Flashcards in 26 Clinical Use of Hormones: Focus on Steroids Mak Deck (73):
How much cortisol is released in a normal person every day?
Non-stressed patients secrete cortisol amount equivalent to 5mg prednisone daily (>5mg considered supraphysiologic, may cause HPA (hypothalamus, Pituitary, Adrenal axis) suppression)
What are the steps in the HPA axis?
Hypothalamus releases CRH (corticotropin releasing hormone) which acts on the Anterior pituitary which releases ACTH (adrenocorticotropic hormone) which acts on the Adrenal cortex which releases Cortisol (which has a negative feedback function on H and P)
What are the short acting corticosteroids?
What are the intermediate acting corticosteroids?
Prednisone. Prenisolone. Triamcinolone. Methyl-prednisone
What are the long acting corticosteroids?
What are the Mineralcorticoids?
Which corticosteroids have the highest potency?
Long acting > intermediate > short
Which corticosteroids have the highest anti-inflammatory potency?
Long acting > intermediate > short
How often do long acting corticosteroids need to be taken?
Once a day or every other day (half-life: 36-54 hours)
How often do intermediate acting corticosteroids need to be taken?
Once a day (half-life: 12-36 hours)
What is the half-life of short acting corticosteroids?
half-life: 8-12 hours
What does Cortisol do?
Regulates metabolism of proteins, CHO, and lipids. Breakdown protein and fat. Promote gluconeogenesis (can cause glucose intolerance)
What can Cortisol deficiency cause?
Severe fatigue, weakness, weight loss, hyperpigmentation, nausea, loss of appetite
What can excess Cortisol cause?
Weight gain, fatigue, easy bruising, muscle weakness, redness in the face, pink stretch marks, mood swings
What is Cortisol products based on?
Diurnal cycle. Stress and feedback mechanism
What does Aldosterone (mineralcorticoid) do?
Sodium and water retention. Increases potassium excretion. Increases circulating blood volume (HTN, edema, exertional HA)
What does Aldosterone (mineralcorticoid) deficiency do?
Reduced blood pressure, dizziness on standing, salt craving, muscle cramps
What are oral glucocorticoids classified by?
Duration of action. Generally QD dosing except for replacement therapy (Addison's). Longer acting agents have greater glucocorticoid activities
What will exogenous administration of glucocorticoids lead to?
Suppression of HPA axis (dose and duration related, administration time, routes, hence ADRs)
What is the dosing strategy for Glucocorticoids in chronic long-term suppression of immune response?
Daily or alternate day regimen
What is the dosing strategy for glucocorticoids to break an acute immune response?
IVP for emergency cases. Pulse therapy = high dose for a short period. Should consider tapering off
When are Glucocorticoids usually taken?
QD between 6-8am. BID for larger doses to reduce GI irritation
How can you decrease the ADRs with Glucocorticoids?
Alternate dose (e.g. 5mg prednisone one day, 2.5mg the other). Intermediate acting agents appropriate. May not minimize risk of osteoporosis or cataract formation
How can you prevent disease flare-ups with Glucocorticoids?
Tapering. Supraphysiologic doses x short duration (< 2 weeks) may be stopped without tapering. Individualize schedule. May switch to shorter acting agents when ~5mg prednisone for further tapering
What type of disease state could cause a higher risk of ADRs with Glucocorticoids?
Diseases causing lower serum albumin (e.g. Hypothyroidism)
What are some other Non-PO routes of Glucocorticoid administration?
Inhaled. Nasal. Ocular. Parenteral
How do the different Glucocorticoids compare in potency for inhaled and nasal products?
Flunisolide ~ TMC < Beclomethasone ~ Budesonide < Fluticasone ~ Mometasone
What is the PO PK of Glucocorticoids?
Completely absorbed. Peak levels in 30-100 minutes, delayed by food; bound to proteins. Hepatic metabolism and renally eliminated (Prednisone --> Prednisolone. Cortisone --> Hydrocortisone)
What is the Topical PK of Glucocorticoids?
Absorption increased by skin temperature, hydration, integrity of skin, occlusive dressing. Ointment > cream delivery. Enter systemic circulation and metabolized
What is the Inhaled PK of Glucocorticoids?
Work like poor PO absorption and extensive first-pass metabolism
What is the Nasal PK of Glucocorticoids?
Rapid absorption in respiratory and GI tract; undetectable in plasma
What is the Eye PK of Glucocorticoids?
Some systemic absorption, infrequent systemic ADRs
What is the IV and IM PK of Glucocorticoids?
Based on solubility of agents
How do the effects of topical Glucocorticoids differ?
By concentrations, dressings, vehicle
What are the local skin effects of topical Glucocorticoids?
Face most sensitive, more susceptible to systemic absorption. Fluorinated agents may produce a rosacea-like eruption
What type of topical Glucocorticoids forms are preferred for intertriginous and hair-bearing skin?
