Epinephrine Bitartrate Research Articles

An integrated strategy to explore the potential role of melatonin against copper-induced adrenaline toxicity in rat cardiomyocytes: Insights into oxidative stress, inflammation, and apoptosis

AimsCircumstantial anxiety as well as chronic stress may stimulate the release of stress hormones including catecholamines. Adrenaline toxicity has been implicated in many cardiovascular conditions. Considering previous literature that suggests the oxidative potential of the adrenaline-copper entity, we have investigated its potential nocuous role in isolated adult rat cardiomyocytes, the underlying molecular mechanism, and its possible protection by melatonin. Main methodsGiven the mechanistic congruity of adrenaline-copper (AC) with the well-established H2O2-copper-ascorbate (HCA) system of free radical generation, we have used the latter as a representative model to study the cytotoxic nature of AC. We further investigated the cardioprotective efficacy of melatonin in both the stress models through scanning electron microscopy, immunofluorescence, flow cytometry, and western blot analysis. Key findingsResults show that melatonin significantly protects AC-treated cardiomyocytes from ROS-mediated membrane damage, disruption of mitochondrial membrane potential, antioxidant imbalance, and distortion of cellular morphology. Melatonin protects cardiomyocytes from inflammation by downregulating pro-inflammatory mediators viz., COX-2, NF-κB, TNF-α, and upregulating anti-inflammatory IL-10. Melatonin significantly ameliorated cardiomyocyte apoptosis in AC and HCA-treated cells as evidenced by decreased BAX/BCL-2 ratio and subsequent suppression of caspase-9 and caspase-3 levels. The isothermal calorimetric study revealed that melatonin inhibits the binding of adrenaline bitartrate with copper in solution, which fairly explains the rescue potential of melatonin against AC-mediated toxicity in cardiomyocytes. SignificanceFindings suggest that the multipronged strategy of melatonin that includes its antioxidant, anti-inflammatory, anti-apoptotic, and overall cardioprotective ability may substantiate its potential therapeutic efficacy against adrenaline-copper-induced damage and death of adult rat cardiomyocytes.

Comparative Evaluation Of The Effectiveness Of Dexamethasone And Adrenaline With 2% Lignocaine For Pterygomandibular Nerve Blocks: A Randomized Controlled Clinical Study

Background and Aim: Dexamethasone, a glucocorticoid, has been used in local anesthetics as an additive for various locoregional nerve blocks. Although, its use in the dental field has not been unexplored and concealed. The current study was conducted to evaluate and compare the calibre of anesthesia, their hemodynamic response, vasoconstrictive effects, and control of pain while administering pterygomandibular nerve blocks using 2% Lignocaine hydrochloride solution with Dexamethasone(4mg/ml) with that of the standard 2% Lignocaine hydrochloride solution and Adrenaline bitartrate (1:80000). Materials and Methods: This triple-blind randomized controlled study included 80 healthy subjects, aged between 18-45 years with an indication for surgical removal of impacted mandibular third molars. With the aid of a computer-generated sequence, the subjects were arbitrarily assigned into 2 groups (40/group)- Group 1: patients administered with 2% Lignocaine hydrochloride and Dexamethasone Sodium Phosphate (4mg/ml) solution, and Group 2: patients administered with 2% Lignocaine hydrochloride with Adrenaline bitartrate (Adr) 1: 80,000 (12.5 μgm/ml) solution. The variables were assessed based on their time of onset, depth (pain) and duration of anesthesia, systolic, diastolic, and mean arterial blood pressures, heart rate, and blood loss. Results: Statistically significant difference (P<0.05) was noticed for the onset (shorter onset in Group 1) and duration of action (prolonged in group 1) and number of analgesics required (less in grp 1). Statistically non-significant difference between 2 groups (P>0.05) for pain, blood loss, cardiovascular variables (systolic, diastolic and mean arterial blood pressures and heart rate) at various intervals was noted. Conclusion: Dexamethasone added to Lignocaine shortens onset, prolongs duration of action and yields better control of post-operative pain as compared to Lignocaine with Adr. Vasoconstrictive properties, hemodynamic variables and intra-op pain control were comparable. Bangladesh Journal of Medical Science Vol.22 (Special Issue) 2023 p.172-178

