Adrenal Corticosteroid drugs

Question 1

what are the effects of glucocorticoids?

Answer 1

antiinflammatory
immunosuppressive

Question 2

glucocorticoids can be produced naturally _

glucocorticoids can be produced synthetically _

Answer 2

cortisol

hydrocortisone/prednisone

Question 3

pharmalogical doses of corticosteroids are used to treat patients with

Answer 3

inflammation, allergic disorders, immunologic disorders

Question 4

in endocrine patients corticosteroids are give to? (3)

Answer 4

establish a diagnosis of cushings syndrome
treat adrenal insuficciency
treat congential adrenal hyperplasia

Question 5

what are the corticosteroid agonists

Answer 5

glucocorticoids and mineralcoticoids

Question 6

what is a glucocorticoid synthetic

Answer 6

prednisone

Question 7

what is a mineralocorticocoid synthetic

Answer 7

fludrocortisone

Question 8

what are the corticosteroid antagonists

Answer 8

receptor antagonsits and synthesis inhibitors

Question 9

what are the corticosteroid sythensis inhibitors

Answer 9

ketoconazole

Question 10

what are the corticosteroid receptor antagonists

Answer 10

glucocorticoid antagonists: mifepristone

mineralcorticoid antagonsits: spironolactone

Question 11

adrenal corticosteroids belong to the receptor _

Answer 11

superfamily

steroid nuclear receptor

ligand binds displacing HSP90 and the glucocorticoid receptors and mineralocorticoreceptors are activated

Question 12

once the mineralocorticoid receptor is stimulated what is released

what about the glucocorticoid receptor

Answer 12

aldosterone

cortisol

they have equal affinities

Question 13

what is the parent compound of steroids

Answer 13

cholesterol

Question 14

what enzyme takes active steroids to their inactive form

Answer 14

11B dehydrogenase 2

Question 15

side effects of corticosteroids

Answer 15

infections, myopathies, osteoporosis, skin thinning, HPA insufficiency , hypertension, hyperglycemia !

Question 16

what are some factors that influence theraputic and adverse effects of corticosteroids

Answer 16

potency (inherent strength of steroid)
pharmokinetics (short vs long term)
daily dose (how frequently)
timing og dose (given in AM)
metabolism differences
duration of treatment

Question 17

how do you treat primary adrenal insufficiency (addisons)

Answer 17

give a glucorticoid (hydrocotisone) and a mineralocorticoid (fludrocortisone)

this is the same way you would treat congential adrenal hyperplasia

Question 18

give common examples of non-endocrine conditions we treat with steroids

Answer 18

following bone marrow transplant, autoimmune diseases (MS/psoriasis), hematological cancers, IBD, asthma, RA, hypersensitivity rxns, skin diseases

Question 19

can corticosteroids be given in medical emergencies?

Answer 19

yes, high doses for a few days with little risk

DO NOT GIVE MORE THAN A FEW DAYS AND DO NOT REPLACE OR DELAY PRIMARY THERAPIES

Question 20

can steroids be given for chronic conditions?

Answer 20

yes but you really must monitor your patients: you need to see if there is evidence for therapy in a particular preparation: dosem frequency, route of administration, and assessement of theraputic efficacy

closely monitor patients

Question 21

steroids cannot be given chronically without the risk of

Answer 21

adverse events

Question 22

only initiate steroids id there is published evidence of objective theraputic _

Answer 22

benefit

Question 23

use steroids after other therapies have _

Answer 23

failed

Question 24

you must identify the specific _ objective and have criteria to gage the response of the steroid

Answer 24

theraputic

administer as much to get theraputic effect, taper off when no longer necessary, terminate if expected result has not be achieved, complications arise or maximum benefit has occurred.

