Usage of Steroids in Pediatric Practice

A child is not a compressed or mini man, so the method of scaling down the adult dose of a drug on the basis of body weight is not an accurate method for treating children. The pediatric pharmacology is a complex science since the drug requirements of neonates, older infants and children are quite different from adults due to difference in the absorption, biotransformation and renal excretion of drugs. Steroids are the most important drugs discovered after antibiotics. Though the steroids are not actual therapy but they provide immediate symptomatic relief. Steroids have been used both for their systemic action as well as topical actions. Steroids should not be misused and used only when indicated. Proper doses are very important for effective therapeutic effect.

In pediatric practice systemic use of steroids is indicated in many conditions. Three major dose related categories for systemic use of steroids are: (1) Replacement Therapy, (2) Therapeutic Doses (For treating hematological, renal and immunological disorders) and (3) Massive Doses (For treating hematological and renal disorders).

1) Steroids as replacement therapy:

Use of steroids as replacement therapy in congenital adrenal hyperplasia (CAH) and Addison's disease is very much indicated. The CAH is caused due to deficiency of 21-hydroxylase, so that 17-hydroxy progesterone is not converted into cortisol but is converted into adrenal androgens. Female babies with congenital adrenal hyperplasia (CAH) will be having ambiguous genitalia and male babies will show precocious puberty. The patients with CAH may also have mineralocorticoid deficiency. The other common type of CAH is represented by 11-hydroxylase deficiency and these patients are hypertensive and have masculinized looks. Both types of patients with CAH need replacement therapy with prednisolone (5mg/m² body surface area in two divided doses) or cortisone (20mg/m²body surface area in three divided doses). The dose of steroid is monitored by the estimation of 17-ketosteriod excretion, skeletal maturation and growth rate.

2) Therapeutic doses of Steroids :

Use of steroids is extremely indicated for treating hematological, renal and immunological disorders.

1. Use of Steroids in Hematological Disorders: Steroids have important role in the treatment of acute lymphatic leukemia, idiopathic thrombocytopenic purpura (ITP). Remission of acute lymphatic leukemia can be achieved with prednisolone (40mg/m² body surface area) within 4-6 weeks. However, success rate is around 80%. A success rate of around 95% is achievable if prednisolone is combined with Vincristine. In acute ITP steroids are the drug of choice to save life and are administered at a dose of 1-2mg/kg body weight for about 3 weeks or till the platelet count improves. Around 25% of patients may develop chronic ITP and may need steroid therapy (on alternate days) for about 3-6 months.
   
   


2. Use of Steroids in Renal Disorders: Treatment of nephrotic syndrome with steroids shows remarkable results. Prednisolone is given at a dose of 2mg/kg body weight daily for 4 weeks and the same dose is given at alternate days for another 4 weeks. Around 60-65% of patients show significant response in 4 weeks another 20-25% of cases will go into remission within 8 weeks of treatment. Around 8% cases may require prolonged treatment, while 3-5% may need other modes of therapy.
   
   


3. Use of Steroids in Immunological Disorders: Steroids remain the therapy of great importance in the treatment of Lupus nephritis, SLE, dermatomyositis, polyarteritis nodosa. Prednisolone is given at a dose of 2mg/kg body weight till the remission and then tapered off to minimum maintenance dose.
   
   


4. Use of Steroids in other diseases: Severe cases of asthma and status asthmaticus, where bronchodilators alone fail to control the disease; treatment with hydrocortisone and prednisolone is indicated. Steroids have been found to be useful in the treatment of ulcerative colitis. Acute cases of ulcerative colitis can be managed well with retention enema with steroids.
   
   

3) Massive Doses:

Massive doses of steroids are administered in patients affected by endotoxic shock. In these cases, steroids decrease the peripheral resistance, increase tissue perfusion and venous return. Such cases need Hydrocortisone in doses of 50-100mg/kg body weight initially and there may be need to repeat the dose 4-6 hourly for 24-48 hours. In 'rapidly progressive glomerulonephritis' (RPGN) and 'idiopathic apastic anemia' remarkable results have been achieved with higher doses of methyl prednisolone.

Renal impairment and Drug Metabolism

Renal diseases can cause considerable variability in drug response, which may present as enhanced or diminished drug response. Renal diseases (kidney diseases) affect the glomerular blood flow, glomerular filtration, tubular reabsorption and secretion. Renal bioactivation affects the drug metabolism, which causes alterations in drug absorption, bioavailability, distribution, binding of drugs to proteins and renal or non-renal clearance. Accumulation of drug metabolites and exogenous substances may make it necessary for the clinician to adjust the dose of drugs for the renal disease and associated ailments otherwise this variability can lead to either enhanced efficacy or enhanced toxicity depending on the drug characteristics. Renal diseases (renal disorders) may affect both pharmacokinetic and pharmacodynamic characteristics of a drug (as thiopental has been observed to cause prolongation of its anesthetic action and gentamycin to cause increased toxicity).

Dosage adjustment is usually needed if >30% drug is excreted unchanged in urine or is removed by dialysis in patients with renal impairment or renal failure. Impaired and compromised renal function effects the drug elimination and leads to accumulation of drug. The accumulation of drug further depends on the frequency of drug administration and half life of drug. The treating physician needs to know the pharmacokinetics and pattern of accumulation of drugs in renal failure and tentative time to achieve the steady concentration in plasma for the adequate dose adjustments.

Primary influence of renal disease on drug absorption is almost negligible. However, a few secondary influences like vomiting and diarrhoea due to uremia lead to dehydration and further lead to decreased perfusion and absorption of drugs from intramuscular and intestinal sites. Diabetic and uremic gastroparesis leads to altered rates of absorption of short acting drugs like sulfonylureas. Acid base imbalance and alteration in the levels of potassium in serum affects gastrointestinal tract mobility and rate & extent of drug absorption. Commonly used antacids bind and chelate dietary phosphates and lead to hypophosphatemia, also impair the absorption of drugs like iron and ketaconazole which need an acidic pH for optimal absorption. Impaired protein binding may also impair absorption of drugs. Edema caused by nephrotic syndrome or congestive heart failure has been documented to slowdown the drug absorption and cause increased bioavailability of drugs.