Raynaud Phenomenon Medication

  • Author: Heather Hansen-Dispenza, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Sep 22, 2011
 

Medication Summary

Secondary Raynaud phenomenon may require pharmacologic therapy. Drugs with clear evidence of benefit shown through randomized controlled trials include calcium channel blockers and the vasodilator, iloprost (oral and intravenous). Studies have failed to demonstrate strong evidence for the role of ACE inhibitors in Raynaud phenomenon.

A randomized controlled trial by Gliddon et al showed no significant difference in attack frequency or severity between quinapril and placebo.[21] High-quality, well-designed, randomized controlled trials are needed to study the effect of other pharmacotherapy. Drugs should be used to vasodilate the affected circulation with attention to maintenance of systemic blood pressure.

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Calcium channel blockers

Class Summary

These agents are used for vasodilation and possible antiplatelet effects. The dihydropyridine class of agents contains potent vasodilators and is the first line of treatment after nondrug therapy.

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Nifedipine (Adalat, Procardia, Nifediac CC, Nifedical XL)

 

Start with lowest dose available and titrate upward as tolerated. Result should be a diminution in the frequency or severity of attacks. Usually preparations that are not strong negative inotropes are preferred. ER dosage form is most commonly used. If this drug cannot be used, the alternative preparations (nicardipine, amlodipine, diltiazem) are worth considering.

On average, moderate reduction of up to 35% improvement can be expected.

Nifedipine among the dihydropyridines has been extensively studied; however, in the same category, felodipine, amlodipine, and isradipine seem to be equally effective.

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Nicardipine (Cardene, Cardene SR)

 

Used for vasodilatation and possible antiplatelet effects. Start with lowest dose available. Extended dose preparations and agents with fewer negative inotropic effects are preferred.

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Amlodipine (Norvasc)

 

Relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery. Benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. Can be used during pregnancy if clinically indicated.

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Diltiazem (Cardizem CD, Cardizem SR, Dilacor XR, Diltzac, Tiazac)

 

During depolarization, inhibits calcium ions from entering the slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Causes some vasodilatation but not as potently as nifedipine.

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Prostaglandins

Class Summary

Agents in this class have potent vasodilatory effects.

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Iloprost (Ventavis)

 

Synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. Indicated for pulmonary arterial hypertension (WHO Group I) in patients with NYHA class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.

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Epoprostenol (Flolan, Veletri)

 

Analogue of PGI2 has potent vasodilatory properties, immediate onset of action, and half-life of approximately 5 min. In addition to vasodilator properties, also contributes to inhibition of platelet aggregation and plays role in inhibition of smooth muscle proliferation.

Continuous chronic infusion should be administered through central venous catheter.

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Endothelin Antagonists

Class Summary

These agents inhibit vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 (ET-1) receptors ETA and ETB in endothelium and vascular smooth muscle.

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Bosentan (Tracleer)

 

Endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension in patients with WHO class III or IV symptoms to improve exercise ability and to decrease rate of clinical worsening. This leads to significant increase in cardiac index (CI) associated with significant reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP).

Recently, prevention of digital ulcers was demonstrated in a randomized prospective, placebo-controlled trial that involved 122 patients with scleroderma.

Case series also reported complete cessation of Raynaud symptoms in 4 patients.

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Angiotensin II receptor antagonists

Class Summary

These agents are used for vasodilation and for their possible antifibrotic and anti-inflammatory effects.

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Losartan (Cozaar)

 

Nonpeptide angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors. Does not affect the response to bradykinin and is less likely to be associated with cough and angioedema. For patients unable to tolerate ACE inhibitors. Less effective in patients with scleroderma than with primary Raynaud phenomenon. May modify some serum markers of vascular damage and possibly modulate some of the underlying tissue damage in scleroderma.

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Serotonin reuptake inhibitors

Class Summary

SSRIs do not have consistent evidence showing sustained benefit; however, they may be chosen if hemodynamic side effects develop with CCBs or prostacyclin analogues. Serotonin is a potent vasoconstrictor that is released from nerve endings and during platelet activation. Fluoxetine (20 mg) versus nifedipine (40 mg) in patients with primary and secondary Raynaud phenomenon showed that fluoxetine statistically improved the frequency and severity of Raynaud attacks, while nifedipine did not reach statistical significance. A better response was seen in patients with primary Raynaud disease versus patients with secondary Raynaud phenomenon.

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Fluoxetine (Prozac)

 

Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine.

May cause more gastrointestinal adverse effects than other SSRIs now currently available, which is the reason it is not recommended as a first choice. May be given as a liquid or a capsule.

May give as 1 dose or divided doses. Presence of food does not appreciably alter levels of the medication. May take up to 4-6 weeks to achieve steady state levels of the medication, as it has longest half-life (72 h).

Long half-life is both an advantage and a drawback. If it works well, an occasional missed dose is not a problem; if problems occur, eliminating all active metabolites takes a long time. The choice depends on adverse effects and drug interactions. Adverse effects of SSRIs seem to be quite idiosyncratic; thus, relatively few reasons exist to prefer one over another at this point if dosing is started at a conservative level and advanced as tolerated.

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Phosphodiesterase type 5 enzyme inhibitors

Class Summary

Agents in this class have potent vasodilatory effects.

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Sildenafil (Revatio)

 

Phosphodiesterases are a complex group of enzymes that help to tightly regulate the degradation of intracellular cyclic nucleotides. Intracellular responses to both NO and prostacyclin are mediated by the cyclic nucleotides cGMP and cyclic-AMP (cAMP) respectively. So, by bolstering the vasodilatory effect of both NO and prostacyclin, these agents may be useful in the treatment of Raynaud phenomenon.

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Vasodilators

Class Summary

These agents are used for their local vasodilatory effects. A new topical nitrate, MQX-503, has shown promising results in a large placebo-controlled study.

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Nitroglycerin IV (Nitro-Bid, Minitran, Nitro-Dur)

 

Decreases coronary vasospasm, which increases coronary blood flow. Also induces vessel dilatation, decreasing cardiac workload.

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Contributor Information and Disclosures
Author

Heather Hansen-Dispenza, MD  Rheumatology Fellow, University of Arizona College of Medicine

Heather Hansen-Dispenza, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

S Anita Narayanan, MD  Fellow in Rheumatology, University of Arizona College of Medicine

S Anita Narayanan, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Medical Association

Disclosure: Nothing to disclose.

Jeffrey R Lisse, MD, FACP  Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine

Jeffrey R Lisse, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Geriatrics Society, and Sigma Xi

Disclosure: Genentech Consulting fee Consulting; Centacor Consulting fee Consulting; Novartis Consulting fee Review panel membership

Mayra Oberto-Medina, DO  Fellow, Section of Rheumatology, University of Arizona

Disclosure: Nothing to disclose.

Specialty Editor Board

John Varga, MD  Professor, Department of Internal Medicine, Division of Rheumatology, Northwestern University

John Varga, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Central Society for Clinical Research, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elliot Goldberg, MD  Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

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A 9-year-old with Raynaud phenomenon. Notice the discoloration of the fingers.
Photo of a patient with Raynaud phenomenon that resulted from working with a jackhammer. Courtesy of the CDC.
 
 
 
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