Corticosteroids 24613

7/30/2019 Corticosteroids 24613

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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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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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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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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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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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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


- 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

Corticosteroids 24613

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