The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes.

OBJECTIVE: To study the effects of a topically applied prostaglandin F2 alpha analogue, PhXA41 (Latanoprost; 13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-isopropyl ester), on aqueous dynamics in the human eye. DESIGN: A randomized, double-masked study was carried out on 20 normal and 20 ocular hypertensive humans. One eye of each subject was treated with 0.006% PhXA41, while the contralateral eye received placebo twice daily for 5 days. MAIN OUTCOME: Compared with placebo, PhXA41 reduced intraocular pressure in both groups by approximately 20%. RESULTS: Tonographic facility of outflow was increased 24% in the normal group and 30% in the ocular hypertensive group; no changes were observed in the rates of aqueous humor flow in either group. The changes in tonographic facility were insufficient to fully explain the ocular hypotensive effect of the drug, suggesting that PhXA41 enhances outflow via the uveoscleral pathway. The suitability of fluorophotometry as a measure of flow was confirmed by three methods of comparing blood-aqueous barrier permeability: polarization of cameral fluorescence, intensity of backscattered light from the anterior chamber (flare), and cameral fluorescence after oral administration of fluorescein sodium. All of these measured parameters were normal, suggesting that this compound has no clinically significant effects on the blood-aqueous barrier or on the accuracy of fluorophotometry. PhXA41 was well tolerated in both groups. Only four of 40 subjects reported a transient foreign-body sensation, and only one of 40 subjects was observed to have greater than moderate conjunctival hyperemia. Most subjects had no symptoms and no measurable hyperemia. CONCLUSIONS: These results suggest that PhXA41 is a potentially useful ocular hypotensive agent that enhances the egress of aqueous humor via both major outflow pathways. The relative lack of ocular side effects in this study further suggests that this agent has promise for the treatment of chronic glaucoma.

Chronic diarrhea due to surreptitious use of bisacodyl: case reports and methods for detection.

Surreptitious abuse of laxatives is a common cause of severe chronic diarrhea. Standard laboratory screening studies of urine and stool specimens may identify phenolphthalein, diuretics, and magnesium-containing agents. An assay for bisacodyl, a commonly used over-the-counter laxative, however, is not included in routine screening tests. Herein we describe two patients with chronic watery diarrhea of large volume; analysis of stool and urine samples revealed that surreptitious use of bisacodyl was the cause. In one patient, nonspecific inflammatory changes of the colonic mucosa were noted on biopsy, and fecal leukocytes were detected in both patients. In a prospective study of eight patients who received bisacodyl as part of a preparation for colonoscopy, we analyzed serial urine samples for bisacodyl diphenol during a 48-hour period. This metabolite was found in seven of eight hydrolyzed urine samples obtained 12 hours after oral administration of bisacodyl but not in samples obtained 24 and 48 hours after ingestion of the laxative. We recommend that urinalysis and, in some cases, stool analysis for bisacodyl should be considered in the diagnostic assessment for surreptitious use of laxatives.

Effects of exercise conditioning on aqueous humor flow.

Twenty-four subjects were studied to determine the effect of a 12-week program of aerobic exercise on the rate of daytime aqueous humor flow. Exercise increased the maximum oxygen consumption from 36 +/- 1.6 (mean +/- SE) to 40 +/- 2.2 ml/kg/min. No changes in resting intraocular pressure (12.4 +/- 0.44 before and 12.2 +/- 0.36 mm Hg after) or resting aqueous flow (3.03 +/- 0.11 before and 3.06 +/- 0.13 mul/min after) were observed. We conclude that a moderate and short-term program of aerobic exercise conditioning does not have a clinically significant effect on the resting rate of aqueous humor flow in young, healthy human subjects.

Intravenous epinephrine stimulates aqueous formation in the human eye.

An experiment was done to determine if intravenously administered epinephrine would stimulate the rate of aqueous humor flow in sleeping human subjects. Twenty normal volunteers participated in a double-masked randomized placebo-controlled study. The rate of aqueous humor flow was measured by the rate of clearance of topically applied fluorescein. Measurements were made on two separate nights while the subjects slept, once during a placebo infusion and again during an intravenous infusion of epinephrine (rate, 1 microgram/hr; a rate calculated to be threefold the basal adrenal secretion in supine sedentary human subjects). Compared with placebo, epinephrine infusion had no effect on the blood pressure of sleeping subjects, increased the heart rate by 10%, and increased aqueous flow by 27%. Systolic blood pressure was 112 +/- 9 mmHg (mean +/- standard deviation) during placebo infusion and 114 +/- 13 during epinephrine infusion. The heart rate was 60 +/- 10 beats/min during placebo and 67 +/- 14 during epinephrine infusion (P = 0.011). Aqueous flow was 1.11 +/- 0.51 microliters/min during placebo and 1.42 +/- 0.52 during epinephrine infusion (P = 0.016). It was concluded that adrenal medullary secretion can stimulate aqueous formation and may explain in part the circadian rhythm of aqueous flow.