Steroids Flashcards
MOA of Glucocorticoids
3 things
- Effects mediated by glucocorticoid recepters
- Hormone enters cell and binds receptor -> transported to nucleus -> affects RNA transcription and protein synthesis
- Feedback suppression for ACTH
ADME of Glucocorticoids
- A/D: 75% bound to corticosteroid-binding protein (CBG), 5% bound to albumin, 20% free
- M: half-life 60-90 minutes
Dosage of Glucocorticoids
4 things
- Regimen based on seriousness of disease, amount required for desired effect, duration of therapy
- Lowest possible dose
- Do NOT stop abruptly
- Alternate day dosing: increase in efficacy and decrease in ADRs (useful when large doses are required for prolonged periods)
ADRs of Glucocorticoids
- Metabolic (5)
- Catabolic (2)
- Anti-inflammatory (4)
- CNS (5)
- Dermatologic (5)
- GI (3)
- Renal (3)
- Other (3)
- Metabolic: increase activities for gluconeogenesis, increaed serum glucose, lipolysis, and insulin*, muscle catabolism increases AA availability,
- Catabolic: decreased muscle mass and weakness, osteoporosis
- Anti-inflammatory: decreases prostaglandins, inhibits leukocytes and tissue macrophages, causes vasoconstriction
- CNS: can decrease seizure threshold, NO increase in intracranial pressure, anxiety, insomnia, steroid psychosis
- Derm: SQ fat redistribution (moon face), skin thinning, acne, impaired wound healing, fungal infections
- GI: increased acid and pepsin, increased fat absorption, decreased calcium absorption (through vit. D)
- Renal: decreased GFR, excess water retention, adrenal suppression (when used more than 2-3 days)
- Other: suppresion of ACTH, TSH, and FSH, increased platelets and RBCs, surfactant production in unborn babies
Endogenous Glucocorticoids
Cortisol (made from cholesterol and released under influence of ACTH)
Short/Medium acting glucocorticoids (3)
- Hydrocortisone
- Prednisone
- Prednisolone (methylprednisolone)
Intermediate/Long acting glucocorticoids (3)
- Triamcinolone
- Betamethasone
- Dexamethasone
Intra-articular injections (glucocorticoids)
5 things
- Treat joint disease (esp. RA)
- Fast impact on pain and stiffness
- Painful, may cause flushing, deterioration, HTN
- Do NOT repeat more than every 3 months (leads to necrosis)
- Drugs used: betamethasone, dexamethasone, methylprednisolone, triamcinolone
Epidural injections (glucocorticoids) 3 things
- Treat leg or back pain
- Not first line treatment
- Drugs used: hydrocortisone, methylprednisolone, triamcinolone)
Dose packs (glucocorticoids) 2 things
- High dose initially, then tapers off
- Drugs used: methylprednisolone, dexamethasone, betamethasone, triamcinolone
Topical (glucocorticoids)
3 things
- Very affective for skin disease
- Absorption increased by increased skin temperature and hydration
- Ointment better than creams
Opthalmic (glucocorticoids)
3 things
- For eye disease
- Systemic absorption is rare
- Not for glaucoma or cataracts
Enemas (glucocorticoids)
2 things
- For ulcerative colitis
- Drugs used: hydrocortisone
Aerosols (glucocorticoids)
2 things
- For asthma and allergic rhinitis
- Local effect only, first pass effect decreases systemic absorption
Stimulation of Lung Maturation in the Fetus
If premature newborn is under 34 weeks, betamethasone can be given to stimulate surfactant production in the lungs.
