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Anesthesiology Research and Practice 2024To compare the effects of oral gabapentin (GBP) and pregabalin (PGB) in pain control after orthopedic surgery on the upper limb.
The Effect of Oral Gabapentin and Pregabalin as a Prodrug in Pain Control after Orthopedic Surgery on the Upper Limb: A Double-Blind Parallel Randomized Clinical Trial Study.
OBJECTIVE
To compare the effects of oral gabapentin (GBP) and pregabalin (PGB) in pain control after orthopedic surgery on the upper limb.
METHODS
In this double-blind randomized clinical trial study, 80 patients who were the candidates for elective orthopedic surgery on one of the parts of the upper limb were divided into two groups using balance-block randomization. For the first group, a 150 mg capsule of PGB (one hour before the surgery) and for the second group, a 300 mg capsule of GBP (two hours before the surgery) were prescribed. Patients were subjected to standard monitoring at the beginning and during surgery. The pain scores were evaluated at before surgery, in PACU (postanesthesia care unit), and 6 and 12 hours after the surgery by VAS (visual analog scale).
RESULTS
In this study, 37 subjects were allocated to each group. The participation rate was 92.5%. The mean with 95% confidence interval (CI) of pain scores over 4 times in the PGB group was 4.03 (3.25-4.79), 3.76 (3.02-4.49), 3.65 (3.06-4.23), and 3.41 (2.88-3.93) and in the GBP group was 4.08 (3.33-4.83), 2.78 (2.11-4.45), 2.3 (2.05-2.54), and 2 (1.51-2.50), respectively. The within-group comparisons showed a significant decrease in the pain score over time ( < 0.001). Also, the between-group comparison showed significant differences between the two groups in terms of pain score ( < 0.001). In the end, results showed that there is a significant interaction between time and intervention for pain score (=0.042).
CONCLUSION
Although two medicines led to a reduction in the pain score, but the rate reduction in the PGB group was significantly more than that in the GBP group. This trial is registered with IRCT20211013052759N1.
PubMed: 38741578
DOI: 10.1155/2024/7193599 -
The Journal of Pharmacy and Pharmacology May 2024This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced...
OBJECTIVES
This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice.
METHODS
The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve.
KEY FINDINGS
DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice.
CONCLUSIONS
Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.
PubMed: 38733604
DOI: 10.1093/jpp/rgae057 -
International Journal of Molecular... Apr 2024Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which... (Review)
Review
Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.
Topics: Humans; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Pain, Postoperative; Chronic Pain; Risk Factors; Pain Management; Analgesics
PubMed: 38731944
DOI: 10.3390/ijms25094722 -
Cureus Apr 2024Cavum vergae (CV) cysts constitute a small proportion of intracranial cysts, and although generally asymptomatic, there are occasional cases where they might exhibit...
Cavum vergae (CV) cysts constitute a small proportion of intracranial cysts, and although generally asymptomatic, there are occasional cases where they might exhibit clinical manifestations. We present a clinical case of a 79-year-old female patient who had a clinical manifestation of headache on the occipital side of the head with irradiation to the shoulder girdle as well as numbness, dizziness, visual impairment, sleep disturbances, and tingling in the hands for three months. Vertigo and rightward staggering had been experienced for two weeks. On physical examination, it was discovered that there was smoothed physiological lordosis, restricted and painful movements, and paravertebral muscle rigidity in the cervical region. The patient had bilaterally reduced biceps and triceps reflexes, painful Erb's points, and hypesthesia over the C5 and C6 dermatomes on the right side. The patient had decreased coordination and displayed staggered movement to the right. A CT scan discovered dilated subarachnoid spaces of the convexity and a CV cyst. The patient was prescribed conservative therapy consisting of etoricoxib oral at a dosage of 2 × 60 mg for seven days, tolperisone hydrochloride orally at a dosage of 2 × 150 mg for seven days, pregabalin 75 mg, one pill in the evening for seven days, ozoid (a gel containing ozone) for external application, and vinpocetine 2 × 10 mg orally for two months. Following the conservative treatment, the patient exhibited improvement in her symptoms and no longer had challenges carrying out her daily tasks. Furthermore, six months after the therapy, the patient did not experience any symptoms. Long-term follow-up will be conducted in cases of symptom recurrence or cyst enlargement.
