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Advances in Clinical and Experimental... Mar 2019Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings.
BACKGROUND
Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings.
OBJECTIVES
The aim of the study was to evaluate the safety of initiating and maintaining propranolol therapy for IH.
MATERIAL AND METHODS
The study involved 55 consecutive children with IH being treated with propranolol. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during and after the therapy. Each time, the following monitoring methods were used: physical examination, cardiac ultrasound (ECHO), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and biochemical parameters: blood count, blood glucose, aspartate transaminase (AST), alanine transaminase (ALT), and ionogram. The therapeutic dose of propranolol was 2.0 mg/kg/day divided into 2 doses.
RESULTS
Four children were excluded during the qualification or the initiation of propranolol; a total of 51 patients were subject to the final analysis. All the children presented clinical improvement. There was a significant reduction in the mean HR values only at the initiation of propranolol. There were no changes in HR during the course of the therapy. Blood pressure values were within normal limits. Both systolic and diastolic values decreased in the first 3 months. Bradycardia and hypotension were observed sporadically, and they were asymptomatic. Electrocardiography did not show significant deviations. The pathological findings of the ECHO scans were not a contraindication to continuing the therapy. There were no changes in biochemical parameters. Apart from 1 symptomatic case of hypoglycemia, other low glucose episodes were asymptomatic and sporadic. The observed adverse effects were mild and the propranolol dose had to be adjusted in only 6 cases.
CONCLUSIONS
Propranolol is effective, safe and well-tolerated by children with IH. The positive results of the safety assessment support the strategy of initiating propranolol in outpatient settings. Future studies are needed to assess the benefits of the therapy in ambulatory conditions.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Blood Pressure; Child; Heart Rate; Hemangioma; Humans; Infant; Propranolol; Skin Neoplasms; Treatment Outcome
PubMed: 30659785
DOI: 10.17219/acem/94136 -
The Journal of Pain Dec 2015Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work... (Comparative Study)
Comparative Study
UNLABELLED
Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 β-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible β-AR intrinsic agonist activity and displayed a full competitive antagonist profile at β(1)/β(2)/β(3)-ARs, producing a unique blockade of β(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible β-AR intrinsic agonist activity and unique blockade of β(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions.
PERSPECTIVE
The S enantiomer of bupranolol, a β-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique β-adrenergic receptor compound to advance future clinical pain studies.
Topics: Adrenergic beta-Antagonists; Analgesics; Animals; Bupranolol; Disease Models, Animal; Female; Male; Mice; Nociception; Pain Measurement; Propranolol; Receptors, Adrenergic, beta; Stereoisomerism
PubMed: 26456674
DOI: 10.1016/j.jpain.2015.09.004 -
Acta Otorhinolaryngologica Italica :... Aug 2012Haemangiomas represent the most common benign tumours in infancy, affecting 1-2% of newborns. The present meta-analysis aimed to critically review the current evidence... (Meta-Analysis)
Meta-Analysis Review
Haemangiomas represent the most common benign tumours in infancy, affecting 1-2% of newborns. The present meta-analysis aimed to critically review the current evidence on the efficacy of propranolol in the management of airway haemangiomas, and explore potential adverse events and treatment failures. A literature review was performed in Medline and other available database sources, along with critical analysis of pooled data. Seventeen studies were included in the analysis. No study represented Level I evidence. The total number of treated patients was 61; 14 patients received propranolol as single-treatment. The comparative effectiveness of propranolol vs. systemic steroids was documented in 35 children, and showed superior outcome in the vast majority (94%, p < 0.001). The mean obstruction before propranolol administration was 72%, and after intervention was 20% (p < 0.001). The mean referral-age for children with airway haemangiomas was 2.4 months, the mean starting-age of propranolol treatment was 5.1 months and the mean follow-up period was 8.4 months. Four children failed to respond (6.5%), and in seven the haemangioma relapsed after discontinuation of treatment (11.5%). The results of the present study suggest that propranolol can be recommended for the treatment of airway haemangiomas, as it was found to be effective and outperformed the previously-considered gold standard treatment methods, with fewer side-effects. Immediate treatment with propranolol should be initiated once a diagnosis of symptomatic airway haemangioma is confirmed, and cardiovascular assessment has been performed. Children should remain on propranolol until the haemangioma enters the phase of involution. Active parental monitoring is essential to ensure treatment safety.
