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Expert Opinion on Pharmacotherapy Aug 2022Priapism is a compartment syndrome, defined as an unwanted penile erection lasting longer than 4 h, unrelated to sexual stimulation, and persistent even after... (Review)
Review
INTRODUCTION
Priapism is a compartment syndrome, defined as an unwanted penile erection lasting longer than 4 h, unrelated to sexual stimulation, and persistent even after ejaculation/orgasm. Ischemic priapism is considered a urologic emergency requiring time-sensitive management. Studies have documented that untreated priapism is associated with progressive ischemic histological changes in the corpora cavernosa, such as widespread smooth muscle necrosis, blood vessel and nerve attrition, and trabecular fibrosis. Treatment options include conservative management, corporal irrigation, pharmacologic therapy, and surgery. We herein provide an overview of the emergency pharmacology for priapism.
AREAS COVERED
The American Urological Association (AUA) and the European Association of Urology (EAU) both recommend penile aspiration in conjunction with intracavernosal injection of sympathomimetics as the initial management of ischemic priapism. We have performed a retrospective review of the literature from 1914 to 2022 by using PubMed and a review of the treatment guidelines from the AUA and the EAU to discuss the various therapies for ischemic priapism in the emergent setting.
EXPERT OPINION
After a thorough overview of the literature regarding the treatment of ischemic priapism in the emergent setting, we conclude that intracavernosal phenylephrine is superior to other agents due to its demonstrated efficacy and limited systemic side effects.
Topics: Humans; Male; Penile Erection; Penis; Phenylephrine; Priapism; Sympathomimetics
PubMed: 35815373
DOI: 10.1080/14656566.2022.2099271 -
Minerva Anestesiologica Oct 2020
Topics: Humans; Phenylephrine; Vasoconstrictor Agents
PubMed: 32613813
DOI: 10.23736/S0375-9393.20.14716-3 -
Survey of Ophthalmology 2022Intracameral phenylephrine is commonly used in ophthalmic surgery as an alternative or supplement to mydriatic eye drops; hence, the importance of an evidence-based... (Review)
Review
Intracameral phenylephrine is commonly used in ophthalmic surgery as an alternative or supplement to mydriatic eye drops; hence, the importance of an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of intracameral phenylephrine. Articles from 1958 to 2021 with the following keywords were used: "intracameral phenylephrine," "intracameral mydriatics," "phenylephrine," "pupil dilation," "complications." Intracameral phenylephrine was first used in 2003 as an alternative to topical mydriatics. Since then, it is being increasingly used with a variety of benefits, including rapid onset of mydriasis, and cost-effectiveness. There are various case reports, however, of ocular and systemic complications associated with intracameral phenylephrine such as generation of free radicals, toxic anterior segment syndrome, inconsistent pupillary dilation during surgery, and ventricular fibrillation. Alternatives to intracameral phenylephrine such as iris hooks, a Malyugin ring, intracameral epinephrine, and intracameral tropicamide were compared with intracameral phenylephrine. Intracameral phenylephrine appears to have a good safety profile.
Topics: Humans; Lidocaine; Mydriatics; Ophthalmic Solutions; Phacoemulsification; Phenylephrine; Pupil
PubMed: 35691387
DOI: 10.1016/j.survophthal.2022.06.002 -
Eye (London, England) Nov 2019We investigated the effects of topical phenylephrine 2.5% instillation on choroidal thickness (CT), peripapillary choroidal thickness (pCT) and retinal nerve fibre layer...
OBJECTIVES
We investigated the effects of topical phenylephrine 2.5% instillation on choroidal thickness (CT), peripapillary choroidal thickness (pCT) and retinal nerve fibre layer (RNFL).
METHODS
Healthy control patients underwent enhanced depth imaging (EDI) by spectral-domain optical coherence tomography (OCT) before and 30 min after phenylephrine instillation, using eye-tracking and follow-up software. Changes in 14 different locations of CT, 2 locations of pCT and RNFL were assessed.
RESULTS
The study included 119 eyes of 62 patients (19 males and 43 females), with a mean age of 59.8 ± 15.3 years (range: 26-88 years). Within 30 min after instillation, the mean subfoveal CT both in vertical and horizontal scan were significantly thinned (p = 0.005 and p = 0.018, respectively). In total, 1500, 1000 and 500 µm temporal CT measurements showed also a significant thinning (p = 0.021, p = 0.037 and p = 0.020, respectively), as well as 500 µm both superior (p = 0.045) and inferior (p = 0.009). 1500, 1000 and 500 µm nasal CT, and 1500 and 1000 µm CT superior and inferior measurements showed no significant thinning after phenylephrine instillation. pCT was significantly thinned after phenylephrine in both superior (p = 0.016) and inferior (p = 0.050) measurements. RNFL analysis did not significantly change after phenylephrine instillation (p = 0.209).
