Topical Application Of Drugs Research Articles

Vasodepressor effects obtained by drugs acting on the ventral surface of the brain stem.

1. In cats anaesthetized with I.P. pentobarbitone sodium and atropinized with intravenous atropine methyl nitrate, the effects on arterial blood pressure were examined of nicotine, physostigmine, carbachol, glycine and pentobarbitone sodium applied to the exposed ventral surface of the brain stem by means of paired Perspex rings placed across the medulla. The drugs were placed inside each ring in a volume of 10mul. 2. Nicotine (0-5-6mg/ml.) produced a fall in blood pressure when the upper limit of the areas covered by the rings was about 5-6 mm caudal, but not when it was just caudal to the trapezoid bodies. The depressor effect was obtained both on bilateral and unilateral application. After application the nicotine sensitive area became for several minutes insensitive to its renewed application. 3. The depressor effect of nicotine was sensitive to hexamethonium (50 mg/ml.) but resistant to atropine (50 mg/ml.) similarly applied. 4. When the nicotine sensitive areas had become insensitive to nicotine, bilateral carotid occulusion produced its normal sustained pressor response. 5. By applying the nicotine through a single Perspex ring which could be moved stepwise along and across the medulla, the nicotine sensitive area was localized and the highest sensitivity was found in a region around and a little caudal to the rootlets of the XIIth cranial nerve. 6. Physostigmine (25 and 50 mg/ml.) and carbachol (6 mg/ml.) produced a fall in blood pressure when the uppermost limits of the areas covered by the paired rings were 5-6 mm caudal to and also when they were just caudal to the trapezoid bodies. From both regions the effects were obtained on bilateral and unilateral application. Their depressor effects were sensitive to atropine but resistant to hexamethonium similarly applied. 7. Glycine (200 mg/ml.) and pentobarbitone sodium (100 mg/ml.) produced scarcely any blood pressure effects when applied bilaterally to the nicotine sensitive areas but produced strong depressor effects on more rostral application, i.e. when the uppermost limit of the areas covered by the rings were just caudal to the trapezoid bodies. 8. It is concluded that the ventral surface of the medulla contains at least two bilateral areas from which vasodepressor effects are obtained on topical application of drugs: a more caudally situated one which is sensitive to nicotine, but insensitive to glycine and pentobarbitone sodium; a more rostrally situated one which is insensitive to nicotine but sensitive to glycine and pentobarbitone sodium; and both areas are sensitive to carbachol and physostigmine.

Cholinergic Control of Blood Flow in the Cerebral Cortex of the Rat

Local blood flow was measured in the somatosensory cortex of urethanized rats by means of the hydrogen clearance method. The variations of cortical blood flow in the course of the anesthesia and the effects of the topical application of atropine, eserine and cholinomimetic drugs were studied. During urethan anesthesia, the electrical activity of the cerebral cortex fluctuated between a synchronized and a desynchronized state. During desynchronization, local cortical blood flow increased significantly. This increase in blood flow could be prevented by topical application of atropine and exaggerated by topical eserine. Topical application of arecoline, carbaminoylcholine, pilocarpine or acetylcholine with eserine significantly increased cortical blood flow. It is concluded that the increase in cortical blood flow that accompanies cortical desynchronization in the urethanized rat is mediated, at least in part, by a neurogenic mechanism that involves a cholinergic step at the cortical level.

Education, not legislation.

In June of 1971, the General Assembly of the state of Rhode Island enacted a bill defining the actions of optometrists. This bill included ... the topical application of drugs to the eye, to wit, mydriatics, miotics, and the use of topical anesthetics.... The only control over those using these drugs is by the Board of Examiners in Optometry and the Chief of Pharmacy in the Department of Health. The bill was enacted despite medical testimony to the House, Senate, and directly to the governor of Rhode Island. This law is a landmark because it makes legal the use of drugs by people who have had little, if any, medical training. It opens the door for intrusion into the practice of medicine not only by optometrists but other health workers. One could question the ability of those without a medical background to treat the cardiovascular and respiratory emergencies that can be

Education, Not Legislation

IN June of 1971, the general assembly of the state of Rhode Island enacted a bill defining the actions of optometrists. This bill included: "... the topical application of drugs to the eye, to wit, mydriatics, miotics, and the use of topical anesthetics...." The only control over those using these drugs is by the Board of Examiners in Optometry and the Chief of Pharmacy in the Department of Health. The bill was enacted despite medical testimony to the House, Senate, and directly to the Governor of Rhode Island. This law is a landmark because it makes legal the use of drugs by people who have had little, if any, medical training. It opens the door for intrusion into the practice of medicine not only by optometrists but other health workers. One could question the ability of those without a medical background to treat the cardiovascular and respiratory emergencies that can be

