cardiovascular-agents and Raynaud-Disease

Raynaud phenomenon may be a primary disorder or associated with a variety of other autoimmune processes. Raynaud phenomenon produces digital vasospasm, which can lead to ischemia and ulceration. The treatment of Raynaud phenomenon has been difficult because multiple medical treatments have not provided uniform resolution of symptoms. Many patients have turned to surgery and sympathectomies for the treatment of unrelenting vasospasm. Botulinum toxin has been shown to be an effective alternative to surgery, with a single treatment being capable of resolving pain and healing ulcer. This article reviews the use of botulinum toxin for the treatment of Raynaud phenomenon.

Topics: Botulinum Toxins, Type A; Cardiovascular Agents; Hand; Humans; Ischemia; Neuromuscular Agents; Raynaud Disease; Vasoconstriction

Raynaud's phenomenon (RP) and digital ulcers (DU) are the clinical manifestations of vasculopathy in systemic sclerosis. Both interfere with hand function and hold the possibility of severe complications, thus adversely influencing patients' quality of life. Managing RP and DU is often a challenge for the treating physician, who has to establish a treatment plan based upon knowledge of the current therapeutic options. The first step is to differentiate primary from secondary RP, where combining history and physical examination with diagnostic modalities, such as nailfold capillaroscopy, aids in reaching the correct diagnosis. Next a wide range of treatment options is offered nowadays, starting from first-line agents, as calcium channel blockers, to the more targeted-ones, like endothelin receptor antagonists. Research and clinical experience with each agent are reviewed in the text, as well as the combinations that more recently gain field in the treatment of DU.

Topics: Bosentan; Calcium Channel Blockers; Cardiovascular Agents; Endothelin Receptor Antagonists; Enzyme Inhibitors; Fingers; Humans; Phosphodiesterase 5 Inhibitors; Prostaglandins I; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Vasodilator Agents

Here we give an overview over treatment recommendations propagated by the European League Against Rheumatism (EULAR), EULAR Scleroderma Trials and Research Group, the German Network for Systemic Sclerosis, the European Respiratory Society, and the International Society of Heart and Lung Transplantation. As response to immunosuppressant (IS) therapy is usually weaker in systematic sclerosis (SSc) compared to other connective tissue disorders IS should be considered with caution. To prevent scleroderma renal crisis steroid doses should not exceed 15 mg/d. The definitive role of a number of new immunosuppressant drugs and the effects of autologous stem cell transplantation in systemic clerosis (SSc) have to be elucidated. Prostanoids, especially iloprost, are widely used as intravenous formulas for the treatment of severe Raynaud's phenomenon (RP) and digital ulcers (DU). Calcium antagonists are of limited therapeutic value. Bosentan, an oral endothelin receptor antagonists (ETRA), was shown to prevent new DU, but failed to heal existing DU, while the oral phopshodiesterase inhibitor (PDI) Sildenafil reduces the occurrence of RP and might be effective in ulcer healing. Combination therapies of PDI with ETRA are currently evaluated. Therapy of pulmonary arterial hypertension (PAH) is usually started as oral monotherapy, frequently using an ETRA. When this first-line therapy is not tolerated ETRA is substituted by PDI. If treatment goals are not reached with monotherapy combinationtherapy is started, for example by adding a PDI to an existing ETRA. In general, treatment of PAH in patients with connective tissue disease follows the same algorithms as in idiopathic PAH.

Topics: Antihypertensive Agents; Cardiovascular Agents; Drug Therapy, Combination; Europe; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Practice Guidelines as Topic; Raynaud Disease; Scleroderma, Systemic; Societies, Medical; Stem Cell Transplantation; Treatment Outcome; Ulcer

Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.

Topics: Blood Vessels; Cardiovascular Agents; Fibrosis; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Inflammation; Kidney Diseases; Lung Diseases, Interstitial; Raynaud Disease; Scleroderma, Systemic; Skin; Transforming Growth Factor beta; Treatment Outcome

In Raynaud's phenomenon few new medical treatment options have become available in recent years, but the merits and demerits of drugs already longer available have been established more firmly. Calcium antagonists remain the treatment of first choice even despite their frequent side effects. Prostacyclin analogues are effective but oral formulations are still eagerly awaited. In PAOD attention is shifting from the often disappointing medical treatment of symptoms to possible secondary prevention. Except for the effects of some prostanoids little clinical benefit is obtained from vasodilators and rheologically active drugs. Attempts to influence skeletal muscle metabolism with carnitine-analogues like 1-carnitine are interesting but clinical benefit has not yet been proven. In the next few years results of trials with lipid-lowering drugs to stop progression of atherosclerotic lesions will become available.

Topics: Arterial Occlusive Diseases; Arteriosclerosis; Cardiovascular Agents; Humans; Raynaud Disease; Vasodilator Agents

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Epoprostenol; Female; Humans; Iloprost; Moxisylyte; Nifedipine; Raynaud Disease

Topics: Cardiovascular Agents; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Predictive Value of Tests; Raynaud Disease; Scleroderma, Systemic; Treatment Outcome; Ulcer

Topics: Cardiovascular Agents; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease

Topics: Arterial Occlusive Diseases; Arteriosclerosis Obliterans; Cardiovascular Agents; Humans; Ischemic Attack, Transient; Raynaud Disease

Thirteen patients with Raynaud's phenomenon secondary to systemic sclerosis received three 8-hour infusions of a synthetic prostacyclin analogue (Iloprost) on consecutive days and were followed-up over a period of 10 weeks during the winter of 1985/86. Six weeks after infusion, digital peripheral vascular resistance had fallen (P less than 0.05) and dicrotic notch proportion of pulse amplitude increased (P less than 0.05). Digital blood flow and pulse amplitude (measured by photoplethymography) were also increased but did not reach statistical significance. The trend of improvement in these blood flow parameters was still evident after 10 weeks. The number of cutaneous lesions (digital ulcers, etc) fell from 26 lesions before infusion to only 7 lesions by the end of the study, confirming the subjective improvement reported by the patients.

Topics: Adult; Cardiovascular Agents; Epoprostenol; Female; Fingers; Humans; Iloprost; Infusions, Intravenous; Male; Microcirculation; Middle Aged; Raynaud Disease; Regional Blood Flow; Scleroderma, Systemic; Vascular Resistance

Topics: 1-Propanol; Arteriosclerosis Obliterans; Cardiovascular Agents; Diabetic Angiopathies; Geriatrics; Humans; Isoxsuprine; Muscle Relaxants, Central; Phenethylamines; Raynaud Disease; Thromboangiitis Obliterans; Vasodilator Agents

Topics: Arteriosclerosis Obliterans; Cardiovascular Agents; Drug Therapy; Humans; Raynaud Disease; Tolperisone; Vasodilator Agents