antiinflamm 2

Question 1

where are corticosteroid hormones produced?

Answer 1

adrenal cortex

Question 2

what do glucocorticoids do?

Answer 2

increase blood glucose levels; inhibit inflammation & immune function
> affect essentially every tissue in some manner

Question 3

how are glucocorticoids produced? where are they? what do they do?

Answer 3

cholesterol from diet used to synthesize corticosteroids in adrenal cortex
-glucocorticoids are glucose regulating corticosteroids
>increase blood glucose conc.
>anti-inflammatory effects
>immunosuppressive effects
eg. cortisol

Question 4

mechanism of glucocorticoid action - what are their useful actions as a drug? how do they compare to NSAIDs?

Answer 4

Glucocorticoids indirectly inhibit PA2

GCs bind to cytoplasmic receptor > activated drug-receptor complex enters cell nucleus > up-regulates synthesis of proteins that inhibit phospholipases

This inhibits the synthesis of AA, and therefore the synthesis of not only PGs, but also leukotrienes
>inhibits inflammation & essentially all WBC functions
>a more profound effect than NSAIDs

Question 5

what may account for some of the effects of glucocorticoids that occur too rapidly to be a result of changes in gene transcription?

Answer 5

plasma membrane receptors for corticosteroids have been discovered

Question 6

which cells have glucocorticoid receptors?

Answer 6

essentially all

Question 7

To elevate blood glucose, glucocorticoids:

Answer 7

• Stimulate hepatic glucose synthesis from amino acids and lipids
• Inhibit glucose uptake by muscle & adipose
• Stimulate fat breakdown in adipose
• Mobilize amino acids from non-hepatic tissues

Question 8

glucocorticoid relation to gene expression

Answer 8

About 10-20% of all expressed genes are regulated by glucocorticoids

Question 9

immune system effects of glucocorticoids

Answer 9

Glucocorticoids inhibit virtually all leukocyte functions

Question 10

excessive levels of glucocorticoids lead to what?

Answer 10

hyperadrenocorticism
a.k.a. Cushing’s Syndrome

Catabolic effects:
* Decreased muscle mass
* Thinning of skin
* Osteoporosis
Also cause “centripetal” redistribution of fat, antagonize effect of vitamin D on calcium absorption, etc.

Question 11

osteoporosis is connected to glucocorticoids in what way?

Answer 11

Osteoporosis is a common adverse effect of chronic glucocorticoid administration

Question 12

glucocorticoid absorption, distribution, metabolism, and excretion. Where are they activated? species differences?

Answer 12

Absorption
-Oral; IM / SQ; intra-articular; topical

Distribution
-Carried in blood by albumin & transcortin

Metabolism
-Hepatic ADRs possible
-Some are activated in liver:
Cortisone > hydrocortisone
Prednisone > prednisolone
-Humans & dogs absorb oral prednisone and convert it to prednisolone
-Oral absorption of prednisone in cats is poor (4-fold better for prednisolone); obese cats develop glucocorticoid concentrations twice as high as cats of normal weight; dosing should be based on lean body mass
-Horses do not absorb oral prednisone (but do absorb prednisolone)

Excretion
Urine / feces

Question 13

after what time period of taking glucocorticoids could we start to see serious adverse effects?

Answer 13

usually only seen after ~2 weeks of continuous therapy (dose-dependent)

Question 14

possible adverse effects of glucocorticoids

Answer 14

Numerous, possibly severe if not used properly:
* Increased appetite, thirst, & urination
* Impaired wound healing/thinning of skin
* Hypertension (mineralocorticoid activity, RAS activation, etc.)
* Edema
* Negative calcium balance (osteoporosis)
* Gastric ulcers
* Psychoses / euphoria
* Infection
* ‘Centripetal’ fat distribution & hair loss

Question 15

The risk of adverse effects from glucocorticoids is related to

Answer 15

duration of therapy as well as dose

Question 16

glucocorticoid of note with high Na+ retention potency? high anti-inflammatory potency?

Answer 16

-prednisone with high Na+ retention potency
-dexamethasone with high anti-inflammatory potency

Question 17

Therapeutic principles for glucocorticoid use

Answer 17

1) Except for replacement therapy, use is largely empirical
> alleviation of a patient’s symptoms until initial insult has been resolved (if possible)
2) Consider risks / benefits in that patient
* Goal is toleration of condition, not complete relief
3) Dose very dependent on disease/patient > trial and error
* Use smallest possible dose
4) Re-evaluate periodically
* Gradually reduce dose to minimum acceptable
5) Generally, even large single doses are harmless
* Crisis situation
6) < 1 week unlikely to be harmful
7) Time & dose related to toxicity (> 1 week)
8) With chronic use, abrupt cessation > adrenal insufficiency e.g., hypoglycemia +/- hyperkalemia, hyponatremia, hypotension
MUST wean patient off drug GRADUALLY

Question 18

most important therapeutic principles of glucocorticoid use

Answer 18

• Goal is toleration of condition
• Use smallest possible dose
• Gradually reduce dose to minimum acceptable
  MUST wean patient off drug GRADUALLY

Question 19

common clinical uses of glucocorticoids

Answer 19

**Arthritis
-Provide early to minimize damage from inflammation - patient should exercise affected joints moderately to slow disease progress
-Caution re: “masking” of pain
> patient may overuse & injure inflamed joints (e.g., athletes)

**Hypersensitivities: oral, inhaler Use injectable drug for anaphylaxis