Concentrations Of Pilocarpine Research Articles

Comparison of the ocular effects of topical etomidate and pilocarpine in rabbits

Etomidate, (R-(+) ethyl-1-(phenylethyl) 1H-imidazole-5-carboxylate), when administered as drops to the eyes of normal New Zealand white rabbits in concentrations of 2%, 4% and 8% in arachis oil has been shown to significantly lower the intraocular pressure in these animals. The intraocular pressure was measured with the Perkins handheld applanation tonometer. The intraocular pressure reducing effect of the 2% and 4% were better than that of 1% pilocarpine; the two per cent etomidate solution reduced intraocular pressure from a pretreatment mean of 13.6mm Hg to a new mean of 7.7mm Hg after three weeks treatment, while the 4% etomidate solution lowered the intraocular pressure from a pretreatment mean of 14.4mm Hg to a new mean of 7.3mm Hg also after three weeks treatment. Pilocarpine (1%) reduced the intraocular pressure from a pretreatment mean of 13.7mm Hg to 10.7mmHg after three weeks treatment in the same group of rabbits. Etomidate (8%) solution also showed a more significant reduction of intraocular pressure than the 2% solution of pilocarpine. The eight percent etomidate reduced the pretreatment mean intraocular pressure of 14.0mm Hg to a new mean of 6.5mm Hg after three weeks treatment while 2% pilocarpine lowered a pretreatment mean of 13.9mm Hg to 9.0mm Hg after three weeks treatment in the same group of rabbits. There was a persistence of the low intraocular pressure produced by the various concentrations of etomidate in arachis oil after treatment with these drops was stopped. However, this feature was also shown by the two concentrations of pilocarpine used but not in as marked an extent as the etomidate solutions with regard to duration of effect and height of reduction of the intraocular pressure. During a three week period of topical application of drops to the rabbits eyes, the etomidate solutions were found to have no effect in the iris sphincter.

Effect of oily vehicle on ocular pilocarpine concentration.

The effect of 1.4% polyvinyl alcohol (PVA) vehicle and of castor oil vehicle on ocular pilocarpine concentration was studied by radioactive method in the rabbit eye. Statistically higher radioactivities were measured from the anterior surface structures of the eyes dropped with oily vehicle when compared to PVA vehicle at 120 min. It is concluded that the conjunctiva and the cornea serve as a drug reservoir for the longlasting drug effect observed in the literature after oily pilocarpine drops.

Transcorneal Flux of Topical Pilocarpine to the Human Aqueous

Aqueous fluid was withdrawn from eyes of patients undergoing cataract extraction at various intervals after administration of two drops of 2% pilocarpine HCl in a standard manner. Determination of aqueous pilocarpine concentration was made both by spectroscopy of a ferric hydroxylamine complex and by gas-liquid chromatography. Results of both methods were consistent in indicating that concentration does not rise at any time following such topical instillation beyond 5 microgram/ml, with an average of 1.67 microgram/ml, representing a flux efficiency of 0.03%. These findings correlate well with previous investigations of transcorneal flux of pilocarpine for the rabbit in a transport chamber system, in which comparable low flux efficiency was found after simulated drop administration. This serves in some measure to validate an extrapolation of other findings in chamber experiments to the living human eye.

Vehicle Effects on Ocular Drug Bioavailability II: Evaluation of Pilocarpine

The influence of vehicle composition on ocular penetration of pilocarpine was studied in the albino rabbit. Increasing the pH of a vehicle promoted increased corneal penetration for pilocarpine, in accordance with the pH-partition hypothesis, but a similar series of experiments with a nonionizable drug, glycerin, gave similar results. The extent of pH-induced lacrimation by the vehicle and its effect on precorneal drug concentration also was determined. Increased pilocarpine absorption at neutral to slightly alkaline pH was due primarily to its peculiar solubility characteristics coupled with less irritation and lacrimation rather than a direct pH effect on the molecule. Incorporation of pilocarpine into a petrolatum-based ointment vehicle resulted in increased aqueous humor pilocarpine levels above those provided by an equivalent dose of aqueous solution. The mechanism of this increase was determined to be a higher effective concentration of pilocarpine in the ointment vehicle coupled with an increase in contact time of the dose. The ointment system also exerted an unusual form of vehicle control in that it promoted the corneal penetration of pilocarpine while impeding uniform mixing of the dose with tears and thereby imposed a restriction on the amount of pilocarpine available to the ocular tissues.

Problems associated with measuring sweat chloride concentration with an ion-specific electrode.

