Pathophysiology And Mechanisms Of Action Of Oral Corticosteroids In Asthma
The anti-inflammatory nature of OCS is the key to their efficacy in asthma. At present, it is suspected that at least half of all patients with asthma have predominantly eosinophilic inflammation, including the majority with early onset disease associated with allergy.8 It is this population with eosinophilic inflammation that are the best understood and studied, especially with respect to the efficacy of corticosteroids. In these individuals, a complex interaction between genetics, airway damage and a maladaptive immune response within the airways leads to the development of asthma.9 Meanwhile, re-exposure to allergen, infection or other irritants initiates an inflammatory pathway mediated by cell signalling molecules, namely interleukins -4, 5 and 13. The term type 2 inflammation has been used to describe this eosinophilic pathway for inflammation in the patient with asthma, which is differentiated from non-type 2 inflammation, thought to be predominantly associated with neutrophilic or paucigranulocytic sputum phenotypes, and with potentially different pathobiological mechanisms. The inciting irritants and subsequent type 2 inflammatory cascade lead to recruitment of mast cells, eosinophils and CD4+ T lymphocytes and further release of their associated type 2 cytokines. The presence of this inflammation is associated with increased thickness of the smooth muscle layer, excessive and variable airway narrowing and increased secretion of mucus.10
How Do Steroids Help Asthma
The steroids used to treat asthma are known as corticosteroids. Corticosteroids are copies of hormones your body produces naturally.
Steroids help asthma by calming inflamed airways and stopping inflammation. This helps ease asthma symptoms such as breathlessness and coughing. It will also help prevent your lungs reacting to triggers.
Youre more likely to avoid high doses of steroids if you take your preventer inhaler every day as prescribed, says Dr Andy Whittamore, Asthma UKs in-house GP.
Selecting An Oral Prednisolone Liquid For Children
Erika Giblin, PharmD Candidate 2015University of Florida, College of PharmacyGainesville, Florida
Professor, Pharmacotherapy and Translational ResearchProfessor of Pediatrics Gainesville, Florida
ABSTRACT: Asthma affects approximately one in 10 children in the United States. More than half of these pediatric patients experience an asthma exacerbation each year. Often, the exacerbation requires a short course of oral corticosteroids. Prednisolone, a liquid formulation of prednisone, is commonly prescribed to these children due to its ease of administration. A short course of prednisolone drastically reduces the need for hospitalization and shortens the length of the exacerbation. Poor adherence due to the bitterness or laxative qualities of prednisolone often limits its effectiveness, however, and careful selection must be made between the available forms .
Asthma is the most common cause of hospitalizations and emergency department visits for pediatric patients in the Unites States.1 These admissions are costly, cause missed school and work days, and utilize healthcare resources.2 Standard therapy with inhaled corticosteroids and short-acting bronchodilators will not prevent episodic viral-induced exacerbations in these patients.3
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Sensitivity Analysis And Power Of Studies
There was no change in direction of effect size on sensitivity analysis for the variables: relapse rate, hospital readmission, and vomiting at home. However, when the results of Qureshi et al. and Cronin et al. were eliminated individually the pooled analysis demonstrated no difference between dexamethasone and prednisone for vomiting in ED .
Figure 7. Sensitivity analysis for vomiting at home with elimination of trials of Qureshi et al. Cronin et al. .
The calculated power of individual studies based on the weighted mean effect size at = 0.05 is presented in Table 2 . For the outcome variables, relapse rate and hospital readmission rate, all studies were underpowered. The weighted mean effect size for relapse rate was 0.0316 and for hospital readmission rate was 0.0132. Based on these values, a total sample size of 8,162 participants and 45,041 participants are required for detecting difference in relapse rate and hospital readmission rate, respectively . The power of our meta-analysis for detecting significant difference in relapse rate was 25.8% and for hospital readmission was 7.92%. For the variables, vomiting at ED and vomiting at home, the weighted mean effect sizes were 0.1156 and 0.0944, respectively. The power of our meta-analysis at = 0.05 was 96.9% for both these variables.
