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Biomedical subjects

F Estelle R Simons

Publications and source records attributed to F Estelle R Simons.

At least 55 records · Page 3Linked to original sources
PubMed2003

Inhaled corticosteroids in childhood asthma: Income differences in use.

Asthma hospitalization rates in children increase with decreasing level of household income. This research was undertaken to determine whether use of inhaled corticosteroid drugs, which can prevent asthma hospitalizations, followed a similar socioeconomic gradient in children with asthma. We performed a cross-sectional study of association, using population-based prescription and healthcare data sources. Our subjects were 16,862 Manitoba children, aged 5-15 years, with prescriptions for asthma drugs during January 1995-March 1996. Our measures were adjusted for asthma severity, physician specialty, and proportion of children with an inhaled corticosteroid prescription by neighborhood income. Forty-five percent of children treated for asthma had at least one inhaled corticosteroid prescription during January 1995-March 1996. The proportion of children with inhaled corticosteroid prescriptions decreased with successive decreases in neighborhood income. The socioeconomic gradient in the likelihood of an inhaled corticosteroid prescription was most evident among children with mild-moderate asthma who were not in the care of an asthma specialist. In conclusion, a socioeconomic gradient in the use of inhaled corticosteroids prescriptions can be found among children with universal access to healthcare and drug insurance.

Administration, Inhalation↗
PubMed2003

H1-Antihistamines: more relevant than ever in the treatment of allergic disorders.

Histamine is an important chemical mediator of inflammation, vasodilation, increased vascular permeability, decreased peripheral resistance, airway smooth muscle contraction, and sensory nerve stimulation causing itching. It also plays a significant role in neurotransmission and in cardiac function. In allergic rhinoconjunctivitis and urticaria, there is strong evidence for the role of H(1)-antihistamine treatment. In asthma, additional dose-response studies, including higher doses of antihistamines than those used in allergic rhinitis, are needed to determine the role of antihistamines. In atopic dermatitis, the itch-relieving topical glucocorticoid-sparing effects of H(1)-antihistamines also require further documentation. The potential benefits of each H(1)-antihistamine should be weighed against the potential risks, and second-generation H(1)-antihistamines with excellent, well-documented safety records should be used in preference to older, less safe H(1)-antihistamines. Second-generation H(1)-antihistamines are more relevant than ever in the treatment of allergic disorders.

Dose-Response Relationship, Drug↗
PubMed2003

H1-antihistaminic activity of cetirizine and fexofenadine in allergic children.

The clinical pharmacology of H1-antihistamines has not yet been optimally studied in children and other special groups of patients. Our objective was to determine the onset, extent, and duration of H1-antihistaminic activity of cetirizine and fexofenadine in the pediatric population. We performed a prospective, randomized, placebo-controlled, double-blind, crossover, single-dose study of these H1-antihistamines in 15 allergic children, mean+/-SEM age 8.8+/-0.5 years. We used suppression of the histamine-induced wheal and flare as the primary outcome. Compared with pre-dose baseline, cetirizine 10 mg suppressed the wheals significantly (p<or=0.05) from 2 to 24 h and the flares significantly from 1 to 24 h, achieving 77+/-SEM 10% to 86+/-9% suppression of the wheal from 2 to 7 h and 85+/-6% to 88+/-6% suppression of the flare from 2 to 24 h, inclusive. Compared with baseline, fexofenadine 30 mg did not suppress the wheals or flares significantly at any time, achieving 40+/-9% to 54+/-9% wheal suppression from 2 to 7 h and 45+/-11% to 68+/-9% flare suppression from 2 to 7 h, inclusive. Compared with placebo, cetirizine suppressed the wheals and flares significantly from 2 to 24 h. Compared with placebo, fexofenadine suppressed the wheals significantly at 4 and 6 h, and the flares from 4 to 7 h. Cetirizine suppressed the wheals and flares significantly more than fexofenadine at 2 h (wheals), and at 3 and 24 h (flares). Placebo did not suppress the wheals and flares significantly at any time. In children age 6-11 years, cetirizine 10 mg has a rapid onset of H1-antihistaminic activity, a 24-h duration of action, and greater H1-activity than fexofenadine 30 mg. Higher doses of fexofenadine should be tested in children.

