Corticosteroids

Question 1

Adrenocorticoids

Answer 1

Glucocorticoids
Mineralcorticoids

Question 2

Glucocorticoids

Answer 2

Stress hormones
Increase circulating glucose concentrations
Potent anti-inflammatory effects

Question 3

Mineralocorticoids

Answer 3

Na+ retention
Increase blood volume
Increase blood pressure

Question 4

T/F: Epinephrine and Cortisol contrast each other

Answer 4

True

Question 5

Adrenal insufficiency other name

Answer 5

Hypoadrenalism - Decreased secretion of steroid hormones by the adrenal cortex

Question 6

Adrenal insufficiency causes

Answer 6

Destruction of the cortex by tuberculosis or atrophy (primary: Addison’s disease)
-Decreased secretion of ACTH due to diseases of anterior pituitary (secondary; no hypoaldosteronism

Question 7

Adrenal insufficiency symptoms

Answer 7

Extreme weakness
Anorexia, anemia, nausea, vomiting
Low blood pressure (in primary only)
Mental depression

Question 8

Cessation of long-term systemic glucocorticoid therapy can lead to

Answer 8

Addisonian symptoms

Question 9

Cushing’s disease other name

Answer 9

Hyperadrenalism

Question 10

Cushing’s disease causes

Answer 10

Tumors in the adrenal cortex (adrenal)
Increased production of ACTH due to non-pituitary carcinoma (pituitary)
Ectopic production of ACTH due to non-pituitary carcinoma (ectopic)

Question 11

Cushing’s disease causes

Answer 11

Increased protein catabolism (easy bruising, wound healing, muscle wasting) increased glucose levels
Osteoporosis
opportunistic infections

Question 12

Long-term therapeutic use of systemic glucocorticoids can lead to

Answer 12

Cushing’s symptoms

Question 13

Change of cortisol to cortisone

Answer 13

OH on 11 is changed to ketone on 11

Question 14

T/F: the conversion of cortisol to cortisone is reversible

Answer 14

True

Question 15

T/f: cortisone is effective as cortisol, when used systemically

Answer 15

True

Question 16

T/F: Cortisone should be used in patients with impaired liver function

Answer 16

False

Question 17

Short acting systemic corticosteroids (8-12 hrs)

Answer 17

Hydrocortisone
Cortisone

Question 18

Intermediate acting systemic corticosteroids (12-36hrs)

Answer 18

Prednisone
Prednisolone
Methylprednisolone
Traimcinolone

Question 19

Long-acting systemic corticosteroids (36-54 hrs)

Answer 19

Dexamethasone
Betamethasone

Question 20

Fludrocortisone

Answer 20

Synthetic glucocorticoid
9a-F
Greater glucocorticoid activity
Strong mineralocorticoid activity
Intense Na+ retention leading to edema
Used in mineralocorticoid replacement therapy
(ADDITION OF F)
(intermediate)

Question 21

Prednisone/Prednisolone

Answer 21

Synthetic Glucocorticoids
Extra double bond between CI and C2
Altered ring structure
More potent glucocorticoid activity
Stronger binding to the glucocorticoid receptor
Reduced mineralocorticoid activity
Interconvertible by 11B hydroxysteroid dehydrogenase
(DOUBLE BOND ON THE TOP OF FIRST RING)
(intermediate)

Question 22

Methylprednisolone

Answer 22

Synthetic glucocorticoids
6a-methyl group
Potency similar to that for prednisolone
Reduced mineralocorticoid activity
(ADDITION OF METHYL ON CARBON 6)
(Intermediate)

Question 23

Triamcinolone

Answer 23

Synthetic glucocorticoids
9a-F and 16a-OH
Glucocorticoid activity similar to prednisone
Reduced mineralocorticoid activity
Increased hydrophilicity
Low oral bioavailability
(F AND OH)
(intermediate acting)

Question 24

Dexamethasone

Answer 24

16a-methyl group
Increased lipophilicity
Increased receptor binding
Significantly stronger effect
Increased stability in human plasma
Reduced mineralocorticoid activity
(Long duration)

