Sedative and physiological effects of brimonidine tartrate ophthalmic solution in healthy cats

Objective

To determine the effects of brimonidine tartrate ophthalmic solution on sedation, heart rate (HR), respiratory frequency (f_R), rectal temperature (RT) and noninvasive mean arterial pressure (MAP) in healthy cats.

Effects of Brimonidine Ingestion on Cardiovascular Responses and Renal Function in Conscious Dogs

The effects of brimonidine, an α₂-adrenoceptor agonist, on blood pressure, heart rate, respiratory rate, renal function and some blood parameters were investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2 mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The α₂-adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of 0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The results demonstrated that after administration of brimonidine, mean arterial blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups, respectively. Heart rate was decreased in a similar manner and both remained low at 5 h after brimonidine administration. Respiratory rate was decreased by 50%, while the electrocardiogram showed prolongation of the PR interval. Glomerular filtration rate (GFR) and effective renal blood flow were reduced when measured at 4 h after brimonidine ingestion in both groups, but the effect was more pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both LD and HD groups. The packed cell volume was decreased and hyperglycaemia was detected. Most of the effects can be reversed completely after administration of yohimbine. However, yohombine can restore GFR only partially. These data suggest that brimonidine caused cardiovascular and respiratory depression. The adverse effects of this drug can be antagonized by yohimbine, suggesting that these effects were mediated via the α₂-adrenoceptor.     

Effect of single and multiple doses of 0.2% brimonidine tartrate in the glaucomatous Beagle

The objective of this study was to evaluate the changes in intraocular pressure (IOP) in glaucomatous dogs after instillations of 0.2% brimonidine once, twice and three times daily in single day studies, and after twice and three times daily for 4 days in multiple dose studies. We studied eight Beagles with inherited primary open angle glaucoma. Applanation tonometry (IOP), pupil size (PS) and heart rate (HR) measurements were obtained at 8 am, 10 am, 1 pm, 3 pm and 5 pm. The studies were divided into: eight glaucoma dogs and five of the eight dogs that demonstrated greater response to 0.2% brimonidine. Single-dose drug studies are divided into placebo (0.5% methylcellulose), 0.2% brimonidine administered once daily (8 am); twice daily (8 am and noon); and three times daily (8 am, noon and 5 pm). The 5-day multiple-dose studies included: day 1, no drug; and 4 days, 0.2% brimonidine instillations either twice daily (8 am and 2 pm) or three times daily (8 am, 2 pm and 9 pm). Statistical comparisons between drug groups included control (nondrug) and treated (placebo/0.2% brimonidine) eyes for both single- and multiple-dose studies. The mean +/- SEM diurnal decrease in IOP in the eight glaucomatous Beagles for the control and placebo eyes were 3.4 +/- 4.7 and 5.4 +/- 2.8 mmHg, respectively. The mean +/- SEM diurnal decrease in IOP after 0.2% brimonidine once, twice and three times daily was 6.4 +/- 3.5, 8.0 +/- 6.1 and 9.8 +/- 8.1 mmHg, respectively; this trend was not significant statistically. Significant miosis occurred starting 2 h postinstillations, and the resultant mean +/- SD pupil size was 2.7 +/- 0.3 mm. A significant decrease in heart rate also occurred (12%). In the five most responsive dogs the changes in PS and HR during these studies were similar to the larger group, but significant decreases in IOP occurred at most measurement times. In the multiple-dose study with 0.2% brimonidine twice daily the mean +/- SEM decrease in IOP for day 1 to day 4 was 5.0 +/- 1.3, 5.7 +/- 1.3, 1.4 +/- 3.3 and 4.9 +/- 1.3 mmHg, respectively. When 0.2% brimonidine was instilled three times daily the mean +/- SEM diurnal IOP decrease was from day 1 to day 4 and was 0.75 +/- 1.3, 2.4 +/- 1.5, 1.2 +/- 2.7 and 1.4 +/- 1.8 mmHg, respectively. The mean change in pupil diameter was 1.3 +/- 0.5 mm. Decrease in HR averaged 22%. In the same single-dose studies with the five most responsive dogs, PS and HR were similar, but the decreases in IOP were significant at more measurement intervals. We conclude that 0.2% brimonidine produces a decrease in IOP in dogs, a statistically significant miosis, and a reduced heart rate (12-22%). However, because of the limited drug-induced ocular hypotension, brimonidine should be combined with other drugs when used for the glaucomas in the dog.