cardiovascular-agents and Pain

Chronic venous disease (CVeD) is a highly prevalent condition in the general population, and it has a significant impact on quality of life. While it is usually manifested by obvious signs, such as varicose veins and venous ulcers, other symptoms of the disease are less specific. Among the other symptoms, which include heaviness, swelling, muscle cramps and restless legs, pain is the symptom that most frequently compels CVeD patients to seek medical aid. However, there is a substantial discrepancy between pain severity and clinically detectable signs of CVeD, questioned by several opposing studies. Further evaluation is needed to clarify this subject, and to analyse whether pain development predicts objective CVeD progression. General management of CVeD starts with advising lifestyle changes, such as lowering body mass index and treating comorbidities. However, the mainstay of treatment is compression therapy, with the additional use of pharmacological substances. Venoactive drugs proved to be the drugs of choice for symptom alleviation and slowing the progression of CVeD, with micronized purified flavonoid fraction being the most effective one. Interventional therapy is reserved for advanced stages of the disease.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Endovascular Procedures; Humans; Pain; Risk Assessment; Risk Factors; Risk Reduction Behavior; Stockings, Compression; Treatment Outcome; Varicose Veins; Venous Insufficiency

Chronic venous disease (CVD) is both prevalent and unavoidable in many people as a result of persistent or unalterable risk factors, the most important of which are advanced age, excess body weight, and family history. Given this inevitability, medical treatment is required to alleviate symptoms and slow disease progression. Venoactive drug therapy is emerging as a valuable treatment option for many CVD patients and micronized purified flavonoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available. Recent evidence from animal models of venous hypertension and from clinical trials, as well as from systematic reviews, shows that MPFF is effective at alleviating many of the most common symptoms of CVD including leg pain, leg heaviness, sensations of swelling, cramps, and functional discomfort. In addition, MPFF improves the clinical signs of redness, skin changes, and edema, and improves quality of life. Collectively, these findings support the strong recommendation for MPFF treatment found in the 2018 international guidelines for the management of CVD.Funding: Servier.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Diosmin; Humans; Male; Pain; Risk Factors; Varicose Veins; Venous Insufficiency

The main cause of pulmonary hypertension in newborn babies results from the failure of the pulmonary circulation to dilate at birth, termed 'persistent pulmonary hypertension of the newborn' (PPHN). This syndrome is characterized by sustained elevation of pulmonary vascular resistance, causing extrapulmonary right-to-left shunting of blood across the ductus arteriosus and foramen ovale and severe hypoxaemia. It can also lead to life-threatening circulatory failure. There are many controversial and unresolved issues regarding the pathophysiology of PPHN, and these are discussed. PPHN is generally associated with factors such as congenital diaphragmatic hernia, birth asphyxia, sepsis, meconium aspiration and respiratory distress syndrome. However, the perinatal environment-exposure to nicotine and certain medications, maternal obesity and diabetes, epigenetics, painful stimuli and birth by Caesarean section-may also affect the maladaptation of the lung circulation at birth. In infants with PPHN, it is important to optimize circulatory function. Suggested management strategies for PPHN include: avoidance of environmental factors that worsen PPHN (e.g. noxious stimuli, lung overdistension); adequate lung recruitment and alveolar ventilation; inhaled nitric oxide (or sildenafil, if inhaled nitric oxide is not available); haemodynamic assessment; appropriate fluid and cardiovascular resuscitation and inotropic and vasoactive agents.

Topics: Adaptation, Physiological; Cardiovascular Agents; Cesarean Section; Environment; Extracorporeal Membrane Oxygenation; Female; Hemodynamics; Humans; Infant, Newborn; Maternal Exposure; Pain; Persistent Fetal Circulation Syndrome; Pregnancy; Pulmonary Circulation; Respiration, Artificial; Risk Factors; Stress, Physiological; Tobacco Smoke Pollution; Treatment Outcome

Voltage-gated calcium channels underlie a plethora of physiological functions in the cardiovascular and nervous systems. Calcium channels are considered important targets for the treatment of conditions such as absence epilepsy and hypertension, and significant efforts are increasing to discover novel calcium-channel modulators for the treatment of pain. An overview of advances in the development of calcium-channel therapeutics in the areas of pain, epilepsy and disorders associated with cardiovascular function are discussed.

