STEROIDS IN GENERAL PRACTICE

Transcription

1 Steroid therapy in general medical practice Ronald Carey, Assistant Professor, Dept. Of Medicine, CMC Vellore Abstract: Corticosteroids are useful and life saving drugs. However they have to be used with caution because of potentially dangerous and serious adverse effects. Steroids are beneficial in conditions involving almost all major organ systems especially in diseases where inflammation plays an important role in pathophysiology. Steroids if used rationally, while following some important principles, can be a potent adjunct therapeutic measure that can save lives and cause significant symptomatic relief. Introduction Despite their notoriety for causing several adverse effects, steroids are very useful and life saving drugs. They are used in a variety of conditions where inflammation plays a major role in the pathophysiology. Steroids, however, are also one of the most grossly misused medications in the community both by doctors and the public. In a study done in the central suburbs of Mumbai in which 443 allopathic practitioners were interviewed about their knowledge and practice of childhood asthma, only 18.2% of them prescribed corticosteroids in a rational manner. Dexamethasone and Betamethasone were wrongly prescribed for acute attacks. (1) Scientific literature on the misuse of glucocorticoids in India is virtually nonexistent apart from a handful of articles. Steroids are often used for conditions for which they are not indicated, used in very higher doses, stopped abruptly and also found mixed in a variety of medications in alternative medicine practice.(2). The fact that steroids are freely available as over the counter medications is an important reason for the wide spread misuse of steroids. In a study from Duncan hospital in rural Bihar which studied patients who presented with features of glucocorticoid abuse, 45.5% were prescribed by local practitioners and 50% were self medicated. That such misuse leads to many complications is underscored by the data from the same study which revealed that ten of the 22 patients had cataracts, six had developed type 2 diabetes mellitus and five had recent-onset hypertension. 12 people had altered calcium metabolism and 12 had osteoporotic fractures of the spine. (3) In our experience in CMC, we have seen disseminated tuberculosis, Strongyloides hyperinfestation and Nocardiosis in patients who were abusing glucocorticoids. In light of this grim reality, there is a need for doctors to have a clear idea of when and how to employ this useful yet potentially dangerous group of drugs. Box 1: General principles to be considered in steroid therapy To maximize the usefulness of corticosteroids and to minimize the adverse effects, the following principles need to be kept in mind: 1. Steroid therapy for acute conditions should always be for a shortest duration possible and should be replaced as soon as possible by the primary therapy required for the condition. 2. Chronic therapy should be initiated only when there is a considerable body of evidence to support its use. 3. Objective measurements for assessing the efficacy of steroid use, if present, should always be measured and therapy should be adjusted based on the measurements. For example, 24 hour urine protein in Nephrotic syndrome. 4. A subjective sense of well being should never be considered as indicative of the efficacy of steroid therapy as it is present even in people without any underlying problem. 5. As far as possible non systemic, local therapy should be preferred. For example, inhaled corticosteroids in Bronchial Asthma. 6. Even topical steroids when used for prolonged periods can cause significant side effects. 7. Alternative day oral therapy results in less HPA (Hypothalamo-pituitary-adrenal axis) suppression but reduced efficacy CM1 13:1 51 Jan 2014

2 Box 2: Common conditions where corticosteroids are used Endocrine Diagnosis of Cushing's syndrome Treatment of Addison's disease Congenital adrenal hyperplasia Respiratory Bronchial Asthma COPD Hypersensitivity pneumonitis Interstitial lung disease Rheumatologic disorders Rheumatoid arthritis Sarcoidosis SLE Vasculitis Polymyalgia rheumatica Inflammatory myopathies Infectious diseases Septic shock Tb meningitis Tb pericardial effusion Acute pyogenic meningitis Gastroenterological and liver disorders Autoimmune hepatitis Inflammatory bowel disease Alcoholic hepatitis Eye disorders Uveitis Keratoconjunctivitis Hematological disorders Autoimmune haemolytic anaemia Immune thrombocytopenia Lymphoma Allergic disorders Allergic rhinitis Urticaria Angioedema Contact dermatitis Anaphylaxis Skin disorders Pemphigus vulgaris Others Post transplant Multiple sclerosis Use of steroids in specific conditions commonly managed in general practice Bronchial Asthma Inhaled corticosteroids are the mainstay of therapy in chronic Bronchial Asthma. In the management of mild intermittent Bronchial Asthma, there is no role for inhaled corticosteroids. For mild persistent Asthma, long acting inhaled glucocorticoids are preferred. They reduce risk of exacerbations, improve quality of life and reduce symptoms. In moderate persistent Asthma, low doses of glucocorticoids along with long acting beta agonist such as Salmetrol is preferred. For severe persistent Asthma, medium to high doses of inhaled glucocorticoids with long acting beta agonist is preferred. There is no role for oral steroids in the long term management of Bronchial Asthma. A Cochrane meta-analysis which included seven studies that compared Formetrol and Budesonide combination with Salmetrol and Fluticasone revealed that there is insufficient evidence to show the equivalence or difference with regards to their safety profile. (4). Despite the lack of very strong evidence for their use, most international guidelines recommend the use of inhaled LABA and corticosteroid combinations in persistent Asthma. In acute exacerbations, however, systemic glucocorticoids are to be given. A peak flow of less than 40% certainly requires systemic steroids. However, the judgment could be made clinically as well. It should be remembered that the effect of CM1 13:1 52 Jan 2014

