B.13

Question 1

Mineralocorticoids. Topically applied glucocorticoids. Adrenocortical antagonists, inhibitors of corticosteroid synthesis

Answer 1

1. MC: Fludrocortisone
2. Topically applied GCs: Fluocinolone, Mometazone, Budesonide, Fluticasone
3. Inhibitors of corticosteroid synthesis (11β-Hydroxylase inhibitor): Metyrapone

Question 2

Mineralocorticoids receptors

Answer 2

1. Genomic:
   - Na/K ATPase transcription↑
   - ENaC activity↑
   - Expression of fibrotic molecules (e.g. TGF-β)↑
   - NADPH oxidase expression ↑; ROS↑ →proinflammatory effects
2. Non-genomic:
   - Proinflammatory effects (via EGFR & ERK1/ERK2)

Question 3

Mineralocorticoids effects

Answer 3

Na+ reabsorption↑
K+ & H+ excretion↑ (collecting tubule & duct)

Question 4

Fludrocortisone

Answer 4

MOA: potent synthetic MC (→activates MC-R→ ↑Na+ absorption, ↑K+ and H+ excretion), has a STRONG salt retaining effect;
IND: Drug of choice in replacement therapy (adrenal hypofunction, acute/chronic adrenal insufficiency, post-adrenalectomy);
SEs: Edema, BP↑, Hypokalemia (weakness, tetany), metabolic alkalosis, Pro-inflammatory effect;
Kinetics: DOA-8-12h

Question 5

Fluocinolone, Mometazone, Fluticasone,Budesonide

Answer 5

MOA: Synthetic GCs (have anti-inflammatory effect), they have good surface activity on mucus membranes or skin surface;
Classification: classified based on potency→
-class I (very potent),
-class II (potent),
-class III (mild);
IND: Asthma (aerosol adm.→Fluticasone, Mometazone, Budesonide), Allergic rhinitis (nasal spray adm.→ Budesonide, Triamcinolone), Ophthalmology, Dermatology (ointment/solution adm.→ Fluocinolone +acetonide to ↑topical activity), IBD (suppository /enema adm.), Joint diseases (intra-articular adm.), timed release tablets (physiology-like cortisol levels: high morning, low evening);
SEs: potential local SEs with long term adm.→ skin atrophy, striae, rosacea, perioral dermatitis, acne, purpura

Question 6

Metyrapone

Answer 6

MOA: 11β-hydroxylase inhibitor (inhibits formation of hydrocortisone and corticosterone);
Kinetics: fairly quick action (some days);
IND: Diagnostic tests of adrenal functions (mainly), in combination with Aminogluthetimide for Cushing’s syndrome due to adrenocortical cancer not responding to mitotane

Question 7

mineralocorticoid antagonists

Answer 7

spironolactone, Eplerenone
clinical use:
K+ sparing diuretics
Spironolactone is primarily for hyperaldosteronism
Eplerenone is mostly for HTN, HF