W13 Corticosteroids

Question 1

4 steroidal classes

Answer 1

1. Adrenocorticoids
2. Sex hormones
3. Bile acids
4. Vitamins

Question 2

ICS target on asthma

Answer 2

INFLAMMATION

Mast cell stabilisers
LK modification
monoclonal anti-IgE

Question 3

Describe the structure of steroids

Answer 3

4 ring system

2 faces: A & B face

Question 4

Describe GLUCOCORTICOID structure

Compare B/A faces

Answer 4

TRANS ring junctions
2 faced:
B face (top) is HYDROPHILIC & binds to receptors
A face (bottom) is HYDROPHOBIC

Question 5

Steroid hormone synthesis starting material -

Answer 5

Cholesterol

Question 6

Mechanism of glucocorticoid secretion

Answer 6

FEEDBACK MECHANISM
Low circulating adrenocorticoids
CRF -  hypothalamus
ACTH - anterior pituitary
adrenocorticoids - adrenal cortex
High circulating adrenocorticoids
CRF inhibition

Question 7

Which structures are involved in glucocorticoid secretion?

Answer 7

hypothalamus, pituitary gland, adrenal cortex

Question 8

3 pharmacological effects of glucocorticoids

Answer 8

ANTI-INFLAMMATORY
CYTOKINE INHIBITION
AUTOCOID INHIBITION (from mast cells)

Question 9

anti-inflammatory mechanism

Answer 9

PROTEIN SYNTHESIS INTERFERENCE

Lipocortin inhibits Phospholipase A

Question 10

CK inhibition mechanism

Answer 10

Inhibits IL-1
&laquo_space;T/B cells
IMMUNOSUPPRESSION

Question 11

AUTOCOID inhibition mechanism

Answer 11

Inhibition of HISTAMINE & AUTOCOID release from mast cells

Question 12

pharmacological uses of glucocorticoids

Answer 12

anti-inflammatory: allergy & immune response in lungs suppressed
RA therapy
Tissue transplants & lymphocpoiesis

Question 13

AUTOCOIDS

Answer 13

‘mini-hormones’ which are released & act locally for a short duration

Question 14

effects of corticosteroids on structural cells

Answer 14

EPITHELIAL: CK & mediators «
ENDOTHELIAL: &laquo_space;leak
AIRWAY SMOOTH MUSCLE:&raquo_space; B2 receptor activity, &laquo_space;CK
MUCUS GLAND: &laquo_space;mucus secretion

Question 15

which aspects of glucocorticoids denote their activity?

Answer 15

Trans junctions of PREGNANE SKELETON
A-ring enone
17B-ketol side chain (C20-keto-C21-hydroxy)
Free C-21 for corticosteroid activity

Question 16

3 metabolic targets on glucocorticoids:

Answer 16

RING A reduction
C17 OXIDATION
C11 KETO-ENOL ISOMERISATION

Question 17

What are PRODRUGS

Answer 17

Chemical derivatives of the parent drug which undergo chemical enzymatic transformation in vivo to release the active parent drug.

Question 18

Pharmacological effects of prodrugs

Answer 18

prolong duration of action (t1/2)

prolong onset of action & metabolism of parent drug

enhance drug permeation by increasing LIPOPHILICITY & improved water solubility

Question 19

Uses of prodrugs

Answer 19

site-specific drug delivery - reduced systemic effects & ADRs

overcome barriers to drug formulation

Question 20

Commonest prodrug (func group)

Answer 20

ESTERS

Question 21

SYSTEMIC GLUCOCORTICOID drugs for asthma

Answer 21

Hydrocortisone (Cortisol)
prednisolone
methylprednisolone

Question 22

INHALED GLUCOCORTICOID drugs for asthma

Answer 22

Beclomethasone
Budesonide
ciclesonide
flunisolide
fluticasone
mometasine