3 steroids takes about 6 hours to manifest as symptom improvement. Prednisolone at a dose of 0.5 to 1 mg/kg is preferred. The course could be as short as 5 days. Oral and intravenous preparations are similar in efficacy and therapy for less than 3 weeks does not require tapering. COPD In COPD patients who have had 2 exacerbations per year or one hospitalization for an exacerbation, inhaled corticosteroids along with long acting beta agonists may be used. Salmetrol or Formetrol in combination with budesonide or fluticasone may be used. There are two large trials - TORCH and INSPIRE, which looked at the benefit from inhaled corticosteroids and LABA combination. TORCH trial compared fluticasone and salmeterol combination with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. There was no difference in the primary outcome of all cause mortality across all comparisons. (5) INSPIRE trial compared Salmetrol and fluticasone combination with Tiotropium alone. There was no difference in the primary outcome of frequency of exacerbations. (6) A Cochrane metaanalysis that compared inhaled LABA and corticosteroid combination with inhaled LABA alone concluded that there is evidence for the superiority of the combination therapy. While there was a non significant improvement in quality of life, symptoms score, rescue medication use and improvement in FEV1, there was also an increased risk of pneumonia with the combination therapy(7). Keeping with this evidence, inhaled corticosteroids should be added only in those patients who continue to remain symptomatic when on inhaled LABA. Long term systemic corticosteroids should be avoided in COPD patients. For acute exacerbations of COPD, systemic steroids are beneficial. Parenteral route is not superior to oral route. Prednisolone at a dose of 40 mg per day for duration of 5 to 14 days is preferred. Tapering of the dose is not required. Septic shock In patients with septic shock, defined as systolic BP less than 90 mm Hg) who do not show improvement with adequate fluid resuscitation, hydrocortisone 50 mg intravenously given every 6 hours is useful. It may be continued for 5 to 7 days and tapered and stopped. The benefits are more likely to be seen in patients with refractory septic shock. Steroids may be harmful in less severely ill patients. Tuberculous meningitis Tuberculous meningitis is a dreadful disease which might lead to many complications such as nerve palsies, hemiplegia and blindness. The complications are attributed to the proliferative arachnoiditis and vasculitis seen in these patients. It was assumed that steroids could reduce the complication rates by reducing the inflammation in the meninges. The evidence for the use of steroids comes from a well conducted randomised controlled trail from Vietnam in which a total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). (8) Treatment with dexamethasone was associated with a reduced risk of death (32 Vs 41%; relative risk, 0.69; P=0.01). For patients weighing >25 kg, dexamethasone should be given at a dose of 0.3 to 0.4 mg/kg/day for two weeks, then 0.2 mg/kg/day in week three, then 0.2 mg /kg /day in week four, then 4 mg per day and followed by a 1 mg taper of daily dose each week. Tb pericardial effusion Apart from tuberculous meningitis, steroids can also be used in Tb pericarditis. In this condition they should be used only in patients who have a high risk of developing constriction as evidenced by large effusions, high pericardial fluid WBC count, early clinical signs of constriction. The adult treatment regimen is Prednisone 60 mg/day for four weeks, followed by 30mg/day for four weeks, 15 mg/day for two weeks, and 5 mg/day for one week. When used in patients who are likely to develop CM1 13:1 53 Jan 2014