Topics: Hemangioma, Capillary; Humans; Infant; Propranolol; Respiratory Tract Neoplasms; Treatment Outcome
PubMed: 23093810
DOI: No ID Found -
Drug Design, Development and Therapy 2017Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial...
OBJECTIVE
Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial proliferation and resolve without consequence, intervention is required in a subset of IHs, which develop complications resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment for this subset of IHs is pharmacological intervention, and propranolol has become the new first-line treatment for complicated hemangiomas. Here, we evaluated the efficacy of propranolol on proliferation IH in a clinical cohort including 578 patients.
METHODS
We retrospectively reviewed a total of 578 IH patients who were treated with oral propranolol from January 2010 to December 2012. Responses to the propranolol treatment were graded as: excellent, good, poor, or no response. Based on the response to propranolol treatment (once daily at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily total dose of 2 mg/kg for patients older than 2 months), additional pharmacotherapies or surgery were used for IH patients for satisfactory clinical outcome.
RESULTS
Five hundred and sixty (96.9%) of 578 IH patients in our study responded to oral propranolol treatment, and the response rate was significantly different for different ages of patients (<0.05), with the youngest patients having the highest response rate. The mean time of treatment was 6 months (range, 3-12 months). For example, response rate to propranolol was 98.1% in patients younger than 2 months, compared with 93.3% in patients older than 2 months and younger than 8 months, and 73.7% in patients older than 8 months. One hundred and thirty one patients who exhibited incompletely involuted hemangiomas were further treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and seventeen (89.3%) of 131 patients showed a positive response. There were no instances of life-threatening complications after propranolol. However, minor side effects were observed including 10 (1.73%) cases of sleep disturbance, 7 (1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm.
CONCLUSION
IH requires early intervention. During the involution phase, tapering propranolol dosage can be done to minimize side effects before discontinuing treatment. For patients exhibiting telangiectasia and chromatosis after propranolol treatment, administration of a 0.5% solution of timolol maleate or pulse dye laser is an effective therapeutic approach for complete involution.
Topics: Administration, Oral; Hemangioma; Humans; Propranolol; Retrospective Studies
PubMed: 28507428
DOI: 10.2147/DDDT.S134808 -
Biological Psychiatry Jun 2021Posttraumatic stress disorder can develop after a traumatic event and results in heightened, inappropriate fear and anxiety. Although approximately 8% of the U.S....
BACKGROUND
Posttraumatic stress disorder can develop after a traumatic event and results in heightened, inappropriate fear and anxiety. Although approximately 8% of the U.S. population is affected by posttraumatic stress disorder, only two drugs have been approved by the Food and Drug Administration to treat it, both with limited efficacy. Propranolol, a nonselective β-adrenergic antagonist, has shown efficacy in decreasing exaggerated fear, and there has been renewed interest in using it to treat fear disorders.
METHODS
Here, we sought to determine the mechanisms by which propranolol attenuates fear by utilizing an activity-dependent tagging system, ArcCreER x eYFP mice. 129S6/SvEv mice were administered a 4-shock contextual fear conditioning paradigm followed by immediate or delayed context reexposures. Saline or propranolol was administered either before or after the first context reexposure. To quantify hippocampal, prefrontal, and amygdalar memory traces, ArcCreER x eYFP mice were administered a delayed context reexposure with either a saline or propranolol injection before context reexposure.
RESULTS
Propranolol decreased fear expression only when administered before a delayed context reexposure. Fear memory traces were affected in the dorsal dentate gyrus and basolateral amygdala after propranolol administration in the ArcCreER x eYFP mice. Propranolol acutely altered functional connectivity between the hippocampal, cortical, and amygdalar regions.
CONCLUSIONS
These data indicate that propranolol may decrease fear expression by altering network-correlated activity and by weakening the reactivation of the initial traumatic memory trace. This work contributes to the understanding of noradrenergic drugs as therapeutic aids for patients with posttraumatic stress disorder.
Topics: Amygdala; Animals; Basolateral Nuclear Complex; Fear; Humans; Memory; Mice; Propranolol
PubMed: 33766406
DOI: 10.1016/j.biopsych.2021.01.005 -
International Journal of Molecular... Jul 2023Resistance to chemotherapy represents a persisting medical problem, ranking among main causes of chemotherapy failure and cancer mortality. There is a possibility to...
