Repurposing cilostazol for Raynaud's phenomenon

2020 ◽  
Vol 27 ◽  
Author(s):  
Nehme El-Hachem ◽  
Manal M. Fardoun ◽  
Hasan Slika ◽  
Elias Baydoun ◽  
Ali H. Eid

: Raynaud's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesteraseIII, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of action of cilostazol serving to enhance blood perfusion in RP patients.

VASA ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 201-212 ◽  
Author(s):  
Birgit Linnemann ◽  
Matthias Erbe

Abstract. The primary goal of therapy is to reduce the frequency and intensity of Raynaud’s attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud’s phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient’s quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a secondary, possibly reversible process that is causing or aggravating the clinical symptoms.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aaron Douen ◽  
Jeremy Oh ◽  
Wesley Romney ◽  
Ryan Panetti ◽  
Prakash Ramdass ◽  
...  

Introduction: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well known for upregulating ACE2 receptors. SARS-Cov-2 (COVID-19) infection utilizes the ACE2 receptor for proliferation and infection of host cells. Hypothesis: We hypothesize that the use of ACEI/ARBs will lead to a higher mortality and hospitalization rate among COVID-19 infected patients. Methods: The electronic health database at a public hospital in New York City was queried retrospectively for patients 18 years and older with a positive test for COVID-19 between 3/1/2020 - 4/1/2021. We examined baseline characteristics including comorbidities and whether they were prescribed ACEI/ARBs versus other medications including beta-blockers, calcium channel blockers, thiazides, or hydralazine. We categorized patients based on ACEI/ARB. The primary outcomes were all-cause mortality and hospitalization. The secondary outcomes were acute kidney injury, ventricular arrhythmia, myocardial infarction, heart failure, and intubation. We adjusted for comorbidities using multivariate logistic regression. Results: We identified 23,068 patients positive for SARS-CoV-2; 1,385 on ACEI/ARBs and 21,683 not on ACE/ARBs. The mean age in years was 65.90 +- 14.35 (SEM 0.386) and 44.01+-16.76, (SEM 0.114) for ACEI/ARB and non-ACEI/ARB respectively (p<0.001). The incidence of all cause mortality and hospitalization rate were significantly greater in the ACEI/ARB group. However, when adjusted for comorbidities using multivariate logistic regression, OR for mortality was 0.41 (CI 0.32-0.52, p<0.001) and for hospitalization was 4.12 (CI 3.49-4.86 p<0.001). For the secondary outcomes, non-ACEI/ARB patients had significantly increased unadjusted odds of all outcomes (p<0.001), except for ventricular tachycardia (p<0.618) and intubation (p< 0.214). Conclusion: Patients in the ACEI/ARB group demonstrated significantly lower mortality and increased hospitalization rates. Increased hospitalization may be due to more comorbidities. These results highlight the importance of continuing the use of ACEI and ARBs in COVID-19 patients for treatment of comorbidities and cardioprotective effects.


Author(s):  
Santenna Chenchula ◽  
Rupesh Gupta ◽  
Balakrishnan S. ◽  
Akash Vishwe ◽  
Pushparaj Gour ◽  
...  

Background: There are many groups of drugs to decrease microalbuminuria like angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers and direct vasodilators. Among these, ACEI and ARBs are commonly used for this purpose. If side effects occur, ACEI are replaced with ARBs. Many ARBs have been studied for their effect on reducing microalbuminuria, but data on telmisartan with its additional unique properties are scarce in Indian population.Methods: This cross sectional observational study was carried out in a tertiary care centre. We first measured base line urine albumin levels in included patients, 3 months after treatment with telmisartan using ‘hemocue urine albumin analyser’. We collected and compared both baseline and after treatment data of microalbuminuria and analysed in descriptive statistics.Results: A total of 110 patients participated in this study; out of which 10 patients were excluded from the study because they were not available for follow up. As compared to baseline, urine albumin level decreased by 30.42% after 12 weeks treatment with telmisartan (P <0.001).Conclusions: Microalbuminuria is one of the leading cause of end stage renal disease and coronary heart diseases in diabetic hypertensive patients. Drugs like ACE inhibitors, Angiotensin receptor blockers, Calcium channel blockers and direct vasodilators are used to prevent these complications. In this present study, we concluded that telmisartan decreases urine albumin excretion around 30.42% from baseline after 12 weeks of treatment.


ESC CardioMed ◽  
2018 ◽  
pp. 180-184
Author(s):  
Stéphane Laurent

Antihypertensive and antianginal agents are differentially able to vasodilate small resistance arteries, large conducting arteries, and epicardial coronary arteries. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and alpha-adrenergic antagonists are not addressed here, since they are discussed in specific chapters. This chapter discusses the pharmacology of calcium channel blockers, nitrovasodilators, and direct-acting vasodilators. Dihydropyridines, such as nifedipine and amlodipine, are compared to the non-dihydropyridine agents verapamil and diltiazem. Organic nitrates, such as nitroglycerine and isosorbide dinitrate, are compared to inorganic nitrates, such as sodium nitroprusside. Molsidomine and nicorandil are also discussed. Finally, the pharmacology of direct-acting vasodilators focuses on minoxidil and hydralazine. Pharmacology of mechanisms of action is detailed to better understand therapeutic indications and side effects.


2019 ◽  
Vol 5 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Jan-Gerd Rademacher ◽  
Chris Wincup ◽  
Björn Tampe ◽  
Peter Korsten

Background: Systemic sclerosis is a rare autoimmune disease characterized by skin and organ fibrosis, and vasculopathy. Raynaud’s phenomenon is almost universally present in systemic sclerosis and can be the most debilitating symptom. Raynaud’s phenomenon may lead to the development of digital ulcers, potentially complicated by infection, tissue necrosis, and auto-amputation. Recommended treatments have variable efficacy. Methods: We report the case of a 30-year-old woman with diffuse systemic sclerosis suffering from severe Raynaud’s phenomenon and digital ulcers with digital tissue necrosis who was treated with combination therapy of an endothelin receptor antagonist and phosphodiesterase 5 inhibitor. In addition, we reviewed the literature on the topic. Results: Previous therapy with calcium-channel blockers, intravenous iloprost, and bosentan had all failed to control symptoms. We added sildenafil in combination with bosentan and observed a rapid and sustained treatment effect. Raynaud’s phenomenon severity, number of attacks, and attack duration decreased within 2 weeks of initiating treatment. Furthermore, this resulted in the healing of established digital ulcers. Conclusion: Our case report suggests that combination therapy may be a feasible treatment for the most severely affected and refractory patients. In our literature review, we found one retrospective study and three additional cases with similarly encouraging results.


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