Sustainable spectrophotometric resolution techniques for a spectrally overlapping mixture of Articaine Hydrochloride and Epinephrine Bitartrate with challenging formulation ratio

Five clear and eco-friendly spectrophotometric methods were investigated to treat and amplify, accurately and precisely, the spectral signals of analyte concentrations that are deemed critical. The presented techniques were employed to simultaneously assess Articaine Hydrochloride (ART) and Epinephrine Bitartrate (EPI) in their authentic form and pharmaceutical formulation. Several challenges were encountered in the current study: spectra of the cited drugs were totally overlapped, and both drugs presented in their marketed formulation in a highly challengeable ratio of 4000:1 for ART and EPI, respectively. Additionally, no UV method had been reported to resolve the binary mixture in any matrices. The introduced techniques depended on the mixture's special spectral aspects, utilizing standard addition and spectrum addition techniques without any initial separation. Namely, they are factorized zero order absorption spectrum, dual wavelength, bivariate, constant extraction, and ratio difference methods. The proposed methods were validated according to the ICH guidelines and the results were found within the acceptable limits and linear over concentration ranges of 5–60 μg mL−1 for ART and 5–110 μg mL−1 for EPI. Furthermore, a statistical comparison of the observed data with the data from the official methods excluded any significant difference between the two results, and the same result was obtained using the one-way ANOVA. Adherence of the developed methods to green analytical chemistry (GAC) was assessed and compared with a published voltammetric method using national environmental methods index (NEMI), analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness (AGREE) metric.

歯科用局所麻酔剤アーティカイン塩酸塩 (アルチカイン塩酸塩)・アドレナリン酒石酸水素塩注射剤 (OKAD01) の安全性および血中薬物動態の検討 (第I相, 単施設, 非盲検試験)

歯科用局所麻酔剤アーティカイン塩酸塩 (アルチカイン塩酸塩)・アドレナリン酒石酸水素塩注射剤 (OKAD01) の安全性および血中薬物動態の検討 (第I相, 単施設, 非盲検試験)

Comparative Evaluation of Effectiveness of 2% Lignocaine Hydrochloride with Clonidine Hydrochloride versus 2% Lignocaine Hydrochloride with Adrenaline Bitartrate as Local Anesthetic for Adult Patients Undergoing Surgical Extraction of Impacted Mandibular Third Molars: A Randomized Controlled Clinical Study.

Background and Objectives:Clonidine is a common additive to local anesthetics for various regional and local nerve blocks. However, its effectiveness in dentistry has not yet been fully explored. Thus, this study was performed to evaluate the quality of anesthesia, vasoconstrictive effects, hemodynamic response, and pain control using a solution of 2% lignocaine hydrochloride with clonidine hydrochloride in comparison with the standard solution of 2% lignocaine hydrochloride and adrenaline bitartrate for pterygomandibular nerve blocks.Materials and Methods:A parallel arm, triple-blind randomized controlled study was conducted on 152 patients belonging to ASA-I (American Society of Anesthesiologists) category in the age group of 18-45 years, requiring surgical extraction of impacted mandibular third molars. The patients were divided equally into two groups randomly by computer-generated sequence; Group 1: 2% lignocaine hydrochloride with 1 ml of clonidine hydrochloride (150 μg/ml) and Group 2: 2% lignocaine hydrochloride with adrenaline bitartrate 1: 80,000 (12.5 μg/ml). The variables evaluated were systolic, diastolic, and mean arterial blood pressures, heart rate (HR), blood loss, onset, depth (pain), and duration of anesthesia.Results:There was a statistically nonsignificant difference seen between the two groups (P > 0.05) for the onset of anesthesia, pain assessed, and blood loss, whereas a statistically highly significant difference was seen for cardiovascular variables (systolic, diastolic and mean arterial blood pressures, and HR) at various intervals with higher values for Group 2 (P < 0.001) and for the duration of action of local anesthesia (LA), with higher values for Group 1 (P < 0.001).Conclusions:Clonidine as an additive to lignocaine has proved to have the onset of action, vasoconstrictive properties, and pain control, equivalent to adrenaline. However, with better stability of hemodynamic variables and prolonged duration of action of LA with clonidine, it can be considered as a better, safer, and more effective additive to lignocaine than adrenaline