Propranolol, Promising Chemosensitizer and Candidate for the Combined Therapy through Disruption of Tumor Microenvironment Homeostasis by Decreasing the Level of Carbonic Anhydrase IX.
Resistance to chemotherapy represents a persisting medical problem, ranking among main causes of chemotherapy failure and cancer mortality. There is a possibility to utilize and repurpose already existing therapeutics which were not primarily intended for oncological treatment. Overactivation of adrenergic receptors and signaling dysregulation promotes tumor progression, metastatic potential, immune system evasion, tumor angiogenesis and drug resistance. The non-selective beta-blocker propranolol, approved in infantile haemangioma treatment, has a high potential for use in cancer therapy. We analyzed the effects of propranolol and 5-fluorouracil combination on sensitive and resistant cells derived from colorectal carcinoma in monolayers, single-component and co-culture spheroids and in vivo mouse models. Our results revealed that propranolol is able to exert its effect not only in chemosensitive colorectal cells, but also in 5-fluorouracil resistant cells. Propranolol disrupts the hypoxic adaptation machinery by inhibiting HIF1α, carbonic anhydrase IX, and activates apoptosis, which may be important in the management of chemo-resistant patients. We showed that propranolol slows down the growth of xenografts formed from colorectal cancer cells, even from cells already adapted to the β-blocker. We provide clear evidence that blockade of β-adrenergic receptors affects essential signaling pathways modulating tumor microenvironment and thus the response to anticancer therapy. Our findings indicate that propranolol could be repurposed to serve as chemosensitizer in combined therapy aimed at disrupting homeostasis of tumor microenvironment.
Topics: Humans; Animals; Mice; Carbonic Anhydrase IX; Propranolol; Tumor Microenvironment; Antigens, Neoplasm; Neoplasms; Fluorouracil; Cell Line, Tumor
PubMed: 37446271
DOI: 10.3390/ijms241311094 -
Eye (London, England) Oct 2011Capillary haemangioma or infantile haemangioma (IH) is the most common congenital vascular tumour in the periocular region. Several treatment modalities have been... (Review)
Review
Capillary haemangioma or infantile haemangioma (IH) is the most common congenital vascular tumour in the periocular region. Several treatment modalities have been documented, with variable degree of success. Propranolol has recently been reported to be an effective and safe alternative. The aim of this systematic review is to examine the evidence base for the use of propranolol administered orally in the management of periocular capillary haemangioma, and use this information to guide future research. A systematic review of literature was carried out by two independent reviewers using the search strategies highlighted below. A total of 100 cases of oral propranolol use in periorbital or orbital capillary haemangiomas have been documented in the literature. Of the 85 cases that had details of previous treatment, it was used as first-line treatment in 50 (58.8%). The commonest dose used was 2 mg/kg/day. Adverse events were documented in one-third of cases; in most cases these were minor. Improvement or complete resolution of the lesions occurred in 96% of cases. Recurrence was noted in one-fifth of cases. Propranolol has shown a lot of promise in the therapy of IH and further research in the form of properly designed randomized trials is certainly warranted. Treatment guidelines based on literature available to date is included in this review.
Topics: Administration, Oral; Antineoplastic Agents; Child, Preschool; Disease Progression; Evidence-Based Medicine; Female; Hemangioma, Capillary; Humans; Infant; Infant, Newborn; Male; Orbital Neoplasms; Propranolol; Treatment Outcome
PubMed: 21738233
DOI: 10.1038/eye.2011.164 -
Drug Design, Development and Therapy 2021The study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a...
AIM
The study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a systematic whole-body physiologically based pharmacokinetic (PBPK) model-building approach for suggesting model informed propranolol dosing in liver cirrhosis patients with different stages of disease severity.
METHODS
A whole-body PBPK model was developed by using population simulator PK-Sim by using reported physicochemical and clinical data for propranolol in healthy and liver cirrhosis populations. The model evaluation was done by visual verification and comparison of PK parameters using their observed/predicted ratios (R).