Topics: Animals; Calcium Channel Blockers; Calcium Channels; Calcium Channels, T-Type; Cardiovascular Agents; Epilepsy; Humans; Mice; Mice, Knockout; Pain

Approximately 25,000 patients have been treated to date with the humanized anti-HER2 monoclonal antibody, Herceptin. This therapy has proved effective and well tolerated in patients with HER2-positive metastatic breast cancer; adverse events were generally infusion-related fever and chills of mild-to-moderate severity. Cardiotoxicity and infusion-related reactions emerged as the two main safety concerns with the use of Herceptin. Retrospective analysis revealed a higher incidence of heart failure when Herceptin was combined with anthracyclines than that expected with anthracyclines alone. Age, anthracycline exposure and cardiac risk factors were found to be predictors of cardiac adverse events. Patients experiencing cardiac dysfunction responded well to standard cardiac medication and the majority improved. Cardiac function should be monitored regularly and Herceptin should be discontinued if significant heart failure develops unless the benefits for an individual patient outweigh the risks. Of 25,000 patients, 74 (0.3%) were reported to have experienced a serious infusion-related reaction. The majority occurred during or shortly after the first infusion and were characterized by respiratory symptoms. Most patients were successfully treated; a total of 33 patients continued Herceptin therapy with no recurrence of infusion reactions. Although the benefit to risk ratio of Herceptin remains favorable, physicians must be vigilant and aggressive in managing cardiotoxicity and infusion-related reactions.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Chills; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; Female; Fever; Heart Diseases; Heart Failure; Humans; Immunotherapy; Infusions, Intravenous; Neoplasm Metastasis; Pain; Palliative Care; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Safety; Salvage Therapy; Trastuzumab; Treatment Outcome

The treatment of pain in the acute phase of a suspected acute myocardial infarction is often insufficient and has remained unchanged during recent years. The introduction of substances with a potential to limit the infarct size, such as thrombolysis and beta-blockade, have, however, decreased the requirement for narcotic analgesics (which are still the drugs of choice in many hospitals). Knowledge is still lacking regarding the duration of pain relief, the time between drug administration and pain relief, and optimal doses for various analgesics. Future research should aim at the development of drugs with a more rapid onset of action, less side effects and more complete analgesia.

Topics: Analgesics; Analgesics, Opioid; Cardiovascular Agents; Humans; Myocardial Infarction; Pain

The aim of this study was to compare the clinical acceptability of two dose regimens of micronized purified flavonoid fraction (MPFF): a single 1000 mg tablet once daily versus 500 mg twice daily in patients suffering from chronic venous disease (CVD).. In an international, randomized, double-blind, parallel-group study, 174 patients (Clinical Etiological Anatomic Pathophysiologic [CEAP] class C0s to C4) were randomized to MPFF 1000 mg once daily or MPFF 500 mg twice daily for 8 weeks. Adverse events (AEs) were recorded in patient-kept diaries (weeks 0, 2, 4, 8) and leg pain was assessed using a Visual Analog Scale (VAS).. No serious AEs occurred. A total of 30 treatment-emergent adverse events (EAE) were reported (15 in each group). Three treatment-EAE in the MPFF 1000 mg group (constipation, dyspepsia, allergic dermatitis) were considered by the investigator to be related to treatment. All were of mild intensity and resolved when treatment finished. Both MPFF regimens were associated with a significant reduction in leg pain score with a reduction of 4.21 cm for MPFF 1000 mg once daily (P<0.001) and 4.01 cm for MPFF 500 mg twice daily (P<0.001). The reduction in pain was noted after 2 weeks of treatment and continuously throughout the treatment.. Both treatment regimens were well tolerated and associated with similar reductions in leg pain after 8 weeks of treatment. The new MPFF 1000 mg dose regimen has a similar safety profile to two MPFF 500 mg tablets with the advantage of one tablet per day and potential improved patient adherence.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Compounding; Female; Flavonoids; Humans; Male; Middle Aged; Pain; Pain Measurement; Russia; Serbia; Tablets; Time Factors; Treatment Outcome; Venous Insufficiency; Young Adult

Long-term nitrate treatment of stable angina is associated with side effects that can interfere with health-related quality of life (HRQoL) and medication adherence. The aim of the present study was to compare HRQoL and adherence to treatment in patients with stable angina undergoing nitrate withdrawal or maintenance.. This study is a randomized clinical trial. Patients were allocated to an intervention group (nitrate withdrawal followed by introduction of placebo) or a control group (nitrate maintenance). The assessments were made at baseline and 30 and 120 days using the Short Form Health Survey and the Seattle Angina Questionnaire. Treatment adherence was measured on the basis of the Morisky scale and pill count.. A total of 105 patients with stable angina were randomized for replacement of nitrate with placebo (n=51) and for maintenance of treatment with nitrate (n=54). After 4 months, Short Form Health Survey scores increased for bodily pain (P=0.005) and general health (P=0.004) in the nitrate maintenance group. Decreased Seattle Angina Questionnaire scores were also noted for physical limitations (P=0.039) and angina frequency (P=0.011) in the nitrate maintenance group. However, the effect size was small (≤0.44) when the intervention and control groups were compared. At the end of the study, adherence was significantly higher in the placebo group (P=0.041), but no difference was detected between the groups with the pill count method.. HRQoL was similar in patients with stable angina using nitrate regularly as compared with patients undergoing nitrate withdrawal. However, adherence to treatment was lower in nitrate users according to the Morisky scale.

