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Brain Sciences May 2023Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life... (Review)
Review
Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients.
PubMed: 37239274
DOI: 10.3390/brainsci13050802 -
European Journal of Translational... Jan 2022This article was not intended to be a complete review of the electromyography of pathological muscle states, but it was written to illustrate how the "Coletti Method of...
This article was not intended to be a complete review of the electromyography of pathological muscle states, but it was written to illustrate how the "Coletti Method of EMG ChemoDenervation" (CMECD®) protocol for the treatment of chronic pain resulting from chronic muscle spasm was developed and established. That process led to an unexpected understanding of the underlying pathophysiology of chronic muscle spasm, which represents a paradigm shift in our understanding and ultimately in our treatment of muscle spasm-induced chronic pain. Other investigators had brought to light the presence of spontaneous electrical activity (SEA) in states of muscle spasm. Those findings were all but ignored by standard EMG/Nerve conduction studies in clinical practice. Starting with a simple EMG device I experimented with various medications to treat patients with chronic pain associated with chronic muscle spasm. Suppression of SEA with long-acting medications resolved both the chronic spasm and chronic pain. A successful protocol using phenoxybenzamine was established and clinical outcomes were followed. More than 200 patients were successfully treated during last 12 years. Correlating known exercise muscle physiology with the development of the pathological state of chronic muscle spasm as seen by electromyography led to the postulation of the ischemic model of chronic muscle spasm. Light microscopy pathophysiologic supportive findings are presented and discussed. Predictions from this model to various aspects of treatment were supportive. Implications regarding treatment by the CMECD procedure, as well as other standard therapies, are discussed. Application of the ischemic model to other pain conditions was explored with implications of therapeutic modification. Recommendations for changes in rehabilitation therapy are discussed.
PubMed: 35044134
DOI: 10.4081/ejtm.2022.10323 -
Atherosclerosis Jul 2017Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments... (Review)
Review
Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression.
Topics: Animals; Arteries; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Humans; Prognosis; Risk Factors; Time Factors; Vascular Diseases; Vasoconstriction
PubMed: 28363516
DOI: 10.1016/j.atherosclerosis.2017.03.019 -
Frontiers in Endocrinology 2020
Topics: Humans; Angiotensin-Converting Enzyme 2; Arthritis, Rheumatoid; Autoimmune Diseases; Drug Combinations; Gastrointestinal Neoplasms; Inflammation; Inflammatory Bowel Diseases; Neurodegenerative Diseases; Phentolamine; Receptors, G-Protein-Coupled; Vasoactive Intestinal Peptide
PubMed: 33101216
DOI: 10.3389/fendo.2020.588157 -
Anesthesia Progress Apr 2022Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the... (Review)
Review
Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the contemporary practices of sedation providers and anesthesiologists. Reversal or "antidote" drugs, such as flumazenil and naloxone, are often used in unintentional overdose situations involving significant benzodiazepine- and/or opioid-induced respiratory depression. Within the context of skeletal muscle relaxation, neostigmine and sugammadex are routinely used to reverse the effects of nondepolarizing neuromuscular blocking agents. In addition, the alpha-adrenergic antagonist phentolamine is used in dentistry as a local anesthetic reversal agent, decreasing its duration of action by inducing vasodilation. This review article discusses the pharmacology, uses, practical implications, adverse effects, and precautions needed for flumazenil, naloxone, neostigmine, sugammadex, and phentolamine within the context of sedation and anesthesia practice for dentistry.
Topics: Anesthesia, Dental; Anesthetics; Humans; Neostigmine; Sugammadex
PubMed: 35377935
DOI: 10.2344/anpr-69-01-09 -
Environmental Science and Pollution... Feb 2022Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the... (Review)
Review
Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.
Topics: COVID-19; Drug Combinations; Humans; Phentolamine; SARS-CoV-2; Vasoactive Intestinal Peptide
PubMed: 34846667
DOI: 10.1007/s11356-021-17824-5 -
Journal of Plastic, Reconstructive &... Oct 2021The use of Wide Awake Local Anaesthetic No Tourniquet (WALANT) amongst Plastic and Orthopaedic Hand Surgeons has been accelerated by the impact of the COVID-19 pandemic...
The use of Wide Awake Local Anaesthetic No Tourniquet (WALANT) amongst Plastic and Orthopaedic Hand Surgeons has been accelerated by the impact of the COVID-19 pandemic and associated risks of general anaesthesia. Benefits of WALANT include a bloodless field, improved recovery, on-table testing, as well as cost and time savings. Whilst more clinical trials are underway to fully elucidate safety-profile and outcomes, there is a lack of consensus and clarity over contraindications to WALANT. A survey of trainees identified that only one-in-five were aware of the appropriate reversal agent in the event of inadequate perfusion. We feel that a WALANT checklist should be developed and implemented for use immediately prior to administration of local anaesthetic with adrenaline to an extremity, building on the successes of the World Health Organisation (WHO) and the Royal College of Anaesthetists checklists. Such a checklist should include contraindications to WALANT and make the operator aware of the availability, dose and location of Phentolamine as a reversal agent. Introducing this checklist will help to facilitate safer and more effective use of WALANT within Hand Surgery.