The measurement of sweat chloride concentration was investigated by using the Orion 417 skin chloride electrode. The effects of variation in pilocarpine concentration, iontophoresis period, and sweat collection period were also investigated. The results show that the sweat chloride concentration is directly related to the amount of sweat produced. When the amount of sweat collected falls below a certain level, there is an apparent increase in sweat chloride concentration. A procedure is recommended for the measurement of sweat chloride concentration which offers good precision (coefficient of variation 9.8%) and the minimum of inconvenience to the patient.

Simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations by liquid chromatography

A liquid chromatographic assay method is described for the simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations. The method involves separation of the isomers on a high‐resolution ion‐exchange column, followed by detection of pilocarpine and isopilocarpine by UV absorption in the 217‐nm region. The specificity of the method is such that pilocarpine and isopilocarpine can be assayed separately in the presence of one another and in the presence of the excipients commonly found in commercial pilocarpine solutions. Its sensitivity for isopilocarpine is at least 25 ppm (independent of the concentration of pilocarpine). In contrast, USP methods lack both specificity and sensitivity. It is concluded that this method is applicable to the routine analysis of commercial pilocarpine preparations and is an improvement over the official methods.

Management of Reactivated Prostatic Cancer

Publisher Summary This chapter discusses the management of reactivated prostatic cancer. The basis for manipulation of the hormonal milieu of patients with prostatic cancer is based upon several experimental evidence. The volume and acid phosphatase concentration of pilocarpine stimulated canine prostatic fluid have been proved to be reliable indices of androgenic stimulation of the prostate in experimental situations. Antiandrogens are also known to have demonstrable effects on various species, including the canine, in terms of various criteria of prostatic function. Pre- and postoperative measurements of growth hormones exhibit a typical flat curve following open hypophysectomy. The initial reduction of androgenic hormone by bilateral orchiectomy and/or estrogen therapy has been noted to produce a regression of advanced prostatic carcinoma. A marked decrease of the 11-deoxy-17-ketosteroids is consistently noted in previously castrated patients. This has been noted in follow-up periods extending up to 1 year and beyond and is associated with clinically evident and suitable signs of subjective and objective response. The major cause of death following adrenalectomy is disseminated disease. It is suggested that because of ease of administration, effectiveness, and lack of toxicity, oral Estracyt may be considered the method of choice in such cases for failures following conventional hormonal therapy.

Pilocarpine-induced lens changes. An ultrasonic biometric evaluation of dose response.

High resolution ultrasonic biometry was performed on ten eyes of five normal young volunteers (ages 21 to 26 years) prior to and at regular intervals following topical administration of 1%, 4%, and 8% pilocarpine hydrochloride. All eyes showed a narrowing of the anterior chamber and axial lens thickening following pilocarpine administration. There was a dose-related response of maximal anterior chamber depth and lens thickness changes, but comparison of the means of maximal changes of the two dimensions did not reveal statistically significant differences. Increasing concentrations of pilocarpine had a more rapid onset of action, greater peak effect, and prolonged duration of action. A statistically significant prolongation of effect on anterior chember depth and lens thickness after instillation of the drug was obtained with the higher concentrations of pilocarpine.

Antagonism of the effect of isoprenaline on heart rate by pilocarpine.

1 The interaction of pilocarpine and isoprenaline on heart rate was investigated in the spontaneously beating, right isolated atrium of the rat.2 The log dose-effect curve of isoprenaline, measured in the presence of various concentrations of pilocarpine, was not modified when the concentration of the latter did not exceed 10(-6)M even though significant slowing of the heart had occurred. At concentrations higher than 10(-6)M a rapid but graded shift to the right of isoprenaline response curves occurred so that at pilocarpine 10(-5)M the pD(2) of isoprenaline was reduced from 11 to 3.3; cocaine slightly reduced this antagonism.3 It is concluded that pilocarpine antagonizes isoprenaline by some mechanism which is not of the simple competitive type.

MECHANISM OF CATECHOLAMINE ANTAGONISM IN RAT HEART PRODUCED BY PILOCARPINE AND RELATED DRUGS

1 High concentrations of pilocarpine and methacholine consistently lowered the potencies of a series of adrenoceptor agonists as shown by displacement of complete cumulative dose-effect curves for their positive chronotropic action on rat isolated atria. The order of potency of the agonists was characteristic of beta-adrenoceptor activation and this was converted to the type which characterizes alpha-adrenoceptor activation when pilocarpine was present.2 Propranolol effectively blocked the adrenoceptor agonists in the presence of pilocarpine and phentolamine abolished the antagonistic actions of pilocarpine. Atropine, which by itself did not affect the action of the adrenoceptor agonists, abolished both the bradycardia and antagonism produced by pilocarpine.3 It is concluded that pilocarpine antagonizes adrenoceptor agonists by muscarinic cholinoceptor activation without involving classical adrenoceptors.

