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Biomedical subjects

R K Ferguson

Publications and source records attributed to R K Ferguson.

At least 55 records · Page 3Linked to original sources
PubMed1984

Relationship of morphine-induced miosis to plasma concentration in normal subjects.

The relationship between morphine plasma concentration and pupil diameter was evaluated 2-10 h following intravenous administration of morphine sulfate (10 mg). Seven healthy male volunteers received 10 mg of morphine intravenously following pretreatment for 4 d with either cimetidine (300 mg po four times a day) or placebo in a single blind, balanced crossover study. Pupil diameters were measured directly from contact prints using calipers and a photographed millimeter scale. Cimetidine pretreatment had no significant effect on pupil size either before or after morphine administration or on morphine pharmacokinetics. The relationship between morphine plasma concentration (2-10 h postdose) and pupil diameter was evaluated from the pooled data from both morphine treatment periods by perpendicular least-square regression. In each individual, a strong relationship existed between morphine plasma concentrations and pupil diameter (r = -0.76 to -0.91; p less than 0.05). Weaker correlations for both pupil diameter (r = -0.65; p less than 0.0001) and the absolute change in pupil diameter from baseline (r = 0.72; p less than 0.0001) for the grouped data probably reflect intersubject variation in morphine sensitivity. Thus, the miotic response to an intravenous dose of morphine varies in proportion to morphine plasma concentration.

Adult↗
PubMed1984

Influence of food on the bioavailability of enalapril.

In a randomized, two-period crossover study in 12 normal volunteers, serum and urine concentrations of the angiotensin-converting enzyme inhibitor enalapril and its active metabolite enalaprilat were determined following administration of a single 40-mg tablet of enalapril maleate administered both in the fasting state and with a standard breakfast. A 7-d interval separated the two treatment periods. Area under the serum concentration-time curves for enalaprilat and urinary recoveries for enalaprilat and total drug did not differ significantly between the fed and fasted conditions. The mean observed maximum serum concentration of enalaprilat was slightly higher for the fasting treatment, but the time to peak concentration was almost identical for the two treatments. Enalapril maleate is unlike the prototype angiotensin-converting enzyme inhibitor captopril in that a standard meal does not appear to influence absorption of this new drug.

Adult↗
PubMed1984

Clinical applications of angiotensin-converting enzyme inhibitors.

Although only recently introduced, angiotensin-converting enzyme inhibitors have been utilized to treat a wide variety of clinical disorders. Their uses to date, approved by the Food and Drug Administration, have been in the treatment of refractory hypertension and congestive heart failure. However, they have been evaluated with mixed results in numerous other conditions in which the renin-angiotensin-aldosterone system may play a role. Their current status in the treatment of hypertension, congestive heart failure, and these other conditions is reviewed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Hemodynamic and humoral responses to enalapril and nifedipine in the rat.

The hemodynamic and humoral effects of enalapril, an angiotensin converting enzyme (ACE) inhibitor, and nifedipine, a calcium-entry blocker, were evaluated in conscious spontaneously hypertensive rats (SHR). Rats received enalapril (5 mg/kg, po) or vehicle, followed in one hour by nifedipine (2.5 mg/kg, ip) or its vehicle. After treatment with enalapril alone, systolic blood pressure (BP) declined over a 3 hour period from 204 +/- 4 (mean +/- SE) to 168 +/- 6 mm Hg and remained suppressed for an additional 4 hours. Heart rate (HR) did not change. Plasma renin activity (PRA) increased approximately 9-fold and serum ACE was maximally inhibited. BP response to nifedipine was more rapid, greater in magnitude (-59 +/- 6 mm Hg) and shorter in duration; heart rate increased and remained elevated for 2.5 hours. PRA only rose two-fold. After the drugs in combination, BP declined as rapidly and to the same degree as after nifedipine and remained reduced for a longer duration. Treatment with enalapril attenuated the reflex tachycardia observed after nifedipine. These data suggest that coadministration of an ACE inhibitor and calcium-entry blocker may provide better blood pressure control than either drug class alone and at the same time prevent the reflex tachycardia frequently observed after nifedipine.

Animals↗
PubMed1984

Overview: the role of angiotensin-converting enzyme inhibitors in cardiovascular therapy.

Angiotensin-converting enzyme (ACE) inhibitors favorably modify control mechanisms that are disturbed in hypertension and congestive heart failure, principally, but perhaps not exclusively, through reduction in angiotensin II levels. Pharmacodynamic actions are vasodilation, increased sodium excretion, and lowering of blood pressure. Investigations with captopril and enalapril in the treatment of hypertension indicate efficacies comparable to each other and to current step 1 and 2 agents. Enalapril is more potent than captopril and has a longer duration of action. The hemodynamic mechanism of action is reduction in peripheral vascular resistance. Addition of a diuretic potentiates blood pressure lowering and proportion of patients responding. When used in congestive heart failure, ACE inhibitors exert a balanced vasodilator effect on arterial and venous beds and do not induce tachycardia or fluid retention. Cardiac output is increased whereas systemic vascular resistance, central pressures, and systemic blood pressure are reduced acutely and chronically. Although captopril is associated with certain side effects, possibly resulting from the sulfhydryl group in its structure, this profile has not been encountered thus far in clinical investigations with enalapril. The effects of ACE inhibitors on the natural histories of hypertension (independent of blood pressure lowering) and congestive heart failure are yet to be determined.

Aldosterone↗
PubMed1984

Initial evaluation of the non-sulfhydryl-containing converting enzyme inhibitor MK-521 in hypertensive humans.

