PHARM - Adrenal Corticosteroid Drugs

Question 1

What are the 3 primary uses of CS? What are the 3 Endocrine uses?

Answer 1

Inflammation, allergic rxns, and immunologic disorders

Dx of Cushing’s Syndrome, Tx of Adrenal Insuff, Tx of CAH

Question 2

How do CS upregulate transcription of specific genes?

Answer 2

CS will bind to either Glucocorticoid receptors or Mineralcorticoid receptors, thus displacing the hps90 protein and allowing binding to occur

Question 3

What two key enzymes are functional during the conversion between active sterols and inactive sterols?

Answer 3

11beta HSD2 (11b- dehydrogenase) == Cortisol (active) to cortisone (inactive)

11beta HSD1 (11-ketoreductase) == cortisone to Cortisol

Question 4

What are the durations of the short, intermediate and long acting CS?

Answer 4

Short = less than 12 hours

Intermediate = 12-36 hours

Long = 36-72 hours

Question 5

What are the 5 short acting Glucocorticoids?

Answer 5

1. Hydrocortisone (cortisol)
2. Cortisol
3. Prednisone
4. Prednisolone
5. Methylprednisone

Question 6

What is the one intermediate acting glucocorticoid?

Answer 6

triamcinolone

Question 7

What are the two long acting glucocorticoids?

Answer 7

Betamethasone

Dexamethasone

Question 8

Criteria for starting therapy?

Answer 8

Medical emergency == give high dose for a few days

Chronic therapy == various dose and frequency

Question 9

Common Applications:

1. Endocrine replacement tx for what?
2. Immunosuppresion of ?
3. Inflamm and allergies such as?

Answer 9

1. primary adrenal insuff (addisons) and CAH

give Hydrocortisone and fludracortisone for both

2. following bone marrow transplant, autoimmune dz, leukemia
3. RA, IBD, COPD, allerig rhinitis, psoriasis

Question 10

What is the ultimate metabolic effect of CS?

effects on 3 organs

Answer 10

HYPERGLYCEMIA

liver = increaed gluconeogenesis

adipose == increased glucose output

sk ms == increased glycogen synth

and decreased glucose synth

Question 11

Two known inhibitors of 11b-HSD2

and result

Answer 11

Glycyrrhizin and carbenoxolene

cortisol not inactivated results in Na and H20 retention, K+ loss

and ultimately increased BP

Question 12

Key Adverse effects of CS

ROS

Answer 12

Psych == sleep disturbances, mood

Skin = cushingoid, striae, acne, hirsituism

CV = HTN

MSK = osteoporosis and myopathy

Endo = diabetes and adrenal cortex suppresion

Immuno = lymphocytopenia and immunosuppression

Eyes = Cataracts

Develop = growth retardation

Question 13

What is the dosing of CS?

Answer 13

Lowest does for shortest duration

give locally to reduce systemic distribution (topical and inhalation)

give single dose in AM

gradually taper off dose if possible

Question 14

Glucocorticoid drug of choice

MOA

IND

PK

Adverse

Answer 14

Prednisolone

activates GR thus increasing gene txn

Inflammation, or organ transplant

DOA is longer than 1/2 life

Suppression of Adrenal

Question 15

GC-receptor Antagonist

MOA

IND

PK

Adverse

Answer 15

Mifeprostone

blocks GC and Progesterone receptors\

Medical Abortion

oral

Vaginal bleeding and Abd pain

Question 16

Mineralcorticoid Agonist

MOA

IND

PK

Adverse

Answer 16

Fludrocortisone

stims MC and GC receptors

Adrenal Insuff (Addisons)

Long DOA

excess Na and H20 retention == CHF

Question 17

Mineralcortiocoid Antagonists (2)

MOA

IND

PK

Adverse

Answer 17

Spirolactone

block MC receptor, tx for hyperaldosteronsim or hypokalemia

slow on and off (24-48 hours), A = hyperkalemia, gynecomastia

Eplerone

blocks binding of aldosterone, tx of HTN

short 1/2 life (3-6 hours), A = hyperkalemia

Question 18

Synthesis Inhibitors

MOA

IND

PK

Adverse

Answer 18

Ketoconazole

blocks fungal and mammalian CYP 450s thus blocking steroid synth

fungal infections or excess steroid

oral topical

many drug-drug interactions hepatic dysfunction

Question 19

In general, what is the most common endogenous Mineralcorticoid?

where does it act?

what is the result?

Answer 19

Aldosterone

kindey

increases Na and H20 retention and excretion of K+

Question 20

Patient populations in which GC admin is problematic

Many (8)

think ROS and adverse effects

Answer 20

1. Immunocompromised (HIV AIDS)
2. Diabetics
3. Infections
4. Peptic Ulcers
5. CV conditions
6. Psych conditions
7. Osteoporosis
8. Children