Influência de fármacos no sistema-renina-angiotensina do globo ocular de cães hígidos: desenvolvimento farmacotécnico e avaliação clínica

Abstract

Glaucoma is a disease that causes more blindness in dogs and has no cure, only treatment. The difficulty in the drainage of aqueous humor (AH) results in an increase in intraocular pressure (IOP), representing a significant risk factor for the occurrence of this condition, leading to irreversible damage to the progressive loss of visual field and vision as a whole death of retinal ganglion cells (RGC), loss of axons in the optic nerve and excavation of the same. In addition to this, several mechanisms may contribute to the development and progression of this disease, for example, unbalances of the renin-angiotensin-system (RAS), and cardiovascular and renal diseases. The measurement of IOP and the examination of the fundus are the methods used to diagnose this condition. The treatment of choice is based on eye drops that stimulate drainage of HA and / or decrease their production resulting in IOP control; however in many cases the treatment does not attain the desired effect, culminating in blindness. In an attempt to change this therapeutic perspective, this study compared, in healthy and normotensive Beagle dogs, systemic and ocular action of three drugs: timolol maleate 0.5% (non-selective beta-blocker used in cases of glaucoma) , captopril 0.1% and 0.5% (ECA1 inhibitor never before studied in greater concentration in dogs) and aceturato of diminazene - DIZE 0.1% and 0.5% (endogenous activator of ACE2, never before researched in eyes canines). The latter two drugs were formulated for ophthalmic use for the reduction of IOP, since it is known about the existence of SARS eye level, and that they have been successfully administered systemically at reducing systemic arterial pressure (SAP). Thus, before and after treatment, 18 dogs underwent the Schirmer Tear Test (TLS1) and blood collection for measuring the concentration of angiotensin-converting enzyme (ECA1) serum. For three consecutive days before treatment and at three times (6h, 12h and 18h) all animals have gone through four exams, always following the same order: evaluation of pupil size, IOP measurement, measurement of HR and SAP. After obtaining the normal range, the animals had the left eye subjected to predetermined protocols initially with 1 drop every 12 hours, 7 days a lower concentration and, in the other seven days, in the highest concentration. The adelfos eyes were control and every day in the three different times dogs went through the same initial exams. All drugs were good penetration and no adverse eye level. As for tear production, captopril is the most suitable for glaucoma patients and patients with keratoconjunctivitis sicca, while timolol is contraindicated for them. All decreased IOP values, and in the second week of treatment, with higher concentrations, reductions were more significant. The bradycardia was observed in captopril-treated animals 0.5%, with a reduction of almost 9% in HR compared to captopril in lower concentrations