Topics: Aged; Angina, Stable; Cardiovascular Agents; Female; Humans; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Nitrates; Pain; Quality of Life; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time; Treatment Outcome

Pain is one of the major symptoms of the osteoarthritis (OA). The objective of the study was to evaluate impact of combined therapy with diclofenac, aescin and original glucosamine sulfate on pain severity in patients with OA of different localizations in real life clinical settings in Russia and Ukraine.. Design--prospective, non-controlled, before and after post-marketing study. Study was performed in 38 cities across Russia and Ukraine in 2012. Registered anti-inflammatory and symptomatic slow acting drugs were used according to the registered indications and dosages. In Russian sites combined therapy A using diclofenac ("Dorosan" formulation, Rottapharm S.p.A., aerosole 1%, 3-4 times/day) for two weeks, original glucosamine sulfate ("Dona" formulation, Rottapharm S.p.A.) intramuscular (ampule 200 mg/ml, 2 ml 3 times/week) for 4 weeks and per os (powder 1500 mg, once/day) for 8 weeks was used. In Ukraine sites (scheme B) diclofenac was substituted with topical aescin ("Reparil-Gel" formulation, Madaus AG, tube 400 mg, 2-3 times/day) anti-inflammatory product. Physicians were free to change therapy and study organizers had no impact on prescribing and management practice. Patients with OA of different localizations were included into the study. Pain severity was assessed using numeric rating scale. Total duration of the study was 8 weeks. Questionnaires were distributed to patients via physician out-patient offices. The only endpoint was the difference in median pain severity at the end of the study compared with the baseline level.. In total 4931 patients were included into the study (mean age 57 +/- 12 years, 75% were females). Scheme A was used in 3956 patients and scheme B in 975 patients. The median pain severity decreased from 0.7 at the baseline (interquartile range +/- 0.2) to 0.2 (interquartile range +/- 0.2) after 8 weeks of the study in both treatment regimens (p < 0.001). Limitations of the study include absence of the control group, collection of the questionnaires from physician offices, rather than directly from patients, limited range of clinical data collected and use of single instrument to assess pain severity.. Post-marketing study of combined therapy of OA of different localizations using diclofenac, aescin and original glucosamine sulfate in Russia and Ukraine demonstrated decrease of the pain severity, assessed by numeric rating scale, after 8 weeks of the treatment.

Topics: Aged; Anti-Inflammatory Agents; Cardiovascular Agents; Diclofenac; Drug Therapy, Combination; Escin; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Prospective Studies; Russia; Treatment Outcome; Ukraine

The aim of this study was to investigate the effect of a red-vine-leaf extract (AS195, Antistax(®), Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany) on the volume of the leg and clinical symptoms in patients with chronic venous insufficiency (CVI).. A multicentre, randomised, double-blind and placebo-controlled study was carried out with 720 mg AS195 per day over 12 weeks in CVI patients (CEAP Grades 3-4a) and moderate-to-severe clinical symptoms. Efficacy endpoints were changes in limb volume determined by water displacement volumetry, clinical CVI symptoms assessed on a 10-cm visual analogue scale and global efficacy evaluations.. The full-analysis set included 248 patients (placebo: n = 122; AS195: n = 126). After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA). The standardised effect size of 0.28 for volume reduction indicates a clinically relevant effect. On Day 84, the symptom of 'pain in the legs' assessed by visual analogue scale decreased in the AS195 group compared with the placebo group: mean difference -6.6 SD 3.3 mm (95% CI: -13.1,-0.1; p = 0.047). Other symptoms showed no significant change. The tolerability of AS195 was similar to that of placebo.. AS195 treatment for 84 days resulted in an approximately 20 ml reduction of limb volume in the active treatment group compared with the placebo group. Patients reported subjective improvement following treatment with AS195 compared with placebo. However, patients' overall rating of efficacy did not correlate well with measured reductions in limb volume.. ClinicalTrials.gov NCT00855179.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Edema; Female; Germany; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebo Effect; Plant Extracts; Plant Leaves; Quercetin; Tablets; Time Factors; Treatment Outcome; Venous Insufficiency; Vitis; Young Adult