Anti-Allergic Agents↗
PubMed2003

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.

BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. CONCLUSION: The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Anti-Allergic Agents↗
PubMed2003

Safety of cetirizine in infants 6 to 11 months of age: a randomized, double-blind, placebo-controlled study.

BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic disorders in infants and children; however, there are few prospective, randomized, double-blind, controlled studies of these medications in young children, and to date, no such studies have been conducted in infants. OBJECTIVE: This prospective, randomized, parallel-group, double-blind, placebo-controlled study was designed to evaluate the safety of the H(1)-antihistamine cetirizine, particularly with regard to central nervous system and cardiac effects, in infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry criteria for age and had a history of treatment with an H(1)-antihistamine for an allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all-cause or treatment-related adverse events were observed between the cetirizine- and placebo-treated groups. A trend was observed toward fewer adverse events and sleep-related disturbances in the cetirizine group compared with the placebo group. No prolongation in the linear corrected QT interval was observed in cetirizine-treated infants compared with either baseline values or with values in placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine in this short-term investigation, the first randomized, double-blind, placebo-controlled study of any H(1)-antihistamine in infants. Additional prospective, randomized, double-blind, placebo-controlled, long-term studies of cetirizine and other H(1)-antihistamines are needed in this population.

Cetirizine↗
PubMed2003

First do no harm: managing antihistamine impairment in patients with allergic rhinitis.

Antihistamines are effective medications that have been used for decades in the management of allergic rhinitis; however, they may be administered or selected in an inappropriate fashion and may be the source of drug-related morbidity. Our objective is to present relevant background information and an expert consensus statement on the use of antihistamines in treatment of allergic rhinitis. In July 2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment assessment were invited to participate in a roundtable conference to present current concepts and develop a consensus statement on the clinical management of allergic rhinitis with antihistamines. Many of the antihistamines used to treat allergic rhinitis, as well as the disease itself, may produce sedation, impairment, and reduced quality of life. Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture. Although there is some debate surrounding the varying degrees of efficacy of second-generation antihistamines, it is known that some agents may produce varying levels of drowsiness or impairment, especially at higher than recommended doses. The differences with regard to safety among the second-generation antihistamines are smaller than are the differences between the first and second generations. A nonsedating, nonimpairing (even at higher than recommended doses), second-generation antihistamine is preferred for all patients, particularly those with a higher risk for the development of adverse effects. We recommend that primary care and specialist physicians, nurse practitioners, physician assistants, pharmacists, and all other health professionals involved in the diagnosis and treatment of allergic rhinitis follow this consensus document and share this information with patients for whom antihistamine therapy is recommended. In addition, further epidemiologic studies on the effects of antihistamines should be performed.

Diagnosis, Differential↗
PubMed2003

Efficacy and safety of desloratadine in the treatment of perennial allergic rhinitis.

