Drug used to treat adrenal insufficiency if you cannot get sufficient water and salt retention with glucocortiocoids alone

Answer 2

Fludrocortison

Question 3

What is the major endogenous corticosteroid?

Answer 3

Cortisol

Question 4

What is the synthetic form of cortisol?

Answer 4

Hydrocortisone

Question 5

How does cortisol circulate in plasma?

Answer 5

Bound to cortisol binding protein

Question 6

Why are most actions of cortisol slow onset and long acting?

Answer 6

Circulates bound to protein

Binds to cytoplasmic receptor —> stimulates gene transcription (slow process)

BUT it DOES have SOME rapid actions

Question 7

Which effects of cortisol are RAPID?

Answer 7

Anti-inflammatory

Question 8

Effect of glucocorticoids on carbs, proteins, and fats

Answer 8

Increases circulating levels of GLUCOSE, free fatty acids, and AAs

ANTAGONIZES insulin —> reduced uptake of glucose by muscles —> HYPERGLYCEMIA

Redistribution of body fat (extremities —> central)

Breakdown of muscle for use by liver (muscle atrophy)

Question 9

CV effects of glucocorticoids

Answer 9

Increased vascular responsiveness to SYMPATHETIC stimulation (That’s why it’s great for ASTHMA)

Some Na+ and H20 retention

Increased CO (incr blood volume —> incr preload —> incr stroke volume) —> increased catecholamine effect

Question 10

Normal range of cortisol to aldosterone like effects of corticosteroids?

Answer 10

200:1

Synthetic versions have increased ratio (minimize aldosterone effects)

Question 11

Endocrine effects of glucocorticoids

Answer 11

Suppresses other hormone systems due to direct negative feedback on hypothalamus (CRH —> dec ACTH)

Inhibits action of vitamin D —> dec Ca2+ deposition
Increased PTH —> inc Ca2+ loss form bone

Question 12

Why are the endocrine effects of glucocorticoids a big deal for long term use?

Answer 12

Inhibited Vit D and increased PTH —> bone loss

Question 13

What are the immune system effects of glucocorticoids?

Answer 13

Immunosuppression with CHRONIC treatment

Blocks all steps in inflammation (RAPID effect)
• Reduces PLA2, COX2, Cytokines, IgE responses

Suppression of wound healing

Question 14

CNS effects of glucocorticoids

Answer 14

Acute - occur rapidly!

Mood elevation
Insomnia, restlessness
Anxiety
Depression
Psychosis
Increased appetite

Question 15

Cushing’s syndrome is due to …

Answer 15

Glucocorticoid excess

If ACTH excess if the reason - pituitary tumor

If cortisol excess is the reason - adrenal tumor or excess exogenous glucocorticoids

Question 16

Lack of cortisol is a disease called…

Answer 16

Addison’s

Can be due to adrenal malfunction or pituitary malfunction

Question 17

How is Cushing’s diagnosed

Answer 17

Dexamethasone suppression test

Measure baseline cortisol level in AM, administer dexamethasone in PM, measure again the following morning

Abnormal result = cortisol levels ≥50% suppressed (normally would cause extreme suppression of cortisol)

Question 18

What is an Addisonian crisis?

Answer 18

Acute adrenal insufficiency

Must be treated immediately with corticosteroids to avoid circulatory collapse, dehydration, vomiting, hyperkalemia, DEATH

Question 19

Hydrocortisone works as both ______ and ______, while newer synthetics only have _______ effects.

Answer 19

Replacement and weak anti-inflammatory

Anti-inflammatory only

Question 20

Hydrocortisone and cortisone both have equal parts…

Answer 20

Mineralocorticoid and glucocorticoid properties

Question 21

What is the relationship between hydrocortisone/cortisone?

Answer 21

Cortisone must first be converted to hydrocortisone in the liver in order to be active - it therefore has slightly lower potency than hydrocortisone

Question 22

What is the main indication for the use of hydrocortisone?

