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Corticosteroids (2 of 2)
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Corticosteroids
HistorySynthesis
Pharmacological
Actions
Pharmacokinetics
Preparations
Therapeutic principles
Dosage schedule &
Steroid withdrawal
Uses:
Therapeutic
Diagnostic
Adverse reactions
Contraindications
Precautions during
therapy
Glucocorticoid
antagonists
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Pharmacokinetics
Absorption:all are rapidly & completely absorbed(Except DOCA)
Transport: Transcortin 75%
Albumin 5%
Free form 20%
Metabolism:
by liver enzymes, conjugation & excretion by urine partly excreted as 17-ketosteroids.
t1/2 of cortisol 1.5 hours
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Preparations
GlucocorticoidsShort acting
Intermediate acting
Long acting
Mineralocorticoids
Inhalant steroids
Topical steroids
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Short Acting Preparations (t1/2 < 12 h)
Drug Anti-inflam. Salt retaining Preapartions & dose
Cortisol 1 1.0 5 mg tablet
100 mg/vial (i.m., i.v)
Topical; enema
Cortisone 0.8 0.8 5 mg tablet
25 mg/vial (i.m)
Intermediate Acting Preparations (t1/2 = 12 -36 h)
Prednisone 4 0.8 -Prednisolone 5 0.3 5, 10 mg tablet
20 mg/vial (i.m, intrarti)
Methyl
prednisolone
5 0 0.5, 1.0 gm inj. for i.m.
or slow i.v.
Triamcinolone 5 0 4 mg Tab.,
10, 40 mg/ml for i.m. &
intrarticular inj.
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Drug Anti-
inflam.
Salt retaining Preapartions & dose
Long ActingPreparations (t1/2 > 36 h)
Dexamethasone 25 0 0.5 mg tab.
4mg/ml inj (i.m., i.v.)
Betamethasone 25 0 0.5, 1 mg tab.
4mg/ml inj (i.m., i.v.)
Paramethasone 10 0 2- 20 mg/day (oral)
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Mineralocorticoids - Preparations
Drug Anti-
inflammatory
Salt retaining Preapartions &dose
Fludrocortisone 10 150 100 mcg tab.
DOCA 0 100 2.5 mgsublingual
Aldosterone 0.3 3000 Not used
clinically
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Inhalant Steroids: Bronchial Asthma
Beclomethasone
dipropionate
50,100,200 mcg/md inhaler
100, 200, 400 mcg Rotacaps
Fluticasonepropionate 25, 50 mcg/md inhaler25,50,125/md MDI
50, 100, 250 mcg Rotacaps
Budesonide 100,200 mcg/md inhaler
0.25, 0.5 mg/ml respules
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Drug Topical preparation Potency
Beclomethasone
dipropionate
0.025 % cream Potent
Betamethasone benzoate
& B. valerate
0.025 % cream, ointment
0.12 % cream, ointment
Potent
Clobetasol propionate 0.05 % cream Potent
Halcinonide 0.1 cream Potent
Triamcinolone actonide 0.1 % ointment Potent
Fluocinolone actonide 0.025% ointment Moderate
Mometasone 0.1 % cream, ointment ModerateFluticasone 0.05 % cream Moderate
Hydrocortisone acetate 2.5 % ointment Moderate
Hydrocortisone acetate 0.1 1.0% ointment Mild
Topical steroids
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Topical Steroids
Benefits due to anti-inflammatory, immunosuppressive,
vasoconstrictor and anti-proliferative actions
Good response Slow response
Atopic eczema,
Allergic contact dermatitis,
Lichen simplex,
Primary irritant dermatitis,
Seborrheic dermatitis,Psoriasis of face,
Varicoseeczema
Cystic acne
Alopecia areata
Discoid LE
Hypertrophied scars
Keloids
Lichen planus
Psoriasis of palm, sole,
elbow & knee
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Topical steroids are combined with