CONCLUSIONS
A significant thinning of CT and pCT occurred following phenylephrine instillation. Future studies analysing CT and pCT should detail if this mydriatic agent was used or not.
Topics: Administration, Ophthalmic; Adult; Aged; Aged, 80 and over; Choroid; Female; Healthy Volunteers; Humans; Macula Lutea; Male; Middle Aged; Mydriatics; Nerve Fibers; Ophthalmic Solutions; Optic Disk; Phenylephrine; Pupil; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 31164729
DOI: 10.1038/s41433-019-0478-z -
The Journal of Urology Nov 2021Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given...
PURPOSE
Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction.
MATERIALS AND METHODS
A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report.
RESULTS
This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement.
CONCLUSIONS
All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.
Topics: Acute Disease; Adult; Combined Modality Therapy; Emergency Treatment; Erectile Dysfunction; Humans; Ischemia; Male; North America; Penile Erection; Penis; Phenylephrine; Priapism; Societies, Medical; Time Factors; Ultrasonography, Doppler; Urology
PubMed: 34495686
DOI: 10.1097/JU.0000000000002236 -
ELife Sep 2022Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac...
Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury. Fibroblast-ablated mice demonstrated a substantive reduction in cardiac fibroblasts, but fibrillar collagen and the ECM proteome were not overtly altered when evaluated by quantitative mass spectrometry and N-terminomics. However, the distribution and quantity of collagen VI, microfibrillar collagen that forms an open network with the basement membrane, was reduced. In fibroblast-ablated mice, cardiac function was better preserved following angiotensin II/phenylephrine (AngII/PE)-induced fibrosis and myocardial infarction (MI). Analysis of cardiomyocyte function demonstrated altered sarcomere shortening and slowed calcium decline in both uninjured and AngII/PE-infused fibroblast-ablated mice. After MI, the residual resident fibroblasts responded to injury, albeit with reduced proliferation and numbers immediately after injury. These results indicate that the adult mouse heart tolerates a significant degree of fibroblast loss with a potentially beneficial impact on cardiac function after injury. The cardioprotective effect of controlled fibroblast reduction may have therapeutic value in heart disease.
Topics: Angiotensin II; Animals; Calcium; Collagen; Fibroblasts; Fibrosis; Mice; Myocardial Infarction; Myocardium; Phenylephrine; Proteome; Receptor, Platelet-Derived Growth Factor alpha
PubMed: 36149056
DOI: 10.7554/eLife.69854 -
The Journal of Obstetrics and... Jul 2023The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine,... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section.
METHODS
The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores.
RESULTS
About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 μg norepinephrine and 81-120 mg phenylephrine; 121-150 μg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 μg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 μg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 μg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores.
CONCLUSIONS
Based on this study, 5-10 mg ephedrine and 13-16 μg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Phenylephrine; Ephedrine; Norepinephrine; Vasoconstrictor Agents; Cesarean Section; Bradycardia; Network Meta-Analysis; Bayes Theorem; Anesthesia, Spinal; Hypotension; Hypertension; Anesthesia, Obstetrical; Double-Blind Method
PubMed: 37170779
DOI: 10.1111/jog.15671 -
Current Eye Research Feb 2022To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation.
PURPOSE
To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation.
METHOD
One hundred and thirty-one eyes from 66 patients enrolled this cross-sectional study. An extensive ocular examination was carried out prior to tropicamide and phenylephrine instillation. Power and axis value from flat, steep, and mean keratometry were calculated using an Auto Kerato-Refractometer (AKR). Later, topography and tomography maps were evaluated with Pentacam HR® (Oculus, Wetzlar, Germany). Subsequently, a single drop of tropicamide 1% and phenylephrine hydrochloride 10% were instilled twice, with a five-minute gap between each instillation. After 30 minutes, the AKR and Pentacam HR® tests were repeated.
RESULTS
Incyclotorsion was found in 59 eyes (45.1%) and mean absolute incyclotorsion change was 3.91 ± 3.62 degrees (0.10 to 14.20). Excyclotorsion was found in 72 eyes (54.9%) and mean excyclotorsion change was 4.99 ± 5.94 degrees (0.20 to 36.20). We observed that 74.6% and 68.1% of eyes experienced incyclotorsion and excyclotorsion within 0 to 5 degrees, respectively. Fewer patients experienced incyclotorsion and excyclotorsion changes within 5 to 10 degrees, precisely 11.8% and 19.4%, respectively. Eyes that experienced over 10 degrees of incyclotorsion and excyclotorsion were 13.6% and 12.5%, respectively.
CONCLUSION
Astigmatism axis could change after combined tropicamide and phenylephrine instillation. Reference axis marking in astigmatism correction surgery should be performed under the same circumstances as the astigmatism axis has been measured.
