Pharmacology Steroids

Question 1

what are all corticosteroids derived from?

Answer 1

cholesterol

Question 2

if cortisol is used as a drug, what is it called?

Answer 2

hydrocortisone (given IV in patients)

Question 3

why can giving a lower dose of dexamethasone achieve the same effect as giving a higher dose of cortisol?

Answer 3

dexamethasone= more potent

Question 4

effects of cortisol in body?

Answer 4

glycogenolysis, gluconeogenesis in liver, causing hyperglycameia
proteolysis- free up aa
lipolysis at low concs, lipogenesis at high concs e.g. in cushings disease, and with very potent steroid drugs
redistribution of fat- cushing’s syndrome, high dose of steroid drug

Question 5

effects of glucocorticoid deficiency in body?

Answer 5

hypoglycameia
weight loss
hypotension
nausea
underweight

Question 6

effects of excess glucocorticoids in body?

Answer 6

hyperglycaemia
weight gain-water retention, increased appetite
hypertension
cushinoid

Question 7

effects of mineralocorticoid deficiency?

Answer 7

hyponatraemia
dehydration
hypotension
hyperkalaemia

Question 8

effects of high mineralocorticoids in body?

Answer 8

hypernatraemia
hypertension
hypokalaemia

Question 9

examples of steroid drugs selective for glucocorticoid receptors in body, with minimal effect at mineralocorticoid receptors?

Answer 9

dexamethasone

betamethasone

Question 10

example of a steroid drug that is much more selective for mineralocorticoid receptors in body, rather than glucocorticoid receptors?

Answer 10

fludrocortiosone

would use if wanted to mimic aldosterone in body

Question 11

why do steroid drugs have good oral bioavailability?

Answer 11

very good lipid-solubility, so easily absorbed in gut

passive factor

Question 12

how are steroids metabolised in the body?

Answer 12

by the liver, via both phase I and II metabolism, II= glucuronidation
small amount of metabolism capable in kidney- can convert cortisol in body to cortisone=inactive.

Question 13

steroids given IV?

Answer 13

methylprednisolone

hydrocortisone

Question 14

what route could you give a steroid to treat eczema, and give an example of a steroid given this way?

Answer 14

topical
betamethasone
very well absorbed across skin due to being highly lipid soluble

Question 15

passive factors affecting oral bioavailability of a drug?

Answer 15

size
charge
lipid solubility

Question 16

example of a steroid drug that can be given as an intra-articular for inflammatory joint conditions?

Answer 16

triamcinolone

Question 17

how do corticosteroids suppress inflammation?**

Answer 17

transrepression and transactivation= switch on protein synthesis, of genes
inhibit B and T cell responses
inhibit nuclear factor kappa B
reduced transcription of cytokines
reduced expression of cell adhesion molecules
reduced phagocytic function
immunosuppression

Question 18

mechanism of action of steroids?

Answer 18

lipophilic- cross cell membrane to enter cytoplasm, where bind to cytoplasmic receptor, often associated with heat shock proteins, heat shock protein dissociates and activated receptor passes across nuclear membrane into nucleus, DNA binding domain has been unmasked on receptor following steroid binding. Bind onto hormone response element of DNA= glucocorticoid response element for steroid drugs.
some can access nucleus directly, binding to receptor in nucleus and then to hormone response element in DNA.
transcription switched on and off for particular proteins

takes time to happen

Question 19

examples of proteins transactivated by steroid drugs?

Answer 19

annexin 1- inhibits phospholipase A2 which normally forms arachidonic acid, so inhibit PG production by producing annexin-1

Question 20

ADRs of steroid drugs can occur with cis-repression of particular proteins. what examples are there of these proteins?

Answer 20

POMC- contains sequence for ACTH
osteocalcin- secreted by osteoblasts and promotes bone formation, so reduction causes increased risk of osteoporosis.
keratin- reduced so skin thinned, alongisde effect of increased proteolysis in steroid tment

trans-repression reduces inflammatory mediators

Question 21

how can NF kappa B be inhibited by glucocorticoids, inhibiting inflammatory pathway?

Answer 21

receptor with steroid bound can bind to CBP (cAMP response element binding protein) which inhibits NF kappa B.

Question 22

steroids used in replacement therapy?

Answer 22

hydrocortisone
fludrocortisone

e.g. addison’s disease, or adrenolectomy

Question 23

what have steroids been co-administered with in malignancy which have shown improved outcomes?

Answer 23

chemotherapy

Question 24

use of steroid drugs clinically?

Answer 24

asthma
GI inflamm diseases e.g. Crohn's and UC
inflammatory skin conditions: eczema, psoriasis
nephrotic syndrome
haematological conditions
vasculitis
sarcoidosis
cerebral oedema
RA

women in premature labour- induce surfactant production in fetus to mature lungs by stimulating type 2 pneumocytes= simple cuboidal cells. steroids lipid soluble so can cross placenta. big problem with premature birth in past= resp distress syndrome= restrictive lung defect e.g. dexamethasone.

Question 25

mineralocorticoid SEs of given steroid drugs?

Answer 25

fluid retention- ptn may complain of putting on weight, feeling bloated, moon shaped face
hypertension
hypokalaemia

Question 26

glucocorticoid ADRs?

Answer 26

immunosuppression, increased infection risk e.g. oral candidiasis
hypertension
osteoporosis
cushinoid appearance- central obesity, moon shaped face, easy bruising, purple striae, buffalo hump= dorso-cervical fat pad- redistribution of fat in body.
hyperglycameia, diabetes
avascular necrosis
peptic ulcers- *trasnrepression of COX-1 in stomach responsible for PGE2 production necessary for protective mucus and HCO3- prod in stomach against gastric acid.
impaired growth in children
skin thinning
cataracts
corneal damage

Question 27

what factors mean that steroid drugs increase risk of osteoporosis?

Answer 27

inhibit osteoblast formation
increased osteoclast proliferation
reduced Ca2+ absorption in gut
reduced sex steroid production- oestrogen necessary to maintain balance between osteoblast and clast activity.

Question 28

why must a patient not be suddenly taken off steroids?

Answer 28

will have HPA suppression, so adenals not stimulated.
suppression occurs after 3 wks
abrupt withdrawl can cause adrenal insufficency crisis

Question 29

surgery is a big stress to body? what must be done if patient on steroidds is going to have surgery?

Answer 29

must increase dose of steroid

ptnt must carry steroid card with them to tell drs

Question 30

bicohemical disturbances in hypoadrenal crisis?

Answer 30

hypotension
hypoglycaemia
hyponatraemia
hyperkalaemia
severe dehydration
death if untreated