steroid therapy in children

Steroid therapy in children

Dr. Devendra Nargawe

Corticosteroids

The adrenal gland secrets steroidal hormones which have glucocorticoid, mineralocorticoid and weakly androgenic activities.

Conventionally ,the term corticosteroid includes natural gluco- and mineralo-cortcoids and their synthetic analogues.

Stimuli Part Principal product

Angiotensin II Zona glomerulosa

ACTH Zona fasiculata & reticularis

Sympathetic nervous system

Medulla

Synthesis of corticosteroids

Mineralo-corticoids

Gluco- corticoids

Adrenaline &Nor-adrenaline

Types of Steroids

Glucocorticoids

• Short acting:(<12hr) hydrocortisone

• Intermediate acting: (12-36hr) • Prednisolone• methylprednisolone• triamcinolone

• Long acting: (>36hr) dexamethasone

Mineralocorticoids

• Aldosterone• Fludrocortisone• desoxycorticosterone

acetate

Mineralocorticoids Action

• Enhancement of sodium reabsorption in the DCT in kidney

• Increase in potassium and H+ excretion.

Mineralo- corticoid

s

Glucocorticoids actions• Promoting gluconeogenesis• Inhibit glucose utilization by

peripheral tissues• Increase protein breakdown and

mobilization of amino acid from peripheral tissues

On carbohydrate and protein metabolism

• Promote lipolysis due to glucagon growth hormone, thyroxine and cAMP induced breakdown of triglycerides is enhanced.

On fat metabolism

• Inhibit intestinal absorption and enhance renal excretion of calcium.

on calcium metabolism

• Enhance secretary activity of renal tubules

On water excretion

• Restrict capillary permeability • Maintain tone of arterioles and

myocardial contractility• When applied topically , they cause

cutaneous vasoconstriction

On CVS

• Optimum levels are needed for normal muscular activity

On skeletal muscles

• Maintain the level of sensory perception and normal excitability of neurons.On CNS

• Increase Secretion of gastric acid and pepsinStomach

• Enhance the rate of destruction of lymphoid cells

• Increase the number of RBCs , platelet and neutrophils in circulation.

• Decrease lymphocytes, eosinophils and basophils

Lymphoid tissue and

blood cells

• Covers all stage of inflammation . This include reduction of – increased capillary permeability , local exudation, cellular infiltration, phagocytic activity and late events like capillary proliferation, collagen deposition, fibroblastic activity and ultimately scar formation.

• Cardinal signs of inflammation – redness, heat, swelling and pain are suppressed .

Inflammatory responses

Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

• Suppress all type of hyper sensitization and allergic phenomena

• Suppression of recruitment of leukocytes at the site of contact with antigen and of inflammatory response to immunological injury.

• Suppression of CMI in which T-cells are primarily involved.

Immunological and allergic responses

• Inhibit cell division or synthesis of DNA

• Delay the process of healing• Retard the growth of children

Growth and Cell division

Therapeutic Indications For The Use Of corticosteroids

Rheumatic disease of childhood

• Indicated only in severe cases as adjusents to NSAIDs when distress and disability persists despite of other measures.

Rheumatic arthritis

• Corticosteroids are used only in severe cases with carditis and CHF.Rheumatic fever

• In stable child – oral prednisolone 2 mg/kg/day• Children with GIT involvement iv methyl

prednisolone 30mg/kg/day (max.1g/day)

Juvenile dermatomyositits

• Induction period – oral pred. until manifestation improved

• Than gradually tapered in 6 -12 monthSarcoidosis

• Oral prednisone improves only GI symptoms and joint pain.HSP

Rheumatic disease of childhood

• Significant manifestation of SLE ; iv methylprednisolone (30mg/kg/day) or prednisolone 2 mg/kg/day

Systemic lupus erythematosus

• Oral prednisone or iv methyl prednisolone pulse therapy typically used.

Polyarteritis nodosa

• Superficial morphea – topical steroids • Lesions involving deeper structures- systemic therapy( iv methyl pred. 30mg/kg/day or oral pred. 0.5-2 mg/kg/day) includes 3 consecutive days in a month for 3 months.

Scleroderma

Allergic reactions

• Intranasal spray of beclomethasone and budesonide used in severe cases.

Allergic rhinitis

• Severe serum sickness require systemic cortcosterids

Serum sickness

• Delayed pressure urticaria requires oral corticosteroidsUrticaria

Hematological disorders

• In ITP oral therapy induce rapid rise in platelet count than untreated pt.

Idiopathic Thrombocytopenic

Purpura

• Glucocorticoids reduce hemolysis by blocking macrophage function, decreasing autoantibody and enhancing elution of antibody from the RBCs.

• 2mg/kg/day till rate of hemolysis decrease.

Auto Immune Hemolytic Anemia

• Due to lymphocytic action of corticosteroids are an essential component of combined chemotherapy in ALL ,Hodgkin’s and other lymphoma.

Malignancies

Bronchial asthma • Iv hydrocortisone 10mg/kg

stat followed by 5mg/kg/dose 6 hourly

Status asthmatcus

• Short course of intermediate acting CS (over several weeks to months), should be considered with close monitoring of patient’s symptoms and lung function.

