Pharmacology Ii - 1/22/10

Front 1

What are the 3 zones of the adrenal gland and what does each zone produce?

Back 1

Zona Glomerulosa - Mineralocorticoids (via angiotensin II)
Zona Fasciculata - Glucocorticoids (CRH, ACTH)

Zona Reticularis - Androgens (CRH, ACTH)

Front 2

What is the difference in protein binding between Cortisol and synthetic glucocorticoids?

Back 2

Cortisol binds primarily to CBG, which has high affinity meaning that cortisol will circulate for a long time and have a lower bioavailability.

Synthetics bind primarily to albumin, which has a lower affinity and is more bioavailable

Front 3

How is cortisol metabolized?

Back 3

The kidney converts cortisol to the inactive form cortisone via 11B-HSDII Type II

The liver can convert cortisone back to cortisol via 11B-HSDII Type I
The liver also conjugates cortisol to make it more soluble for excretion.

Front 4

Glucocorticoids like cortisol have metabolic and anti-inflammatory efffects. What are the metabolic effects?

Back 4

Raises blood glucose (antagonizes insulin)
Raises amino acid levels (increase muscle catabolism)
Raises triglyceride levels (increase hormone sensitive lipase activity)

Front 5

Describe the anti-inflammatory effects of cortisol.

Describe the antiimmunogenic effects and the feedback loop associated with it.

Back 5

Stress releases cortisol, which limits mediators of inflammation such as eicosanoids and bradykinin.

The release of inflammatory cytokines is inhibited by cortisol. These cytokines feedback to the pituitary to increase release of CRH.

Front 6

Describe ACTH's effect on the adrenal gland? What parts does it effect? What part doesn't it effect?

Back 6

Chronically elevated ACTH causes cortex hypertrophy. ACTH absence causes atrophy.

This occurs in the zona fasciculata and zona reticularis but NOT the zona glomerulosa.

Front 7

What is the disease state associated with adrenal insufficiency? Adrenal excess?

Back 7

Addisons disease

Cushings disease/syndrome

Front 8

What is the difference between primary and secondary/tertiary addisons disease?

Back 8

Primary - adrenal autoimmune destruction

Secondary/Tertiary - Hypothalamic/Pituitary disorders & prolonged GC administration causing decreased cortisol and androgen synthesis ( but not MC synthesis)

Front 9

What is the difference between cushings disease and cushings syndrome?

Back 9

Cushings Disease - ACTH secreting pituitary adenoma

Cushings Syndrome - (1) Ectopic ACTH secretion (2) Cortisol secreting tumors (3) Iatrogenic - secondary to treatment with exogenous GC's

Front 10

What is the difference in dosing between treatment of adrenal insufficiency with GC's and treatment of inflammation with GC's?

Back 10

Adrenal insufficiency is treated at physiologic doses

Inflammation is treated at pharmacologic doses.

Front 11

What synthetic cortisol agent is first line therapy for AI?

Back 11

Prednisolone (Cortisol + double bond)

The hydroxyl group at C-11 is vital for maximal GC activation.

Front 12

What are the other 3 synthetic cortisol agents? Describe their structural and functional differences.

Back 12

Methyprednisolone (Prednisolone + methyl at C-6) - 5x more potent

Fludrocortisone (Cortisol + fluorine) - Increased GC and MC activity

Dexamethasone (Cortisol + double bond + fluorine + methyl group) - 18x AI activity, no MC activity

Front 13

What are the 3 main characteristics of SGC?

Back 13

Lower protein affinity
Increased lipophilicity
Increased affinity for the GR receptor

The result is longer plasma half-life and increased duration of action for these compounds.

Front 14

What is the GC of choice for replacement therapy (adrenal insufficiency)?
What is needed for Primary adrenal insufficiency? Why?

Back 14

Oral hydrocortisone - This is good for secondary addison's disease because only GC replacement therapy is needed.

Fludrocortisone is needed because the entire adrenal cortex is destroyed and MC replacement is required as well.

Front 15

What are the 5 major adverse effects of prolonged GC administration?

Back 15

Immune system - susceptibility to infection
Glucose - Hyperglycemia
Muscle - Atrophy of fast twitch fibers
Bone - Slowed linear bone growth/Vitamin D inhibition - bone resorption
Lipids - Fat redistribution (peripheral wasting and central obesity)

Front 16

Why is abrupt cessation of GC's or switch from oral to inhaled GC's dangerous?

Back 16

Prolonged GC administration suppresses CRH and ACTH leading to atrophy of the adrenal cortex. Abrupt cessation can cause acute adrenal insufficiency. It's important to taper GC therapy over months.

Inhaled GC's stay mainly locally in the lungs. Oral GC's are distributed everywhere, so switching can cause adrenal insufficiency.

Front 17

Describe the dosing of GC's for acute allergic reactions

Back 17

They are given in large doses initially and tapered down over 5-7 days.

Front 18

Name 3 example routes for local GC administration.

What are 3 main advantages of these routes of GC administration?

Back 18

Inhaled
Cutaneous
Intra-articular

Minimized systemic effects
Prevention of HPA suppression that can cause cushings syndrome
GC dosing is safer for children

Front 19

Name the 4 drugs available for inhaled formation.

Back 19

Fluticasone
Beclomethasone
Flunisolide
Triamcinolone

Front 20

What are these formulations indicated for?

Back 20

Allergic Rhinitis
Asthma

80% is swallowed and eventually absorbed into systemic portal circulation but first pass metabolism inactivates it. 20% is delivered to the lung

Front 21

How do you treat acute adrenal insufficiency caused by the switch from oral to inhaled GC?

Back 21

Large dose IV GC

Front 22

How do you avoid the infection of opportunistic organisms that may thrive in the oral and pharyngeal mucosa?

Back 22

Antifungal mouthwash after each administration of aerosolized GC.

Front 23

Name the 3 topically administered GC formulations.

What are these indicated for?

Back 23

Hydrocortisone
Methylprednisone
Dexamethasone

Psoriasis, lichen planus, atopic dermatitis

Front 24

Name a low, moderate and high dose cutaneous GC formulation.

Back 24

Low - Desonide (face and eyes)
Moderate - Clobetasol
High - Fluocinonide and desoximetasone

Front 25

What is used for intra-articular injection?

Back 25

Methylprednisolone

Rheutamoid arthritis
Also used in acute attacks of gout

Front 26

What is used during pregnancy to promote fetal lung maturation?
Why does it work over prednisone?

Back 26

Dexamethasone

It is a poor substrate for 11B-HSD II in the fetal placenta which converts prednisolone back to prednisone after the materal liver converts prednisone to prednisolone (active).