Long-term monitoring of the effects of thymoxamine hydrochloride tablets in the management of patients with Raynaud's disease

Aylward, Mansel; Bater, Penelope A.; Davies, D. E.; Dewland, Peter; Lewis, Peter; Maddock, J.

doi:10.1185/03007998209112378

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…Thymoxamine, an (XI receptor blocking agent, has been evaluated in RP also, [52] in a dosage of between 40 and 80mg 4 times daily. In a doubleblind, placebo-controlled, crossover study of patients with RP and other patients with chilblains, there did appear to be a decrease in the frequency of vasospastic attack.…”

Section: Vasodilatorsmentioning

confidence: 99%

“…In a doubleblind, placebo-controlled, crossover study of patients with RP and other patients with chilblains, there did appear to be a decrease in the frequency of vasospastic attack. However, this was a fairly small study containing only 41 patients.l 53 ] The drug appeared to perform better in an open study [52] and in a study in which objective blood flow monitoring was carried out. [54] The clinical benefits obtained from these small studies are, however, not strong enough to allow a firm recommendation to be made for the use of this compound in RP.…”

Section: Vasodilatorsmentioning

confidence: 99%

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Pharmacotherapy of Raynaudʼs Phenomenon

Belch

1996

Drugs

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Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help.

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Section: Vasodilatorsmentioning

confidence: 99%

Section: Vasodilatorsmentioning

confidence: 99%

Pharmacotherapy of Raynaudʼs Phenomenon

Belch

1996

Drugs

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“…Side effects are reported as less than with prazosin. 66 ' 67 More experience is needed with this agent; it is not available in the United States.…”

Section: Sympathofytic Agentsmentioning

confidence: 99%

Raynaud's phenomenon. An update.

Coffman

1991

Hypertension

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The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the a^-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of o>2-adrenergic receptors, increased levels of a^-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to a^-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of /J-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial. (Hypertension 1991;17:593-602)

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“…16 3 The explanation for this selective effect may be the unique 10:1 ratio of (al to a2 adrenoceptor activity.25 Three randomised control studies have shown that in patients with Raynaud's syndrome (mostly primary) thymoxamine not only gives subjective relief of symptoms but also abolishes the prolonged vasoconstriction after a cold stimulus as shown by measurement of blood velocity and skin temperatures by Doppler ultrasonography (P M Dewland et al, first international congress of clinical pharmacology and therapeutics, London 1980).25 38 At doses of 40 and 80 mg four times a day thymoxamine had no effect on blood pressure and side effects were rare. In view of the low incidence of side effects thymoxamine is at present the drug of choice in patients with primary Raynaud's syndrome who continue to get attacks of Raynaud's phenomenon despite giving up smoking and protecting themselves from cold.…”

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confidence: 99%