凍結療法により治癒した環状肉芽腫の1例

A case of granuloma annulare appearing on 52 year-old male was presented. The multiple eruptions have appeared on both legs and forearms 1.5years ago. Each eruption was ring-formed and had brown-red color with sharply demarked border. Histologically, the typical change on subcutaneous connective tissue was observed. Treatment was done by topical application of corticosteroid and anti-tuberculosis drugs, but the lesions were not improved. Then freezing therapy by use of dry ice was tried, and the lesions were successfully cured after several times application.

Iatrogenic oral candidosis.

SUMMARY.— Two distinct varieties of iatrogenic oral candidosis can be induced by topical application of drugs. Acute pseudomembranous candidosis developed with topical betamethasone-17-valerate, in the presence of significant titres of IgG, IgA and IgM class of Candida antibodies before infection, and without a change in the plasma cortisol level, in 23% of patients. This side effect was not observed with hydrocortisone hemisuccinate and betamethasone disodium phosphate, but was found in 1 of 17 patients using triamcinolone in orabase. Topical tetracycline induced acute atrophic candidosis, in the absence of significant Candida antibody levels before infection, in 64% of patients. In acute pseudomembranous candidosis there was a further rise in titre of IgG and IgA type of Candida antibodies, but predominantly IgG class of antibodies rose to low levels during the acute atrophic infection.

Blood flow and pressure propagation in the canine femoral artery

A series of experiments has been performed on the femoral artery of 20 anesthetized dogs in order to test the predictions of a theoretical, hemodynamic model. Simultaneous measurements of intra-arterial pressure and differential pressure, external vessel diameter and volume blood flow were recorded on analog tape and subsequently subjected to Fourier series analysis. Recordings were taken during control conditions and during periods of unilateral vagal stimulation and topical drug application. From the Fourier analysis of the recorded variables, values of hydraulic fluid impedance and propagation characteristics were computed for comparison to the model. Experimental values of fluid impedance, resistance and inductance compared well with the predictions of the model within the limitation of experimental errors. The propagation characteristics of the model were tested on data from the literature. The latter were used to compute values of phase velocity and attenuation coefficient, which were found to be in good agreement with the theoretical predictions of the model. The apparent propagation constant, obtained from pressure and differential pressure data, were used to compute values of (true) phase velocity. These were also found to agree well with the theoretical model. The ability of linearized wave propagation models to predict blood flow and pressure propagation values in the canine femoral artery has several important implications.

Topical application of cytotoxic drugs: clarification

The article on topical application of cytotoxic drugs (July 5, 1968, p. 55) stated that demecolcine, methotrexate and 5-fluouracil had been used in concentrations ranging from 0.1% to 20%. This was in no way a recommendation, but we should like to make it clear that Ciba advise caution in the use of extemporaneously prepared ointments containing demecolcine, especially in concentrations greater than 0.5%. Lederle advise that local applications of methotrexate should contain no more than 1%. 5-Fluouracil should not be used at a concentration greater than 5%.

A new long-lasting lozenge for applying drugs to the oral mucous membranes: II. Studies in volunteer dental and dental hygiene students

T he clinician is well aware of the fact that many diseases of the oral mucous membranes and skin are often best treated by the topical application of drugs to the surfaces of the lesions and that these active agents may be more suitably prepared for topical application by incorporation into demulcent, protectant, and adhesive vehicles. It is also generally accepted that the vehicle thus used for topical administration of drugs to the oral mucosae should have certain basic qualities and properties : (1) it should be nonirritating to mucosal tissues ; (2) when ingested, as it usually is, the vehicle should be innocuous to the gastrointestinal system ; (3) it should be compatible with the active agent incorporated in it ; (4) it should have a pleasant feel and taste ; (5) it should be easily administered; and (6) it should be long lasting ins0fa.r a,s its dissolution time is concerned, thus assuring prolonged contact of the active agent with the lesion at high concentration. Although there are numerous vehicles whose qualities and properties fully satisfy most of the desirable prerequisites enumerated above (such as the usual candied lozenges, petrolatum and oil formulations, and various paste and powder vehicles), none fulfills the last and perhaps one of the most desirable prerequisites, namely, that of possessing a long-lasting quality or capacity. Thus,

Topical application of drugs to subcortical brain structures and selected aspects of electrical stimulation.

