Adrenal Gland Pharmacology Flashcards Preview

DEMS: Unit III > Adrenal Gland Pharmacology > Flashcards

Flashcards in Adrenal Gland Pharmacology Deck (36):
1

Metabolic effects of glucocorticoids

  • Carbohydrates: ↑ gluconeogenesis, ↑ blood glucose, ↑ insulin
    • Excess = diabetes like state
  • Protein: ↓ protein synthesis, ↑ AA to glucose
    • Excess: muscle wasting, weakness, skin- connective tissue atrophy
  • Fat: ↑ lipolysis peripherally, ↑ FFA
    • Excess: ↑ lipogenesis (centrally via insulin) → centripetal obesity (moon facies and buffalo hump)

2

Drugs that must be activated @ liver

  • Ketone at carbon 11 means must be activated in liver
  • Hydrocortisone (Solu-Cortef®) → inactive until goes through liver
  • Prednisone → inactive until goes through liver where it is converted into Prednisolone

3

Drugs that are physiologically active as given

  • Drugs have Hydroxyl at Carbon 11 which means physiologically active.
  • Prednisolone has C1=C2 (double bond) which ↑ anti-inflammatory effects
  • Methylprednisolone (Solu-Medrol®) → has C1=C2 (double bond) + α-methyl group on C-6 which ↑ anti-inflammatory activity (5-6x stronger than cortisone)
  • Fludrocortisone has a fluorine at C-9 which ↑ mineralocorticoid activity
  • Dexamethasone has a fluorine at C-9 + α-methyl group on C-16: which ↑ anti-inflammatory effects 18x and essentially eliminates mineralocorticoid activity (of the fluorine group)
  • Triamcinolone is active and a topical/oral/injectable.

4

Tx of addison's disease (acute and chronic)

  • Chronic: administer hydrocortisone with increased dose during stress.
    • Fludrocortisone is usually required for sufficient salt-retaining effect (unless mild case).
  • Acute (i.e. life threatening, immediate treatment):  High IV cortisol dose until stable (correct fluid/electrolyte abnormalities).  
    • Sometimes fludrocortisone needs after switch to lower oral cortisol dose

5

Tx of Cushing's disease

  • Surgery is treatment of choice (pituitary/chest/abdomen).  
  • Pharmacotherapy is adjunctive in refractory or inoperable cases = cortisol synthesis inhibitors.

6

Pharmacotherapy in Cushing's disease/syndrome

  • ACTH Secretion Inhibitors
    • Cabergoline, Pasireotide
  • Cortisol Synthesis Inhibitors
    • Ketoconazole, Metyrapone, Etomidate
  • Adrenolytic Agents
    • Mitotane
  • Cortisol Receptor Blockers
    • Mifepristone

7

Tx of Primary Aldosteronism

  • Aldosterone antagonists (Spirinolactone + eplerenone)
  • hypertensive medications (Thiazide, CCB, ACE-I, ARBs)

 

8

Tx of Pheochromocytoma

  • Surgical removal of tumor but first need preoperative α blockade:  
    •   α-blockade:  phenoxybenzamine: irreversible α1 + α2 antagonist
    •   β-blockade:  metoprolol always after adequate α-receptor blockade.
  • Then maybe Ca2+  blocker (nifedipine), then catecholamine synthesis inhibitor (metyrosine).  
  • Then adrenalectomy - if inoperable or metastatic.

9

Tx of glucocorticoid insufficiency

  • Hydrocortisone
  • Prednisone
  • Dexamethasone

10

Tx of mineralcorticoid insuffiency 

Fludrocortisone

11

Tx of Sex Steriod insuffieciency

DHEA

12

Hydrocortisone: GC v. MC vs. Anti-inflammatory actions & clinical uses

  • GC: MC: AI = 1:1:1
  • Uses
    • Acute (ER)
    • GC + MC replacement
    • Addison’s disease

13

Prednisone: GC v. MC vs. Anti-inflammatory actions & clinical uses

  • GC: MC: AI = 4:1:4
  • Use
    • Steroid burst ==> GC + (less) MC

14

Methylprednisolone: GC v. MC vs. Anti-inflammatory actions & clinical uses

  • GC: MC: AI = 5:0:5
  • Use
    • steroid burst

15

Triamcinilone: GC v. MC vs. Anti-inflammatory actions & clinical uses

  • GC: MC: AI = 5:0:5
  • Use
    • Potent systemic agent with excellent topical activity.

16

Dexamethasone: GC v. MC vs. Anti-inflammatory actions & clinical uses

  • GC: MC: AI = 30:0:30
  • Use
    • Most potent α-inflammatory, used in cerebral edema, chemo-induced vomiting.

    • Greatest suppression of ACTH secretion

17

Hydrocortisone: administration routes

  • Oral
  • Injectable
  • Topical

18

Prednisone: administration routes

oral only

19

Methylprednisolone: administration routes

  • Oral
  • Injectable
  • Parenteral

20

Triamcinolone: administration routes

  • Topical (53)
  • Oral
  • Injectable

21

Dexamethasone: administration routes

  • Oral
  • Injectable
  • Topical

22

Salt-retaining activity of drug correlates to...

MC activity

23

ACTH suppression of drug correlates to..

GC activity

24

Corticosteroids that can be used topically

  • hydrocortisone
  • triamcinolone
  • dexamethason

25

General dosing consideration for use of corticosteroids for anti-inflammatory use

  • REMEMBER:  Mineralocorticoid side effects vary with agent
  • Dosage often by trial and error with re-evaluation
  • Consider seriousness of disease - minimal amount for desired effect - duration of therapy
  • Reduce dosage as soon as therapeutic objectives are obtained
     

26

If using large doses of corticosteroids you should...

  • use shorter-acting agent with little MC
    • e.g. methylprednisolone
       

27

Dosing consideration used to minimize adrenal suppression or adrenal insufficiency

  • Alternate day schedule à minimize adrenal suppression
    • Anti-inflammatory actions outlast HPA suppression
  • Terminate administration gradually (duration > 7-28 d)
    • Minimizes  disease rebound and potential for  symptoms of adrenal insufficiency (adrenal crisis)
       

28

Potential toxicity of acute, short course, high dose

•Mineralocorticoid effects:  Salt and water retention  ==> edema  ==> increased blood pressure, hypokalemia
•Glucocorticoid effects:  Glucose intolerance in diabetics, mood changes (up or down), insomnia, GI upset
 

29

Glucocorticoid effects of high dose sustained corticosteroid therapy

  • Iatrogenic Cushing’s syndrome 
  • Hypothalamic-pituitary-adrenal axis suppression
  • Mood disturbance
  • impaired wound healing
  • increased susceptibility to infection

30

Characteristics of iatrogenic cushing's syndrome 

  • hyperglycemia
  • protein wasting (muscle)
  • lipid deposition (weight gain)
  • ==> diabetes-like state
     

31

Characteristics of HPA axis suppression

  • Can result in insufficient response to stress
  • More suppression with dexamethasone and betamethasone
  • Also may cause decrease  in ACTH, GH, TSH, LH, sex steroids
     

32

Possible consequences of large, chronic doses of corticosteroids

  • osteoporosis
  • posterior capsular cataracts
  • skin atrophy, loss of collagen support
  • growth retardation in children
  • peptic ulceration

33

Short-medium acting corticosteroids

  • hydrocortisone
  • prednisone
  • methylprednisolone

34

Intermediate-acting corticosteroids

  • tramicinolone
  • fluprednisolone

35

Long-acting corticosteroids

dexamethasone

36

Most common mineralcorticoid agent

fludrocortisone