Table 2. Power analysis of included studies for different outcome variables.
Steroid Preventer Inhalers For Asthma
Preventer inhalers contain a low dose of steroids to prevent inflammation in your airways over time. This means youre less likely to react to your asthma triggers.
If youve been prescribed a preventer inhaler and are using it correctly, youre less likely to need to take steroid tablets, says Dr Andy. Also, theres very clear evidence that if you dont smoke, your preventer inhaler works better, so youre less likely to need steroid tablets.
Your steroid preventer inhaler is an essential part of your asthma care. It lowers your risk of symptoms and an asthma attack. You need to take it every day as prescribed, even if you feel well, to keep your airways protected. This is because it works away in the background to prevent inflammation building up in your airways. If you stop taking it that protection will stop.
Dont stop taking your steroid preventer inhaler before speaking to your GP or asthma nurse. You need your preventer every day to keep the inflammation down in your airways and lower your risk of an asthma attack.
If youre on a high dose, your body can really miss it if you stop it suddenly, says Dr Andy.
Always talk to your GP first before stopping any medicine they have prescribed. And remember to collect your repeat prescription before your inhaler runs out.
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Criteria For Study Inclusion
The guidelines of the PRISMA statement and the Cochrane Handbook for Systematic Reviews of Intervention were followed during the conduct of this review . Only quasi-randomized controlled trials and RCTs were included in our study. Utilizing the PICOS outline for selecting studies, we included trials conducted in pediatric patients with acute asthmatic exacerbation treated in either an ambulatory or ED setting comparing oral dexamethasone with oral prednisone and assessing relapse rates and adverse events . Studies including adult asthma patients and utilizing the parenteral route of administration of dexamethasone or prednisone were excluded. We also excluded non-randomized studies, retrospective studies, case-series, and non-English language studies.
Questions To Ask Your Doctor
Prednisone isnt safe to take while pregnant. You should immediately let your doctor know if you become pregnant while taking prednisone.
Because prednisone acts on the immune system, you may become more susceptible to infections. You should talk to your doctor if you have an ongoing infection or have recently received a vaccine.
There are a number of medications that can interact negatively with prednisone. Its important that your doctor be informed of all of the medications youre taking. You should talk to your doctor if youre currently taking any of the following types of medication:
There are other anti-inflammatory drugs that can be used as part of asthma treatment. These include:
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How Much Will I Take
Prednisone is available as an oral tablet or oral liquid solution in the United States. While similar, prednisone isnt the same as methylprednisolone, which is available as an injectable solution as well as an oral tablet. Typically, oral prednisone is used as a first-line therapy for acute asthma because its both easier to take and less expensive.
The average length of prescription for corticosteroids such as prednisone is 5 to 10 days. In adults, a typical dosage rarely exceeds 80 mg. The more common maximum dose is 60 mg. Dosages greater than 50 to 100 mg per day arent shown to be more beneficial for relief.
If you miss a dose of prednisone, you should take the missed dose as soon as you remember. If its almost time for your next dose, skip the missed dose and take the next regularly scheduled dose.
You should never take an extra dose to make up for a dose that youve missed. In order to prevent an upset stomach, its best to take prednisone with food or milk.
What If I Overdose On Prednisone
The effects of accidental ingestion of large quantities of prednisone over a very short period of time have not been reported, but prolonged use of the drug can produce mental symptoms, moon face, abnormal fat deposits, fluid retention, excessive appetite, weight gain, hypertrichosis , acne, striae , ecchymosis, increased sweating, pigmentation, dry scaly skin, thinning scalp hair, increased blood pressure, tachycardia, thrombophlebitis, decreased resistance to infection, negative nitrogen balance with delayed bone and wound healing, headache, weakness, menstrual disorders, accentuated menopausal symptoms, neuropathy, fractures, osteoporosis, peptic ulcer, decreased glucose tolerance, hypokalemia, and adrenal insufficiency. Hepatomegaly and abdominal distention have been observed in children.
