A hybrid for pain, i.e. bifunctional analgesics in neuropathy

Ból ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 17-24
Author(s):  
Joanna Starnowska-Sokół
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Pain Therapy ◽  
Analgesic Efficacy ◽  
Hybrid Structure ◽  
Multimodal Approach ◽  
Pharmacological Profile ◽  
Hybrid Compounds ◽  
Therapeutic Outcomes ◽  
Promising Perspective

The need of developing new neuropathic pain therapies results from limited potency of currently available treatments, which is underlain by low efficacy of conventional analgesics, complex etiology and pathogenesis of neuropathy, diversity of its symptoms, as well as heightened side effects risk that accompanies the polypharmaceutical strategy, employed commonly to improve the therapeutic outcomes. Designing hybrid compounds, i.e. multimodal molecules that present the affinity to more than one receptor target, offers a promising perspective in this context. The multimodal approach allows to increase the analgesic efficacy of a given compound thanks to aiming at the very pathomechanisms specific for neuropathic pain, and to optimize the pharmacological profile of the drug. Thanks to the hybrid structure, analgesic properties of its moieties can be maximized, even if their action as separate pharmacophores tends to be limited or inconsistent under nerve injury conditions, such as in the case of opioid agonists. The present review discusses selected targets of hybrid compounds in the view of potential neuropathic pain therapy, along with the gains, limitations and challenges related to the use of hybrid compounds.

Continuous Subcutaneous Infusion of Ketorolac in Cancer Neuropathic Pain Unresponsive to Opioid and Adjuvant Drugs. A Case Report

1996 ◽  
Vol 82 (4) ◽  
pp. 413-415 ◽  
Author(s):  
Carla Ripamonti ◽  
Chiara Ticozzi ◽  
Ernesto Zecca ◽  
Carlos H. Rodriguez ◽  
Franco De Conno
Keyword(s):  
Neuropathic Pain ◽  
Case Report ◽  
Side Effects ◽  
Cancer Patient ◽  
Cancer Pain ◽  
Antidepressant Drugs ◽  
Analgesic Efficacy ◽  
Subcutaneous Infusion ◽  
Continuous Subcutaneous Infusion ◽  
Nonopioid Analgesic

Ketorolac is a new non-steroidal anti-inflammatory drug (NSAID) having a potent nonopioid analgesic activity. Administered by continuous subcutaneous infusion (CSI), its analgesic efficacy has been documented in the treatment of somatic and visceral cancer pain whilst it has been shown to be ineffective in the treatment of neuropathic pain. Here is a description of a cancer patient with neuropathic pain unresponsive to anticonvulsant or antidepressant drugs administered in association or not with oral opioids but who was successfully treated with ketorolac alone via CSI. Furthermore, the analgesia lasted over 75 days of treatment without any significant renal and gastric side effects.

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

scholarly journals Buprenorphine: Far Beyond the “Ceiling”

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 816
Author(s):  
Rosmara Infantino ◽  
Consalvo Mattia ◽  
Pamela Locarini ◽  
Antonio Luigi Pastore ◽  
Sabatino Maione ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Drug Abuse ◽  
Side Effects ◽  
National Health System ◽  
Analgesic Drugs ◽  
Third Line ◽  
Dynamic Profile

Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine.

Clinical analgesic efficacy and side effects of dexmedetomidine in the early postoperative period after arthroscopic knee surgery

2007 ◽  
Vol 19 (8) ◽  
pp. 576-582 ◽  
Author(s):  
Maria E. Gómez-Vázquez ◽  
Eduardo Hernández-Salazar ◽  
Abel Hernández-Jiménez ◽  
Arturo Pérez-Sánchez ◽  
Vilma A. Zepeda-López ◽  
...  
Keyword(s):  
Side Effects ◽  
Postoperative Period ◽  
Analgesic Efficacy ◽  
Early Postoperative Period ◽  
Knee Surgery ◽  
Arthroscopic Knee Surgery ◽  
Arthroscopic Knee

scholarly journals Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3305 ◽  
Author(s):  
Giuseppe Tardiolo ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Mental Health ◽  
Neuropathic Pain ◽  
Side Effects ◽  
Neurodegenerative Diseases ◽  
Cognitive Aging ◽  
Nutritional Supplement ◽  
Medical Applications ◽  
Scientific Interest ◽  
Human Diet ◽  
Anti Inflammatory

N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson’s and Alzheimer’s disorders and in neuropathic pain and stroke.

scholarly journals Pharmacological Management of Chronic Neuropathic Pain – Consensus Statement and Guidelines from the Canadian Pain Society

