Raynaud s Phenomenon

DHPs are also used to treat vasospasms of peripheral arteries (e.g., Raynaud s phenomenon) and pulmonary hypertension. 

Raynaud s phenomenon is an exaggerated vascular-response to cold temperature or emotional stress. Clinical symptoms are sharply demarcated color-changes in the skin of the digits. The underlying disorder consists of abnormal vasoconstriction of digital arteries and cutaneous arterioles due to a local defect in normal vascular responses. 

Relcovaptan (SR-49059) is a selective, orally active V1aR antagonist that prevents pain of primary dysmenorrhea and inhibits preterm labour and could be useful in the treatment of Raynaud s phenomenon. The selective ViBR antagonist SSR149415 showed beneficial effects in the treatment of depression and anxiety in several animal models. 

Peripheral vasodilating drugs are chiefly used in the treatment of peripheral vascular diseases, such as arteriosclerosis obliterans, Raynaud s phenomenon, and spastic peripheral vascular disorders. Short-term use is rarely beneficial or permanent. Improvement, if it occurs, takes place gradually during weeks of therapy. 

Immunological abnormalities were reported in 23 adults in Woburn, Massachusetts, who were exposed to contaminated well water and who were family members of children with leukemia (Byers et al. 1988). These immunological abnormalities, tested for 5 years after well closure, included persistent lymphocytosis, increased numbers of T-lymphocytes, and depressed helper suppressor T-cell ratio. Auto-antibodies, particularly anti-nuclear antibodies, were detected in 11 of 23 adults tested. This study is limited by the possible bias in identifying risk factors for immunological abnormalities in a small, nonpopulation-based group identified by leukemia types. Other limitations of this study are described in Section 2.2.2.8. A study of 356 residents of Tucson, Arizona, who were exposed to trichloroethylene (6-500 ppb) and other chemicals in well water drawn from the Santa Cmz aquifer found increased frequencies of 10 systemic lupus erythematosus symptoms, 5 (arthritis, Raynaud s phenomenon, malar rash, skin lesions related to sun exposure, seizure or convulsions) of which were statistically significant (Kilbum and Warshaw 1992). 

Side effects from /1-blockade in the myocardium include bradycardia, AV conduction abnormalities, and acute heart failure. Blocking / -receptors in arteriolar smooth muscle may cause cold extremities and aggravate PAD or Raynaud s phenomenon because of decreased peripheral blood flow. 

Lagerkrist BA, Linderholm H, Nordberg GE Arsenic and Raynaud s phenomenon. Int Arch Occup Environ Health 60 361-364, 1988... 

Miscellaneous Facial swelling weight gain weight loss Raynaud s phenomenon speech disorder earache asthenia malaise fever death. 

Unlabeled Uses Treatment of CHF, chronic angina pectoris, Raynaud s phenomenon... 

Unlabeled Uses Treatment of pralidoxime-induced hypertension, arrhythmias, asthma, bladder instability, cardiac diseases, diabetes mellitus, erectile dysfunction, extravasation (dopamine and epinephrine), hyperhidrosis, myocardial infarction, Raynaud s phenomenon, surgery, sympathetic pain... 

The most common side effects are Raynaud s phenomenon with cold or even cyanotic distal extremities and digits, tiredness or weakness, bradycardia, and sexual impotence. Less common side effects are depression and dysphoria, bronchoconstriction, congestive heart failure, hallucinations, hypotension, vomiting or nausea, diarrhea, insomnia and nightmares, dizziness, and hypoglycemia. When due attention is paid to contraindications and the treatment is carefully monitored, the side effects of beta-blocker treatment are generally mild. 

Peripheral vascular disease In Raynaud s phenomenon, the drugs like prazosin, phenoxybenzamine produce a symptomatic relief. 

Adverse effects include nausea, vomiting, allergic reactions, fever, anaphylaxis, skin rash, Raynaud s phenomenon, stomatitis, pulmonary fibrosis, hyperpigmentation, renal and hepatic toxicity. 

Alpha-receptor-blocking drugs do not seem to be effective in the treatment of peripheral vascular occlusive disease characterized by morphologic changes that limit flow in the vessels. Occasionally, individuals with Raynaud s phenomenon and other conditions involving excessive reversible vasospasm in the peripheral circulation do benefit from prazosin or phenoxybenzamine, although calcium channel blockers may be preferable for most patients. 