Oleic acid as a restorative agent in alleviating adrenaline induced altered morphofunctional milieu of gastric tissue and mitochondria

The role of oleic acid as a protective antioxidant has recently been recognized. The present study is aimed to explore whether oleic acid can afford protection to rat gastric tissue when challenged with adrenaline. Sixty adult healthy male albino rats were divided into 10 groups comprising of 6 animals each. First group constituted the control. Rats of the second group were injected sub-cutaneously with adrenaline bitartrate at the dose of 0.3mg/kg body weight, every day for a period of 17 days. Rats of the third, to the sixth groups were orally fed with different doses of oleic acid (2.5, 5, 10, 20 mg/kg body weight/day) respectively. The rats of seventh to tenth groups were orally fed with doses of oleic acid as mentioned above and subsequently injected with adrenaline bitartrate at 0.3mg/kg body weight sub-cutaneously. After the treatment period, the animals were euthanized through cervical dislocation following light ether anaesthesia and gastric tissues were collected for morphological and biochemical studies. Subcutaneously administered pharmacological dose of adrenaline bitartrate caused oxidative stress inducing gastric lesion in male albino rats as evident from the altered levels of biomarkers of oxidative stress, activities of antioxidant and mitochondrial enzymes related to energy metabolism with changes in tissue morphology. Pre-treatment of rats with oleic acid dose-dependently protected against these gastric injuries induced by adrenaline indicating the potentiality of oleic acid in protecting against adrenaline induced gastric injury in male albino rats where antioxidant mechanisms appear to play a pivotal role in mediating such protection.

Comparative evaluation of effectiveness of 2% lignocaine hydrochloride with 1.5% potassium chloride versus 2% lignocaine hydrochloride with adrenaline bitartrate versus 2% lignocaine hydrochloride as local anaesthetic for adult patients undergoing surgical extraction of impacted mandibular third molars: a randomized controlled clinical study

Background and objective: Administration of some additives with local anesthetics can prolong pain free period post-operatively, thereby reducing need for post-operative analgesics and improving patient comfort. Potassium chloride was found to increase duration and quality of anesthesia in various studies on brachial plexus blockade. This study was designed to evaluate and compare the effect of 2% lignocaine with 1.5% potassium chloride, 2% lignocaine with adrenaline and 2% lignocaine (plain) in pterygomandibular nerve blocks. Materials and methods: A triple blind randomized controlled study was conducted on 120 adults, aged 18–45 years in ASA-I category, requiring surgical extraction of impacted mandibular third molars. The subjects were divided equally into 3 groups randomly by computer generated sequence; Group 1: 2% lignocaine plus 1.5% solution of potassium chloride, group 2: 2% lignocaine with 1:80,000 adrenaline and group 3: 2% plain lignocaine. Onset, duration, depth (pain) of anesthesia, patient satisfaction, systolic and diastolic blood pressures, heart rate and oxygen saturation, were evaluated and compared. Results: Onset was shortest for group1 and longest for grp3, statistically highly significant difference between the 3 groups (p &lt; 0.01). Statistically significant difference (p &lt; 0.05) was found in duration of surgery, duration of analgesia and VAS scores between groups 1 &amp; 3. Duration and depth of anesthesia were comparable for groups 1 &amp; 2. There was no statistically significant difference seen for total amount of dose used, SBP, DBP, HR and SpO2 between the 3 groups (p &gt; 0.05). Conclusion: Potassium chloride, a physiological salt is inert and causes no local/systemic adverse effects when injected with lignocaine in physiologically permissible amounts. The combination achieves satisfactory onset, duration, depth of anesthesia without altering hemodynamic variables. Hence, it may be considered as a safe and effective additive.