BACKGROUND: The evidence base for the use of H1-antihistamines in the treatment of perennial allergic rhinitis is considerably smaller than it is in the treatment of seasonal allergic rhinitis. OBJECTIVE: We hypothesized that desloratadine, a new, nonsedating selective H1-antihistamine, would be efficacious and safe in the treatment of perennial allergic rhinitis. METHODS: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, 676 patients with symptomatic perennial allergic rhinitis were randomly assigned to 4 weeks of treatment with either 5 mg of desloratadine once daily or placebo. Efficacy was assessed by using a morning-evening instantaneous total symptom score (TSS), which was composed of scores for 4 individual nasal symptoms (rhinorrhea, itching, sneezing, and postnasal drip) and 3 individual nonnasal symptoms (itching eyes, watering eyes, and itching of the ears or palate). Secondary outcome measures included a morning-evening reflective TSS, total nasal and nonnasal symptoms scores, and individual symptom scores. Safety evaluations, including 12-lead electrocardiograms, were performed. RESULTS: Six hundred thirty-four patients completed the study. Desloratadine consistently diminished perennial allergic rhinitis symptoms, reducing the morning-evening instantaneous TSS (P =.005), the morning-evening reflective TSS (P =.007), the morning-evening reflective total nonnasal score (P =.023), and the individual nasal symptom scores for rhinorrhea, nasal itching, sneezing, and postnasal drip/drainage (P =.05 to P =.013) during weeks 1 through 4. Improvement in symptoms was observed after the first dose. Dropouts, and the type and frequency of adverse events (headache, viral infection, pharyngitis, and upper respiratory tract infection), were similar in both treatment groups. No clinically significant changes in QTc intervals were observed. CONCLUSIONS: Desloratadine rapidly and safely reduced the symptoms of perennial allergic rhinitis, and its efficacy did not diminish during 4 weeks of treatment.

Adolescent↗
PubMed2002

Comparative pharmacology of H1 antihistamines: clinical relevance.

H1 antihistamines have similar efficacy in the treatment of allergic disorders; however, they differ in terms of their chemical structure, clinical pharmacology, and safety. This review focuses on the clinical pharmacology (pharmacokinetics and pharmacodynamics) of the newer oral H1 antihistamines (acrivastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, and mizolastine). Understanding the pharmacokinetics and pharmacodynamics of these H1 antihistamines provides an objective basis for selection of appropriate dosages and dose intervals. Pharmacokinetic and pharmacodynamic studies provide a rationale for the modified dosage regimens that may be required in special populations, such as the very young, the elderly, those with hepatic or renal dysfunction, or those taking other medications concurrently. Many H1 antihistamines are currently available for use. Clinical pharmacology studies help physicians to select the best H1 antihistamines for their patients.

Administration, Oral↗
PubMed2002

Is epinephrine administration by sublingual tablet feasible for the first-aid treatment of anaphylaxis? A proof-of-concept study.

PURPOSE: In order to explore the feasibility of sublingual administration of epinephrine tablets as a non-invasive first-aid treatment for anaphylaxis, we studied epinephrine absorption from this dosage form in an animal model. METHODS: In a prospective, randomized, four-way crossover study, six rabbits received epinephrine 2.5 or 10 mg as a sublingual tablet, epinephrine 0.03 mg (0.3 ml) by intramuscular (IM) injection (positive control), and 0.9% NaCl (0.3 ml) IM (negative control). Pre- and post-dose blood samples were obtained for measurement of plasma epinephrine concentrations by HPLC-EC. RESULTS: After administration of epinephrine 2.5 mg as a sublingual tablet, the mean (+/-SEM) C(max) was 2369+/-392 pg/ml, and the t(max) was 20.8+/-5.7 min. After administration of epinephrine 10 mg sublingually, the C(max) was 10836+/-2234 pg/ml, and the t(max) was 21.7+/-5.4 min. After IM epinephrine, the C(max) was 6445+/-4233 pg/ml, and the t(max) was 15.8+/-4.7 min. After IM 0.9% NaCl, the C(max) (endogenous epinephrine) was 518+/-142 pg/ml. The t(max) after both of the sublingual epinephrine tablet doses did not differ significantly from the t(max) after IM epinephrine, and the C(max) after the 10 mg sublingual epinephrine tablet dose did not differ significantly from the C(max) after IM epinephrine. CONCLUSIONS: In this proof-of-concept study, administration of epinephrine as a sublingual tablet formulation resulted in rapid achievement of peak plasma epinephrine concentrations. Absorption studies in humans are needed. DEFINITIONS: HPLC-high performance liquid chromatography; EC - electrochemical detection; C(max) - maximum plasma epinephrine concentration after dosing; t(max) - time of maximum plasma epinephrine concentration.