Felodipine 15-20 11-16 Hypertension, Raynaud s phenomenon 5-10 mg orally once daily... 

Nifedipine 45-70 4 Angina, hypertension, Raynaud s phenomenon 3-10 mcg/kg IV 20-40 mg orally every 8 hours... 

In addition to angina, calcium channel blockers have well-documented efficacy in hypertension (see Chapter 11) and supraventricular tachyarrhythmias (see Chapter 14). They also show moderate efficacy in a variety of other conditions, including hypertrophic cardiomyopathy, migraine, and Raynaud s phenomenon. Nifedipine has some efficacy in preterm labor but is more toxic and not as effective as atosiban, an investigational oxytocin antagonist (see Chapter 17). 

A number of studies have investigated the use of PGE1 and PGI2 compounds in Raynaud s phenomenon and peripheral arterial disease. However, these studies are mostly small and uncontrolled, and these therapies do not have an established place in the treatment of this disease. 

Vinyl chloride causes liver cancer (hemangiosarcoma), narcosis, and Raynaud s phenomenon that comprises scleroderma, acro-osteolysis, and liver damage. The appearance of liver tumors is dose dependent but reaches a maximum at about 22% incidence. This seems to be due to the fact that the metabolism that is necessary for the carcinogenicity, is saturated, and/or inhibited by vinyl chloride. The toxic metabolites produced are the epoxide and chloroacetaldehyde. 

Katoh K, Kawai T, Narita M, Uemura J, Tani K, Okubo T. Use of prostaglandin El (lipo-PGEl) to treat Raynaud s phenomenon associated with connective tissue disease thermographic and subjective assessment. J Pharm Pharmacol 1992 44(5) 442-4. 

Langevitz P, Buskila D, Lee P, Urowitz MB. Treatment of refractory ischemic skin ulcers in patients with Raynaud s phenomenon with PGE1 infusions. J Rheumatol 1989 16(ll) 1433-5. 

Belch JJ, Madhok R, Shaw B, Leiberman P, Sturrock RD, Forbes CD. Double-blind trial of CL115,347, a transder-mally absorbed prostaglandin E2 analogue, in treatment of Raynaud s phenomenon. Lancet 1985 l(8439) 1180-3. 

The use of iloprost has been proposed in patients with systemic sclerosis, a disease that is often characterized by pulmonary hypertension and Raynaud s phenomenon. Three patients with systemic sclerosis who were treated with iloprost developed acute thrombotic events (3). In one case, intestinal infarction occurred 1 day after infusion of iloprost. In another patient the left kidney was not perfused 22 days after the last infusion of iloprost because of thrombosis of the left renal artery. The last patient, 9 months after the start of treatment with iloprost, and 5 days after the last infusion, had an anterolateral myocardial infarction. The authors commented that their observations did not allow them to conclude that there is a direct relation between infusion of iloprost and thrombotic events. However, they said that this possibility should be considered, and they suggested that risk factors for thromboembolism should be carefully evaluated in each patient with systemic sclerosis who is receiving iloprost. 

Four women with CREST syndrome or systemic sclerosis had pain and eventually contracture of the masseter muscles during infusion of iloprost for severe attacks of Raynaud s phenomenon (9). The adverse effect was quickly reversed by reducing the infusion rate. There were no electrocardiographic or cardiac enzyme changes. The mechanism of this effect is obscure. 

An oral formulation has been investigated in patients with Raynaud s phenomenon secondary to systemic sclerosis and in patients with severe ischemia due to Buerger s disease or to atherosclerosis. The first reports were not particularly encouraging in terms of efficacy. Tolerance is acceptable 6% of patients discontinued iloprost compared with 2% with placebo (10,11). 

Black CM, Halkier-Sorensen L, Belch JJ, Ullman S, Madhok R, Smit AJ, Banga JD, Watson HR. Oral iloprost in Raynaud s phenomenon secondary to systemic sclerosis a multicentre, placebo-controlled, dose-comparison study. Br J Rheumatol 1998 37(9) 952-60. 

Cyclofenil is a weak non-steroidal estrogen related to diethylstilbestrol. For a number of years it was used for inducing ovulation, but has lost favor more recently there have been studies of its possible effects in Raynaud s phenomenon secondary to scleroderma (1). 

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