Answer 22

Replacement therapy for adrenal insuffiency

Question 23

Prednisone and Prednisolone have more ______ effect than ______

Answer 23

Glucocorticoid > mineralocorticoid

Most commonly prescribed oral glucocorticoid

Question 24

Prednisone must first be converted to ______ in the liver in order to be active

Answer 24

Prednisolone

You therefore would want to use Prednisolone in someone who has poor liver function

Question 25

Triamcinolone (Kenalog) and Methylprednisolone (Medrol) have _______ mineralocorticoid effect

Answer 25

Virtually no True of most newer glucocorticoids Good for acute asthma exacerbations

Question 26

What are the different possible formations for glucocorticoids?

Answer 26

Oral for long term therapy Injections for emergencies or depot administration Inhaled/nasal for asthma and rhinitis Topical

Question 27

Why do topical glucocorticoids cause skin atrophy?

Answer 27

Repeated application —> depot effect

Question 28

What happens when you are on chronic glucocorticoids and you have a stressful event/time period?

Answer 28

You must use increased amounts 2x for minor stress Up to 10x for major stress If not —> acute insufficiency —> life threatening

Question 29

Conditions other than adrenal insufficiency that can be treated with glucocorticoids

Answer 29

RA (decreases inflammation —> reduced pain, inc function) Asthma - inhaled = first line treatment (inconjunction with B2 agonist) Intranasal for rhinitis

Question 30

Therapeutic guidelines for glucocorticoid use

Answer 30

Use only as long as necessary and at the lowest effective dose Start high and slowly taper once inflammation under control Use LOCALLY whenever possible Give on alternate days to avoid suppression of HPA axis

Question 31

Is short term glucocorticoid therapy likely to cause serious problems?

Answer 31

NOPE - 1-2 weeks will be just fine

Question 32

How do glucocorticoids adversely effect infections?

Answer 32

May mask symptoms More susceptible to serious infections But sometimes used in infection to reduce inflammation

Question 33

Adverse effect of glucocorticoids on hyperglycemia

Answer 33

May unmask diabetes in some patients

Question 34

CNS effects of glucocorticoids can occur even with ______

Answer 34

Acute treatment Restlessness, insomnia, psychoses, increased appetite

Question 35

Adverse effect of glucocorticoids on the bones

Answer 35

Can cause Osteoporosis*** Most damaging and therapeutically limiting effect Function of duration and dose Treatments include Ca2+, Vit D, bisphosphonates

Question 36

Why do you have to taper glucocorticoids

Answer 36

>1-2 weeks of high dose therapy suppresses HPA —> abrupt drug cessation can cause ACUTE ADRENAL INSUFFIENCY Stress can also cause acute adrenal crisis in chronic patients

Question 37

Are there any contraindications for use of glucocorticoids in adrenal insufficiency

Answer 37

NO - THEY’LL DIE IF YOU DON’T TREAT THEM

Question 38

C/I for glucocorticoid use

Answer 38

***NONE in adrenal insufficiency*** Systemic bacterial or viral infection Poorly controlled diabetes Osteoporosis or other advanced bone disease Heart disease or HTN with CHF Immunosuppressive patients Childhood Pregnancy (unless using it to mature lungs prior to premature delivery)

Question 39

How does Ketoconazole work as a corticosteroid antagonist

Answer 39

Antifungal that inhibits steroid synthesis at very high doses NON-SELECTIVE - will also suppress androgen synthesis Used for PREOP suppression - one of the first line drugs for Cushing’s before surgery

Question 40

MOA for Mitotane

Answer 40

Adrenocorticolytic - causes adrenocortical atrophy Used in primary adrenal carcinoma when surgery/radiation not feasible (not first line) Causes severe GI distress

Question 41

MOA for Metyrapone (Metopirone)

Answer 41

Selective inhibitor of the terminal enzyme in cortisol synthesis - doesn’t effect other steroid production Short term use while causes of Cushing’s being determined Less toxic than Mitotane

Question 42

Only corticosteroid synthesis inhibitor that can be given in pregnancy

Answer 42

Metyrapone (Metopirone) Because it doesn’t inhibit sex hormone synthesis

Question 43

What are the two receptor antagonists we discussed?

Answer 43

Glucocorticoid receptor antagonist = MIFEPRISTONE • For inoperable Cushing’s patients • Induces abortions (b/c inhibits progesterone receptors) Mineralocorticoid receptor antagonist = SPIRONOLACTONE • Potassium sparing diuretic —> can cause hyperkalemia • Used for hyperaldosteronism and hirsutism