MK-521 is a new orally active, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Single doses of 2.5, 5.0, 10.0, and 20.0 mg were administered to nine hypertensive patients alternating with placebo. All doses of MK-521 caused profound suppression of ACE activity for more than 24 h and decreased standing diastolic blood pressure for more than 12 h without changes in pulse rate. Although there was no further reduction in blood pressure with doses above 5.0 mg, the duration of action was prolonged for more than 24 h with the higher doses. Serum MK-521 concentrations increased with dosage, and ACE was inhibited maximally at concentrations above 10 ng/ml. In this initial study, MK-521 was well tolerated and proved to be a potent and long-acting antihypertensive agent.

Adult↗
PubMed1984

Calcium blockers in smooth-muscle disorders. Current status.

Calcium-entry blockers have proven efficacy in a variety of cardiovascular disorders. The effects of these agents on ionic calcium fluxes and, thus, on smooth-muscle contraction suggest that several noncardiac conditions involving smooth-muscle dysfunction may be managed with calcium antagonists. Beneficial therapeutic results have been reported in various forms of hypertension and Raynaud's phenomenon. The results of preliminary studies in treating pulmonary hypertension, cerebral arterial spasm, migraine headache, esophageal motility disorders, and myometrial hypercontractile states are encouraging. Carefully designed, large-scale and long-term clinical trials are needed to establish the therapeutic value of calcium-entry blockers in these disorders.

Animals↗
PubMed1983

Effect of intravenous carbenicillin, cefoxitin and cefamandole on ADP-induced platelet aggregation and shape change.

The effect of a large daily dose of i.v. carbenicillin, cefoxitin and cefamandole on platelet aggregation with adenosine diphosphate (ADP) and the effect of carbenicillin on ADP induced shape change were evaluated. Six volunteers received carbenicillin 100 mg/kg every 4 hours. Three of them also received cefoxitin 3 gm every 6 hours and cefamandole 2 gm every 4 hours. All treatments were separated by 14 days. Prior to treatment, as well as 1 and 24 hours after the last dose of antibiotic, citrated platelet-rich plasma was tested for the extent of aggregation at a series of ADP concentrations. As previously reported by several groups, carbenicillin decreased the sensitivity of platelets in their aggregation response to ADP. Thus, the concentration of ADP needed to obtain 50% of maximal aggregation response was increased 3.5 +/- 1.7 (S.D.) fold. In addition, when measured separately, the sensitivity of platelets in their shape change response to ADP was decreased to a similar degree. The concentration of ADP needed to produce 50% of maximal shape change response was 2.8 +/- 1.6 (S.D.) fold higher after carbenicillin treatment. The results are in accordance with previous in vitro studies suggesting that carbenicillin interferes with the initial phase of platelet activation. Cefoxitin and cefamandole had no apparent effect on platelet aggregation.

Adenosine Diphosphate↗
PubMed1983

Urinary excretion of prostacyclin and thromboxane A2 metabolites after angiotensin converting enzyme inhibition in hypertensive patients.

The contribution, if any, of various prostaglandins to the antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) is controversial. We studied the effect of the ACEI captopril (CAP) on the urinary excretion of 6-keto-PGF2 alpha (6-KF), the major metabolite of the vasodilatory prostaglandin, prostacyclin, and thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor TxA2, in 8 patients with essential hypertension after placebo, two weeks of CAP 25 mg t.i.d. alone, and the same dose of CAP in combination with hydrochlorothiazide (HCTZ) 50 mg/day. Mean 6-KF and TxB2 (nmol/8 hr post-dosing, respectively) did not differ significantly with any treatment; the mean ratio of 6-KF/TxB2 was also unchanged. Likewise, the excretion of these prostaglandins was also evaluated after placebo, the ACEI enalapril (ENA) (5 or 10 mg/day), and the combination of ENA and HCTZ in another group of 8 patients with essential hypertension. Mean 6-KF and TxB2 (nmol/24 hr post-dosing, respectively) showed no significant treatment-related differences; the mean ratio was again unchanged. No correlation existed between the magnitude of blood pressure responses with any treatment and either 6-KF or TxB2 excretion. Thus, the antihypertensive action of ACEI, alone or in combination with HCTZ, does not appear to involve alterations in these vasoactive prostaglandins.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Disposition of intravenous and intraperitoneal cefoxitin during chronic intermittent peritoneal dialysis.

The disposition of intravenous and intraperitoneal administered cefoxitin was evaluated in four males undergoing intermittent peritoneal dialysis. Each patient received 1 g of cefoxitin intravenously prior to an eight-hour dialysis; subsequently, one patient received another 1 g intravenous dose prior to an 18-hour dialysis while each of the other three patients had 100 mg of cefoxitin added to their eight hourly exchanges of dialysis fluid with 2 L per exchange. Serial blood, dialysate, and urine samples were collected and analyzed for cefoxitin by a microbiologic assay. Twenty-four hours after intravenous administration, serum cefoxitin concentrations were greater than 16 micrograms/mL (therapeutic breakpoint) in each patient. Mean cefoxitin dialysate concentrations averaged 7.8 +/- 3.8 micrograms/mL and were greater than 16 micrograms/mL in only 2 of 43 exchanges. After intraperitoneal administration, serum cefoxitin concentrations were highest after the eighth exchange (range 5.6 to 10.6 micrograms/mL). Thus, diffusion of cefoxitin across the placental membrane was not extensive. Dialysis removed only 10% to 20% of the intravenous dose.

Biological Assay↗