Atherosclerotic peripheral arterial disease is a major health problem in the western world, often manifested as intermittent claudication, affecting 10-20% males above 60 years. Ischemic complications can lead to rest pain, ulceration and gangrene. The treatment of choice for critical limb ischemia (CLI) is vascular reconstruction or endovascular interventions. Medical management with vasodilator antiplatelet prostaglandins, could be considered in patients unsuitable for surgery. Long term follow-up on previous prostaglandin studies has been insufficient to evaluate amputation rates. Hence this study evaluated safety and longer term efficacy of taprostene sodium, a prostacyclin (PGI2) analogue in CLI. The aim of this study was to determine whether Taprostene sodium, a PGI2 analogue, was a safe and effective treatment for CLI.. This paper reports the data from the Scottish-Finnish-Swedish PARTNER Study Group which consisted of a double-blind placebo controlled multi-centre study evaluating Taprostene compared to placebo. The primary endpoints were pain relief and early ulcer healing response at the end of the four week infusion phase and amputation at six months follow-up. The patients were randomly allocated to receive taprostene or placebo in a two to one randomization of active versus placebo. A total of 111 patients with CLI were recruited. Taprostene was given twice a day over two 2 hour periods for four weeks. The early response was evaluated at the end of the four week infusion phase. In patients with rest pain without ulceration, a positive response was complete pain relief without any requirement for analgesic therapy. However in patients with ulceration, a positive response was defined as a decrease in the ulcer size by >30%. Amputation scores were compared at the end of the 6 months follow-up period for all participants.. Seventy-four patients received taprostene and 37 placebo. Overall, 61 male patients were enrolled in the study along with 50 females with 11% more women in the taprostene (active) group. For both patients with and without ulcers there was no statistically significant difference noted in the early response between those receiving taprostene and those receiving placebo infusion. The percentage of patients without any amputations was 43% in the taprostene group compared to 38% in the control group at the end of six months; however, these results were not statistically significant.. Although a reasonable number of patients enrolled in the study it has not been possible to demonstrate any statistically significant benefit of taprostene over placebo. This may be due to more patients with risk factors for peripheral artery disease (PAD) such as hypertension, diabetes mellitus and cigarette smoking in the actively treated group and also due the increased number of women in the active group who are known to generally respond less favourably to antiplatelet agents.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Analgesics; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Double-Blind Method; Drug Administration Schedule; Epoprostenol; Europe; Female; Humans; Infusions, Parenteral; Ischemia; Limb Salvage; Lower Extremity; Male; Pain; Pain Measurement; Placebo Effect; Time Factors; Treatment Outcome; Wound Healing

To evaluate changes on venous diameter and perimeter of lower limbs in chronic venous disorder (CVD) patients after different clinical treatments for four weeks.. Fifty-two female patients classified as C2,s or C2,3,s (CEAP classification) were allocated consecutively in three groups: Cirkan (40 mg of the root extract of Ruscus aculeatus + 100 mg of flavonoid hesperidine methylchalcone + 200 mg of vitamin C per pill); elastic compression stockings (ECS) and no treatment (NT). Diameters were determined by duplex ultrasound and perimeter with Leg-O-Meter.. After treatment, Cirkan significantly decreased popliteal vein and great saphenous vein (GSV) diameters bilaterally and ECS decreased popliteal vein diameter bilaterally and GSV and varices only on the left limb. Perimeters changed only with ECS. Clinical scores changed between Cirkan x NT and ECS x Cirkan. Disability score varied for ECS x NT and Cirkan x NT. chi2 test detected different distribution frequency for C3 and C2 classes according to treatment: ECS (both limbs) and Cirkan (only left limb). Varices and anatomical scores did not change.. ECS emerges as the most effective clinical treatment tested but improvements with Cirkan on vein diameter and CEAP class were also observed. Clinical scores improved due to pain relief and edema reduction (ECS). These findings point to a positive effect of Cirkan, suggesting that venotonic drugs should be taken into account in the treatment of CVD.

