The effect of sucralfate on serum lipids and lipoproteins in normal volunteers [corrected].

Sucralfate is used in the treatment and prophylaxis of peptic ulcer disease. One possible mechanism of action is the binding of bile acids. Because the absorption of dietary fat and cholesterol is dependent on the presence of bile acids in the small intestines, sucralfate therapy may produce changes in serum lipoprotein composition qualitatively similar to bile acid sequestrants, such as cholestyramine, which reduce serum cholesterol levels. Although changes in total serum cholesterol have not been reported in sucralfate efficacy studies, the effect of sucralfate on serum lipoprotein composition has not been specifically addressed. The purpose of this study was to prospectively examine the effect of sucralfate on serum lipids and lipoproteins in normal volunteers. Eight healthy volunteers (six men, two women) were recruited for this 10-week study. Drugs known to affect cholesterol levels were not permitted before or during the study. Diet composition during the study period was unaltered from before the study. Subjects took 1 g sucralfate orally 1 hour before meals and at bedtime (four times a day) for 8 weeks, followed by a 2-week washout period. Fasting blood samples were obtained at baseline and weekly, and were analyzed for serum total and HDL cholesterol and for triglycerides. Levels of LDL cholesterol were estimated. After eight weeks of sucralfate, HDL cholesterol increased from baseline by 2.5 mg/dL (6.6%, from 37.6 +/- 9.5 to 40.1 +/- 8.69 mg/dL), and LDL cholesterol decreased by 7.6 mg/dL (6.4%, from 134 +/- 28.1 to 125.4 +/- 34.1). Total cholesterol decreased by 3.5 mg/dL (1.8%, from 192.9 +/- 34.3 to 189.4 +/- 37.2 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous nitroglycerin on heparin dosage requirements in coronary artery disease.

Patients admitted to the coronary care unit who received both intravenous nitroglycerin and heparin were studied to evaluate heparin dosage requirements. Physicians ordered all nitroglycerin and heparin doses as well as coagulation studies without knowledge of this study. Activated partial thromboplastin time (APTT) values obtained during steady-state heparin administration were considered therapeutic if the ratio of APTT/APTT-baseline was > or = 1.5. Sixty patients with myocardial infarction or unstable angina were included in the study. The initial therapeutic heparin dose of 1,014 +/- 151 units/hour produced an APTT ratio of 2.0 +/- 0.5. At the time of the initial therapeutic dose, the nitroglycerin dose was 110 +/- 108 micrograms/min. There was a significant correlation between the initial therapeutic dose and both total (r = 0.56; p = 0.0001) and lean (r = 0.26; p < 0.05) body weight. Comparison of patients with nitroglycerin doses < and > or = 100 micrograms/min revealed a significant difference in the initial therapeutic dose (971 +/- 147 vs 1,077 +/- 136 U/hour, p < 0.01), but not the initial therapeutic dose standardized to total body weight (14.0 +/- 2.5 vs 13.5 +/- 2.7 U/kg/hour). Similarly, analysis of variance revealed a significant difference in the initial therapeutic dose (p < 0.05), but not the initial therapeutic dose standardized to weight among 5 different nitroglycerin dosage ranges (10 to 533 micrograms/min). Neither aspirin use, thrombolytic therapy nor decreasing or discontinuing the nitroglycerin dose significantly affected heparin requirements. Thus, contrary to prior reports, clinically significant heparin resistance induced by nitroglycerin was not found.

Comparison of the pharmacokinetics and electrocardiographic effects of sublingual and intravenous verapamil.

Using a dog model, a sublingual form of the free base of verapamil (SLV) was developed with the intent of avoiding stereoselective first-pass metabolism and the necessity of intravenous administration. Intravenous verapamil (IVV) 5 mg and SLV 40 mg or 60 mg were sequentially administered to seven healthy human volunteers. Electrocardiograms and serum concentrations were obtained before and periodically from 5 to 480 minutes after each dose. The time to peak serum concentration (mean +/- SD) was 77.6 +/- 38.1 minutes after SLV. Bioavailability of SLV was 58.2 +/- 36.9% compared to IVV. Verapamil half-lives after IVV and SLV were 2.83 +/- 0.93 and 2.28 +/- 0.45 hours (NS), respectively. In one subject, the time to peak effect was delayed and overall change in PR interval was minimum. In the remaining six subjects, the maximum percentage increases in PR interval after IVV and SLV were 20.6 +/- 6.4% and 14.8 +/- 5.5% (p less than 0.05), respectively. Times to peak increase in PR interval were 28.3 +/- 15.7 and 57.0 +/- 17.5 minutes after IVV and SLV (p less than 0.05), respectively. Analysis of plots of percentage change in PR interval versus serum concentration revealed a shift to the right and therefore, lesser effect of SLV than of IVV in six subjects. All seven subjects complained of oral numbness and bitter taste. In conclusion, SLV is inferior to IVV in terms of rate and extent of absorption and pharmacologic effect in delaying atrioventricular nodal conduction. Probably SLV has little clinical utility because of its slow onset and poor tolerance.

Antiplatelet agents in coronary artery disease.

Coronary artery disease pathophysiology and platelet physiology are summarized, and the use of antiplatelet drugs in coronary artery disease is reviewed. Aspirin, sulfinpyrazone, and most other nonsteroidal anti-inflammatory agents alter platelet function by inhibiting the activity of cyclooxygenase, an enzyme necessary for the production of prostaglandins. Drugs that inhibit thromboxane synthetase or antagonize thromboxane A2 at the receptor level are under investigation. Prostacyclin and dipyridamole inhibit platelet function by elevating the concentration of cyclic AMP in platelets, but proof of their efficacy is limited. Most clinical trials of antiplatelet drugs in coronary artery disease have been small and of short duration; many have demonstrated short-term benefits, but long-term benefits are less obvious. Retrospective studies of patients before initial myocardial infarction suggest that regular aspirin ingestion may reduce the occurrence of cardiovascular complications. In prospective trials, the benefit of aspirin therapy for primary prevention of coronary artery disease was balanced by an increased likelihood of stroke. For secondary--after initial infarction--prevention of cardiovascular complications, the administration of aspirin and other antiplatelet agents has consistently decreased the rate of nonfatal myocardial infarction, overall mortality, or both. In the Second International Study of Infarct Survival, patients treated with streptokinase plus aspirin showed the greatest reduction in mortality, while each drug alone was associated with significantly lower mortality than placebo. Aspirin may improve clinical outcome in patients with or without previous myocardial infarction or with unstable angina pectoris. The daily dose should not exceed 325 mg. Antiplatelet therapy should not be used in patients at high risk for bleeding.

The effect of oral cimetidine on total and unbound serum lidocaine concentrations in patients with suspected myocardial infarction.

In this study, we prospectively evaluated the effect of oral cimetidine on serum lidocaine concentrations in 6 patients with suspected myocardial infarction. Compared to baseline lidocaine levels, total lidocaine concentrations increased by 8.2 +/- 7.8% at 6 hours, 16.4 +/- 9.0% at 12 hours and 27.9 +/- 9.4% at 24 hours after two doses of oral cimetidine. Unbound lidocaine concentrations increased by 14.3 +/- 4.1% at 6 hours, and 18.3 +/- 10.3% at 24 hours after cimetidine. In patients with myocardial infarction (3), total lidocaine concentrations increased by 24.2 +/- 10.4%, whereas unbound lidocaine increased by 8.9 +/- 10.2% at 24 hours. Therefore, increases in total lidocaine concentrations after cimetidine administration were considerably less than those previously reported and empiric dosage reductions of lidocaine in patients receiving cimetidine may not be appropriate.