antimicrobial agents for
Impetigo
Furunculosis
Secondary infected dermatoses Napkin rash
Otitis externa
Intertriginous eruptions
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Guidelines for topical steroids
Penetration differs at different sites:
High: axilla, groin, face, scalp, scrotumMedium: limbs, trunk
Low: palm, sole, elbow, knee
Occlusive dressing enhance absorption (10 fold)
Absorption is greater in infants & Children Absorption depends on nature of lesion:
High: atopic & exfoliative dermatitis
Low: hyperkeratinized & plaque forming lesions
More than 3 applications a day is not needed Choice of vehicle is importantLotions & creams: for exudative lesions
Sprays & gels: for hairy regions
Ointments: for chronic scaly lesions
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Therapeutic principles
Dose selection by trial & error; Needs frequentevaluation
Single dose: No harm
Few days therapy unlikely to be harmful
Incidence of side effects related to duration of
therapy
Use is only palliative (except replacement therapy)
Inter-current illness: Dose is doubled
Abrupt cessation of prolonged high dose leads to
adrenal insufficiency (contraindicated)
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Goal of therapy:To relieve pain or distressing symptom (e.g.,
rheumatoid arthritis):start with low dose
To treat life threatening condition (e.g., pemphigus):
initial dose must be high
Prevention of HPA axis suppression:
Single dose (morning)
Alternate dose therapy (short lived glucocorticoids)
Pulse therapy (higher glucocorticoid therapy)
Dosage schedule
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Longer the duration of therapy, slower the withdrawal
Less than 1 week: withdrawal in few steps
Rapid withdrawal: 50% reduction of dose every day
Slow withdrawal: 2.5 5 mg prednisolone reduced at an interval
of 2-3 days
Longer period & high dose:
Halve the dose weekly until 25 mg prednisolone or equivalent is
reached
Later reduce by about 1mg every 3-7 days.
Steroid withdrawal
HPA axis recovery may take months or up to 2 years
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Acute adrenal insufficiency
Primary adrenocortical insufficiency
Ad. Insufficiency second. to Ant. Pituitary
Congenital adrenal hyperplasia
Therapeutic uses:Endocrine & Non-endocrine
Endocrine Disorders
Isotonic saline Glucose
Hydrocortisone inj. i.v.
Gradullay substitue
with i.m ororal
Addisons disease Oral cortisol (20 +10 mg)
Fludrocortisone
(0.1 or 0.2 mg daily, p.o.)
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Congenital adrenal hyperplasia
Familial disorder
Signs of cortisol deficiency
Increased ACTH
Excessive androgens
Deficiency of 21- hydroxylase and11 - hydroxylase enzymes
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Cholesterol
Pregnenolone
Progesterone
Corticosterone
11-Desoxy-corticosterone
18-Hydroxy-
corticosterone
ALDOSTERONE
17-- Hydroxy
pregnenolone
11- Desoxy-
cortisol
17- Hydroxy
progesterone
21, hydroxylase
CORTISOL
11, hydroxylase
Dehydro-epi
androsterone
Andro-
stenedioneOestrone
Oestriol
TESTOSTERONE OESTRADIOL
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Non-endocrine diseases (1/7)
1. Arthritis
Not the drug of first choice
Prednisolone 5 or 7.5 mg
Intra-articular injection
2. Rheumatic carditis
Not responding to salicylates
Severely ill pts.