Administration, Sublingual↗
PubMed2002

EpiPen Jr versus EpiPen in young children weighing 15 to 30 kg at risk for anaphylaxis.

BACKGROUND: The EpiPen Jr (0.15 mg) and EpiPen (0.3 mg) auto-injectors, widely prescribed for the out-of-hospital treatment of anaphylaxis, have not been compared prospectively in young children. OBJECTIVE: The purpose of this investigation was to study the rate and extent of epinephrine absorption after use of the EpiPen Jr and the EpiPen in children weighing 15 to 30 kg. METHODS: In a randomized, double-blinded, parallel-group pilot study, children at risk for anaphylaxis self-injected epinephrine using either an EpiPen Jr or an EpiPen with the aid of a physician. Plasma epinephrine concentrations, blood glucose, blood pressure, heart rate, and adverse effects were monitored before and for 180 minutes after the injection. RESULTS: Children (age [mean +/- SEM], 5.4 +/- 0.4 years; weight [mean +/- SEM], 18.0 +/- 0.6 kg) who injected epinephrine with an EpiPen Jr achieved a maximum plasma concentration (mean +/- SEM) of 2037 +/- 541 pg/mL at 16 +/- 3 minutes. Children (6.6 +/- 0.5 years; 25.4 +/- 1.5 kg) who injected epinephrine with an EpiPen achieved a maximum plasma concentration of 2289 +/- 405 pg/mL at 15 +/- 3 minutes. Mean systolic blood pressure 30 minutes after epinephrine injection was significantly higher with the EpiPen than with the EpiPen Jr. After injection with the EpiPen Jr, every child experienced transient pallor; some also experienced tremor and anxiety. After injection with the EpiPen, every child developed transient pallor, tremor, anxiety, and palpitations or other cardiovascular effects; some also developed headache and nausea. CONCLUSION: Epinephrine injection with the EpiPen rather than the EpiPen Jr raised the systolic blood pressure significantly but also caused more adverse effects. The beneficial pharmacologic effects and the adverse pharmacologic effects of epinephrine cannot be dissociated. For the out-of-hospital treatment of anaphylaxis, additional premeasured, fixed doses of epinephrine would facilitate more precise dosing in young children.

Anaphylaxis↗
PubMed2002

Epinephrine dispensing patterns for an out-of-hospital population: a novel approach to studying the epidemiology of anaphylaxis.

BACKGROUND: The underlying rate of occurrence of anaphylaxis from all potential triggers in the general population is unknown. OBJECTIVE: We sought to obtain a perspective on the epidemiology of anaphylaxis in a defined general population by studying epinephrine dispensing patterns in an out-of-hospital setting. METHODS: Using an administrative claims pharmaceutical database, we analyzed dispensing data for all epinephrine formulations prescribed for out-of-hospital treatment over 5 consecutive fiscal years in a population of 1.15 million persons in the province of Manitoba, Canada. We identified the number and percentage of individuals in the general population for whom epinephrine was dispensed on one or more occasions, their age and sex, and the type of formulation dispensed. In addition to performing these analyses for the entire population of children, adults, and elderly individuals, we also performed analyses by 5-year age groupings; furthermore, for individuals younger than 5 years of age, we performed a detailed analysis by 6-month age groupings. RESULTS: During the 5-year period, 0.95% of this defined general population had injectable epinephrine dispensed for out-of-hospital treatment. There were substantial variations in epinephrine dispensing rates across subsets of the population, ranging from 1.44% for individuals younger than 17 years of age, to 0.9% for individuals 17 to 64 years of age (inclusive), to 0.32% for those age 65 years or older. In infancy, childhood, and early adolescence boys were more likely to have epinephrine dispensed than girls. Beginning at age 15 years and continuing into adulthood, girls and women were more likely to have epinephrine dispensed than boys and men. In the elderly there were no differences in dispensing patterns between the sexes. The highest epinephrine dispensing rate (5.3%) was found for boys age 12 to 17 months. CONCLUSIONS: Epinephrine dispensing data provide a novel and practical approach for studying and monitoring the epidemiology of anaphylaxis in a community. Using this approach, we provide evidence that anaphylaxis from all triggers peaks in early childhood and then gradually declines into old age.

