Adrenocorticosteroids

Question 1

Glucocorticoids/Mineralocorticoids- Available Drugs

Answer 1

Short Acting:
Cortisone (inactive)/ Hydrocortisone (Cortisol- Active)

Intermediate Acting:
Fludrocortisone
Prednisone (inactive)/ Prednisolone (Active) Triamcinolone

Long Acting:
Dexamethasone
Beclamethasone

Question 2

Glucocorticoids/Mineralocorticoids- Clinical Use

Answer 2

PHSIOLOGIC LEVELS FOR HORMONE THERAPY (HYDROCORTISONE, DEXAMETHASONE, FLUDROCORTISONE):
ADRENAL INSUFFICIENCY
ADRENAL CRISIS
ADDISON'S DISEASE
CONGENITAL ADRENAL HYPERPLASIA

PHARMACEUTICAL LEVELS FOR NON-ENDOCRINE USES:
RA (PREDNISOLONE), GOUT, SLE
ALLERGIES, ASTHMA, INSECT BITES- (PREDNISONE FOR SEVERE DISEASE; TRIAMCINOLONE, BECLOMETASONE, FLUTICASONE INHALED FOR LESS SEVERE)
INFLAMMATORY CONDITIONS
KIDNEY NEPHROTIC SYNDROME
ORGAN TRANSPLANT
CANCER THERAPY
RESPIRATORY DISTRESS SYNDROME- (DEXAMETHASONE)
CEREBRAL EDEMA

PO can use active or inactive
Topical must use active forms
Direct injections must use active form
FOR IN UTERO TREATMENT GIVE MOTHER DEXAMETHASONE (ISN’T INACTIVATED BY PLACENTA)

Question 3

Glucocorticoids/Mineralocorticoids- Adverse Effects/Contraindications

Answer 3

ABRUPT WITHDRAWAL:
DISEASE FLARE UP
HPA SUPPRESSION
RISK OF ADRENAL CRISIS

CHRONIC TREATMENT:
CUSHINGOID SYNDROME
WEIGHT GAIN
FACIAL PLETHORA
HYPERGLYCEMIA/DIABETES
RISK OF INFECTION
EDEMA
HYPERTENSION/CVD
EUPHORIA/MANIA
BONE LOSS
PEPTIC ULCER
IMPAIRED WOUND HEALING

Question 4

Corticosteroid Synthesis Inhibitors- Available Drugs

Answer 4

ketaconazole
etomidate
metyrapone
mitotane

Question 5

Ketaconazole- Mech of Action

Answer 5

inhibit CYP11A1 (Cholesterol to Pregnenolone) and CYP11B1 (11Deoxycortisol to Cortisol)–>inhibit synthesis of ALL adrenal steroids

also inhibit fungal CYP450

most effective and fastest acting

Question 6

Etomidate- Mech of Action

Answer 6

inhibit CYP11A1 (cholesterol to pregnenolone) and CYP11B1 (11deoxycortisol to cortisol)–>inhibit synthesis of ALL adrenal steroids

IV- used in patients who cannot take oral medication

Question 7

Metyrapone- Mech of Action

Answer 7

Inhibit CYP11B1 and CYP11B2–> inhibit cortisol synthesis

ONLY SYNTHESIS INHIBITOR THAT’S SAFE IN PREGNANCY

Question 8

Mitotane- Mech of Action

Answer 8

ABLATION ON ADRENOCORTICAL PRODUCING CELLS

usually spares the androgen and mineralocorticoid producing cells

Question 9

Corticosteroid Synthesis Inhibitors- Clinical Use

Answer 9

CUSHING’S SYNDROME

Question 10

Ketoconazole, Etomidate, Metyrapone, Mitotane- Adverse Effects/Contraindications

Answer 10

risk of adrenal insufficiency

Question 11

Mitotane- Adverse Effects/Contraindications

Answer 11

complete destruction of cortisol producing cells= require supplementation for life

not well tolerated- nausea, vomiting anorexia, rash, diarrhea, ataxia

Contraindicated in pregnancy- fetal adrenal destruction

Question 12

Mifepristone- Mech of Action

Answer 12

glucocorticoid receptor antagonist at high doses= decreased cortisol response

Question 13

Mifepristone- Clinical Use

Answer 13

REFRACTORY CUSHING’S SYNDROME

ABORTION

Question 14

Mifepristone- Adverse Effects/Contraindications

Answer 14

adrenal insufficiency

Contraindicated in pregnancy