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Department of Pharmacology
NEIGRIHMS, Shillong
Steroids
Steroids are fast catching up with antibiotics
as the most abused class of drugs today
Introduction
The adrenal produces various
classes of hormones, each of which
aid in dealing with the stress faced by
animals and people almost daily
At least two of these groups
Glucocorticoids and
Mineralocorticoids
Corticosteroids
are
necessary for or
lifecorticoids refer
to natural
gluco- and mineralo-corticoids and
their
Contents
History
1855 Addison`s disease
1856 Adrenal glands essential for life
1930 Cortex > medulla
1932 Cushings syndrome
1952 Aldosterone
Anatomy
An inner medulla, is a
source of catecholamine
adrenaline and nor-adrenaline
Chromaffin cell is the principal
cell type
Medulla is richly innervated by
sympathetic fibres and is
considered as extension of
sympathetic nervous system
Medulla develops from
ectoderm (neural crest)
Adrenal Cortex
Steroid Class
Prototype
Physiological effect
Na, K and water
homeostasis
Biosynthesis
Basal Secretion
Group
Hormone
Daily
Glucocorticoids
Cortisol
Corticosterone
5 30 mg
2 5 mg
Mineralocorticoids
Aldosterone
11- deoxycorticosterone
5 150 mcg
Trace
DHEA
Progesterone
Oestradiol
15 30 mg
0.4 0.8 mg
Trace
Sex Hormones
Androgen
Progestogen
Oestrogen
Regulation of Synthesis
Synthesized
and
released under
influence of ACTH - Ant.
Pituitary (HPA axis)
Regulated by CRH
from hypothalamus
and by feedback
levels of blood
concentrations
2.
Control by circadian
rhythm (Diurnal
rhythm) morning
rise
Stress:
hypoglycaemia,
physical stress etc.
Glucocorticoids - MOA
Not stored:
Glucocorticoids - MOA
Glucocorticoids - MOA
Actions
Numerous and widespread actions:
Direct Actions
Permissive Actions
Lipolytic effects
Effect on BP
Effect on bronchial muscles
(e.g.,sympathomimetic amine)
Gluconeogenesis
Fat Metabolism
Actions of Glucocorticoids
Water excretion:
Calcium Balance:
Skeletal muscle:
CNS:
Actions of Glucocorticoids
Glucocorticoids anti-inflammatory
and immunosuppressive effects
Glucorticoids - Multiple
Mechanisms
Contd.
Corticosteroids
Lipocortin
Phospholipids
Phospholipase A2
Arachidonic acids
Cycylooxygenase
lipoxygenase
Leukotriene
PAF by lipocortin
Prostaglandins,
Thromboxane
Prostacyclins
Glucocorticoids Anti-inflammatory
and Immunosuppressive effects
Glucocorticoids - Pharmacokinetics
Steroid Preparations
An ideal GC should have no
mineralocorticoid activity
Structural changes to the basic cortisol
molecule resulted in a number of
compounds with
Important agents
Injectable:
Betamethasone
Prednisolone
Hydrocortisone
Oral:
Betamethasone
Prednisolone
Methylprednisolone
Fludricortisone
Prednisone
Topical:
Betamethasone
Flucinolone
Dexamethasone
Methylprednisolone
Triamcinolone
Clobetasol
Mometasone
Inhalation:
Beclomethasone
Flunisolode
Budesonide
Chemical Structures
Pharmaceutical steroids are usually obtained from
cholic acid (obtained from cattle) or sapogenins found
in plants of Liliacaceae
Cyclopentanoperhydrop
henanthrene skeleton
Relative Activity
Compound
Duration
GC
MC
Equivalent
dose (mg)
Hydrocortisone
SA
20
Prednisolone
IA
0.8
Methyl
Prednisolone
IA
0.5
Triamcinolone
IA
Dexamethasone
LA
25
0.75
Betmethasone
LA
25
0.75
Aldosterone
MC
0.3
500 - 3000
NU
Desoxycortisone
acetate (DOCA)
MC
100
2.5 (S.
lingual)
Corticosteroids - Clinical
Pharmacology
Therapeutic uses
Replacement Therapy
Adrenal insufficiency acute/chronic
CAH
Replacement Therapy
Hydrocortisone
Prednisolone or dexamethasone long acting
Fludrocortisone for mineralocorticoid effects
Anti-inflammatory Uses
Intra-articular Steroids
Can be used in inflammatory
Non-inflammatory diseases
Knee joint
Shoulder joint
Tennis elbow
Carpal tunnel syndrome
Autoimmune diseases
ITP
Renal diseases
SLE
Organ Transplant
Combined with other immunosuppressants
cyclosporin, azathioprine
For prolonged use:
Prednisolone or methylprednisolone are
used
Allergic Disorders
Bronchial Asthma
Methylprednisolone
Acute attacks:
*Inhaled beclmethasone, budesonide, flunisolide
alone or combined with beta-2 agonists/ipratropium
*Oral steroids
Infectious Diseases
Indicated only in severe infective diseases
Ocular Diseases
Skin Diseases
Pemphigus
vulgaris
Pemphigus vulgaris
Exfoliative dermatitis
Stevens-Johnson syndrome
GIT
Malignancy
Hodgkin`s
lymphoma
Cerebral Oedema
Cerebral oedema due to tumors
(neoplasms)
Traumatic and poststroke oedema (?)
(Dexamethasone or betamethasone is
preferred because no Na+ retaining
activity)
Other CNS conditions - spinal chord injury,
Bell`s palsy and neurocysticercosis
(Oral Prednisolone is the preferred drug)
Other Uses
from drowning
Hyperthyroidism thyroid storm
Adverse Effects
Two types:
Withdrawal
Adverse Effects
Cushing`s habitus
Contraindications
Peptic ulcer
Hypertension and Diabetes mellitus
Viral and fungal infections
Tuberculosis and other diseases
Osteoporosis
Epilepsy and psychosis
CHF and renal failure
Choosing a Steroid
Benefit/risk ratio is a major consideration
Drugs with primary glucocorticoid activity
are used
Minimal dose to achieve the desired
effects is chosen
Topical or local therapy is preferred
whenever possible
Single
dose
Steroid
Adrenocorticosteroid Inhibitors
Must Know!
Biosynthesis and Regulation of
Corticosteroids
Mechanism of action of Corticosteroids
Name of commonly used Glucocorticoids
Anti-inflammatory and immunosuppressive
actions of Glucocorticoids
Important Adverse effects of Corticosteroids
Therapeutic uses of Corticosteroids
Thank You