Aerosol sprays and foams
What are the early symptoms of Addison Crisis?
Fatigue, weight loss, hyperpigmentation, NVD, muscle/joint pain, depression
What is the main problem causing Addison Crisis?
Adrenal glands not functioning
In Addison Crisis, what are some of the steps when Cortisol (hydrocortisone, cortisone acetate, prednisone, or dexamethasone) are very low or absent?
Liver function decreases, extremely low sugar, leads to COMA and DEATH
In Addison Crisis, what are some of the steps when Aldosterone (Florinef) is very low or absent?
Kidney (water and sodium loss), leads to low fluid volume and low blood pressure, leads to SHOCK, then COMA and DEATH
In Addison's Disease, what can gland destruction be due to?
Tuberculosis, tumors, lymphomas, histoplasmosis, medications
What medications can possibly cause Addison's Disease?
Steroid withdrawal. Adrenal antagonists (metyrapone/aminoglutethamide). Heparin and warfarin, excessive causing adrenal hemorrhage. Rifampin and other CYP inducers with pre-existing problems
What are the treatments for Addison's Disease?
Chronic replacement: 1) Glucocorticoids (cortisone, prednisone. Avoid dexamethasone (more ADRs, no mineralcorticoid effects)). 2) Mineralcorticoids (fludrocortisone). Pre-op and stress supplements necessary
What are the functions/implications of decreased GH?
Inadequate growth or development. Fatigue, weakness in adults
What are the functions/implications of decreased ACTH?
Lower cortisol secretion. Adrenal deficiency
What are the functions/implications of lower FSH?
Inadequate sexual development. Hypoganodism
What are the functions/implications of lower LH?
Lower secretion of testosterone/estrogen/progesterone
What are the functions/implications of lower Prolactin (PRL)?
Inadequate breast development and milk production
What are the functions/implications of lower ADH?
Diabetes Insipidus with polyuria and polydipsia
What is the treatment option for low GH?
What is the treatment option for low ACTH?
What is the treatment option for low FSH?
What is the treatment option for low LH?
What is the treatment option for low ADH?
What are Glucocorticoids mainly used for?
Adrenal insufficiency (Enhance metabolic effects. Modify immune response)
What is Hydrocortisone used for?
Replacement in adrenocortical deficiency. Anti-inflammatory effects. IV for acute situation
What is the DOC for maintenance therapy for GLucocorticoids?
What do Thyroid hormones do?
Influence growth and maturation of tissues (normal growth, normal metabolism, normal development)
What are ADH replacements that can be used?
What is Vasopressin therapy for?
Replace Vasopressin (IM/SQ). Vasopressor effect (promotes vascular smooth-muscle contractino). ADH activity (increases water resorption at the distal renal tubular epithelium)
What is Desmopressin therapy for?
Longer acting ADH derivative (nasal). Increases cellular permeability of collecting ducts and resorb water
What do growth hormones do?
Stimulates growth of linear bone, skeletal muscle, organs. Stimulates erythropoietin. Maintain adequate functionality (decrease central obesity, maintain muscle mass, improve attention and memory)
What does Testosterone do?
Promotes and maintains secondary sex characteristics for androgen deficiency
What does Estrogen do?
Promotes and maintains female reproductive system and secondary sex characteristics and organs
What are some complications from HPA suppression?
Musculoskeletal (osteoporosis, myopathy, avascular necrosis). Ophthalmic (cataracts, glaucoma). GI. Cardiovascular. Dermatological. CHO and lipid metabolism. CNS (anxiety, depression, insomnia, euphoria, psychosis). Infection
What is the Etiology of Cushing's Syndrome?
Adrenal tumors. Adrenal hyperplasia. Pituitary dysfunction. Latrogenic
What is the mnemonic (CUSHING) for the symptoms of Cushing's Syndrome?
C: Central obesity. U: Urinary cortisol/glucose. S: Striae, Suppressed immunity. H: Hyper-cortisol, tension, glycemia, lipidemia, hisurtism. I: Iatrogenic causes. N: Noniatrogenic causes, neurological symptoms. G: Growth retardation in children
What are the treatment choices for Cushing's Disease?
What are the medical options for Cushing's Disease?
Inhibition of ACTH (cyproheptadine, bromocriptine). Inhibition of cortisol synthesis (aminoglutethamide, ketoconazole). Inhibition of cortisol/block synthesis (metyrapone). Destruction of adrenal cells that synthesize cortsiol (mitotane)
What is a drug interaction when using steroids and diuretics and amphotericin?
What should be avoided while using steroids?
Live attenuated or bacterial vaccines, or tuberculin skin tests. Contact with others with chickenpox or measles. NSAIDs, ASA, EtOH
What are the monitoring parameters for steroid use?
BP. Weights in CHF. Glucose, lipid levels. UA. BMD. Slit lamp eye exams. IOP