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Anesthesia Progress 2012Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that... (Comparative Study)
Comparative Study Review
Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article.
Topics: Adrenergic alpha-Antagonists; Anesthesia Recovery Period; Anesthesia, Dental; Anesthesia, Local; Anesthetics, Local; Carticaine; Drug Hypersensitivity; Drug Interactions; Humans; Lidocaine; Maximum Tolerated Dose; Phentolamine; Vasoconstrictor Agents
PubMed: 22822998
DOI: 10.2344/0003-3006-59.2.90 -
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 -
Scientific Reports Feb 2022Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in...
Incomplete functional recovery after peripheral nerve injury (PNI) often results in devastating physical disabilities in human patients. Despite improved progress in surgical and non-surgical approaches, achieving complete functional recovery following PNI remains a challenge. This study demonstrates that phentolamine may hold a significant promise in treating nerve injuries and denervation induced muscle atrophy following PNI. In a sciatic nerve crush injury mouse model, we found that phentolamine treatment enhanced motor and functional recovery, protected axon myelination, and attenuated injury-induced muscle atrophy in mice at 14 days post-injury (dpi) compared to saline treatment. In the soleus of phentolamine treated animals, we observed the downregulation of phosphorylated signal transducer and activator of transcription factor 3 (p-STAT3) as well as muscle atrophy-related genes Myogenin, muscle ring finger 1 (MuRF-1), and Forkhead box O proteins (FoxO1, FoxO3). Our results show that both nerve and muscle recovery are integral components of phentolamine treatment-induced global functional recovery in mice at 14 dpi. Moreover, phentolamine treatment improved locomotor functional recovery in the mice after spinal cord crush (SCC) injury. The fact that phentolamine is an FDA approved non-selective alpha-adrenergic blocker, clinically prescribed for oral anesthesia reversal, hypertension, and erectile dysfunction makes this drug a promising candidate for repurposing in restoring behavioral recovery following PNI and SCC injuries, axonal neuropathy, and muscle wasting disorders.
Topics: Animals; Axons; Humans; Male; Mice; Muscle, Skeletal; Muscular Atrophy; Nerve Regeneration; Peripheral Nerve Injuries; Phentolamine; Recovery of Function; Sciatic Nerve; Sciatic Neuropathy
PubMed: 35228612
DOI: 10.1038/s41598-022-07253-w -
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 -
Theranostics 2022Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather...
Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension. AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10 μM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs. NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than β-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation. NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.
Topics: Adventitia; Animals; Cell Proliferation; Cells, Cultured; Extracellular Vesicles; Fibroblasts; Hypertension; Muscle, Smooth, Vascular; Norepinephrine; Phentolamine; Rats; Rats, Inbred WKY
PubMed: 35832088
DOI: 10.7150/thno.70974 -
BioMed Research International 2022Pediatric patients are facing greater difficulties in radial catheterization for anatomic variation and smaller diameter. This study is to investigate the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Pediatric patients are facing greater difficulties in radial catheterization for anatomic variation and smaller diameter. This study is to investigate the efficacy of phentolamine accompanied by lidocaine subcutaneously under ultrasound guidance on radial catheterization in pediatric patients.
METHODS
66 pediatric patients were enrolled and randomly divided into saline group, phentolamine group, and phentolamine+lidocaine group. Baseline characteristics and surgical types were collected. Relevant solutions were subcutaneously injected, and catheterization was subsequently conducted under ultrasound guidance. Radial artery diameter and depth were measured, the success rate of catheterization and procedure time were calculated, and the complications were evaluated with ultrasonography.
RESULTS
No significant differences were observed in age, sex, weight, American Society of Anesthesiologists' classification, systolic blood pressure, diastolic blood pressure, heart rate, hemoglobin, and surgical types among three groups. Subcutaneously, the diameter in phentolamine and phentolamine+lidocaine groups increased significantly compared with the saline group. Moreover, the diameter also increased significantly after injection compared with that before injection both in the phentolamine and phentolamine+lidocaine groups. The first-attempt success rates were significantly higher while the procedure times of cannulation were shorter in the phentolamine and phentolamine+lidocaine groups than that in the saline group. Kaplan-Meier analysis showed that the overall procedure time was shorter in the phentolamine and phentolamine+lidocaine groups than the saline group. Overall complications and vasospasm incidence were lower in the phentolamine and phentolamine+lidocaine groups than the saline group.
CONCLUSION
Phentolamine accompanied by lidocaine subcutaneous injection under ultrasound guidance improved the first-attempt success rate and reduced the complication of radial artery catheterization in pediatric patients.
