Bronchodilators, fatal asthma, rebound effect and similitude

Abstract

Bronchodilators, fatal asthma, rebound effect and similitudeSir, After the publication of my article 'Evidence of the principle of similitude in modern fatal iatrogenic events', 1 new evidence was published which I brought to the attention of your readers through a Letter to the Editor. 2 In a similar way to the non-steroidal antiinflammatory drugs (NSAIDs), 3 important new studies were recently published reinforcing the hypothesis that long-acting bronchodilators (b-agonists) may increase the risk for severe or fatal asthma exacerbations, as a consequence of the irreversible paradoxical bronchospasm (rebound effect of modern pharmacology or vital reaction of the homeopathic model).After numerous scientific protests, since GlaxoSmithKline presented the partial data of the 'Salmeterol Multicenter Asthma Research Trial (SMART)' at the Annual International Scientific Assembly of The American College of Chest Physicians in 2003, claiming that 'the interim analysis was inconclusive', the full results of the 26,355 randomized subjects were published in 2006. Exploratory analyses of each outcome event within subpopulations were conducted, finding a significant increase in respiratory-related deaths (RR 2.16, 95% CI 1.06-4.41) and asthmarelated deaths (RR 4.37, 95% CI 1.25-15.34), and in combined asthma-related deaths or life-threatening experiences (RR 1.71, 95% CI 1.01-2.89) in subjects receiving salmeterol vs placebo. African-American subpopulation was particularly affected (compared with Caucasian subjects): respiratory-related deaths or life-threatening experiences (RR 4.10, 95% CI 1.54-10.90) and combined asthma-related deaths or lifethreatening experiences (RR 4.92, in subjects receiving salmeterol vs placebo. 4 In 2006, Salpeter et al published a meta-analysis of 19 randomized, placebo-controlled trials involving 33,826 participants with asthma followed for 16,848 patient-year (mean trial duration 6.0 months). Approximately 15% of the participants were African-American. The long-acting b-agonists used in the studies were salmeterol, formoterol, and eformoterol. During the trials, concomitant inhaled corticosteroids were used in approximately 53% of participants in both groups. The objective of the study was to assess the effects of long-acting b-agonists on severe asthma exacerbations requiring hospitalization, life-threatening asthma attacks, and asthmarelated deaths. Subgroup analyses compared results for salmeterol and formoterol and for children and adults. 5

Homeopatia: prática médica coadjuvante

“…Além do possível agravamento da doença de base (AVE, cetoacidose diabética, IAM, crise asmática grave, respectivamente), a suspensão abrupta e indiscriminada dos medicamentos enantiopáticos poderá desencadear a reação paradoxal ou efeito rebote do organismo (reação vital) causando eventos graves e fatais [6][7][8] . Como desprezar a probabilidade da ocorrência destas iatrogenias nesta conduta homeopática imprudente?…”

Therapeutic use of the rebound effect of modern drugs: "New homeopathic medicines"

“…Since 1998, we have been scientifically grounding the principle of therapeutic similarity through the systematic study of the "rebound effect" of modern drugs ("paradoxical reaction" of the organism), [2][3][4][5][6][7][8][9][10][11][12] showing the manifestation of this secondary and opposite reaction of the organism after the primary action of numerous classes of drugs. At the end of 2013, we published a review on the rebound effect of drugs in this journal, 13 showing the extent of the phenomenon and alerting health professionals about the serious consequences that this unknown adverse event can cause.…”

“…the principle of siMilarity in the light of Modern pharMacology [2][3][4][5][6][7][8][9][10][11][12][13] Building a bridge between the principle of similarity and modern scientific rationality, hundreds of studies de-scribed, in recent medical literature, the occurrence of secondary and opposite reactions of the organism after the primary actions of different drugs, confirming the homeopathic postulate. As mentioned previously, this secondary action or organism's reaction, which manifests itself automatically and instinctively in order to maintain the homeostasis of the system, is described by contemporary pharmacology and physiology as the rebound effect of the drugs, or paradoxical reaction of the organism, respectively.…”

“…Epidemiological studies show that this magnitude can cause severe and fatal events after the suspension of certain classes of drugs (antithrombotics, antidepressants, bronchodilators, anti-dyspeptics and immunomodulators, among others). [4][5][6][7][8][9][10][11][12][13] The rebound effect manifests itself at different intervals (hours to weeks) after the exhaustion of the biological effect (half-life) of the drug, and its duration is also variable. Despite the suspension or discontinuation of the drug being a prerequisite for the manifestation of the rebound effect, given that the primary action of the drug persists while the receptors are being stimulated (biological half-life), studies show that the rebound effect may also occur in the course of treatment due to therapeutic failure or the development of tolerance, tachyphylaxis or desensitization.…”

“…On the other hand, a slow and gradual reduction of doses (tapering) to prevent abrupt discontinuation can minimize the occurrence of the rebound effect. [2][3][4][5][6][7][8][9][10][11][12][13] In analogy to the proposal to be detailed below, reports in the literature describe the use of conventional drugs according to therapeutic similarity. Among these, we can cite the use of biphasic oral contraceptives to promote ovulation and rebound pregnancy in women with functional sterility and the use of central nervous system stimulants (methylphenidate) to treat attention deficit hyperactivity disorder (ADHD).…”