2. • Corticostroids hormones-Corticostroids hormones- Includs
two hormones-
• MineralocorticoidsMineralocorticoids :: effects on
carbohydrate, protein and fat metabolismsrone-
• GlucocorticoidsGlucocorticoids (Glucocorticosteroids)(Glucocorticosteroids)::
cortisol-cortisol- effects Na+ and K+ and fluid
balance.
•
3. • Use of corticosteroids
•Corticosteroids are used:
• to reduce inflammation (asthma, arthritis) and
swelling (cerebral oedema)
• to suppress the immune response (systemic lupus
erythematosis)
• to reduce nausea and vomiting (as in cancer
chemotherapy)
• to reduce terminal pain (associated with cancer)
• as replacement therapy (in Addison's disease)
• Example of -
• hydrocortisone , prednisolone, dexamethasone,
beclomethasone , budesonide , fluticasone
4. Structure and function of adrenal cortex.Structure and function of adrenal cortex.
ZonaZona
ReticularisReticularis
AdrenalineAdrenaline
ZonaZona
FaseciculataFaseciculata
AndrogensAndrogens
5.
6.
7. Basic structure of glucocorticoid drugs:Basic structure of glucocorticoid drugs:
AA BB
CC DD
HH
A.A. Glucocorticoid drugsGlucocorticoid drugs
9. binding to glucocorticoid receptor (GR)binding to glucocorticoid receptor (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene transcriptionregulating related gene transcription
biological effects (usually slow)biological effects (usually slow)
Mechanisms of glucocorticoid actionsMechanisms of glucocorticoid actions
10.
11. 1. Pharmacological effects
Mechanisms of glucocorticoid actions
(1) Effects on metabolisms
(2) Permissive action
(3) Anti-inflammatory effects
(4) Effects on immune and allergy
(5) Anti-shock
(6) Other effects
antipyretic effects
effects on blood and blood-forming organs
skeletal system
CNS effects
12. (2) Permissive action
Potentiating the effects of catecholamines and
glucagon
(3) Anti-inflammatory effects
Acute: inhibiting microvascular leakage
leukocyte infiltration
Chronic: inhibiting fibroblast proliferation
deposition of collagen
13. Anti-shock
Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane: decreasing the release of
myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
14. (6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organs
red cell ↑; lymphocytes ↓; neutrophils ↑ (function ↓); eosinophils ↓;
platelets ↑
c) skeletal system: osteoporosis
d) CNS: increasing excitability (elevated mood, euphoria, insomnia,
restlessness, increased motor activity)
15. 2. ADME properties of commonly used
drugs
Cortisone and prednisone are reduced and
transformed to hydrocortisone and prednisolone
(active forms) in the liver
Metabolism will be increased by hepatic enzyme
inductors (phenobarbital, phenytoin, rifampine,
etc.)
17. Drug features
• Hydrocortisone : Also called cortisol . It is primary
glucocorticoids, and mineralocorticoids as well.
Used replacment therapy for shock, asthamaticus,
adrenal insufficiency ,ulcerative etc. Dose- 20-30
mg/day
• Prednisolone: 4 times more potent then cortisol. It
si more selective to glucocorticoids, have
inermediate duration of action. Used in allergic,
inflammation, autoimmune disease. Dose – 10-60
mg/ day
• Betamethasone: very potent, selective
glucocorticoids, similar to dexamethasone. Used in
allergic, shock, edema etc. Dose-0.5-5mg
18. (1) Immune diseases
a) autoimmune disorders: reumatic fever, reumatic
carditis, rhumatic arthritis, rheumatoid arthritis,
osteoarthritis, systemic lupus erythematosus,
polyarthritis nodosa, nephritic syndrome, etc.
b) rejection of organ transplantation
c) allergic diseases: urticaria, serum sickenss, contact
dermatitis, drug allergic reactions, chronic severe
asthma, status asthmaticus, angioneurotic edema, etc.
Clinical uses
19. (2) Severe infection and inflammation
a) acute severe infections: merely suppressing
inflammatory manifestations but at times lifesaving
Caution: combination with effective anti-microbial①
drugs; Large dose; short term administration !② ③
Usually be not used in viral and fungal infections
except for those with cerebral edema or severe
systemic symptoms
b) prevention of some types of inflammation, such
as in brain, heart, eye, joint, etc.
20. (3) Septic shock:(3) Septic shock:
Causion:Causion: larger dose, short-term, and combined withlarger dose, short-term, and combined with
antimicrobial drugs.antimicrobial drugs.
(4) Hemological diseases:(4) Hemological diseases: acute lymphocytic leukemia,acute lymphocytic leukemia,
lymphomas, aplastic anemialymphomas, aplastic anemia (( 再生障碍性贫血再生障碍性贫血 ),),, hemolytic, hemolytic
anemia, leukocytopenia, thrombocytopenia,anemia, leukocytopenia, thrombocytopenia, etetc.c.
(5) Topical applications:(5) Topical applications: skin, eye, respiratory tract,skin, eye, respiratory tract,
joint (local injection)joint (local injection)
(6) Some types of tumors:(6) Some types of tumors: breast and prostaticbreast and prostatic
cancers, acute lymphocytic leukemia,cancers, acute lymphocytic leukemia, etcetc..
21. 4. Adverse effects
(1) Effects resulting from continued used of
large doses
a) Hypercorticism-like syndrome: central obesity
(moon face, buffalo hump, etc.); hypertension;
glycosuria, hypokalemia; etc.
b) Increasing susceptibility to infections:
Causion: specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system: peptic ulcers, etc.
22. d) Cardiovascular system: hypertension,
arteriosclerosis
e) Myopathy and osteoporosis: vertebral
compression fractures, spontaneous fractures,
especially in postmenopausal women
f) CNS: behavioral disturbances, induction of
epileptic seizures
g) Inhibition or arrest of growth in children
23. Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal
axis
b) Exacerbation of the underlying diseases
(rebound)
Contraindications
psychiatric disorders; epilepsy; active peptic
ulcers; fractures; hypercorticism; severe
hypertension; diabetes mellitus; viral or fungal
infections, etc.
25. (1) Replacement therapy: usually using hydrocortisone
(2) Prompt intensive treatment: i.v. gtt
hydrocortisone, dexamethasone
(3) Long-term therapy: oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes: for less severe and less sustained patients;
less suppression on hypothalamic-pituitary-adrenal (HPA)
axis
(4) Tipical applications: skin; eye; respiratory tract
Applications
26. • Aldosterone 醛固酮
• Na+
excretion ↓, K+
excretion ↑: edema
hypertension
hypokalemia, etc.
used for
adrenocortical
dysfunction with
imbalance of water
and electrolytes
B.B. Mineralocorticoid drugsMineralocorticoid drugs
27.
28. • 2. Corticosteroid synthetase inhibitors
• Mitotane
• Metyrapone
• Aminoglutethimide
• Used for adrenocortical tumors or hypercorticism
C. Adrenocorticotropic hormone and
corticosteroid synthetase inhibitors