Acute asthma exacerbation

• ICS therapy used for severe persistent asthma

• Budesonide DPI/ suspension for nebulization available

• Acc. To NIH guidelines • Step-2 –low dose ICS (0.25-.5

mg/day)• step 3&4 –medium dose ICS

(>0.5-1mg/day)• step 5&6 – high dose ICS ( 1-2

mg/day)

Severe chronic asthma

Other lung disease

• Decrease the edema in the laryngeal mucosa through anti-inflammatory action

• Dexamethasone 0.6mg/kg single dose or nebulized with budesonide for 8 days.

Croup

• Decrease edema of laryngeal mucosa through anti-inflammatory action.

Pulmonary edema due

to drowning

Infants with RDS who require respiratory support or who develop

BPD required systemic corticosteroids

Neurologic disorders

Cerebral edema• Corticosteroids limits the production of

inflammatory mediators which reduce risk of additional neurologic injury with worsening of CNS signs and symptoms

• Iv dexamethasone 0.15mg/kg/dose 6 hourly

Multiple sclerosis• Methyl prednisolone 20-30mg/kg/day for

5days followed by with or without prednisone.

Infections

Tuberculosis In tuberculous meningitis Endobronchial tuberculosis Pericardial effusion Severe miliary tuberculosis

Prescribed regimen is prednisone 1-2mg/kg/day in 2 divided doses for 4 -6 weeks followed by tapering dose.

Eye disease

• Allergic conjunctivitis • Iritis• Iridocyclitis• Keratitis

Topical uses

• Retinitis• Optic neuritis• uveitis

Systemic uses

Skin disordersTopical corticosteroids are potent anti-inflammatory agents

They are divided into 4 categories on the basis of strength

low- hydrocortisone, desonide and hydrocortisone butyrate

Medium –amcinonide , betamethasone cream 0.05%, flurandrenoilde, flucinolone 0.025% oint. , momitasone

High –fluocinonide 0.05% gel & halcinonide

Super potent – betamethasone dipropionate 0.05% and clobetasol 0.05% gel

Skin disease Hemangioma – oral prednisolone

Atopic dermatitis – topical medium potent corticosteroid

Vitiligo – topical steroids

toxic epidermal necrolysis- oral prednisolone

pemphigus vulgaris –iv methyl prednisolone 1-2 mg/kg/day

Pemphigus foliaceus- topical steroids

bullous phemphigoid- iv methyl prednisolone 1-2 mg/kg/day

linear IgA dermatosis- oral therapy with methyl prednisolone 1-2 mg/kg/day for 2 -4 years .

Contact dermatitis ( massive acute bullous reactions )- oral corticosteroids for 2 weeks (1mg/kg/day)

Linchen simplex chronicus – topical steroids.

Seborrheic dermatitis (inflamed lesions) –low potency steroids

Psoriasis – topical steroids used in 1st tier therapy.

Renal disease• 2mg/kg/ day (60mg/m2 /day) for

initial 6 week than 1.5mg/kg/day(40mg/m2 /day) alternate day

Minimal change Nephrotic syndrome

• Immunosuppressive therapy with corticosteroids may be beneficial

IgA nephropathy

• Immunosuppressive therapy with prednisolone

membranous glomerulopathy

• High dose methyl prednisolone with cyclophosphamide and plasmapheresis.

Goodpasture disease

Miscellaneous

In acute exacerbations of crohn disease because they effectively suppress acute inflammation, rapidly relieving symptoms. Prednisone 1-2mg/kg/day

Organ transplantation and skin allograft In thyroid strom- in which corticosteroids reduce

peripheral T4 to T3 coversion. Neurocystisercosis- oral prednisolone

1.5mg/kg/day for 2-4 weeks suppress the reaction to the dying larvae, After kill the cysticerci by albendazole/preziquental.

Adverse Effects

• Sodium and water retention

• Edema• Hypokalemic

alkalosis • Progressive rise in

plod pressure

Mineralo-corticoids

• Cushing’s habitus• Fragile skin , purple

striae• Hyperglycemia • Muscular weakness• Susceptibility of infection• Delayed healing • Peptic ulceration• Osteoporosis• Posterior subcapsular

cataract• Glaucoma• Growth retardion• Pshychiatric disturbance• Suppression of

hypothalamo-pituitary-adrenal axis

Gluco-corticoids

Contraindications

• Peptic ulcer • Diabetes mellitus• Hypertension• Viral and fungal infections• Tuberculosis and other

infections• Osteoporosis • Herpes simplex keratitis• Psychosis• Epilepsy• Congestive heart failure• Renal failure

The following diseases are

aggravated by corticosteroids. All of these are

relative contraindications

ReferencesEssentials of medical pharmacology –KD Tripathi 7th edi.

Nelson textbook of pediatrics -19th edi.

Essential pediatrics – OP Ghai 8th edi.

Basic and Clinical Pharmacology Katzung 13 edi.

Goodman and Gilman's The Pharmacological Basis of Therapeutics 12th Ed. (2011)

Thank you