4 Glucocorticoids Flashcards
What is the one mineralocorticoid?
Fludrocortisone
Mimics aldosterone - has mineralocorticoid and SOME glucocortiocoid activity
Drug used to treat adrenal insufficiency if you cannot get sufficient water and salt retention with glucocortiocoids alone
Fludrocortison
What is the major endogenous corticosteroid?
Cortisol
What is the synthetic form of cortisol?
Hydrocortisone
How does cortisol circulate in plasma?
Bound to cortisol binding protein
Why are most actions of cortisol slow onset and long acting?
Circulates bound to protein
Binds to cytoplasmic receptor —> stimulates gene transcription (slow process)
BUT it DOES have SOME rapid actions
Which effects of cortisol are RAPID?
Anti-inflammatory
Effect of glucocorticoids on carbs, proteins, and fats
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)
CV effects of glucocorticoids
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
Normal range of cortisol to aldosterone like effects of corticosteroids?
200:1
Synthetic versions have increased ratio (minimize aldosterone effects)
Endocrine effects of glucocorticoids
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
Why are the endocrine effects of glucocorticoids a big deal for long term use?
Inhibited Vit D and increased PTH —> bone loss
What are the immune system effects of glucocorticoids?
Immunosuppression with CHRONIC treatment
Blocks all steps in inflammation (RAPID effect)
• Reduces PLA2, COX2, Cytokines, IgE responses
Suppression of wound healing
CNS effects of glucocorticoids
Acute - occur rapidly!
Mood elevation Insomnia, restlessness Anxiety Depression Psychosis Increased appetite
Cushing’s syndrome is due to …
Glucocorticoid excess
If ACTH excess if the reason - pituitary tumor
If cortisol excess is the reason - adrenal tumor or excess exogenous glucocorticoids
Lack of cortisol is a disease called…
Addison’s
Can be due to adrenal malfunction or pituitary malfunction
How is Cushing’s diagnosed
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)
What is an Addisonian crisis?
Acute adrenal insufficiency
Must be treated immediately with corticosteroids to avoid circulatory collapse, dehydration, vomiting, hyperkalemia, DEATH
Hydrocortisone works as both ______ and ______, while newer synthetics only have _______ effects.
Replacement and weak anti-inflammatory
Anti-inflammatory only
Hydrocortisone and cortisone both have equal parts…
Mineralocorticoid and glucocorticoid properties
What is the relationship between hydrocortisone/cortisone?
Cortisone must first be converted to hydrocortisone in the liver in order to be active - it therefore has slightly lower potency than hydrocortisone
What is the main indication for the use of hydrocortisone?
Replacement therapy for adrenal insuffiency
Prednisone and Prednisolone have more ______ effect than ______
Glucocorticoid > mineralocorticoid
Most commonly prescribed oral glucocorticoid
Prednisone must first be converted to ______ in the liver in order to be active
Prednisolone
You therefore would want to use Prednisolone in someone who has poor liver function
Triamcinolone (Kenalog) and Methylprednisolone (Medrol) have _______ mineralocorticoid effect
Virtually no
True of most newer glucocorticoids
Good for acute asthma exacerbations
What are the different possible formations for glucocorticoids?
Oral for long term therapy
Injections for emergencies or depot administration
Inhaled/nasal for asthma and rhinitis
Topical
Why do topical glucocorticoids cause skin atrophy?
Repeated application —> depot effect
What happens when you are on chronic glucocorticoids and you have a stressful event/time period?
You must use increased amounts
2x for minor stress
Up to 10x for major stress
If not —> acute insufficiency —> life threatening
Conditions other than adrenal insufficiency that can be treated with glucocorticoids
RA (decreases inflammation —> reduced pain, inc function)
Asthma - inhaled = first line treatment (inconjunction with B2 agonist)
Intranasal for rhinitis
Therapeutic guidelines for glucocorticoid use
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
Is short term glucocorticoid therapy likely to cause serious problems?
NOPE - 1-2 weeks will be just fine
How do glucocorticoids adversely effect infections?
May mask symptoms
More susceptible to serious infections
But sometimes used in infection to reduce inflammation
Adverse effect of glucocorticoids on hyperglycemia
May unmask diabetes in some patients
CNS effects of glucocorticoids can occur even with ______
Acute treatment
Restlessness, insomnia, psychoses, increased appetite
Adverse effect of glucocorticoids on the bones
Can cause Osteoporosis*** Most damaging and therapeutically limiting effect
Function of duration and dose
Treatments include Ca2+, Vit D, bisphosphonates
Why do you have to taper glucocorticoids
> 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
Are there any contraindications for use of glucocorticoids in adrenal insufficiency
NO - THEY’LL DIE IF YOU DON’T TREAT THEM
C/I for glucocorticoid use
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)
How does Ketoconazole work as a corticosteroid antagonist
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
MOA for Mitotane
Adrenocorticolytic - causes adrenocortical atrophy
Used in primary adrenal carcinoma when surgery/radiation not feasible (not first line)
Causes severe GI distress
MOA for Metyrapone (Metopirone)
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
Only corticosteroid synthesis inhibitor that can be given in pregnancy
Metyrapone (Metopirone)
Because it doesn’t inhibit sex hormone synthesis
What are the two receptor antagonists we discussed?
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