Amelioration of adrenaline induced oxidative gastrointestinal damages in rat by melatonin through SIRT1-NFκB and PGC1α-AMPKα cascades

Adrenaline at high pharmacological doses may lead to oxidative damages in diverse organs including gut. In this study, we attempt to elucidate the potentially protective effects of melatonin on gastrointestinal (GI) tissue damages induced by adrenaline. Rats were injected (s.c.) with different doses (0.125, 0.25 and 0.50 mg/kg) of adrenaline bitartrate (AD) for 15 days with or without melatonin (2.5, 5 and 10 mg/kg; orally). The results showed that adrenaline caused massive histological and ultra-structural GI injuries and melatonin (20 mg/kg) effectively protected these injuries. The protective mechanisms are related to the antioxidant and anti-inflammatory activities of melatonin indicated by increased glutathione levels and antioxidant enzymes as well as decreased oxidative stress markers and pro-inflammatory cytokines in GI tissues. The signal pathways of melatonin include up-regulating expression of Nrf2, SIRT1 and Bcl2, while down-regulating NFκB, TNFα and Bax. Melatonin also targeted mitochondrial energy homeostasis and biogenesis by up-regulating expression of PGC1α, AMPKα and SOD2 and reduced leakage of cytochrome c. The SIRT1-NFκB and PGC1α-AMPKα signal transduction pathways seem to play the central roles involving in melatonin’s protective effects on gastric damages induced by the high doses of adrenaline.

Carbon Quantum Dot-Modified Carbon Paste Electrode-Based Sensor for Selective and Sensitive Determination of Adrenaline.

A carbon quantum dot-based carbon paste electrode was fabricated and used for the determination of adrenaline (AD) at the nanomolar level. This fabricated electrode exhibited tremendous electrocatalytic activity for the oxidation of adrenaline in supporting electrolyte (PBS of pH 7.4). Scan rate variation studies with the modified electrode revealed that the overall electrode process was controlled by a diffusion process. A lower detection limit of 6 nM was achieved by chronoamperometry. Interference by biological molecules such as serotonin (5-HT) and ascorbic acid (AA) in the electrochemical oxidation of AD on the fabricated electrode was tested. It was observed that with the modified electrode, the selective determination of AD was possible. Further, with the fabricated electrode, simultaneous analysis of AA, AD, and 5-HT was performed, and it was observed that the overlapped peaks of these analytes on the naked electrode were well resolved into three peaks on the modified electrode. Along with decent sensitivity and selectivity, the electrode also showed higher stability and antifouling nature. The real-time application of the projected scheme was proven by employing the said electrode for adrenaline in adrenaline bitartrate injections.

Embryonic, Larval, and Early Postlarval Development of the Tropical Black-Lip Rock Oyster Saccostrea echinata

The black-lip rock oyster, Saccostrea echinata, has considerable potential for aquaculture in tropical Australia and the Indo-Pacific region because of its large size, rapid growth rates, and established market acceptance. This article is the first to report on embryonic and larval development of this species reared under hatchery conditions. Developmental biology was examined across three larval cultures over a 21-day period. Newly fertilized eggs had a mean (±SE) diameter of 50 ± 0.4 µm, and postfertilization, the first polar body formed within 20 min. The earliest actively swimming trochophore appeared from 12.5 h postfertiliszation (hpf) and D-stage larvae appeared by 18 hpf. Rapid shell growth resulted in the presence of early umbo larvae at 5–7 days post fertilization (dpf). Pediveliger larvae were present from 18 dpf and the larvae settled with induction by epinephrine bitartrate from 21 dpf when they had reached an anteroposterior shell measurement of approximately 280 µm and could be retained on a 200-µm nylon mesh screen. Despite minor differences, overall, the early ontogeny of S. echinata is consistent with that of other members of the genus. This study fills an important knowledge gap in the literature and will aid the advancement of hatchery protocols for this developing aquaculture species.

