Hyperkalemia in diabetes mellitus. Effect of a triamterene-hydrochlorothiazide combination.

Hyperkalemia is known to occur with increased frequency in the patient with diabetes mellitus and in the elderly when agents that interfere with renal potassium excretion are employed, but the precise frequency has not been established. We employed data from a post-marketing surveillance trial following the introduction of a triamterene-hydrochlorothiazide (Maxzide) combination to estimate the frequency. In patients normokalemic at baseline, hyperkalemia developed with a frequency of 0.59% in 20,809 nondiabetics and in 1.08% of 922 diabetics. Hyperkalemia was threefold to fivefold more likely in those more than 60 years of age, and all of the excess hyperkalemia in diabetics occurred in the elderly. The severity of hyperkalemia was not influenced by the diabetes mellitus. Hypokalemia occurred with a frequency of about 5% and was not influenced by either age or diabetes. In patients who were hypokalemic prior to treatment, hypokalemia was corrected in more than two thirds and hyperkalemia occurred less frequently. Although hyperkalemia indeed occurs with increased frequency in the elderly diabetic when a potassium-sparing combination is employed, the frequency is not so great that such agents should be avoided routinely when their use could be beneficial. Renal function and serum potassium concentration should be assessed prior to instituting treatment and repeated within a few days and a few weeks thereafter in the patient at risk, especially when renal function is suspected, and in the elderly.

Postmarketing surveillance in 70,898 patients treated with a triamterene/hydrochlorothiazide combination (Maxzide)

A postmarketing surveillance study on triamterene 75 mg/hydrochlorothiazide 50 mg was conducted by the Philadelphia Association of Clinical Trials on 70,898 patients. These patients received either a whole table (71% of patients) or half tablet (25.2% of patients); 61.3% of all patients continued to take the same dose throughout the 4-week study. The most frequent adverse reactions were generally nonspecific and typical of therapy with a diuretic. The withdrawal rate due to adverse events was significantly lower (p less than 0.005) with the smaller (4.4%) than with the larger (5.6%) dosage. Although not statistically significant overall, reported adverse reactions also favored a lower dose. In general, adverse reactions occurred more frequently in those taking concomitant medications. No significant difference relating to dose was detected in the percentage of initially normokalemic patients who became hyper- or hypokalemic by the end of the study. Older patients tended to achieve goal blood pressure more frequently than did younger patients. These results suggest that the potential for the development of thiazide-induced hypokalemia and other adverse effects appears to be greatly reduced by the use of a potassium-sparing agent combined with a thiazide diuretic, without incurring a greatly increased risk of hyperkalemia and without sacrificing efficacy.

Sabin inactivated trivalent poliovirus vaccine: first clinical trial and seroimmunity survey.

The most widely used poliovaccine in the United States contains the three live attenuated strains originally produced by Sabin. An inactivated ("killed") formulation of this trivalent polio vaccine has now been prepared. Before testing this new vaccine, we assessed the poliovirus immune status of 39 healthy adult males between the ages of 20 and 44 years and found that 69% had detectable (titer greater than or equal to 1:4) neutralizing antibody to all three types of poliovirus, whereas 31% lacked antibody to 1 or more types even though they had a history of childhood polio immunization. Of interest, the lowest levels of neutralizing antibody were found among young adults in their late 20s, 2 of whom lacked antibody to all 3 polio types. When the Sabin inactivated trivalent poliovirus vaccine was initially administered to 12 seropositive volunteers, all responded with rising titers of neutralizing antibody that persisted for at least 18 months (range, 1:249 to 1:4948). The new vaccine was also given to a second group of 9 individuals with little or no detectable neutralizing antibody to at least one poliovirus type and again all vaccinees manifested a humoral immune response to poliovirus. Except for transient local tenderness at the injection site, no untoward reactions to immunization were observed. Thus, this Phase I study (1) confirmed earlier reports that titers of poliovirus antibody may decline to undetectable levels by early adulthood and (2) demonstrated that adults previously immunized with poliovirus vaccine responded rapidly to all 3 poliovirus types (within 7 days) upon reimmunization with Sabin inactivated trivalent vaccine whether or not there was preexisting detectable antibody.

Prostaglandin E2 analogue elicits renal and hormonal compensatory mechanisms in human hypertension.

Endogenous prostaglandin E2 appears to play an important role in cardiovascular homeostasis. When administered exogenously, it is a potent vasodilator, but the requirement for intravenous administration and its short duration of action have limited studies to its acute effects. A novel prostaglandin E2 analogue, CL 115347, can be administered transdermally on a long-term basis. The cardiovascular responses to the chronic administration of CL 115347 were studied in a double-blind, placebo-controlled trial in 26 subjects with essential hypertension (16 given drug, 10 placebo) maintained on a 100-mEq sodium diet. Administration of CL 115347 produced a fall in diastolic blood pressure of 7.8 +/- 1.3 mm Hg, compared with a 2.3 +/- 1.7 mm Hg fall in controls (p = 0.02), with no change in heart rate. The direct vascular effect of the drug was confirmed by attenuation of the vasoconstrictor response to angiotensin II infusion (13.4 +/- 3.1 vs 21 +/- 2 mm Hg at 3.0 ng/kg/min; p less than 0.05). However, the chronic blood pressure effect of CL 115347 was modest. Subjects receiving active drug showed significant compensatory increases in plasma renin, aldosterone, and norepinephrine levels accompanied by sodium retention and kaliuresis. In summary, chronic administration of this prostaglandin E2 analogue resulted in a modest decrease in blood pressure and antagonism of angiotensin II-mediated vasoconstriction. However, its effects were largely offset by compensatory increases in vasoconstrictor hormones and sodium retention.