PubMed: 38725770
DOI: 10.7759/cureus.57907 -
Veterinary Anaesthesia and Analgesia 2024To investigate the effect of three different doses of oral pregabalin on minimum alveolar concentration of isoflurane (MAC) in cats. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effect of three different doses of oral pregabalin on minimum alveolar concentration of isoflurane (MAC) in cats.
STUDY DESIGN
Prospective, randomized, placebo-controlled, blinded, crossover trial.
ANIMALS
A group of eight healthy adult cats aged 24-48 months.
METHODS
Cats were randomly assigned to three oral doses of pregabalin (low dose: 2.5 mg kg, medium dose: 5 mg kg, high dose: 10 mg kg) or placebo 2 hours before MAC determination, with the multiple treatments administered with a minimum 7 day washout period. Anesthesia was induced and maintained with isoflurane in oxygen until endotracheal intubation was achieved, and maintained with isoflurane with volume-controlled ventilation. MAC was determined in triplicate using the bracketing technique and tail clamp method 120 minutes after pregabalin or placebo administration. Physiologic variables (including heart rate and blood pressure) recorded during MAC determination were averaged and compared between the pregabalin and placebo treatments. One-way analysis of variance and the Friedman test were used to assess the difference for normally and non-normally distributed data, respectively. The Tukey test was used as a post hoc analysis. Values of p < 0.05 were considered significant.
RESULTS
The MAC with the medium- and high-dose pregabalin treatments were 1.33 ± 0.21% and 1.23 ± 0.17%, respectively. These were significantly lower than MAC after placebo treatment (1.62 ± 0.13%; p = 0.014, p < 0.001, respectively), representing a decrease of 18 ± 9% and 24 ± 6%. The mean plasma pregabalin concentration was negatively correlated with MAC values. Physiologic variables did not differ significantly between treatments.
CONCLUSIONS AND CLINICAL RELEVANCE
Doses of 5 or 10 mg kg pregabalin, administered orally 2 hours before determining MAC, had a significant isoflurane-sparing effect in cats.
Topics: Animals; Pregabalin; Isoflurane; Cats; Anesthetics, Inhalation; Pulmonary Alveoli; Male; Cross-Over Studies; Female; Administration, Oral; Drug Interactions; Dose-Response Relationship, Drug; Analgesics; Anesthesia, Inhalation
PubMed: 38719760
DOI: 10.1016/j.vaa.2024.04.007 -
Clinical Oral Investigations May 2024To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the effects of pregabalin and dexamethasone coadministration on preemptive multimodal analgesia and anxiety in third molar surgeries: a triple-blind randomized clinical trial.
OBJECTIVE
To evaluate the efficacy of pregabalin and dexamethasone coadministration in preemptive analgesia and anxiety control in lower third molar surgery.
MATERIALS AND METHODS
A triple-blind, split-mouth clinical trial conducted with patients divided into two groups: control group, receiving placebo and dexamethasone, and test group, receiving pregabalin and dexamethasone preoperatively. The evaluated variables were pain, measured by the Visual Analog Scale (VAS), anxiety assessed through the State-Trait Anxiety Inventory (STAI) questionnaires, hemodynamic parameters [Blood Pressure (BP), Heart Rate (HR), Oxygen Saturation (SpO)], and sedation assessed by the Ramsay scale.
RESULTS
A total of 31 patients were included. The test group exhibited a significant reduction in pain at 2,4,6,8,12,16,24, and 48 h after surgery and in the consumption of rescue analgesics. Anxiety, evaluated by STAI and VAS, showed a significant decrease in the test group (p < 0.001). Additionally, there was a significant decrease in BP at most of the assessed time points (p < 0.05) and a significant reduction in HR at two different time intervals (p = 0.003 and p = 0.009), indicating a positive effect in the test group. There was no significant difference in SpO between the groups. Sedation assessment revealed a significant difference at all time points favoring the test group (p < 0.05). There were no significant postoperative adverse effects.
