Corticosteroids Flashcards
Adrenocorticoids
Glucocorticoids
Mineralcorticoids
Glucocorticoids
Stress hormones
Increase circulating glucose concentrations
Potent anti-inflammatory effects
Mineralocorticoids
Na+ retention
Increase blood volume
Increase blood pressure
T/F: Epinephrine and Cortisol contrast each other
True
Adrenal insufficiency other name
Hypoadrenalism - Decreased secretion of steroid hormones by the adrenal cortex
Adrenal insufficiency causes
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
Adrenal insufficiency symptoms
Extreme weakness
Anorexia, anemia, nausea, vomiting
Low blood pressure (in primary only)
Mental depression
Cessation of long-term systemic glucocorticoid therapy can lead to
Addisonian symptoms
Cushing’s disease other name
Hyperadrenalism
Cushing’s disease causes
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)
Cushing’s disease causes
Increased protein catabolism (easy bruising, wound healing, muscle wasting) increased glucose levels
Osteoporosis
opportunistic infections
Long-term therapeutic use of systemic glucocorticoids can lead to
Cushing’s symptoms
Change of cortisol to cortisone
OH on 11 is changed to ketone on 11
T/F: the conversion of cortisol to cortisone is reversible
True
T/f: cortisone is effective as cortisol, when used systemically
True
T/F: Cortisone should be used in patients with impaired liver function
False
Short acting systemic corticosteroids (8-12 hrs)
Hydrocortisone
Cortisone
Intermediate acting systemic corticosteroids (12-36hrs)
Prednisone
Prednisolone
Methylprednisolone
Traimcinolone
Long-acting systemic corticosteroids (36-54 hrs)
Dexamethasone
Betamethasone
Fludrocortisone
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)
Prednisone/Prednisolone
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)
Methylprednisolone
Synthetic glucocorticoids
6a-methyl group
Potency similar to that for prednisolone
Reduced mineralocorticoid activity
(ADDITION OF METHYL ON CARBON 6)
(Intermediate)
Triamcinolone
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)
Dexamethasone
16a-methyl group
Increased lipophilicity
Increased receptor binding
Significantly stronger effect
Increased stability in human plasma
Reduced mineralocorticoid activity
(Long duration)
Betamethasone
Synthetic glucocorticoid
Enantiomer of dexamethasone at 16
Has similar properties as dexamethasone
(Long duration)
21 esters properties
The hydroxyl group at 21 can be modified to an ester to control the property of glucocorticoids
Prodrugs activated through hydrolysis by esterases
21 esters: Acetates
Acetate:
Increased lipophilicity
Prolonged action upon IM or intra-articular injection
21 esters: Succinate
Soluble
Slow hydrolysis
21 esters: Phosphate
Increased solubility
Rapid hydrolysis by phosphatases (~10 min)
IV or IM injection for emergency conditions
Inhaled Glucocorticoids: Desired properties
High potency
Minimal systemic effects
Prolonged action
Inhaled glucocorticoids: Solutions
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
Triamcinolone acetonide
Inhaled glucocorticoid:
Acetonide is resistant hydrolysis
8x more potent than prednisolone
(ADDITION OF STICKS)
Beclomethasone dipropionate
Converted rapidly to 17-monopropionate by hydrolysis
14x more potent than deamethasone
Flunisolide
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
Budesonide
Inhaled Glucocorticoids
1:1 mix of epimers at 16,17-butylacetal
Faster topical uptake
Low oral bioavailability
Extensive first-path metabolism
Mometasone furoate
Inhaled glucocorticoids
Highly potent
More rapid onset of action
Negligible systemic availability
Rapid metabolism
low oral bioavailability (<1%)
Fluticasone Propionate
Inhaled Glucocorticoids
Inactivated by hydrolysis of thioester
Rapid first-path metabolism
Highly lipophilic and insoluble
Highly potent
Poor absorption from GI
Rapid topical uptake
Topical Glucocorticoids desired properties
High lipophilicity for fast absorption
Minimal systemic effect
Prolonged action
T/F: Topical Glucocorticoids are Halogenated analogues
True
Topical Glucocorticoids examples
Triamcinolone acetonide
Fluocinonide
Betamethasone valerate (medium potency)
Acetonide or ester forms have better potency for topical applications due to high lipophilicity
21-cholorocorticoids
Clobetasol propionate
Halobetasol propionate
Halcinonide
Substitution of a chlorine atom for the 21-hydroxyl group greatly enhances topical anti-inflammatory activity
Fluticasone propionate and mometasone furoate have - potency
Medium, high lipophilicity and the highest binding affinity, but poor solubility
Poor dissolution into inflamed tissue
Adverse effects of glucocorticoids: crossover mineralocorticoids activity
Sodium and water retention
Development of HTN
Correctable with selective synthetic glucocorticoids
Adverse effects of glucocorticoids: Metabolic effects (increased glucose production):
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
Adverse effects of glucocorticoids:
Cushing’s-like effects - redistribution of fat
-Moon face
