Midriasis farmacológica en conejos inducida por antagonistas de histamina / Pharmacologic midriasis induced by histamine antagonist in rabits

El propósito de este trabajo es determinar el efecto de antagonistas de histamina sobre el esfínter pupilar y la superficie ocular en conejos pigmentados. Para ello se realizó un estudio experimental, longitudinal y comparativo. Se estudiaron 50 ojos de 25 conejos, divididos en 4 grupos: I cimetidina, II clorfenamina, III tropicamida al 1 por ciento y IV fenilefrina al 10 por ciento + ciclopentolato al 1 por ciento. Como resultado, se demostró que la combinación de cimetidina y tropicamida al 1 por ciento produce pérdida de reflejo pupilar a los 5 minutos, midriasisi máxima a los 15 minutos, delcinando a los 45 minutos de su aplicacion. Se concluye que la combinación de cimetidina y tropicamida al 1 por ciento en forma tópica, induce pérdida del reflejo pupilar y midriasis a corto plazo desapareciendo rápidamente el afecto

Mechanisms of chlorpheniramine maleate release from hydrophilic swellable polymer systems

The main objective of this work is to attempt to understand better the mechanism of release of highly water soluble drugs from a swellable polymer and to quantify the amount of drug released. Tablets containing 10 per cent w/w drug, hydroxypropylmethylcellulose E4M (10 per cent w/w, 20 per cent w/w and 30 per cent w/w), 1 per cent w/w magnesium stearate and quantity sufficient to 100 per cent w/w with Lactose Fast Flo as diluent were prepared using the direct compression method. The amount of drug released due to Fickian diffusion and non-Fickian diffusion (polymer relaxation) was quantified at different time intervals. In order to determine if the drug release was Fickian diffusion or non-Fickian diffusion, the exponent n obtained from the equation: Mt/M yen = Ktn was calculated. It was found to be above 0.5 for restricted and unrestricted systems indicating non-Fickian diffusion. Also, the approximate contribution of Fickian diffusion and polymer relaxation to the non-Fickian anomalous release process was calculated. The data obtained from one tablet surface and all surfaces exposed to the dissolution medium demonstrated that Fickian diffusion predominated for the first hour. After one hour of testing dissolution, the relaxational mechanism predominated. The percent drug release from restricted matrices at 6 hours of dissolution testing was 77.9 per cent by polymer relaxation and 27.9 per cent by Fickian diffusion.

Enhanced histamine H1 receptor blockade with chlorpheniramine in the asthmatic tracheo-bronchial tree: further evidence for increased drug delivery in asthma

We have measured the competitive antagonistic effect of chlorpheniramine in bronchi of 8 normal and 12 asthmatic subjects. Classical pharmacological theory states that the degree of competitive antagonism depends only upon 1] antagonist concentration at the receptor, and 2] receptor affinity. Delivery and affinity also influence agonist responsiveness, but measurement of bronchial antagonism allows study of these factors in isolation. Bronchial responsiveness to histamine was measured as the dose required to produce a 35% fall in specific conductance [sGaw], called PD [35] On different days, 2 measurements of control PD[35] were made on each subject. Measurements of PD[35] were also repeated after inhalation of 1.45 mg chlorpheniramine and intravenous injection of 0.17 mg/kg chlorpheniramine. Antagonist effect of chlorpheniramine was measured as Dose Ratio-1 [DR-1], where DR= PD [35] after chlorpheniramine/control PD[35] Geometric mean of DR-I with inhaled chlorpheniramine in asthmatic subjects [5.8] was 6.8 times that of normal subjects [0.86] [p=0.002], and DR-1 with intravenous chlorpheniramine in asthmatic subjects [4.4] was 2.75 times that of normal subjects [1.6] [p=0.005]. There were significant negative correlations between PD[35] and DR-1, whether chlorpheniramine was administered by inhalation [r= -0.87, p<0.001] or intravenously [r= -0.62, p<0.005]. There was also a significant correlation between DR-I obtained by two routes of administration [r= 0.77, p<0.001]. Taken with our previous study showing enhanced antagonism with atropine at bronchial muscarinic receptors in asthma, these results suggest that drug delivery by inhaled and parenteral routes may be increased in asthmatic bronchi