Question 25

steroids decrease production of _ and _

Answer 25

prostaglandins and leukotrienes

Question 26

steroids _ production of proteolytic enzymes and _ apoptosis of immune cells

Answer 26

decrease increase

Question 27

steroids _ transmigration of neutrophils and macrophages from the blood into tissues

Answer 27

decrease

Question 28

steroids _ expression of cell adhesion molecules

Answer 28

decrease

Question 29

consequences of steroids

Answer 29

decreased inflammation, immune suppresion, decreased allergies/hypersentitivity reactions

Question 30

metabolic effects of steroids

Answer 30

carbohydrate metabolism - hyperglycemia lipid metabolism - lipolysis, fat redistribution (hump back) protein metabolism- myopathy and muscle wasting, dreased AA uptake, decreased protein synthesis

Question 31

in what patient populations are systemic glucocorticoids problematic

Answer 31

immunocompromised, diabetics, people with infections, peptic ulcers, cardiovascular conditions, physciatric conditions, osteoporosis, children

Question 32

decreased activity/inhibition of the enzyme 11BHSD2 results in excessive activation of _ mediated by _

Answer 32

MR mediated by cortisol this increases Na+ and water retention leading to K+ loss and increased BP

Question 33

what are known inhibitors of 11B-HSD2

Answer 33

glycyrrhizin (licorice root extract) carbenoxolone

Question 34

glucocorticoids have an anti _ action

Answer 34

insulin they increase gluconeogenesis, decrease glucose uptake, and increase lipolysis all leading to hyperglycemia

Question 35

what are the short to medium acting glucocorticoids (12 hrs)

Answer 35

hydrocortisone (cortisol) and cortisone

Question 36

what are the intermediate acting glucocorticoids (12-36 hrs)

Answer 36

prednisone predinisolone methylprenisolone triamicnolone

Question 37

what is a long acting steroid (>36 hrs)

Answer 37

betamethasone, dexamethasone

Question 38

corticosteroid drug dosing

Answer 38

use the lowest doe for the shortest duration possible use short/intermediate vs long acting use topical/inhalation over systemic give single doses in the AM can do alternate day with short course pulse therapy taper off- for HPA recovery

Question 39

how can you test the integrity of the HPA axis

Answer 39

morning cortisol ACTH test CRH test

Question 40

prednisolone MOA applications pharmaokinetics toxicities

Answer 40

activates the GR receptors and alters gene transcription inflammatory conditions, cancers, transplantation etc. intermediate acting 12-36 hrs adrenal suppresion, hyperglycemia, osteoporosis, salt retention (high blood pressure)

Question 41

mifepristone MOA applications pharmokinetics effects (adverse)

Answer 41

anatagonist at glucocorticoid and progesterone receptors medical abortion and CUSHINGS disease oral administration vaginal bleeeding, gi upset, diarrhea

Question 42

mineralocorticoids are a class of steroid hormones that influence _ and _ balance

Answer 42

salt and water

Question 43

mineralocorticoids primarily act on the _ where they cause sodium and water retnetion and excretion of _ and _

Answer 43

kidney postassium and protons

Question 44

the primary mineralocortcoid is _

Answer 44

aldosterone (also progesterone and deoxycorticosterone )

Question 45

fludrocortisone MOA applications pharmokinetics toxicities

Answer 45

agonsit at mineralocortioid receptors and glucocorticoid receptors primary adrenal insuffuciency (addisons) long duration of action salt and fluid retention, hyperglycemia, CHF

Question 46

what are the mineralocorticoid receptor antagonisrs?

Answer 46

spironolactone and eplernone

Question 47

spironolactone MOA applications pharmokinetics toxicities

Answer 47

antagonists at mineralocorticoid receptor and weak antagonist at androgen receptors aldosteronism and hypokalemia (applications) slow onsent and offset toxicities: hyperkalemia, gynecomastia

Question 48

eplernone MOA clinical applications pharmacokinetics toxicities

Answer 48

mineralocorticoid receptor anatgonist (specific) HTN cleared ny cypP450 metabolism hyperkalamia and increased creatine

Question 49

ketaconazole MOA application pharmacokinetics toxcicities

Answer 49

blocks fungal and mammalian CYP450 enzymes inhbitis steroid hormone synthesis and fungal ergosterol synthesis oral/topical administration hepatic dysfunction, CYP450 interactions

Question 50

what is metyrapone

Answer 50

a medication used in the diagonsis of adrenal insufficiency and occasionally in the treatment of cushing disease