Topics: Adult; Anthropometry; Ascorbic Acid; Brazil; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Chymotrypsin; Disability Evaluation; Drug Combinations; Female; Hesperidin; Humans; Lower Extremity; Middle Aged; Pain; Pain Measurement; Phytosterols; Popliteal Vein; Saphenous Vein; Stockings, Compression; Time Factors; Treatment Outcome; Trypsin; Ultrasonography, Doppler, Duplex; Vascular Diseases

The RELIEF study (Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [CVI]) is a prospective, controlled, multicenter, international study performed in patients with or without venous reflux. This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI. The European countries, the subject of this report, were represented by the Czech and Slovak Republics, Hungary, Poland, Russia, and Spain. The principal aims of the study were: 1. To validate the first quality-of-life scale specific to chronic venous insufficiency (CMVIQ) in different languages and to assess the evolution of quality of life in patients suffering from CVI, with or without venous reflux, treated with micronized purified flavonoid fraction (MPFF*) (1,000 mg/day). 2. To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography. 3. To assess the evolution of symptoms and signs with a specific emphasis on edema through validated Leg-O-Meter measurement (heaviness, pain, cramps, sensation of swelling, edema) in patients suffering from CVI and treated with MPFF, 1,000 mg/day, during 6 months. The first country-by-country statistical analysis and the European consolidated analysis are now available. The CIVIQ questionnaires adapted to each participating country have been validated with highly significant validity and reproducibility (p<0.0001). All dimensions have demonstrated a highly significant and evolving improvement during the study. The results show several interesting findings concerning the epidemiologic data and, of these, two were particularly interesting: - More than 50% of patients suffering from CVI (class 0 to 4 of the CEAP classification) were reflux-free, which means that they were suffering from functional CVI. Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months' treatment with MPFF; the number of patients in the more severe classes decreased to the benefit of the less severe classes. Symptoms such as pain, leg heaviness, sensation of swelling, and cramps were significantly improved (p=0.0001). This was associated with a significant decrease in edema, when present, measured by leg circumferences with the Leg-O-Meter (p=0.0001). In conclusion, the European results of the RELIEF study showe

Topics: Cardiovascular Agents; Chronic Disease; Diosmin; Edema; Female; Humans; Leg; Male; Middle Aged; Muscle Cramp; Pain; Photoplethysmography; Prospective Studies; Quality of Life; Regional Blood Flow; Reproducibility of Results; Sensation; Ultrasonography, Doppler; Venous Insufficiency

Topics: Adenosine Diphosphate; Blood Platelets; Cardiovascular Agents; Clinical Trials as Topic; Collagen; Epoprostenol; Humans; Iloprost; Male; Pain; Platelet Aggregation; Random Allocation; Vascular Diseases

The effects of iloprost, a chemically stable compound with prostacyclin mimetic activity, on exercise capacity and platelet aggregation were assessed in 24 patients with effort angina and proved critical (at least 70% diameter narrowing) coronary artery disease. Upright bicycle ergometer testing (25-W increments every 2 minutes) was performed during drug and placebo infusions using a crossover, randomized, single-blind protocol. Samples for measurements of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma were obtained in all patients before and during the study. Compared with placebo, intravenous iloprost consistently (p less than 0.001) prolonged exercise duration and time to onset of significant (0.1 mV) ST depression. Angina and ST depression occurred at a greater heart rate and rate-pressure product. Benefits were remarkable in some patients (67%) and not in others. Iloprost administration resulted in reduced platelet aggregation at peak exercise in all patients, whether they had consistent or little response to the drug. Thus, iloprost administration may improve exercise capacity in patients with stable exertional angina pectoris. Improvements are independent of changes in the major determinants of myocardial oxygen demand and associated with markedly reduced platelet aggregation, which may account for increased myocardial perfusion in patients with high sensitivity to coronary constriction.

Topics: Angina Pectoris; Cardiovascular Agents; Clinical Trials as Topic; Electrocardiography; Epoprostenol; Exercise Test; Female; Humans; Iloprost; Male; Middle Aged; Pain; Platelet Aggregation; Random Allocation

