Frank A. Finnerty

The antihypertensive effects of an imidazoline compound

The antihypertensive properties of a new imidazoline compound, ST 155, were examined in man. Oral administration of 75 to 150 mcg. consistently produced an average fall of about 15 per cent in mean arterial pressure within one hour. Repeated administration was associated with drug resistance which was prevented by the simultaneous use of thiazide diuretics. The combination of ST 155 in a dosage of 450 mcg. with a diuretic in patients with moderately severe hypertension resulted in an average fall in mean arterial pressure of about 25 per cent. The only side effects were dryness of the mouth and sedation, whichdecreased after the first month of therapy.

Intravenous clonidine in hypertensive patients

Clonidine (Catapres), a new imidazoline derivative with antihypertensive properties, was administered parenterally to 20 hypertensive patients. Thirteen patients with stable hypertension received clonidine electively. After a brief pressor phase, the patients with stable hypertension had a good antihypertensive response (a 17% average reduction in mean arterial pressure from 139 ± 11 to 115 ± 12 mm Hg). In 7 patients with accelerated hypertension who received clonidine intravenously, the pressor phase was of greater magnitude, lasted for a longer period of time, and was not associated with an antihypertensive response. It is concluded that transferring drug‐response data from patients with stable hypertension to those in an accelerated phase and vice versa may give erroneous impressions. Since the major need for a parenteral antihypertensive drug is for the therapy of hypertensive crises, the usefulness of intravenous clonidine appears limited.

Hypertensive vascular disease: The long term effect of rapid repeated reductions of arterial pressure with diazoxide∗

Abstract The long term effect of repeated acute reductions of arterial pressure has been evaluated in 16 patients with severe hypertension who had become unresponsive to antihypertensive therapy. During a 20 day period, 300 mg. of diazoxide was administered intravenously and repeated on a daily basis as often as necessary to keep the arterial pressure more than 20 per cent below control levels. At the end of the 20 day period diazoxide had been successful in reducing the arterial pressure in 14 of 16 patients. In addition, retinopathy had cleared in 2, cardiac size significantly decreased in 4 and congestive heart failure had lessened in 4 and completely cleared in one patient. All 14 patients were then restarted on a combination of chlorthalidone and reserpine. Cardiovascular-renal function continued to improve with this therapy over a 30 month period in 7 patients. In the remaining 7 patients the addition of hydralazine or methyldopa administered in one-half the previous effective dose was needed to maintain the beneficial effect. Thirty months after the rapid reduction of arterial pressure, the average mean arterial pressure in the 14 patients was 123 + 6.7, compared to 112.5 ± 11.7 mm. Hg immediately after diazoxide. Retinopathy and congestive heart failure had cleared, and heart size was reduced in all patients. Since rapid reduction of arterial pressure with diazoxide was accomplished effectively, safely and in a short period of time, and since, at least in 14 of 16 patients studied here, beneficial effects were observed as long as 30 months it would seem: (1) that such aggressive therapy might be incorporated into the routine of treating patients with severe hypertension, and (2) the usefulness of such an approach might be evaluated in the therapy of patients with less severe types of hypertension.

Long Term Follow-Up of Aggressive Medical Therapy of Accelerated Hypertension With Azotemia:

Department of Medicine, Georgetown University School of Medicine and the Georgetown University Medical Division, District of Columbia General Hospital, Washington, D.C. With the development of potent antihypertensive agents, the therapy of . accelerated hypertension has changed markedly in the past decade. As recently as the mid 1960’s it was routinely taught that azotemic patients with hypertension should be treated conservatively and that if the blood urea nitrogen was greater than 60 mg/100 ml no antihypertensive therapy was indicated.’ It was not until 1967 that Woods and Blythe2 hypothesized that patients with malignant hypertension and azotemia died before healing of the