Topical application of drugs to subcortical brain structures and selected aspects of electrical stimulation.

Congenital malformations induced by dimethyl sulphoxide in the golden hamster

ABSTRACT Dimethyl sulphoxide (DMSO) is a relatively simple organic compound with a molecular weight of 78. It has been reported to be exceptionally non-toxic and has been used extensively in biological systems as a cell preservative, including freeze storage (Porterfield & Ashwood-Smith, 1962; Dougherty, 1962), and as a radioprotective agent against X-irradiation in mice (Ashwood-Smith, 1961). Recent clinical investigations in man have suggested that DMSO has a remarkable array of effects, including anti-inflammatory activity, bacteriostatic effects, and analgesic activity (Jacob, Bischel & Herschler, 1964). It has been used extensively as a vehicle for the topical application of various drugs because of its dramatic effect on enhancement of penetration of various drugs through the skin (Kligman, 1965).

Post-primary cortical responses to flashes and their specific potentiation by steady light

1. 1. A classification of the components of the primary flash-evoked response of the visual cortex was attempted in the unanesthetized cat ( ac>e ́ or immobilized with Flaxedil). 2. 2. The primary response is particularly analysed; an early biphasic component (a) and mainly positive post-primary components (b at 50–120 msec and c at 140–180 msec latencies) are described. A secondary response appears with a latency exceeding 180–200 msec. Experimental evidence (simultaneous recording in specific and unspecific subcortical nuclei, convergence processes, recovery cycle, topical application of drugs) indicates the extracortical origin of the early a component, and the intrinsic cortical nature of the post-primary b and c components. 3. 3. Steady light induces diminution of the initial component, simultaneous with enhancement of the post-primary components. The levels at which steady light exerts these different influences are analysed. The specific facilitatory effect of steady light upon the intrinsic cortical components of the flash-evoked response is discussed.

Effects of various drugs on activity of the neuronally isolated cerebral cortex

The topical application of strychnine, d-tubocurarine, pentylenetetrazole, picrotoxin, and physostigmine evoked different patterns of electrical activity in a portion of the acutely isolated suprasylvian gyrus of dogs. Pentylenetetrazole and picrotoxin evoked a similar pattern of activity in the isolated gyrus by both topical application and intravenous administration. Reasonable systemic doses of strychnine, d-tubocurarine and physostigmine did not produce activity similar to that seen on topical application. Therefore, the effects obtained by topical application of drugs to the cerebral cortex must be interpreted cautiously as regarding the usual pharmacological actions of these agents. Adrenergic agents, administered systemically, exerted a diphasic effect upon chemically and electrically evoked activity. An initial depression and subsequent enhancement were observed. These actions were exceedingly variable and did not appear to be secondary to vascular effects. On the other hand the effects of acetylcholine and arecoline did seem to be secondary to their cardiovascular effects. Since entirely different patterns of spontaneous and evoked electrical activity could be recorded simultaneously from the isolated and nearby intact portions of the cortex, it was concluded that the neuronally isolated cerebral cortex gave rise to independent activity.

Inhibition of histamine-stimulated secretion by topical application of antihistaminics to the canine mucosa.

Summary and conclusions1. Topical application of several antihistaminic drugs to the mucosa of canine corpus pouches significantly inhibited the acid secretory responses of these pouches to parenterally administered histamine. One local anesthetic agent elicited similar inhibition. These inhibitory substances were effective also against a vagomimetic stimulant, urecholine. 2. In an effort to explain these phenomena, 3 possible modes of action of the antihistaminics present themselves: (1) a specific (antihistaminic) effect, (2) an atropine effect, (3) a local anesthetic effect. The evidence presently available does not as yet permit of any preference among these several hypotheses.

ANESTHESIA FOR SURGERY OF THE NOSE, PHARYNX, LARYNX, AND TRACHEA

Most otolaryngologists perform their own local anesthesia and engage an anesthetist (doctor or nurse) to administer the general anesthesia. This paper does not attempt to markedly alter the anesthesia methods preferred by the otolaryngologist or by his anesthetist. The sole purpose of this paper is to make whatever anesthetic is administered safer for the patient. Therefore, it will (1) show how the all too frequent incidence of severe or fatal reactions to the topical application of local anesthetic drugs may be reduced; (2) discuss the advantages and the disadvantages of administering chlorpromazine (Thorazine, Largactil) as sedation before regional block anesthesia; (3) accent the importance of endotracheal anesthesia during the operation and in the immediate postoperative period; (4) detail how laryngospasm during thiopental (Pentothal) anesthesia may be rapidly corrected; (5) emphasize our method of using succinylcholine (Anectine) prior to intubation, which has reduced the incidence of laryngeal granuloma following intubation from

Anesthesia for surgery of the nose, pharynx, larynx, and trachea.

