Dextrothyroxine

Abstract: Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract: Niacin was one of the treatments compared in the Coronary Drug Project, a placebo-controlled, multicenter trial of lipid-lowering drugs in the secondary prevention of coronary heart disease. A total of 1119 men, aged 30–64 at entry, were randomized to niacin and 2789 to placebo by the end of recruitment in March 1969. Although side-effects interfered with adherence to the niacin regimen, it was the most effective agent in achieving cholesterol-lowering (10% overall); other agents in the trial were clofibrate, dextrothyroxine, and conjugated equine estrogens. At the scheduled conclusion of the trial in February 1975, the niacin-treated group exhibited a statistically significantly lower incidence of definite, non-fatal myocardial infarction (MI) than the placebo group. There was a trend toward improvement in the life-table mortality curve, but this was not statistically significant. In 1981 an extended follow-up was carried out concerning vital status for the 6008 men who were still alive at the end of treatment and active follow-up in the trial in 1975 (827 in the niacin group and 2008 in placebo groups). Vital status was determined for 99.1% of these men after a mean of 9 years from conclusion of the trial. In the group previously randomized to niacin, there were 69 (11%) fewer deaths than were expected on the basis of mortality in the placebo group. This difference was significant (z = - 3.52;P = 0.0004). The data also suggested that patients with a higher baseline cholesterol experienced greater benefit from niacin therapy, as did those with the best response to the drug. No such efficacy was noted in the other regimens, although the two estrogen groups and dextrothyroxine were discontinued before completion of the trial because of adverse effects. The extended follow-up did not provide data on the use of lipid-lowering agents or other treatment in members of either the niacin or the placebo group subsequent to 1975. It was concluded that the late benefit in the niacin group may have been the result of earlier benefit in reducing nonfatal reinfarction, the result of cholesterol lowering, or both.

Abstract: ANY new therapeutic agent brings with it the problem of identifying side effects that would not ordinarily be attributed to the particular drug. The effectiveness of dextrothyroxine in reducing serum cholesterol has been previously reported.1 , 2 Earlier, we observed that anticoagulated patients receiving this drug tended to require lower anticoagulant dosages (this has been reported by other observers3). It is the purpose of this work to investigate this effect of dextrothyroxine on the clotting mechanism. Methods A group of 14 patients, 7 males and 7 females, were studied. Eleven of these were selected from those attending the anticoagulant clinic of . . .