Topics: Astigmatism; Cornea; Corneal Diseases; Corneal Topography; Cross-Sectional Studies; Humans; Phenylephrine; Tropicamide
PubMed: 34437825
DOI: 10.1080/02713683.2021.1971720 -
Toxicology Dec 2019In the present study, the toxicity of phenylephrine, a selective α1-adrenergic receptor agonist, in corneal epithelial cells and its underlying mechanisms were...
In the present study, the toxicity of phenylephrine, a selective α1-adrenergic receptor agonist, in corneal epithelial cells and its underlying mechanisms were investigated using an in vitro model of human corneal epithelial cells (HCEPCs) and an in vivo model of New Zealand white rabbit corneas. The HCEPCs treated with phenylephrine at concentrations from 10% to 0.078125% displayed abnormal morphology, decline of cell viability and elevation of plasma membrane permeability time- and dose-dependently. Moreover, 10%-1.25% phenylephrine induce necrosis characteristics of marginalization and uneven distribution of chromatin through up-regulation of RIPK1, RIPK3 and MLKL along with inactivation of caspase-8 and caspase-2, whereas 0.625% phenylephrine induced condensed chromatin, S phase arrest, phosphatidylserine externalization, DNA fragmentation and apoptotic body formation in the HCECs through activation of caspase-2, -8, -9 and -3 as well as down-regulation of Bcl-2, up-regulation of Bad, ΔΨm disruption and release of cytochrome c and AIF into cytosol. At last, 10% phenylephrine induced destruction of the corneal epithelia and apoptosis of corneal epithelial cells in rabbit corneas. In conclusion, 10% to 1.25% phenylephrine cause necroptosis via RIPK1-RIPK3-MLKL axis and 0.625% phenylephrine induce apoptosis via a mitochondrion-dependent and death receptor-mediated signal pathway in HCEPCs.
Topics: Adrenergic alpha-1 Receptor Agonists; Animals; Apoptosis; Cell Cycle; Cell Membrane Permeability; Cells, Cultured; Cornea; Dose-Response Relationship, Drug; Epithelial Cells; Humans; Male; Necroptosis; Phenylephrine; Rabbits; Receptor-Interacting Protein Serine-Threonine Kinases; Time Factors
PubMed: 31605733
DOI: 10.1016/j.tox.2019.152305 -
Journal of the American Heart... Apr 2023Background Pathological cardiac hypertrophy is regarded as a critical precursor and independent risk factor of heart failure, and its inhibition prevents the progression...
Background Pathological cardiac hypertrophy is regarded as a critical precursor and independent risk factor of heart failure, and its inhibition prevents the progression of heart failure. Switch-associated protein 70 (SWAP70) is confirmed important in immunoregulation, cell maturation, and cell transformation. However, its role in pathological cardiac hypertrophy remains unclear. Methods and Results The effects of SWAP70 on pathological cardiac hypertrophy were investigated in knockout mice and overexpression/knockdown cardiomyocytes. Bioinformatic analysis combined with multiple molecular biological methodologies were adopted to elucidate the mechanisms underlying the effects of SWAP70 on pathological cardiac hypertrophy. Results showed that SWAP70 protein levels were significantly increased in failing human heart tissues, experimental transverse aortic constriction-induced mouse hypertrophic hearts, and phenylephrine-stimulated isolated primary cardiomyocytes. Intriguingly, phenylephrine treatment decreased the lysosomal degradation of SWAP70 by disrupting the interaction of SWAP70 with granulin precursor. In vitro and in vivo experiments revealed that knockdown/knockout accelerated the progression of pathological cardiac hypertrophy, while overexpression restrained the cardiomyocyte hypertrophy. SWAP70 restrained the binding of transforming growth factor β-activated kinase 1 (TAK1) and TAK1 binding protein 1, thus blocking the phosphorylation of TAK1 and downstream c-Jun N-terminal kinase/P38 signaling. TAK1 interacted with the N-terminals (1-192) of SWAP70. (193-585) overexpression failed to inhibit cardiac hypertrophy when the TAK1-SWAP70 interaction was disrupted. Either inhibiting the phosphorylation or suppressing the expression of TAK1 rescued the exaggerated cardiac hypertrophy induced by knockdown. Conclusions SWAP70 suppressed the progression of cardiac hypertrophy, possibly by inhibiting the mitogen-activated protein kinases signaling pathway in a TAK1-dependent manner, and lysosomes are involved in the regulation of SWAP70 expression level.
Topics: Animals; Humans; Mice; Cardiomegaly; DNA-Binding Proteins; Guanine Nucleotide Exchange Factors; Heart Failure; Mice, Knockout; Minor Histocompatibility Antigens; Myocytes, Cardiac; Nuclear Proteins; Phenylephrine; Signal Transduction
PubMed: 36974751
DOI: 10.1161/JAHA.122.028628