Fade and desensitisation in guinea-pig ileum and vas deferens

Segments of guinea-pig ileum were exposed to a range of concentrations of acetylcholine, carbachol, methacholine, choline, pilocarpine or histamine from 1 pM to 300 mM. Peak response, fade and desensitisation were recorded isometrically. Noradrenaline was applied to guinea-pig vas deferens and bradykinin to rat uterus and similar observations made. The development of and recovery from desensitisation was examined and observations were made on the effects of antagonists and of alterations in electrolytes in the bathing fluid. The relationship of the molar concentration of the agonist to fade, recorded as a percentage of peak response, is linear for acetylcholine, histamine and noradrenaline but not for pilocarpine. The full dose-response curve is such that with doses above the producing maximal responses, contractions decreased with increasing dose. Autodesensitisation, like peak response and fade, is a consequence of receptor stimulation but heterodensitisation is unrelated to receptor mechanism. It is peculiarly sensitive to alterations in calcium level.

Ocular Penetration of Pilocarpine in Primates

The therapeutic efficacy of pilocarpine in glaucoma has been well established. How­ ever, documentation of the amount of pilo­ carpine that penetrates into the anterior seg­ ment of the eye has been sparse. Harris re­ ported that 2% of topically administered pi­ locarpine enters the eye while von Muller found as much as 20%. Recent reports have suggested that a soft contact lens can enhance the penetration of pilocarpine into the eye. In the therapy of glaucoma, the Bionite soft contact lens com­ bined with 1% pilocarpine drops was more effective in lowering intraocular pressure than 8% pilocarpine alone. The same lens presoaked for two minutes in pilocarpine without preservative and worn for variable time periods, lowered intraocular pressure for as long as 23 hours and was more effec­ tive than the use of drops alone. A study was undertaken to determine the amount of pilocarpine in the aqueous humor of primates after the topical application of various concentrations of pilocarpine or Bionite lenses presoaked in pilocarpine.

Physiological Investigations into the Heart Function of Arthropods

Perfusion of the isolated heart ofPeriplaneta americanawith caffeine, digitalin, acetylcholine, nicotine and lobeline shows that the pacemaker of this heart is different from the “ myogenic centre ” of the vertebrate heart.The action of strychnine, morphine and apomorphine on this heart preparation affords evidence of the existence of a neurogenic pacemaker.This pacemaker is stimulated by suitable concentrations of acetylcholine, nicotine, lobeline and pilocarpine, while it is inhibited by atropine. Acetylcholine and tetraethyl pyrophosphate show a synergistic action. Atropine and tetraethyl pyrophosphate, like acetylcholine and curare, show an antagonistic action. These results prove that the neurogenic pacemaker possesses cholinergic properties.Adrenaline stimulates the insect heart and ergotamine inhibits it, thus suggesting that the insect heart probably also has adrenergic properties.On the basis of the present work and the results obtained by other investigators, a theory is put forward that the heart mechanism of most arthropods consists of a neurogenic pacemaker with adrenergic properties, controlled by a cholinergic accelerating nerve. This mechanism bears some resemblance to the sympathetic nerve system of vertebrates.Rotenone strongly counteracts the action of acetylcholine, tetraethyl pyrophosphate, nicotine, lobeline, pilocarpine and digitalin on the insect heart. Its point of action, however, remains obscure at the moment.The opposing action of rotenone and tetraethyl pyrophosphate is an indication that a combination of these insecticides for pest control is not to be recommended.

CARBAMINOYLCHOLINE CHLORIDE IN THE TREATMENT OF GLAUCOMA SIMPLEX

Carbaminoylcholine is one of a group of synthetic choline derivatives which act principally by parasympathetic stimulation. In chemical structure (chart 1) it is similar to acetylcholine, but its action is more prolonged, since it is stable in the tissues and hydrolysis is slow. The initial experiments on the ocular effects of carbaminoylcholine chloride were made on isolated iris sphincter and indicated that this drug may be the most powerful of all known miotics. 1 However, clinical reports have been conflicting. Guyton 2 in a recent review of the literature found no unanimity of opinion regarding the degree and the duration of miosis but concluded that the miosis is probably greater but less prolonged than that produced by similar concentrations of pilocarpine. Velhagen 3 found the effect of a 0.75 per cent concentration of carbaminoylcholine chloride on the accommodation of the normal human eye to be less than that of a