Recently, attention has been focused on the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the mechanism of and as a treatment target for neuropathic and inflammatory pain. Ivabradine, a blocker of HCN channels, was demonstrated to have an effect on neuropathic pain in an animal model. Therefore, in the present study, we evaluated the effect of ivabradine on inflammatory pain, and under the hypothesis that ivabradine can directly influence inflammatory responses, we investigated its effect in in vivo and in vitro studies.. After approval from our institution, we studied male Sprague-Dawley rats aged 8 weeks. Peripheral inflammation was induced by the subcutaneous injection of carrageenan into the hindpaw of rats. The paw-withdrawal threshold (pain threshold) was evaluated by applying mechanical stimulation to the injected site with von Frey filaments. Ivabradine was subcutaneously injected, combined with carrageenan, and its effect on the pain threshold was evaluated. In addition, we evaluated the effects of ivabradine on the accumulation of leukocytes and TNF-alpha expression in the injected area of rats. Furthermore, we investigated the effects of ivabradine on LPS-stimulated production of TNF-alpha in incubated mouse macrophage-like cells.. The addition of ivabradine to carrageenan increased the pain threshold lowered by carrageenan injection. Both lamotrigine and forskolin, activators of HCN channels, significantly reversed the inhibitory effect of ivabradine on the pain threshold. Ivabradine inhibited the carrageenan-induced accumulation of leukocytes and TNF-alpha expression in the injected area. Furthermore, ivabradine significantly inhibited LPS-stimulated production of TNF-alpha in the incubated cells.. The results of the present study demonstrated that locally injected ivabradine is effective against carrageenan-induced inflammatory pain via HCN channels. Its effect was considered to involve not only an action on peripheral nerves but also an anti-inflammatory effect.

Topics: Animals; Cardiovascular Agents; Carrageenan; Gene Expression Regulation; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Inflammation; Ivabradine; Male; Pain; Potassium Channels; Rats; Rats, Sprague-Dawley

Many oldest-old (> 80-years) with multimorbidity and polypharmacy are at high risk of inappropriate use of medication, but we know little about whether and how GPs would deprescribe, especially in the frail oldest-old. We aimed to determine whether, how, and why Swiss GPs deprescribe for this population.. GPs took an online survey that presented case-vignettes of a frail oldest-old patient with and without history of cardiovascular disease (CVD) and asked if they would deprescribe any of seven medications. We calculated percentages of GPs willing to deprescribe at least one medication in the case with CVD and compared these with the case without CVD using paired t-tests. We also included open-ended questions to capture reasons for deprescribing and asked which factors could influence their decision to deprescribe by asking for their agreement on a 5-point-Likert-scale.. Of the 282 GPs we invited, 157 (56%) responded: 73% were men; mean age was 56. In the case-vignette without CVD, 98% of GPs deprescribed at least one medication (usually cardiovascular preventive medications) stating it had no indication nor benefit. They would lower the dose or prescribe pain medication as needed to reduce side effects. Their response was much the same when the patient had a history of CVD. GPs reported they were influenced by 'risk' and 'benefit' of medications, 'quality of life', and 'life expectancy', and prioritized the patient's wishes and priorities when deprescribing.. Swiss GPs were willing to deprescribe cardiovascular preventive medication when it lacked indication but tended to retain pain medication. Developing tools for GPs to assist them in balancing the risks and benefits of medication in the context of patient values may improve deprescribing activities in practice.

Topics: Aged, 80 and over; Analgesics; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Deprescriptions; Female; Frail Elderly; General Practitioners; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Expectancy; Male; Middle Aged; Pain; Platelet Aggregation Inhibitors; Polypharmacy; Practice Patterns, Physicians'; Quality of Life; Risk Assessment; Surveys and Questionnaires; Switzerland

This study sought to examine the impact of an aggressive approach to anatomic screening and endovascular revascularization in a veterans administration population with critical limb ischemia (CLI) on the primary treatments received and overall clinical outcomes.. The baseline clinical and angiographic characteristics and clinical outcomes of the first consecutive fifty veterans who were referred for the evaluation and treatment of CLI using the strategy outlined were assessed by retrospective review of the computerized medical record and angiographic data.. Among the entire cohort, the primary treatments received were as follows--revascularization n = 44 (88%), primary amputation n = 1 (2%), medical treatment n = 3 (6%), and primary minor amputation n = 2 (4%). Endovascular revascularization was the dominant mode of revascularization (94%), with a procedural success rate of 91%. Repeat revascularization was required in 19% of patients who had an initially successful endovascular procedure. A total of eight deaths and four major amputations occurred in the entire cohort over a mean follow-up of 397 +/- 190 days. The 1-year Kaplan-Meier estimates for survival and amputation-free survival for the entire cohort were 90 and 81%, respectively. Resolution of rest pain or complete wound healing was achieved in 85% of patients at a mean of 157 +/-126 days.. An aggressive approach to anatomic screening and contemporary endovascular treatment of CLI resulted in a higher rate of revascularization as the primary treatment for CLI than previously reported, and was associated with high rates of overall and amputation-free survival.