RESULTS
The developed model has effectively described the disposition of propranolol after intravenous and oral application in healthy and liver cirrhosis populations. All the model predictions were comparable to the observed clinical data and the R for all the PK parameters were within a 2-fold range. A significant increase in plasma concentration of propranolol and decrease in drug clearance was observed in progressive stages of liver cirrhosis. The developed model after evaluation with the reported clinical PK data was used for suggesting model informed propranolol dosing in different stages of liver cirrhosis based on systemic unbound drug concentration.
CONCLUSION
The developed PBPK model has successfully described propranolol PK in healthy and cirrhosis populations after IV and oral administration. The evaluated PBPK propranolol-cirrhosis model can have many implications in predicting propranolol dosing in liver cirrhosis patients with different stages of disease severity.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Dose-Response Relationship, Drug; Drug Development; Humans; Liver Cirrhosis; Models, Biological; Propranolol; Severity of Illness Index
PubMed: 33762817
DOI: 10.2147/DDDT.S297981 -
International Journal of Molecular... Feb 2023The SARS-CoV-2 pandemic highlighted the need for broad-spectrum antivirals to increase our preparedness. Patients often require treatment by the time that blocking virus...
The SARS-CoV-2 pandemic highlighted the need for broad-spectrum antivirals to increase our preparedness. Patients often require treatment by the time that blocking virus replication is less effective. Therefore, therapy should not only aim to inhibit the virus, but also to suppress pathogenic host responses, e.g., leading to microvascular changes and pulmonary damage. Clinical studies have previously linked SARS-CoV-2 infection to pathogenic intussusceptive angiogenesis in the lungs, involving the upregulation of angiogenic factors such as ANGPTL4. The β-blocker propranolol is used to suppress aberrant ANGPTL4 expression in the treatment of hemangiomas. Therefore, we investigated the effect of propranolol on SARS-CoV-2 infection and the expression of ANGPTL4. SARS-CoV-2 upregulated ANGPTL4 in endothelial and other cells, which could be suppressed with R-propranolol. The compound also inhibited the replication of SARS-CoV-2 in Vero-E6 cells and reduced the viral load by up to ~2 logs in various cell lines and primary human airway epithelial cultures. R-propranolol was as effective as S-propranolol but lacks the latter's undesired β-blocker activity. R-propranolol also inhibited SARS-CoV and MERS-CoV. It inhibited a post-entry step of the replication cycle, likely via host factors. The broad-spectrum antiviral effect and suppression of factors involved in pathogenic angiogenesis make R-propranolol an interesting molecule to further explore for the treatment of coronavirus infections.
Topics: Animals; Chlorocebus aethiops; Humans; COVID-19; Propranolol; SARS-CoV-2; Vero Cells; Cell Line; Antiviral Agents; Virus Replication
PubMed: 36902020
DOI: 10.3390/ijms24054588 -
Medicine Jan 2021Since 2008, oral propranolol has evolved as the first-line therapy for infantile hemangiomas (IHs). Meanwhile, oral atenolol gradually shows comparative effectiveness...
Since 2008, oral propranolol has evolved as the first-line therapy for infantile hemangiomas (IHs). Meanwhile, oral atenolol gradually shows comparative effectiveness versus oral propranolol with few side effects. Here, we conducted a mobile internal survey among a group of Chinese clinicians about how they choose the dosage, dose regimen, and dose escalation methods of propranolol and atenolol for the treatment of IH.A mobile-ready internal survey on the application of oral propranolol and oral atenolol for IH in mainland China was performed and distributed to 333 potential clinicians from different levels of healthcare institutions in mainland China. Eighty-one doctors responded to the survey. All the respondents had the experience of treating IH with oral propranolol and 32 had the experience with oral atenolol.Most of the doctors from tertiary hospitals chose 2 mg/kg/d twice daily, while most of those with the experience of propranolol from private hospitals chose 1 mg/kg/d once daily. More doctors from tertiary hospitals had the experience of atenolol than those from private hospitals.Oral atenolol has become another medication intervention option for IH in mainland China. This survey is helpful to standardize and develop a guideline of oral atenolol therapy for IH.
Topics: Administration, Oral; Antihypertensive Agents; Atenolol; China; Female; Hemangioma; Humans; Infant; Male; Propranolol; Surveys and Questionnaires; Treatment Outcome
PubMed: 33429792
DOI: 10.1097/MD.0000000000024146