Sensitive Potentiometric Determination of Amphetamine with an All-Solid-State Micro Ion-Selective Electrode

ABSTRACTThe development of amphetamine-ion-selective microelectrodes using electrochemical polymerization and microfabrication technologies is reported in this study. The microelectrodes include polypyrrole films electrochemically polymerized and doped with cosane anion ([3,3′-Co(1,2-C2B9H11)2]−) as the internal solid contact layer between the polymeric sensitive membrane and platinum working microelectrode. Several poly(vinyl chloride)-type membranes with different compositions of plasticizers/ionophore were drop casted on the conducting polymer layer, polypyrrole[3,3′-Co(1,2-C2B9H11)2]. Potentiometric measurements were performed to calibrate the response of the developed chemical sensors. The sensor was highly sensitive to amphetamine using a membrane composition of 26 wt% poly (vinyl chloride), 63 wt% di-butyl phthalate, 6 wt% sodium tetraphenylborate, and 5 wt% dibenzo-18-crown 6-ether. A high and linear response was demonstrated within the concentration range from 10−5 to 10−3 M with a slope of 53 mV/decade and a limit of detection of 4 × 10−5 M. A Reilley diagram shows that the sensor signal is stable for a working pH between 1.50 and 8.50. The chemical sensor was highly selective to amphetamine when compared to other interfering ions and compounds including K+, Na+, , D,L-phenylalanine, caffeine, (±)-epinephrine bitartrate salt, and N-formylamphetamine using the fixed interference method with coefficients of selectivity (Log ) from −1.40 to −1.15.

Changes in platelet morphology and function during 24 hours of storage.

For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood- and PRP-storage times on changes in platelet morphology and function. Blood from apparently healthy subjects was collected according to a standardized protocol and examined immediately after blood collection, four hours and twenty four hours later. The capability of platelets to adhere and form stable aggregates (PFA100, closure time) was examined in sodium citrate anticoagulated whole blood (WB) using the agonists equine type I collagen and epinephrine bitartrate (collagen/epinephrine) as well as equine type I collagen and adenosine-5'-diphosphate (collagen/ADP). Circulating platelets were quantified at each time point. Morphology of platelets and platelet aggregates were visualized microscopically and measured using an electric field multi-channel counting system (CASY). The percentage of activated platelets was assessed by means of P-selectin (CD62P) expression of circulating platelets. Furthermore, platelet factor 4 (PF4) release was measured in platelet poor plasma (PPP) at each time point. Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL - 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 μm diameter) with increasing storage time. The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials.

Efficacy of single buccal infiltrations for maxillary first molars in patients with irreversible pulpitis: a randomized controlled clinical trial

To evaluate the efficacy of a single buccal infitration using 4% articaine hydrochloride (HCl) with 1 : 100,000 epinephrine or 4% articaine HCl with 1 : 100 000 epinephrine bitartrate for obtaining adequate pulpal anaesthesia in the palatal roots of maxillary first molars associated with irreversible pulpitis. In this single-blind randomized clinical trial, fifty subjects were randomly allocated to receive maxillary buccal injections of 1.5 mL 4% articaine with 1 : 100,000 epinephrine (n = 25) or 1.5 mL 4% articaine with 1 : 100,000 epinephrine bitartrate (n = 25). Visual analogue scale (VAS) scores and pulse rate measurements were recorded during access cavity preparation and initial file placement into the mesiobuccal, distobuccal and palatal canals. Data were analysed using Duncan and t-tests. There was no significant difference between the two anaesthetic solutions regarding the VAS scores and pulse rate measurements during endodontic procedures. The mean VAS ratings of the 50 patients during file placement into the palatal canals were significantly higher compared with the other three root canal procedures (P < 0.0001). The heart rates during negotiation of palatal canals were significantly higher than when negotiating the mesiobuccal and distobuccal canals (P < 0.0001). Single buccal infiltration did not achieve adequate pulpal anaesthesia in the palatal root canal of the maxillary first molars associated with irreversible pulpitis.