Topics: Aged; Amputation, Surgical; Cardiovascular Agents; Critical Illness; Female; Hemodynamics; Humans; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Magnetic Resonance Angiography; Male; Mass Screening; Middle Aged; Pain; Pain Measurement; Reoperation; Retrospective Studies; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; United States; United States Department of Veterans Affairs; Vascular Surgical Procedures; Wound Healing

Topics: Amputation, Surgical; Cardiovascular Agents; Critical Illness; Hemodynamics; Humans; Ischemia; Lower Extremity; Magnetic Resonance Angiography; Mass Screening; Pain; Pain Measurement; Reoperation; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures; Wound Healing

Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic spontaneous neuronal activity has been implicated in the development and maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain. Previously, we documented that systemic administration of ZD7288, a specific blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief clinical manifestation of peripheral nerve injury; however, a role for I(h) in spontaneous pain has not been described. Here, in further rat studies, we report that systemic administration of ZD7288 reversed spontaneous pain induced by mild thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast, ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears to be in the skin since intraplantar (local) administration of ZD7288 completely suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous pain due to MTI. Immunohistochemical staining of plantar skin sections detected HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles and Merkel cells). Collectively, these data suggest that expression and modulation of I(h) in the peripheral nervous system, including specialized sensory structures, may play a significant role in sensory processing and contribute to spontaneous pain and tactile allodynia.

Topics: Acute Disease; Animals; Cardiovascular Agents; Chronic Disease; Cyclic Nucleotide-Gated Cation Channels; Disease Models, Animal; Hyperalgesia; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Male; Mechanoreceptors; Merkel Cells; Nociceptors; Pain; Peripheral Nerves; Potassium Channels; Pyrimidines; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Skin

We describe a man with chronic paroxysmal hemicrania, who remained free of headaches on indomethacin, 25 mg once or twice daily. However, in this case, in contrast to typical cases of paroxysmal hemicrania, the pain of the headaches was nonlateralized and was located in the centre of the forehead. The headaches were not associated with local autonomic symptoms or signs involving the eyes or nose. Initially, the pain of the headaches lasted for seconds only and was brought on by coughing.

Topics: Adult; Cardiovascular Agents; Cluster Headache; Diagnosis, Differential; Humans; Indomethacin; Male; Pain; Treatment Outcome; Vascular Headaches

Chromogranin A (CgA) is an acidic protein identified within a large variety of endocrine cells. Colocalized with catecholamines in chromaffin cells, CgA is a prohormone precursor of small biologically active peptides. Vasostatin (CgA 1-76) is the most conserved fragment of CgA and chromogranin A 47-66 peptide (CgA 47-66) possesses potent antimicrobial activities. The aim of this study was to test the hypothesis that CgA 47-66 may be involved in mechanisms modulating nociception. Thus, we used acetic acid (AA) which produces a delayed inflammatory response and episodes of abdominal writhing, a marker of pain, when injected intraperitoneally (i.p.) to rats. Administration (i.p.) of CgA 47-66 induced specific opposite dose-dependent effects depending on concentration. That is, CgA 47-66 below 0.5 mg/kg produced antinociceptive effects, whereas at 2 mg/kg it produced a marked pronociceptive effect. The latter effect was blocked by diltiazem and indomethacin. CgA 47-66-induced antinociceptive effects on AA-induced responses were reversed when the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 was i.p. injected to animals prior to AA and CgA 47-66 administration. The administration of i.p. calcitonin gene-related peptide (CGRP) or substance P (SP) evoked dose-dependent abdominal writhing; this effect was abolished when CgA 47-66 was injected. The present data suggest, for the first time, that a fragment of CgA, CgA 47-66, possesses potent antinociceptive effects at low doses. Although the mechanism triggered by this peptide is unknown, CRF receptors are likely to be involved.

Topics: Acetic Acid; Animals; Calcitonin Gene-Related Peptide; Cardiovascular Agents; Chromogranin A; Chromogranins; Corticotropin-Releasing Hormone; Diltiazem; Dose-Response Relationship, Drug; Indomethacin; Male; Pain; Pain Management; Peptide Fragments; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; Substance P

The sympathetic-adrenal and kallikrein-kinin systems were studied in 225 patients with various coronary heart diseases before and after therapy with lipoic acid (150 mg/day), tocopherol (100 mg/day), anaprilin (40 mg/day), prodectin (750 mg/day) or their combination. Myocardial and adrenal catecholamine levels were measured in experiments on animals exposed to emotional pain stress. Their levels were found to be affected by lipoic acid, tocopherol, obsidan or their combinations in the same doses, taking into account species specificity. Lipoic acid therapy for patients with coronary heart disease decreased epinephrine excretion, enhanced the elimination of vanillylmandelic acid and norepinephrine. Tocopherol lowered daily urinary epinephrine levels and increased the release of vanillylmandelic acid, without changing epinephrine excretion. Emotional pain stress resulted in myocardial epinephrine accumulation and adrenal norepinephrine in the animals. Lipoic acid prevented this accumulation, whereas tocopherol did not possess this effect.