Treatment of acute overdosage is by immediate gastric lavage or emesis followed by supportive and symptomatic therapy. If you or someone you know has taken more than the prescribed dose, call poison control and/or go to the emergency room immediately. For chronic overdosage in the face of severe disease requiring continuous steroid therapy the dosage of prednisone may be reduced only temporarily, or alternate day treatment may be introduced.
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Steroids In Asthma: To Taper Or Not To Taper
Steroids in Asthma: To Taper or Not to Taper?
Cydulka RK, Emerman CL. A pilot study of steroid therapy after emergency department treatment of acute asthma: Is a taper needed? J Emerg Med 1998 16:15-19.
This is a small, carefully executed pilot study of patients treated in the emergency department for asthma exacerbation and judged suitable for discharge. No patients had concomitant respiratory disease and none had used steroids for two weeks prior to enrollment. Subjects were randomized to receive either an eight-day non-tapering course of prednisone 40 mg/d, or an eight-day tapering course of prednisone starting at 40 mg/d and reduced by 5 mg/d. All subjects had cortisol levels assayed and a cosyntropin stimulation test performed, both prior to receiving steroids and again 12 days after discharge. Fifteen subjects participated.
The tapering and non-tapering steroid groups demonstrated no differences in pulmonary function or rate of relapse during the 21-day study period. There was also no difference in plasma cortisol or response to cosyntropin stimulation test between the two groups. Cydulka and Emerman conclude that tapering of steroids does not result in clinical benefit and that a short course of steroids, with or without a taper, does not cause adrenal suppression.
1. ODriscoll BR, et al. Double-blind trial of steroid tapering in acute asthma. Lancet 1993 341:324-327.
Role Of The Data Safety Monitoring Board
A data safety monitoring board will be set up for this study. An initial meeting will occur prior to enrolling the first patient to determine the terms of reference, review Health Canada-mandated SAE reporting and safety outcomes. Given that this trial is a feasibility trial as opposed to an efficacy trial, no interim analysis for efficacy will be performed. The DSMB will meet every 4months after the initial meeting, until study completion. Study results will be analysed after all participants have completed the study.
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Prednisone Dosage Forms And Strengths
Prednisone is taken by mouth as a tablet or oral solution. Prednisone is also available as a delayed-release tablet under the brand name Rayos.
Tablets: 1 milligram , 2.5 mg, 5 mg, 10 mg, 20 mg, 50 mg
Delayed-release tablets : 1 mg, 2 mg, 5 mL
Oral prednisone solution: 5 mg per 5 milliliters
Oral prednisone intensol concentrated solution: 5 mg/1 m
Prednisone Dosage For Allergic Reactions
Low-dose prednisone is used to reduce swelling due to allergic skin reactions and more severe allergic reactions . High-dose prednisone is used to suppress the immune system during attacks of severe and life-threatening allergic skin reactions including Stevens-Johnson syndrome and erythema multiforme.
Standard dosage for adults for allergic reactions: 560 mg per day taken in one to four divided doses
Standard dosage for infants and children: 0.052 mg per kg per day divided into one to four daily doses
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Prednisone Dosage For Pets
Prednisone is commonly used in pets and animals for a variety of conditions. Low-dose prednisone is used to reduce inflammation high-dose prednisone is used to suppress the immune system or fight cancer, and physiological-dose prednisone is used for hormone replacement. Dosage is determined by weight but will depend on the type of animal and medical condition being treated. For dogs, the standard dosage is 0.5 to 1 mg/lb taken by mouth once per day. Cats will typically be given prednisolone, the active form of prednisone.
Oral Prednisolone Dosing In Children Hospitalized With Asthma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|First Posted : November 24, 2005Results First Posted : August 11, 2010Last Update Posted : December 31, 2010|
|Drug: Prednisolone high doseDrug: Prednisolone lower dose||Phase 4|
Practice guidelines for the management of asthma in children universally recommend systemic corticosteroids for the treatment of moderate to severe asthma exacerbations. However, these guidelines vary widely with respect to dose, frequency, method of delivery, and duration of therapy. In actual practice, there is also considerable variation among clinicians in terms of corticosteroid dosing in children hospitalized with asthma exacerbations. At the Children’s Hospital of Philadelphia the current standard is to use an initial dose of 4.0 mg/kg/day although many other pediatric hospitals use a 2.0 mg/kg/day dose . Systematic reviews of the literature have called for a clinical trial to evaluate the effect of different doses of corticosteroids in treating pediatric asthma patients hospitalized with exacerbations.