Most otolaryngologists perform their own local anesthesia and engage an anesthetist (doctor or nurse) to administer the general anesthesia. This paper does not attempt to markedly alter the anesthesia methods preferred by the otolaryngologist or by his anesthetist. The sole purpose of this paper is to make whatever anesthetic is administered safer for the patient. Therefore, it will (1) show how the all too frequent incidence of severe or fatal reactions to the topical application of local anesthetic drugs may be reduced; (2) discuss the advantages and the disadvantages of administering chlorpromazine (Thorazine, Largactil) as sedation before regional block anesthesia; (3) accent the importance of endotracheal anesthesia during the operation and in the immediate postoperative period; (4) detail how laryngospasm during thiopental (Pentothal) anesthesia may be rapidly corrected; (5) emphasize our method of using succinylcholine (Anectine) prior to intubation, which has reduced the incidence of laryngeal granuloma following intubation from

Stimulation of cell-free gastric mucus by the topical application of acetylcholine.

SummaryThe topical application of acetylcholine or related parasympathomimetic drugs to the mucosa of canine fundic pouches results in the secretion of alkaline opalescent viscid mucus which is free of columnar cells. These studies confirm our previous conclusion, that the exfoliation of gastric surface cells is not an essential part of the process of mucus secretion.

Effects of Various Modes of Administration of Pyribenzamine on the Histamine Wheal and Epidermal Sensitivity Reactions

An extensive literature has developed relating the effects of the various antihistamine drugs on the course of dermatoses thought to be based on the mechanism of allergy. Their oral, as well as parenteral administration, has had definite therapeutic effects on those skin eruptions which, like urticaria, have an element of whealing in their pathology (1—7). In dermatoses with mainly epidermal pathology, both allergic and non-allergic in nature, the effects of the antihistamine drugs have varied with the mode of administration. The pruritic element seems to be the factor chiefly affected where beneficial therapeutic results were obtained (8—10). With the introduction of ointments containing histamine antagonists, further evaluation of their therapeutic action has been made in many dermatoses (11—15). The pharmacology of the antipruritic effect of the antihistamine drugs is as yet little understood. There is the possibility, however, that in these topical applications the ointments act only partly in a manner similar to a local anesthetic. That is well demonstrated in the experiments of Mayer (15) and Aaron, Peck and Abramson (16). The therapeutic results with topical application of antihistamine drugs in the form of ointments have varied widely not only in skin eruptions of differing pathology, but in different patients with the same skin disease or even in the same patient at different stages of the eruption. Naturally, the question of absorption of the antihistaminic substance through the skin comes into the foreground in such instances. In this study, we have attempted to evaluate the effects on histamine whealing and allergic epidermal reactions of the administration of Pyribenzamine by oral and parenteral administration, as well as by iontophoresis and the application of Pyribenzamine ointment. Quantitative excretion studies of Pyribenzamine after topical application were made in an attempt to correlate the clinical action of this drug administered in this way with the question of absorption through the skin. The results of these experiments also explain the variability in antipruritic as well as other effects with ointments containing Pyribenzamine.

IONTOPHORESIS WITH CONTACT LENS TYPE AND EYECUP ELECTRODES

IONTOPHORESIS (ion transfer, ionization) has been employed in general medicine for over one hundred years. Although it has been used in the treatment of diseases of the eye for more than fifty years, it is still a comparatively unknown form of ocular therapy. From three to fifteen times greater concentrations of drugs can be obtained in the tissues of the conjunctiva, cornea and anterior segment of the eye by iontophoresis than by the topical application of the same drugs. For this reason mydriasis can usually be obtained by the iontophoretic introduction of atropine sulfate in the case of pupils that are refractory to the topical application or the subconjunctival injection of mydriatics. Anterior synechias may also be broken by this method when other methods fail. The theories and experimental and clinical data of iontophoresis as they apply to general medicine are thoroughly discussed by Abramowitsch and Neoussikine1in their

Improvement on the Procedure of Topical Application of the Sulfa Drugs

Improvement on the Procedure of Topical Application of the Sulfa Drugs