Topics: Adolescent; Adrenal Glands; Adult; Aged; Angina Pectoris; Animals; Cardiovascular Agents; Drug Evaluation; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Kallikrein-Kinin System; Male; Middle Aged; Myocardial Ischemia; Neurotransmitter Agents; Pain; Rats; Stress, Psychological; Sympathetic Nervous System

The records of 268 patients were used to assess the effects of five disease/drug complexes on the number of postinsertion visits in complete denture wearers. The data were analyzed with SAS and BMDP computer packages. The results showed a statistically significant increase in the number of postinsertion visits in patients who had central nervous system or psychiatric disorders. Practitioners are alerted to consider the ergonomic implications at the outset of treatment.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Central Nervous System Agents; Central Nervous System Diseases; Chi-Square Distribution; Dental Care for Aged; Dental Care for Chronically Ill; Denture Retention; Denture, Complete; Diabetes Complications; Diabetes Mellitus; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Masticatory Muscles; Mental Disorders; Metabolic Diseases; Middle Aged; Mouth Diseases; Movement; Office Visits; Pain; Prosthesis Fitting; Respiratory Tract Diseases; Retrospective Studies; Xerostomia

Intraperitoneally (i.p.) administered iloprost produced a writhing response indicating nociception. This effect induced by 4 micrograms/kg iloprost was dose dependently protected by morphine with an ED50 (95% confidence limits) value of 0.039 (0.0018-0.067) mg/kg. On the other hand, indomethacin had no effect on iloprost-induced writhing. Thus, this effect of iloprost seems to be relatively more sensitive than other irritants-induced responses on determining the analgesic potency of narcotic drugs.

Topics: Animals; Cardiovascular Agents; Dose-Response Relationship, Drug; Epoprostenol; Iloprost; Injections, Intraperitoneal; Male; Mice; Morphine; Pain; Time Factors

Topics: Angina Pectoris; Cardiovascular Agents; Humans; Pain; Risk

Topics: Adult; Cardiovascular Agents; Diosmin; Edema; Female; Flavonoids; Humans; Male; Middle Aged; Muscle Cramp; Pain; Vascular Diseases

Topics: Cardiovascular Agents; Humans; Muscle Relaxants, Central; Muscle Spasticity; Pain; Parasympatholytics; Pharmacology; Spasm

Topics: Analgesics; Cardiovascular Agents; Drug Therapy; Muscle Relaxants, Central; Pain; Parasympatholytics; Urologic Diseases; Urology

Topics: Analgesia; Cardiovascular Agents; Dysmenorrhea; Female; Histamine H1 Antagonists; Humans; Muscle Relaxants, Central; Pain; Pain Management

Topics: Atropine; Cardiovascular Agents; Disease; Ergot Alkaloids; Humans; Oxytocics; Pain; Sacrum; Sciatica; Strophanthins

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Cardiovascular Agents; Muscle Relaxants, Central; Pain; Urinary Calculi; Urology

Topics: Analgesia; Cardiovascular Agents; Carisoprodol; Humans; Muscle Relaxants, Central; Pain; Pain Management

Topics: Cardiovascular Agents; Carisoprodol; Disease Management; Muscle Relaxants, Central; Pain; Temporomandibular Joint; Temporomandibular Joint Disorders

Topics: Cardiovascular Agents; Ergoloid Mesylates; Ergot Alkaloids; Osteoporosis; Pain

Topics: Anesthetics; Anesthetics, Local; Cardiovascular Agents; Humans; Pain; Peptic Ulcer

Topics: Cardiovascular Agents; Female; Humans; Labor, Obstetric; Muscle Relaxants, Central; Pain; Pain Management; Parasympatholytics; Pregnancy

Topics: Cardiovascular Agents; Disease; Humans; Muscle Relaxants, Central; Muscles; Muscular Diseases; Myalgia; Pain; Succinylcholine

Topics: Angina Pectoris; Cardiovascular Agents; Ergonovine; Ergot Alkaloids; Ethyl Chloride; Humans; Oxytocics; Pain

Topics: Cardiovascular Agents; Dihydroergotamine; Ergot Alkaloids; Female; Humans; Labor, Obstetric; Morphine; Oxytocics; Pain; Pain Management; Pregnancy

Topics: Cardiovascular Agents; Humans; Muscle Relaxants, Central; Pain; Poliomyelitis; Spasm