Use of neuroactive catecholamines to chemically induce metamorphosis of hatchery-reared flat oyster,Ostrea angasi, larvae

Low numbers and unreliable wild catch of the native flat oyster, Ostrea angasi, spat has resulted in the NSW flat oyster industry being reliant on hatchery-produced spat. The need to produce culchless spat in the hatchery stimulated investigation of several catecholamines to induce metamorphosis in O. angasi larvae. Larvae were treated with one of four neuroactive catecholamines (epinephrine, epinephrine bitartrate, l-Dopa and GABA) at one of four concentrations (10−3, 10−4, 10−5 or 10−6 m) for one of three treatment durations (0.5, 1–2 h) to determine morphogenic action for culchless spat production. Epinephrine bitartrate at 10−3 and 10−4 m and epinephrine at 10−3, 10−4 and 10−5 m, for a treatment duration of 1–2 h, produced significantly greater numbers of spat and culchless spat, compared with any other treatment combination. The other catecholamines tested did not induce a significant increase in the total number of spat or culchless spat, over untreated controls. Separate trials found that long-term treatment (24 h) with epinephrine bitartrate and epinephrine at morphogenic concentrations inhibited metamorphosis. Consecutive daily use of epinephrine bitartrate increased the numbers of spat and culchless spat produced, but did not affect larval or short-term post-larval survival. Treatment with 10−3 m epinephrine bitartrate or 10−4 m epinephrine for 1 h is recommended for routine commercial production of culchless flat oyster spat.

Fast-Disintegrating Sublingual Epinephrine Tablets: Effect of Tablet Dimensions on Tablet Characteristics

ABSTRACTThe purpose of this study was to evaluate the effect of changing dimensions on the hardness (H), disintegration time (DT), and wetting time (WT) of fast-disintegrating epinephrine tablets for sublingual administration as potential first aid treatment for anaphylaxis. Tablet formulations I and II, containing 0% and 10% epinephrine bitartrate, respectively, and weighing 150 mg were prepared by direct compression. Formulations were compressed at a range of forces using an 8/32″ die with concave punches (CP); a 10/32″ and an 11/32″ die with CP and flat punches (FP). Tablet weight variation, content uniformity, thickness, H, DT, and WT were measured. The 8/32″, 10/32″, and 11/32″ dies resulted in tablet thickness of ranges 0.25–0.19″, 0.17–0.1″, and 0.16–0.08″, respectively. The DT and WT using the 8/32″ die were ≤10 and ≤30 sec, respectively, at H ≤5.4 ± 0.2 kg for formulation I, and H ≤5.4 ± 0.3 kg for formulation II. The DT and WT were ≤10 and ≤30 sec, respectively, using 10/32″ die/CP, 10/32″ die/FP, 11/32″ die/CP, and 11/32″ die/FP at H ≤6.2 ± 0.6 kg, ≤6.8 ± 0.4 kg, ≤4.9 ± 0.1 kg, and ≤7.2 ± 0.3 kg, respectively, for formulation I. For formulation II, the DT and WT were ≤10 sec and ≤30 sec, respectively, when H < 4 kg. No difference in DT and WT was observed between concave and flat tablets. The 11/32″ and 10/32″ dies resulted in more ideal tablet dimensions for sublingual administration, but H must be maintained <4 kg to ensure rapid DT and WT.

Fast-disintegrating sublingual tablets: effect of epinephrine load on tablet characteristics.