History Of Oral Corticosteroids Use In Asthma
Before the 1950s, the treatment for asthma was restricted to those compounds that were either plant-derived or adrenaline derivatives. This treatment consisted primarily of bronchodilator agents.4 With the development of steroid and adrenocorticotropic hormone extracts, a 1952 seminal study by McCombs noted the marked improvement that could be derived with respect to asthma symptoms and control using either corticosteroids or adrenocorticotropic hormone.5 It has since been determined that oral and parenteral corticosteroids have no significant difference in bioavailability, and thus oral corticosteroids are by far the most common formulation of systemic corticosteroid used in the treatment of asthma today. It was not until 1958 that the association between successful treatment with OCS and a reduction in eosinophils in the sputum was noted.6 This revelation opened the door to widespread treatment with OCS, both on a chronic and acute basis,4 but with this came increasing recognition of the side effects of systemic corticosteroids. The subsequent development of inhaled corticosteroids and the recognition that these can be equally as effective in the majority of patients with asthma, therefore, led to a decline in the use of OCS, except in the population with severe asthma.7
How Is Prednisone Administered
NOTE: Prednisone can sometimes make it harder to fall asleep, and it is best to take it in the morning with breakfast, unless prescribed twice daily or if your provider suggests alternative directions. Always consult your physician if you are unsure when to take prednisone.
Dosage of RAYOS should be individualized according to the severity of the disease and the response of the patient. For pediatric patients, the recommended dosage should be governed by the same considerations rather than strict adherence to the ratio indicated by age or body weight.
The maximal activity of the adrenal cortex is between 2 am and 8 am and is minimal between 4 pm and midnight. Exogenous corticosteroids suppress adrenocorticoid activity the least when given at the time of maximal activity. RAYOS is a delayed-release formulation of prednisone which releases the active substance beginning approximately 4 hours after intake. The timing of RAYOS administration should take into account the delayed-release pharmacokinetics and the disease or condition being treated.
The initial dosage of RAYOS may vary from 5 to 60 mg per day depending on the specific disease entity being treated. Patients currently on immediate release prednisone, prednisolone, or methylprednisolone should be switched to RAYOS at an equivalent dose based on relative potency.
Method of Administration
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For Severe Persistent Asthma
When used as a controller medicine, the daily dose of oral steroids is prescribed based on the following recommended ranges in adults:
- Prednisone: 5 mg to 60 mg per day
- Prednisolone: 5 mg to 60 mg per day
- Methylprednisolone: 4 mg to 50 mg per day
- Dexamethasone: 0.75 mg to 10 mg per day
The recommended dose in children is calculated at roughly 1 mg/kg per day for prednisone, prednisolone, and methylprednisolone. Dexamethasone is calculated at 0.3 mg/kg per day.
It is always best for those with severe persistent asthma to start with the lowest possible dose of oral corticosteroids and to only increase the dose if symptoms are not effectively controlled. An overdose of these medications can lead to vomiting, weakness, seizures, psychosis, and severe heart rhythm disruptions.
Once treatment is started, it can take up to two weeks before the full benefits are felt.
Randomisation And Baseline Visit
After enrolment, the patients will be randomly allocated to one of the two treatment groups . The randomization schedule will have been previously generated using a computer. Randomisation will be blocked with randomly chosen block lengths of 4 or 6. Treatment assignments will be written on a piece of paper and concealed in sequentially numbered opaque envelopes kept in a secure locked location in the study research office. The PI and analyst will be blinded to the treatment intervention, but the research assistant in charge of screening and randomising patients, as well as the patients treating team will not because of the pragmatic nature of the trial. Demographic data will be collected at baseline.
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