Acute Addison’s Disease
3 things
- Decreased cortisol levels
- Caused by: stress or infection
- Treatment: start early, correct fluid and electrolyte abnormalities as well as underlying cause, hydrocortisone
Chronic Addison’s Disease
3 things
- Decreased cortisol levels
- Hyperpigmentation, weakness, fatigue, weight loss, hypotension, inability to maintain blood glucose
- Treatment: Hydrocortisone and add Fludrocortisone
Congenital Adrenal Hyperplasia
4 things
- Group of disorders characterized by defects in synthesis of cortisol (deficiency in an enzyme needed to convert cholesterol into cortisone: 21-hydroxylase most common)
- May seel virilization, HTN and hypokalemia
- In high risk pregnancies, protect infant by giving mother dexamethasone
- Infant: when CAH is first seen it may be an acute adrenal crisis and should be treated with IV hydrocortison, mineralocorticoids, and electrolytes
Cushing’s Syndrome
4 things
- Increased cortisol levels
- Usually due to bilateral adrenal hyperplasia secondarily to pituitary adenoma
- Moon face, trunk obesity, muscle wasting, thinning of skin, striae, bruising, poor wound healing, osteoporosis, mental disorders, HTN, diabetes
- Treatment: surger (to remove adenoma), radiation, drugs (mitotane, metyrapone, mifepristone)
Aldosteronism
- Increased cortisol levels
- Excessive production of aldosterone by an adrenal adenoma
- HTN, polyuria, polydipsia, weakness, tetany (due to K loss)
Mitotane
2 things
- Drug used for Cushing’s syndrome
- Management of adrenocortical carcinoma
Metyrapone
4 things
- Drug used for Cushing’s syndrome
- Blocks production of cortisol (inhibits 11B-hydroxylase)
- ADRs: salt/water retention and hirsutism
- Adrenal function tests
Mifepristone
4 things
- Drug used for Cushing’s syndrome
- Glucocorticoid receptor antagonist
- Useful to control hyperglycemia in patients who are not surgical candidates
- ADRs: hypokalemia, adrenal insufficiency, endometrial hyperplasia
Nutritional measures to minimize adverse effects of glucocorticoids
6 things
- Increase potassium and sodium intake
- Watch calories
- Increase protein
- Increase vitamin D (to decrease bone loss, may add bisphosphonates)
- Antacids (3/4 times daily)
Mineralocorticoids (3)
- Aldosterone
- Desoxycorticosterone
- Fludrocortisone
Aldosterone
5 things
- Not firmly bound to serum proteins
- Increases sodium reabsorption from urine, sweat, salivary glands, and GI
- Increases excretion of potassium
- Not used clinically due to short DOA
- Synthesized in zona glomerulosa and stimulated by ACTH
Desoxycorticosterone
2 things
- Not used clinically
- Precursor of aldosterone
Fludrocortisone
2 things
- Oral
- Used in Addison’s disease, hypopituitarism, orthostatic hypotension, aldosterone inssufficiency, CAH (only when symptomatic)
Testosterone
4 things
- Schedule II
- Controls development and maintenance of male sex organs and secondary male sex characteristics
- Produces systemic anabolic effects (increased nitrogen, calcium, sodium, potassium, chloride, phosphate) causing increased water retention and bone growth, vascular and less fatty skin, increased erythropoiesis
- Anabolic steroids are chemical derivatives of testosterone
7 uses for anabolic steroids
- Help build tissue and prevent breakdown of tissue in debilitating disease
- Androgen replacement therapy: hypogonadal men
- Protein anabolic agents: after trauma or surgery
- Aplastic anemia, sickle cell, hemolytic anemia
- Osteoporosis
- Growth stimulators in boys with delayed puperty
- Aging-androgen production falls with age
Adverse effects of anabolic steroids
- Dermatologic (3)
- Men (4)
- Women (2)
- Children (1)
- Cardiovascular (5)
- Abuse (5)
- Other (6)
- Derm: acne, oily, hirsutism
- Men: increased libido, atrophy of testicles, aggressiveness, spermatogenesis failure
- Women: masculinization and decreased breast size
- Children: arrested bone growth (due to premature fusion of epiphysis)
- CV: MI, HTN, CHF, thrombosis, cardiac death
- Abusers: paranoid psychosis, mania, eurphoria, depression, withdrawal syndrome
- Other: liver cancer, stroke, hot flashes, headache, edema, weight gain
Anabolic Steroids (4)
- Danazol
- Methenolone
- Nandrolone
- Stanozolol
Danazol
3 things
- Weak androgen
- Binds to androgen, progesterone, and glucocorticoid receptors
- Used for: endometriosis, fibrocystic disease of the breast, hematologic disorders, suppression of ovarian function
Nandrolone
1 thing
Most effect with regard to increase in hematocrit and response rates in chronic renal failure (so is testosterone)
Methenolone
1 thing
Used for: aplastic anemia, breast cancer, osteoporosis
Stanozolol
1 thing
Used for: prophylaxis and treatment of hereditary angioedema
Synthetic human ACTH
Cosyntropin
Androstenedione
- Precursor to testosterone and estrogen
- Does not increase testosterone in young men (increases estrogen and lowers HDL)
- Structurally similar to steroids
- May increase heart diseases and cancers