Topics: Catheterization; Child; Humans; Lidocaine; Phentolamine; Radial Artery; Ultrasonography; Ultrasonography, Interventional
PubMed: 35757477
DOI: 10.1155/2022/6554993 -
Japanese Journal of Pharmacology Jun 2002Erectile dysfunction (ED) is a common problem with a prevalence of approximately 50% in men aged 40 to 70. There are several etiologies for ED including vasculogenic,... (Review)
Review
Erectile dysfunction (ED) is a common problem with a prevalence of approximately 50% in men aged 40 to 70. There are several etiologies for ED including vasculogenic, neurogenic, hormonal and/or psychogenic factors; one-fourth of ED cases can be drug-related. Penile erection involves a complex interaction between the CNS and local factors. It is a neurovascular event modulated by psychological and hormonal factors. Pharmacologically, neural modulation and endocrine status are very important to attaining penile erection. There have been several significant advances for the pharmacologic treatment of ED. Treatments include agents that are not only orally effective, but possess either local or central acting mechanisms of action. Apomorphine, a centrally-acting agent, is effective in the treatment of ED. Sildenafil, another orally effective agent, acts by inhibiting cyclic GMP-specific phosphodiesterase Type V. Testosterone can be effective transdermally. Non-orally active agents include alprostadil and papaverine. Phentolamine and trazodone are effective in selected cases. Some agents can interact with other medications. Several pharmacological agents, some with central-acting mechanisms and some with Iocally-acting vascular effects, are therapeutically useful in the treatment of ED.
Topics: Adult; Aged; Alprostadil; Apomorphine; Drug Interactions; Erectile Dysfunction; Humans; Male; Middle Aged; Papaverine; Penile Erection; Phentolamine; Piperazines; Purines; Sildenafil Citrate; Sulfones; Testosterone; Trazodone
PubMed: 12120751
DOI: 10.1254/jjp.89.101 -
American Journal of Physiology. Heart... Aug 2001The relative contributions of a central neural oscillator and of the delay in alpha-adrenergic transmission within the baroreflex loop in the predominance of...
The relative contributions of a central neural oscillator and of the delay in alpha-adrenergic transmission within the baroreflex loop in the predominance of low-frequency (LF) cardiovascular variability during sympathetic activation in humans are unclear. We measured R-R interval (RR), muscle sympathetic nerve activity (MSNA), blood pressure (BP), and their variability in 10 normal subjects during sympathetic activation achieved by BP lowering with sodium nitroprusside (SNP) and alpha-adrenergic blockade using phentolamine. SNP and phentolamine induced comparable reductions in BP (P > 0.25). Despite tachycardia and sympathetic activation with both SNP and phentolamine, LF variability in RR, MSNA, and BP increased during SNP and decreased during phentolamine (SNP: RR +20 +/- 6%, MSNA +3 +/- 5%, systolic BP +9 +/- 6%, diastolic BP +7 +/- 5%; phentolamine: RR -2 +/- 7%, MSNA -34 +/- 6%, systolic BP -16 +/- 8%, diastolic BP -13 +/- 4%, P < 0.05 except systolic BP, where P = 0.09). Thus LF variability is reduced when sympathetic activation is induced by alpha-adrenergic blockade. This suggests that alpha-adrenergic transmission within the baroreflex loop may contribute importantly to the predominance of LF cardiovascular variability associated with sympathetic excitation in humans.
Topics: Adrenergic alpha-Antagonists; Adult; Baroreflex; Electrocardiography; Heart; Humans; Male; Myocardial Contraction; Nitroprusside; Phentolamine; Sympathetic Nervous System; Vasodilator Agents
PubMed: 11454557
DOI: 10.1152/ajpheart.2001.281.2.H559 -
European Journal of Medical Research Nov 2022To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock.
BACKGROUND
To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock.
METHODS
Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α receptor, α receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively.
RESULTS
In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α, α receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α and α receptor-related signaling pathways in whole lung tissues, and inhibit Ca signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region.
CONCLUSION
In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α and α receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α and α receptor and their downstream signaling pathways.
Topics: Animals; Rabbits; Hominidae; Phentolamine; Pulmonary Embolism; Receptors, Adrenergic, alpha; Shock
PubMed: 36348473
DOI: 10.1186/s40001-022-00842-5 -
The Journal of Physiology Jul 19951. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor...
1. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor antagonist prazosin on fetal breathing movements (FBM) and electrocortical activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the effects of phentolamine were measured during normoxia and hypoxia. In the second group of fetuses (group II; n = 8) the effects of either phentolamine, or combined phentolamine and prazosin, or prazosin alone, were measured during normoxia. 2. In group I fetuses, the incidence of FBM increased after phentolamine treatment. An increase in the incidence and mean episode duration of low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These effects of phentolamine persisted during hypoxia. 3. In group II fetuses a pronounced decrease in the incidence of FBM occurred after administration of prazosin following either phentolamine or saline pretreatment. These effects of prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude that catecholamines have a stimulatory role on FBM mediated via an alpha 1-adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an alpha 1-independent mechanism.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Blood Gas Analysis; Diaphragm; Electroencephalography; Electromyography; Female; Fetal Movement; Phentolamine; Prazosin; Pregnancy; Respiratory Mechanics; Sheep
PubMed: 7562640
DOI: 10.1113/jphysiol.1995.sp020807