2007 ◽  
Vol 12 (1) ◽  
pp. 13-21 ◽  
Author(s):  
DE Moulin ◽  
AJ Clark ◽  
I Gilron ◽  
MA Ware ◽  
CPN Watson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Ease Of Use ◽  
Control Group ◽  
Pharmacological Management ◽  
Randomized Controlled ◽  
Analgesic Agents ◽  
Third Line

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

scholarly journals Regenerative Medicine to Reduce the Side Effects from Radiotherapy Causing Skin Cancer, Fibrosis, Neuropathic Pain and Hair Loss

2021 ◽  
Vol 12 (08) ◽  
pp. 461-477
Author(s):  
E. Russell Vickers ◽  
Junqing Liang ◽  
Peter G. Vickers ◽  
Haitao Wen
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Skin Cancer ◽  
Regenerative Medicine ◽  
Hair Loss

scholarly journals The Comparison of Gabapentin and Amitriptilin Effectivity as Pain Therapy in Herniated Nucleus Pulposus

2015 ◽  
Vol 4 (3) ◽  
pp. 225
Author(s):  
Indriastuti Cahyaningsih ◽  
Rina Handayani ◽  
Setyaningsih Setyaningsih
Keyword(s):  
Neuropathic Pain ◽  
Nucleus Pulposus ◽  
Statistical Difference ◽  
Pain Therapy ◽  
P Value ◽  
Analog Scale ◽  
Peripheral Neuropathic Pain ◽  
Quasi Experimental ◽  
Herniated Nucleus Pulposus

Herniated nucleus pulposus (HNP) is one of peripheral neuropathic pain. Although concensus guidelines for the treatment of neuropathic pain are based on the results of the RCT studies, there are still gaps in the literatures. This study aimed to compare the effectiveness and quality of life of gabapentin and amitriptyline for the treatment of pain in HNP. The method used a quasi experimental with consequtive sampling. This study included 30 patients in the gabapentin group and 26 patients in the amitriptyline group, and each group was evaluated for 1 month. Effectiveness was assessed using Visual Analogue Scale (VAS) every 2 weeks then analized by independent and paired sample t test. The results showed that the use of gabapentin and amitriptilin in 4 weeks showed the decrease of pain score measured by visual analog scale 3.70 ± 0.349 and 3.500 ± 0.34 although there was no statistical difference (p value = 0.704). To sum up, effectiveness of gabapentin and amitriptyline in the treatment of neuropathic pain did not have statistical difference.

scholarly journals A Comparison of Oral Gabapentin and Oral Pregabalin as Preemptive Analgesia for Orthopedic Surgery Under Spinal Anaesthesia

2021 ◽  
Vol 9 (1) ◽  
pp. 74-78
Author(s):  
Neena Jain ◽  
Rahul Bankapur ◽  
Preeti Lamba ◽  
saurav Singh
Keyword(s):  
Side Effects ◽  
Postoperative Pain ◽  
Spinal Anesthesia ◽  
Spinal Anaesthesia ◽  
Orthopedic Surgery ◽  
Lower Limb ◽  
Analgesic Efficacy ◽  
Double Blind Study ◽  
Group A ◽  
Group B

Background and Aims: Gabapentin and pregabalin, by decreasing noxious stimulus induced excitatory neurotransmitter release at central nervous system, may attenuate central sensitization and eventually decrease development of postoperative pain. We evaluated preemptive analgesic efficacy of single dose of oral gabapentin 600 mg and pregabalin 75mg for postoperative pain in patients undergoing lower limb orthopedic surgery under spinal anesthesia. Material and methods: A prospective, randomized, double blind study was conducted on 70 patients aged between 18 to 60 years with ASA grade 1 and 2 posted for lower limb surgeries under spinal anaesthesia. Patients were allocated into Group A and Group B receiving oral gabapentin(600mg) and oral pregabalin (75mg) respectively 1.5 hours before surgery. Primary objective was assessing duration and quality of analgesia by Visual Analogue Scale (VAS) score at 2,4,6,8,10,12,16,20 and 24 hours.Secondary objective was to assess total dose of rescue analgesic in first 24 hours, perioperative hemodynamic change and various side effects. Statistical Analysis used: Categorical data was compared using Chi- square test. Quantitative parametric data was analysed using unpaired student t-test. P value < 0.05 was considered statistically significant. Results: Mean duration of analgesia in Group A (10.53 ± 2.686 hours) was longer than Group B (7.943±3.199hr) (P = 0.0006).Mean number of analgesic dosesrequired in first 24 hourswere less in Group A (1.429 ± 0.5021) ascompared to Group B (1.771±0.6897) (P = 0.0202).All patients remained hemodynamically stable with no significant side effects noted in either group. Conclusion: We conclude that preemptive analgesic efficacy of oral gabapentin 600mg is better in comparison to oral pregabalin 75 mg for patients posted for lower limb orthopedic surgeries under spinal anesthesia.

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