Prednisolone 40mg in divided doses
Salicylates given concurrently to prevent reactivation
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Non-endocrine diseases (2/7)
3. Renal diseases (Nephrotic syndrome)
Prednisolone 60 mg in divided doses for 3 4 weeks
If remission occurs continue for 1 year
Do not modify the course of disease; Some may
benefit4. Collagen diseases
DLE, pemphigus vulgaris, polyarteritis nodosa
Defect in connective tissue proteins in joints, various
organs and deeper layer of skin Prednisolone 1mg/Kg start; gradually reduce the dose
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Non-endocrine diseases (3/7)
5. Allergic diseases
Anaphylactic shock, blood transfusion reaction, hay
fever
Prednisolone (short course)
6. Bronchial asthma
Not routinely used except in Status asthmaticus
Methyl prednisolone sodium i.v. given followed by oral
prednisolone Inhaled steroids (Minimal HPA axis suppression)
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Non-endocrine diseases (4/7)
7. Ocular diseases
Outer eye & anterior segment: local application
Posterior segment: systemic use
Caution: bacterial, viral & fungal conjunctivitis
8. Dermatological conditions Pempigus: Life saving therapy is steroids
Eczema, dermatitis & psoriasis: respond well
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Non-endocrine diseases (5/7)
9. Diseases of intestinal Tract
Ulcerative colitis: cortisol retention enema
10. Cerebral oedema
Questionable value in cerebral oedema following
trauma, cerebrovascular oedema
Valuable in oedema associated with neoplasm and
parasites
11. Malignancy
Part of multi drug regimens for acute lymphaticleukaemia (children), chronic lymphatic leukaemia
(adult)
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Non-endocrine diseases (6/7)
12. Liver diseases
Subacute hepatic necrosis & chronic active hepatitis:
Improves survival rates
Alcoholic hepatitis: reserved for pts. with severe illness
Non-alcoholic cirrhosis: helpful if no ascites
13. Shock
Often helpful but no convincing evidence
14. Acute infectious diseases
Helpful due to its anti-stress & anti-toxic effects
Used in gramve septicemia, endotoxic shock, TB meningitis,miliary T.B., encephalitis
Appropriate anti-microbial agent is a MUST
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Organ transplantation
Bells palsy
Thrombocytopenia Myasthenia gravis
Spinal cord injury
Sarcoidosis
Non-endocrine diseases (7/7)
- Miscellaneous
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Diagnostic Uses
Cushings syndrome:
ACTH dependent (pituitary tumor, ectopicACTH secreting tumors)
Non-ACTH dependent (obesity, tumor ofadrenal cortex)
To locate the source of androgen productionin hirusitism
(Dexamethasone suppress androgen secretion from ad.cortex)
(Dexamethsone suppression test is done)
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Adverse reactions (1/2)
Metabolic toxicity: Iatrogenic Cushings syndrome
Hyperglycaemia, glycosuria, diabetes
Myopathy (negative nitrogen balance)
Osteoporosis(vertebral compression fracture)
Retardation of growth (children)
Hypertension, oedema,CCF
Avascular necrosis of femur
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Adverse reactions (2/2)
HPA axis suppression Behavioral toxicity: Euphoria, psychomotor
reactions, suicidal tendency
Ocular toxicity:steroid induced glaucoma,posterior subcapsular cataract.
Others: Superinfections
Delayed wound healing
Steroid arthropathy
Peptic ulcer
Live vaccines are dangerous
C t i di ti
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Contraindications
Infections
Hypertension with CCF
Psychosis
Peptic ulcer
Diabetes mellitus
Osteoporosis
Glaucoma
Pregnancy : (prednisolone preferred)
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Precautions during therapy
Following examinations of the patient to be
done before, during and after steroid therapy
Body weight
X-ray of spine
Blood glucose
Examination of the eye
B.P.
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Glucocorticoids antagonists
Mitotane:structure similar to DDT, used in
inoperable adrenal cancer Metyrapone: inhibit 11 -hydroxylase Aminoglutethamide: inhibit conversion of
cholesterol to pregnolone, medical adrenelectomy
Trilostane: inhibit conversion of pregnolone toprogesterone; used in Cushings syndrome
Ketoconazole: anti-fungal, inhibit CYP450
enzymes, inhibit steroid synthesis in ad.cortex andtestis; used in Cushings syndrome & Ca.prostate
Mifepristone: glucocorticoid receptor antagonist;anti-progesterone, used in Cushings syndrome
Cholesterol
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Cholesterol
Pregnenolone
Progesterone
Corticosterone
11-Desoxy-corticosterone
18-Hydroxy-
corticosterone
ALDOSTERONE
17-- Hydroxy
pregnenolone
11- Desoxy-
cortisol
17- Hydroxy
progesterone
21, hydroxylase
CORTISOL
11, hydroxylase
Dehydro-epi
androsterone
Andro-
stenedioneOestrone
Oestriol
TESTOSTERONE OESTRADIOL
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Thanks for yourpatience