4 constriction, steroids speeds clinical recovery, reduces need for pericardiectomy and prevents re-accumulation of pericardial fluid. Acute pyogenic meningitis Acute pyogenic meningitis is fraught with complications such as hearing loss and to mitigate them steroids are often considered along with antibiotics. The best available evidence indicate that Dexamethasone at a dose of 0.4 mg per kg given 12 hourly for 4 days is useful in those patients with microbiologically proven(gram's stain) acute pyogenic meningitis. The first dose of dexamethsaone Table 1: Important adverse effects of corticosteroids should be given 2 minutes before the first dose of antibiotics. Rheumatoid arthritis Prednisolone may be prescribed for patients with Rheumatoid arthritis at diagnosis and before the effect of DMARDs is seen. It could be given up to a period of 3 months in a tapering schedule starting at 60 mg. Long term use should be avoided. It can also be used for shorter duration in flares. Intra-articular injections of triamcinolone or depot methylprednisolone are useful in reducing pain in joints but they do not have long term benefits of preventing joint damage. Skin Cardiovascular system GI Purpurae Atherosclerosis Gastritis and acid peptic disease Striae Hypertension Acne CNS Endocrine Mood disorders Infections Diabetes mellitus Psychosis Bacterial pneumonia Amenorrhea Pseudotumour cerebri Skin infections Osteoporosis Tuberculosis HPA axis suppression Eye Strongyloides hyperinfestation Posterior subcapsular cataract Nocardiosis Herpes zoster Prevention of adverse effects Box 3: 1. Use the lowest possible dose for the lowest possible duration 2. Screen for conditions such as diabetes and hypertension that may worsen with steroid therapy 3. Regular monitoring for adverse effects during therapy and doing the necessary intervention 4. All patients who will need steroid therapy for more than 3 months should be given calcium (1200 mg elemental calcium per day) and vitamin D (800 IU per day). Patients with established osteoporosis, those with T scores between - 1 and and those patients who develop fragility fractures while on therapy should be treated with bisphosphonates. The preferred drug is Alendronate at a dose of 70 mg per week. Bone mineral density may be repeated after 1 year of therapy and of stable should be repeated after 1 year. If stable or improving it could be repeated every 2 years. CM1 13:1 54 Jan 2014

5 How do we withdraw patients on long term steroid therapy? Abrupt withdrawal of steroid therapy can result in Addisonian crisis and hence steroid withdrawal should always be done in a careful manner. Unfortunately the evidence for the superiority of one tapering regimen over the other is lacking. In patients who have taken steroids for less than 3 weeks, the medication may be stopped without tapering. In longer duration therapy however the medication should be tapered keeping in mind the activity of the disease that is being treated, the general condition of the patient, age and co-morbid illnesses. In general, 10% of the initial dose may be reduced every 2 to 3 weeks with close monitoring of the patients. For patients who are on 5 mg per day of prednisolone and have difficulty coming off the drug, ACTH stimulation test should be done to assess the adrenal reserve. The standard high dose ACTH stimulation test consist of intravenous administration of 250 microgram of ACTH (Cosyntropin) and measuring cortisol levels before, 30 minutes and 60 minutes after the injection. A normal adrenal reserve is present if the cortisol concentrations are between 18 to 20 microgram per dl. A subnormal response after the injection indicates poor adrenal reserve. References: 1. S Shahid, G Bhinder, J Dhanjal. Knowledge, Attitudes And Practices (KAP) Of Primary Care Physicians Of Central Mumbai Suburbs About Childhood Asthma. The Internet Journal of Asthma, Allergy and Immunology Volume 6 Number /21466.html 3. Nalli C, Armstrong L, Finny P, Thomas N. Glucocorticoid misuse in a rural and semi-urban community of North Bihar: a pilot study. Trop Doct Jul;42(3): Cates CJ(1), Lasserson TJ. Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database Syst Rev Mar 14;3:CD Calverley PM(1), Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med Feb 22;356(8): Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA;INSPIRE Investigators. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med Jan 1;177(1): Nannini LJ(1), Poole P, Milan SJ, Kesterton A. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev Aug 30;8:CD Thwaites GE, Nguyen DB et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med Oct 21;351(17): ********************************************** A little story This is a story about four people named Everybody, Somebody, Anybody and Nobody. There was an important job to be done and Everybody was sure that Somebody would do it. Anybody could have done it, but Nobody did it. Somebody got angry about that because it was Everybody s job. Everybody thought Anybody could do it, but Nobody realized that Everybody would not do it. It ended up that Everybody blamed Somebody when nobody did what Anybody could have done CM1 13:1 55 Jan 2014