Adolescent↗
PubMed2002

Clinical pharmacology of H1-antihistamines in the skin.

BACKGROUND: The extent of the distribution of H(1)- antihistamines into the skin and H(1)-antihistamine activity in the skin are clinically relevant in the treatment of allergic skin disorders. METHODS: In a prospective, randomized, double-blind, parallel-group, multiple-dose study, we gave fexofenadine 180 mg, loratadine 10 mg, or chlorpheniramine 8 mg to 21 men (7 in each group). Before dosing and at 1, 3, 6, 9, and 24 hours after the first antihistamine dose as well as at 168, 192, and 216 hours after the first dose (ie, 12, 36, and 60 hours after the seventh and last consecutive daily H(1)-antihistamine dose), we measured fexofenadine, loratadine, or chlorpheniramine concentrations in plasma and in skin tissue samples obtained through use of punch biopsies, along with suppression of histamine-induced skin wheals and flares. Loratadine metabolites, including desloratadine and its metabolites, were not measured, and chlorpheniramine metabolites were not measured. RESULTS: All 21 participants completed the study. Skin/plasma fexofenadine ratios ranged from 1.2 +/- 0.5 at 1 hour to 110 +/- 74 at 24 hours, and skin fexofenadine concentrations exceeded loratadine and chlorpheniramine skin concentrations at each test time. This was reflected in significant wheal and flare suppression by fexofenadine in comparison with loratadine at 3 hours and in comparison with chlorpheniramine at 6 and 9 hours (wheal) and from 3 to 24 hours and at 192 hours (flare). Compared with fexofenadine, loratadine significantly suppressed the wheal at 192 hours, and compared with chlorpheniramine, it significantly suppressed the wheal at 9 hours and the flare at 24 and 192 hours. At no time did chlorpheniramine suppress the wheal or flare significantly more than fexofenadine or loratadine. CONCLUSIONS: In skin disorders for which H(1)-antihistamines are recommended, these results support the use of fexofenadine or loratadine, and they indicate the need for reexamination of the use of chlorpheniramine.

Adult↗
PubMed2002

Development of a drug treatment-based severity measure in childhood asthma.

Valid measures of severity are crucial in asthma pharmacoepidemiological research. This study reports the development and validation of a severity measure in childhood asthma for application to health care administrative data. A drug treatment-based asthma severity measure was developed following the stepped care approach to treatment, and this was applied to a cohort of 16,862 children who met a case definition for asthma drug prescription use between January 1995 and March 1996. Assessments were made of the measure's reliability, validity, and responsiveness to change over time. The drug treatment-based asthma severity measure classified 42% of children as having mild asthma, 37% as having moderate asthma, 19% as having moderate-severe asthma, and 2% as having severe asthma. Agreement on severity classification between two successive time periods was excellent (kappa = 0.82). Children classified as having severe asthma were significantly more likely than children with mild-moderate asthma to have previous asthma hospitalizations, to visit asthma specialists, to have high physician utilization, and to require hospital critical care. They were more likely to be reclassified as having severe asthma 2 years later. These findings show that a drug treatment-based severity measure in childhood asthma, which can be applied to prescription data, has good reliability and validity, and is responsive to changes in asthma severity over time.

Administration, Inhalation↗
PubMed2002

Systemic chemokine and chemokine receptor responses are divergent in allergic versus non-allergic humans.