Topics: Anesthesia, Local; COVID-19; Comorbidity; Humans; Orthopedic Procedures; Pandemics; Tourniquets
PubMed: 34193391
DOI: 10.1016/j.bjps.2021.05.025 -
Journal of Vascular Surgery Cases and... Dec 2023We present a case of medication-induced priapism that was refractory to conventional urologic methods and required treatment with a caverno-saphenous bypass. The patient...
We present a case of medication-induced priapism that was refractory to conventional urologic methods and required treatment with a caverno-saphenous bypass. The patient had been misusing an injectable erectile dysfunction medication consisting of alprostadil, papaverine, and phentolamine (Trimix), resulting in multiple episodes of priapism. His initial episodes of priapism were successfully treated with the traditional urologic algorithm, including phenylephrine, aspiration, and distal shunting. However, due to his continued medication misuse, these became ineffective, requiring proximal shunt surgery. Priapism requiring an extra-anatomic bypass is exceedingly rare. Following our proximal shunt surgery, he maintained partial sexual function, and his bypass remained patent.
PubMed: 38106342
DOI: 10.1016/j.jvscit.2023.101359 -
Annals of Medicine and Surgery (2012) Jun 2024This article discusses the prevalence and impact of pharmacologically-induced mydriasis, a condition where the pupil becomes excessively dilated due to certain drugs. It... (Review)
Review
This article discusses the prevalence and impact of pharmacologically-induced mydriasis, a condition where the pupil becomes excessively dilated due to certain drugs. It highlights the challenges faced by medical professionals in dealing with this condition and the limitations of current treatments, like pilocarpine and dapiprazole, which come with systemic side effects and specific contraindications, limiting their regular use. The article introduces Ryzumvi, a novel ophthalmic solution approved by the US FDA, which effectively reverses mydriasis caused by adrenergic agonists and antimuscarinic drugs. The article provides insights into its mechanism of action, clinical efficacy, pharmacokinetics, safety, and tolerance based on extensive clinical trials. It emphasizes its rapid onset of action and effectiveness in restoring pupils to their initial size. It also underlines the potential for expanded applications, including in pediatric patients, solidifying its importance in the field of ophthalmology. Furthermore, Ryzumvi represents a promising advancement in managing pharmacologically-induced mydriasis, offering swift and effective relief while highlighting the importance of adhering to safety precautions and the continuous research and development efforts in ophthalmology to comprehensively address vision-related disorders and enhance patient outcomes.
PubMed: 38846833
DOI: 10.1097/MS9.0000000000002058 -
BMC Nephrology Dec 2022Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary... (Randomized Controlled Trial)
Randomized Controlled Trial
Association of periprocedural phentolamine infusion with favorable outcome in patients with chronic kidney disease and chronic coronary syndrome undergoing coronary catheterization: a prospective randomized controlled pilot study.
BACKGROUND
Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary catheterization. We aimed to evaluate the efficacy of phentolamine in prevention of CI-AKI in CKD and CCS patients undergoing percutaneous coronary catheterization for diagnostic angiography ± stenting.
METHODS
Participants with CKD and CCS planned for percutaneous coronary catheterization were included, while participants with normal kidney functions were excluded. A consecutive sample of 107 participants (mean age 58.62 ± 8.96 years, 64.5% males) was selected, underwent diagnostic coronary angiography or percutaneous coronary intervention, and received either conventional CI-AKI prevention strategy (group 1) or periprocedural phentolamine and conventional CI-AKI prevention strategy (group 2).
RESULTS
The percentages of study participants who had CI-AKI were 82.9% for group 1 and 17.1% for group 2, respectively. The incidence rate of CI-AKI was significantly lower in group 2 versus group 1 (p < 0.001). The urine output (ml/kg) and the urine output (ml/hour) within 72 hours post procedure was significantly higher in group 2 versus group 1 (t(105) = - 0.69, p < 0.001, t(105) = - 52.46, p < 0.001, respectively), the peak change in serum creatinine and the percentage of change relative to the baseline serum creatinine at 72 hours post procedure was significantly lower in group 2 versus group 1 (t(102) = 0.2, p 0.018, t(102) = 23.54, p < 0.001, respectively), and the incidence rate of major adverse cardiac and cerebrovascular events within 90 days post procedure was significantly lower in group 2 versus group 1 (t(102) = 1.168, P < 0.001), respectively. There was a statistically significant association of periprocedural phentolamine infusion with prevention of CI-AKI (OR = 0.041, 95% CI 0.0149-0.1128, P < 0.0001).
CONCLUSION
Our study highlights the potential role of phentolamine for protection of the kidney in CKD patients planned for coronary catheterization.
TRIAL REGISTRATION
Pan African Clinical Trial Registry Number: PACTR202209493847741. Date of Trial Registration: 22/09/2022.
Topics: Male; Humans; Middle Aged; Aged; Female; Phentolamine; Contrast Media; Prospective Studies; Pilot Projects; Creatinine; Coronary Angiography; Renal Insufficiency, Chronic; Risk Factors; Acute Kidney Injury; Cardiac Catheterization; Percutaneous Coronary Intervention
PubMed: 36585656
DOI: 10.1186/s12882-022-03050-9