Preliminary Observations on the Value of Diazoxide Administered Intravenously in Man

become available, all of which reduce arterial pressure, enhance the effect of other antihypertensive agents and cause a prompt diuresis and natriuresis. The mode of their antihypertensive action is still obscure. Recent studies indicate that the immediate antihypertensive effects of the thiazides do not depend upon their saluretic or diuretic properties,’ while it is also agreed that after prolonged use of thiazides the fall in arterial pressure is due to other factors than natriuresis or reduction of plasma volume .2, 3 These and other findings4 led to a further exploration of the benzothiadiazine compounds in

Nonemergency use of slow infusions of diazoxide

Slow infusions of diazoxide were administered to 10 hypertensive patients who had stable, nonaccelerated hypertension. The 10‐min diazoxide infusion was associated with a 16% average reduction in arterial pressure, a 21% average increase in heart rate, a 16% average increase in cardiac output, and a 36% reduction in total peripheral resistance. These changes in hemodynamic parameters lasted for an average of 70 min. It was concluded that slow infusions of diazoxide produce a consistent and predictable antihypertensive effect in patients witli stable, nonaccelerated hypertension. Slow infusions of diazoxide may have a limited use in nonemergency situations where an abrupt change in arterial pressure is to be avoided and a parenteral antihypertensive agent is needed.

Canrenoate in normal man.

Canrenoate, which has mineralocorticoid blocking activity, was evaluated in 3 normal subiects. The drug was administered by intravenous iniection twice daily for 7 days after 3 days of placebo. Loss of body weight and changes in serum and urine electrolytes were consistent with mineralocorticoid blocking activity. Canrenoate did not appear to have any effect on arterial blood pressure or cardiac output. A small increase in resting heart rate was demonstrated in 2 of the 3 patients, but this was thought to be secondary to volume depletion due to a diuretic action. A transient cardiac arrhythmia was noted in one sub;ect and was unexplained on the basis of serum electrolytes or plasma drug level. The only advantage of canrenoate over spironolactone appeared to be the parenteral administration.

A simplified accurate method for detecting bacteriuria

Abstract The accuracy of detecting bacteriuria by a combination of the Griess nitrite and diphenylamine tests was compared with standard colony counting methods in 624 asymptomatic pregnant patients. The chemical procedures were performed on first morning voided urine and colony counts were performed on cleanly caught midstream urine samples. In each of the 564 urine samples which were Griess negative and diphenylamine positive, the colony count was negative; whereas, in each of the 7 which were Griess positive and diphenylamine negative the colony count was positive. The chemical combinations in the 53 remaining urine samples did not correlate with the bacteriologic findings. This combination of chemical tests separated the 624 patients into three distinct groups: 564 without bacteriuria, 7 with bacteriuria, and 53 uncertain. There were no false negative or false positive results. A 90 per cent reduction in work load resulted without fear of false negative results.

The treatment of severe essential hypertension.

An early article written to provide diagnosis and treatment guidelines for family physicians, this demonstrates the very limitedn options available for treating hypertension in 1950.

Sodium intake and furosemide administration in hypertensive patients with renal insufficiency.

The effects of various levels of sodium intake and loop diuretic (furosemide) administration upon arterial pressure and renal function were studied in 11 patients with impaired renal function and essential hypertension. The patients were hospitalized in a metabolic ward and continued taking their usual antihypertensive medications. After a stabilization period, all patients followed the following regiments for 5 to 7 days: period I, 20 mEq sodium diet without diuretic administration; period II, 80 mEq sodium diet and furosemide, 80 mg daily; and period III, 200 mEq sodium diet and furosemide, 240 mg daily. Supine diastolic pressure was lower (P is less than 0.05) during period II than during period I and both supine and standing systolic and diastolic pressures were significantly lower in period III than in period I (P is less than 0.01). No significant differences in the renal clearance of inulin were noted between any of the study periods. In patients with essential hypertension and impaired renal function, consumption of a moderate or liberal sodium diet combined with administration of a loop diuretic agent (furosemide) appears to result in better control of arterial pressure without significant changes in renal function than does strict sodium restriction without diuretic administration.