T(h)1- and T(h)2-polarized human T cell clones display distinct patterns of chemokine receptor expression and selective chemokine responsiveness in vitro. We hypothesized that natural exposure to environmental grass pollen would induce differential systemic chemokine and chemokine receptor expression patterns in individuals with allergic rhinitis compared to healthy controls with type 2- and type 1-dominated responses to allergen respectively. To this end, we compared chemokine receptor expression on peripheral blood T cells directly ex vivo and plasma chemokine levels between these two groups of study participants prior to and during the grass pollen season. T(h)1-associated CXC chemokine receptor (CXCR) 3 was strongly expressed on >50% CD4(+)/CD45RO(+) cells of all subjects. When examined longitudinally, CXCR3 expression increased over the grass pollen season (P < 0.0001), solely in non-allergic subjects. In contrast, for both allergic and non-allergic subjects, CC chemokine receptor (CCR) 5 (T(h)1-associated) and CCR3 (T(h)2-associated) were weakly expressed on <10% of CD4(+)/CD45RO(+) cells both prior to and during the grass pollen season. Type 1 chemokines CXC chemokine ligand (CXCL) 9 and CXCL10 (monokine induced by IFN-gamma and IFN-gamma-inducible protein of 10 kDa: CXCR3 ligands), and type 2 chemokines CC chemokine ligand (CCL) 11 (eotaxin: CCR3 ligand), CCL17 (thymus and activation-regulated chemokine: CCR4 ligand) and CCL22 (monocyte-derived chemokine: CCR4 ligand) were readily detectable in the plasma of most participants. Systemic CXCL9 levels decreased from pre- to grass pollen season in allergics (P < 0.05), whereas CCL17 decreased in non-allergics (P < 0.05) over the same period. Taken together, these longitudinal data suggest a systemic shift to more intensely type 1-dominated responses in non-allergic individuals and, conversely, to more type 2-dominated responses in allergic individuals upon natural re-exposure to grass pollen.

Adolescent↗
PubMed2002

Epinephrine fails to hasten hemodynamic recovery in fully developed canine anaphylactic shock.

BACKGROUND: Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). However, there are few data supporting its use in this condition, and most treatment guidelines have been anecdotally derived. In the present study, the time course of hemodynamic recovery from maximal hypotension was investigated in a canine model of AS in which Epi was administered by the intravenous (IV), subcutaneous (SQ) and intramuscular (IM) routes on different occasions. The findings obtained with Epi treatment were compared to those in a nontreatment study. METHODS: Ragweed-sensitized dogs were examined in respective studies approximately 5 weeks apart in which Epi was administered by one of the above routes in a randomized design. Either Epi (0.01 mg/kg) or placebo was administered at maximal hypotension, and hemodynamics were followed for 3 h after shock. The animals were studied while ventilated and anesthetized. Mean arterial pressure (MAP), cardiac output, stroke volume (SV), pulmonary wedge pressure (Pwp) and plasma Epi concentrations were obtained at each measurement interval. RESULTS: In the IV study, Epi produced a transient immediate increase in MAP, SV and Pwp as compared to the nontreatment study (144 vs. 52 mm Hg; 32 vs. 12 ml; 9 vs. 5 mm Hg; p < 0.01), but no differences were observed 15 min after shock. Hemodynamics were not different between Epi and no treatment at any intervals when Epi was given by the SQ and IM routes. AS compared with the placebo study, plasma Epi concentrations were higher in the IV and IM studies, but not in the SQ study. CONCLUSIONS: Although higher Epi concentrations were observed in the IM and IV studies, a sustained benefit in hemodynamic recovery was not observed in this anesthetized, ventilated canine model. In AS, when administered during maximum shock after mediators have already been released, a single IM, IV or SQ dose of Epi may have limited utility in the treatment of cardiovascular collapse. Earlier administration of Epi, before maximal hypotension occurs, may produce a more beneficial effect.

Anaphylaxis↗