Endo II

Adrenals, Testes

aldosterone (mineralocorticoid), cortisol (glucocorticoids), testosterone, oestradiol

What hormones are created from cholesterol

replacement therapy, anti-inflammatory/immunosuppression, anti-glucocorticoid therapy

What are some uses of glucocorticoid related drugs?

Adrenal cortical insufficiency (like Addison’s), acute adrenal crisis (hydrocortisone IV)

What are the indications for glucocorticoid replacement therapy?

allergies, asthma, arthritis, transplant, autoimmune diseases, ARDS

Indications for the use of corticosteroids for anti-inflammatory or immunosuppressive effects?

adrenal corticoid hyperfunction (Cushing’s)

Indications for anti-glucocorticoids

Mifepristone (RU-486), Mitotane, Aminoglutethemide, Ketoconazole, Etomidate, Metyrapone

Examples of anti-glucocorticoids

glucocorticoid receptor antagonist, progesterone receptor antagonist (contraceptive)

MOA for mifepristone

Ketoconzaole

Which glucocorticoid synthesis inhibitor is the MOST potent, has multiple sites of action, and has LOTs of CYP450 inhibition (OG antifungal)?

metrypone

Which glucocorticoid synthesis inhibitors have some degree of selectivity

Increase the amount of lipocortin

How do corticosteroids inhibit the synthesis/release of prostaglandins to contribute to pain relief?

Cushing’s syndrome, Osteoporosis, Retardation of growth, Thin skin (easily bruised), Immunosuppression (increased infection risk), Cataracts/glaucoma, Edema, Suppression of HPA axis, Teratogenic, Emotional disturbances (psychosis, behavioral changes, insomnia), Rise in BP, Obesity (increased appetite and fluid retention) (truncal), Increased hair growth, DM, Striae

ADRs of corticosteroids

duration of use, dose, administration route

Incidence of ADRs with corticosteroids depends on the

Thrush, dry mouth, dysphonia

What are some inhalation specific symptoms of corticosteroids

osteoporosis, glaucoma, cataracts

ADRs common with high doses or oral routes

Stress dose (2-3x maintenance) to compensate for decrease adrenal release, then taper back down

You are managing a patient who is on dexamethasone for her arthritis. She has an upcoming surgery - what should you do with her dosage regimen?

Local application, seldom with a single dose, use stress dose, dose tapering, intermittent schedule, avoid abrupt w/d

What are some ways to prevent adrenal crisis?

short acting corticosteroids (hydrocortisone)

Mineralcorticoid properties like sodium retention are more common with

Long acting corticosteroids (dex, bethamethasone)

Glucocorticoid properties such as anti-inflammatory potential are more common with

prenisone, prednisolone, methylprednisolone, triamcinolone

Examples of medium acting corticosteroids

external genitalia, prostate growth, acne, facial/body hair, scalp hair loss

Actions of DHT on the androgen receptors

Wolffian duct, bone formation, muscle mass, spermatogenesis

Actions of testosterone at the androgen receptor

hypothalamic/pituitary feedback, bone resorption, epiphyseal closure, gynecomastia, vascular and behavioral effects

Actions of Oestradiol at the estrogen receptor

testosterone, methyltestosterone, Fluoxymesterone, danazol

What are some of the medications we can use to replace/augment endogenous androgens?

cyproterone (synthesis inhibitors), androgen receptor antagonist, 5alpha-reductase inhibitor

What are some of the anti-androgens used?

hirsutism in women, M-to-F transition

Indications of cyproterone (anti-androgen)

prostate cancer

Indications for androgen receptor antagonist

block testosterone conversion (5-alpha reductase), block DHT from testosterone receptor, alpha 1 inhibitors (relaxes the bladder neck, urethra, and prostate)

What are some ways you can treat BPH?

tamsulosin, alfuzosin, doxazosin, prazosin, terazosin

Examples of alpha 1 blockers for BPH

Less orthostatic hypotension due to selectivity to alpha a1 receptors

Why are tamsulosin and alfuzosin preferred for BPH?

finasteride (selective - type 2 is prostate only), dutasteride (non-selective - type 1 is everywhere)

Examples of 5-alpha reductase blockers

Alpha 1 blockers (2-4 weeks vs 6-12 months with 5-alpha reductase blockers)

Which treatment for BPH provides relief faster

virilization (female), acne, feminization (male), gynecomastia (male), precocious puberty, stunned growth, testicular atrophy, impotence, decreased sperm count, prostate enlargement, baldness, liver damage, hepatic carcinoma, atherosclerosis, stroke, HTN, mood swings

ADRs for androgen replacement therapy and anabolic steroids

prevents the breakdown of cGMP

MOA for PDE-5 inhibitors

HA, flushing, dizziness, nasal congestion

ADRs of alpha 1 antagonism

nitrates, anti-HTN drugs (especially alpha antagonist), CYP3A4 competition

C/Is and DDIs for PDE5 inhibitors

silfenafil, tadelafil, vardenafil, avanafil

Examples of PDE5 inhibitors

Prostaglandin analog (vasodilator) given by injection

What is special about alprostadil which is used to treat ED?