CONCLUSIONS
Pregabalin coadministered with dexamethasone demonstrated significant efficacy in controlling postoperative pain and anxiety, as well as a sedative effect.
CLINICAL RELEVANCE
The coadministration of pregabalin with dexamethasone may presents potential advantages in both pain modulation and psychological well-being of individuals undergoing third molar surgeries.
TRIAL REGISTRATION
Brazilian Clinical Trials Registry (REBEC), No. RBR-378h6t6.
Topics: Humans; Pregabalin; Dexamethasone; Molar, Third; Male; Female; Pain, Postoperative; Pain Measurement; Analgesics; Tooth Extraction; Adult; Drug Therapy, Combination; Dental Anxiety; Treatment Outcome; Surveys and Questionnaires; Pain Management
PubMed: 38717697
DOI: 10.1007/s00784-024-05700-8 -
Expert Opinion on Drug Metabolism &... May 2024Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since... (Review)
Review
INTRODUCTION
Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023.
AREAS COVERED
Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC.
EXPERT OPINION
Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to and findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.
Topics: Humans; Stroke; Anticonvulsants; Drug Interactions; Anticoagulants; Atrial Fibrillation; Administration, Oral; Secondary Prevention; Hemorrhage; Venous Thromboembolism; Primary Prevention; Animals
PubMed: 38712571
DOI: 10.1080/17425255.2024.2352466 -
Bioinformation 2024Epileptic seizures are directly linked with an anomalous influx of extracellular calcium or sodium anions through voltage-gated channels disturb the chemical and...
Epileptic seizures are directly linked with an anomalous influx of extracellular calcium or sodium anions through voltage-gated channels disturb the chemical and electrical gradients, resulting in seizures or jerking moments. Voltage-gated calcium channel (VGCC) subunit α2δ-1 is the binding site for gabapentinoids used to treat epilepsy and neuropathic pain. However, this class of drugs showed severe side effects associated with CNS and respiratory depression. Hence, we screened a total of 2583 phytochemicals from the Comprehensive Marine Natural Products Database for their drug likeliness and pharmacokinetics (ADME/T) properties. The selected phytochemicals were docked with the VGCC α2δ-1 protein target and the marketed AED Pregabalin is used as standard. The docking results helped to select 45 docked compounds with better binding affinity, among which Acanthiline A showed the maximum binding affinity with the binding energy of -11.9 kcal/mol, thus reflecting its potential anti-epileptic activity.
PubMed: 38712007
DOI: 10.6026/973206300200271 -
Journal of Feline Medicine and Surgery May 2024Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a... (Review)
Review
Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.
Topics: Cats; Animals; Neuralgia; Cat Diseases; Pain Management; Analgesics; Combined Modality Therapy
PubMed: 38710218
DOI: 10.1177/1098612X241246518 -
Tierarztliche Praxis. Ausgabe K,... Apr 2024In 2023, 2 novel pharmaceutical agents for small animals were released on the German market: the structural but non-functional analog of the inhibitory neurotransmitter...
In 2023, 2 novel pharmaceutical agents for small animals were released on the German market: the structural but non-functional analog of the inhibitory neurotransmitter gamma-aminobutyric acid pregabalin with an anxiolytic active component and the dopamine agonist ropinirole in form of eye drops to induce vomiting. Two established active veterinary pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was additionally approved for horses, dogs and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (dexamethasone) in a novel pharmaceutical formulation, one drug with a new route of administration (hydrocortisone aceponate), one drug with a new content of the active ingredient (firocoxib) as well as one veterinary drug with a new combination of active ingredients in a novel pharmaceutical formulation (gentamicin+mometasone+posaconazole). Furthermore, one combination of active ingredients (diprophylline+heptaminol) is available on the market for small animals again.
Topics: Animals; Veterinary Drugs; Dogs; Cats; Horses; Germany; Rabbits
PubMed: 38701806
DOI: 10.1055/a-2291-7019