Question 25

Betamethasone

Answer 25

Synthetic glucocorticoid Enantiomer of dexamethasone at 16 Has similar properties as dexamethasone (Long duration)

Question 26

21 esters properties

Answer 26

The hydroxyl group at 21 can be modified to an ester to control the property of glucocorticoids Prodrugs activated through hydrolysis by esterases

Question 27

21 esters: Acetates

Answer 27

Acetate: Increased lipophilicity Prolonged action upon IM or intra-articular injection

Question 28

21 esters: Succinate

Answer 28

Soluble Slow hydrolysis

Question 29

21 esters: Phosphate

Answer 29

Increased solubility Rapid hydrolysis by phosphatases (~10 min) IV or IM injection for emergency conditions

Question 30

Inhaled Glucocorticoids: Desired properties

Answer 30

High potency Minimal systemic effects Prolonged action

Question 31

Inhaled glucocorticoids: Solutions

Answer 31

High lipophilicity Tighter binding to the receptor Better tissue penetration Prolonged action by forming poorly soluble microcrystals Low oral bioavailability 70-90% of inhaled glucocorticoids is swallowed Rapid Short half-life

Question 32

Triamcinolone acetonide

Answer 32

Inhaled glucocorticoid: Acetonide is resistant hydrolysis 8x more potent than prednisolone (ADDITION OF STICKS)

Question 33

Beclomethasone dipropionate

Answer 33

Converted rapidly to 17-monopropionate by hydrolysis 14x more potent than deamethasone

Question 34

Flunisolide

Answer 34

Inhaled glucocorticoids Rapid absorption from nasal or lung tissue Rapid metabolism by the liver Extensive first-path metabolism Minimal systemic adverse effect with long-term therapy

Question 35

Budesonide

Answer 35

Inhaled Glucocorticoids 1:1 mix of epimers at 16,17-butylacetal Faster topical uptake Low oral bioavailability Extensive first-path metabolism

Question 36

Mometasone furoate

Answer 36

Inhaled glucocorticoids Highly potent More rapid onset of action Negligible systemic availability Rapid metabolism low oral bioavailability (<1%)

Question 37

Fluticasone Propionate

Answer 37

Inhaled Glucocorticoids Inactivated by hydrolysis of thioester Rapid first-path metabolism Highly lipophilic and insoluble Highly potent Poor absorption from GI Rapid topical uptake

Question 38

Topical Glucocorticoids desired properties

Answer 38

High lipophilicity for fast absorption Minimal systemic effect Prolonged action

Question 39

T/F: Topical Glucocorticoids are Halogenated analogues

Answer 39

True

Question 40

Topical Glucocorticoids examples

Answer 40

Triamcinolone acetonide Fluocinonide Betamethasone valerate (medium potency) Acetonide or ester forms have better potency for topical applications due to high lipophilicity

Question 41

21-cholorocorticoids

Answer 41

Clobetasol propionate Halobetasol propionate Halcinonide Substitution of a chlorine atom for the 21-hydroxyl group greatly enhances topical anti-inflammatory activity

Question 42

Fluticasone propionate and mometasone furoate have - potency

Answer 42

Medium, high lipophilicity and the highest binding affinity, but poor solubility Poor dissolution into inflamed tissue

Question 43

Adverse effects of glucocorticoids: crossover mineralocorticoids activity

Answer 43

Sodium and water retention Development of HTN Correctable with selective synthetic glucocorticoids

Question 44

Adverse effects of glucocorticoids: Metabolic effects (increased glucose production):

Answer 44

Steroid myopathy High doses over period of time cause wasting of proximal muscles Reduced long bone growth in children May cause premature closing of epiphyseal junction and stop growth Osteoporosis Pharmacological doses of glucocorticoids inhibit osteoblasts can be prevented by bisphosphonate

Question 45

Adverse effects of glucocorticoids:

Answer 45

Cushing's-like effects - redistribution of fat -Moon face