The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9:1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time, and friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation and content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times of A, and an exponential increase in disintegration and wetting times of B, C, and D. At a mean +/- SD hardness of > or = 2.3 +/- 0.2 kg, all tablet formulations passed the USP friability test. At a mean +/- SD hardness of < or = 3.1 +/- 0.2 kg, all tablet formulations resulted in disintegration and wetting times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times, and wetting times suitable for sublingual administration.

Dose response of dexamethasone for the enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

We have previously shown that administration of epinephrine to the rabbit eye with dexamethasone pretreatment resulted in a significant decrease in intraocular pressure (IOP), compared to the use of epinephrine alone. Furthermore, this decrease in IOP is dose-dependent on epinephrine with the largest response of decrease of IOP occurring at the lower doses of epinephrine. We now extend this study to determine whether the decrease in IOP is dose-dependent on dexamethasone. Rabbit eyes were pretreated with five applications of topical dexamethasone or saline, administered at fifteen-minute intervals. Eyes were then treated with 0.005% epinephrine (0.01% epinephrine bitartrate). IOP was monitored for the next four hours. Different groups of rabbits received varying concentrations of dexamethasone base, from 0.0004% to 0.07% (dexamethasone phosphate), and a dose response curve was obtained. When compared to eyes treated with epinephrine alone, eyes pretreated with dexamethasone showed a significantly greater decrease in pressure at free base dexamethasone concentrations of 0.07%, 0.007% and 0.0007%, with the greatest difference at the 0.007% concentration (mean = 6.8 mm Hg). Similarly, the duration taken for the IOP to return to baseline levels was prolonged in the groups receiving dexamethasone pretreatment. The synergism between dexamethasone and epinephrine in lowering IOP may be a useful alternative in the treatment of ocular hypertension and glaucoma especially using a combination of a low dose of epinephrine with a low dose of dexamethasone.

Enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to epinephrine applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbit eyes were pretreated with five applications of topical 0.07% dexamethasone (0.1% dexamethasone phosphate) or saline drops, administered at ten minute intervals. The eyes were then treated with epinephrine bitartrate drops at concentrations of free base epinephrine of 1.1%, 0.27%, 0.05%, 0.027%, 0.005% or 0.0005%. An additional group of rabbits received dexamethasone pretreatment only. Intraocular pressure (IOP) was measured for the next four hours. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of epinephrine with dexamethasone had the largest decrease in IOP at 135 minutes after instillation of the epinephrine drops (0.005% epinephrine, mean difference +/- standard error of mean = 5.4 +/- 1.1 mmHg). Similarly, the duration of significant decrease of the IOP was prolonged in the groups receiving the lower concentrations of epinephrine (0.005% epinephrine, 255 minutes after administration of epinephrine). The synergism between glucocorticoids and adrenergic agonists in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.

Comparison of some properties of pronethalol and propranolol. 1965.

Comparison of some properties of pronethalol and propranolol. 1965.

Lack of influence of circulating adrenaline on blood pressure in normotensive and hypertensive rats.

The relationship between circulating adrenaline and blood pressure was examined by manipulating plasma adrenaline levels in both normotensive and hypertensive rats: bilateral adrenalmedullectomy was performed in spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats; adrenaline bitartrate was infused chronically (25-32 micrograms/kg/h s.c.) into Wistar Kyoto, Sprague Dawley and stroke-prone rats via osmotic minipumps. Arterial and venous catheters were subsequently implanted for direct measurement of mean arterial pressure, blood sampling and drug administration in conscious rats. Adrenaline infusion for 5-6 weeks in Wistar Kyoto rats did not affect resting blood pressure (118 +/- 3 versus 119 +/- 1 mmHg in controls) even though plasma adrenaline was elevated 12-fold. Plasma noradrenaline was marginally elevated. Blood pressure was also unaffected by adrenaline infusion in Sprague Dawley or stroke-prone hypertensive rats. One week after adrenal medullectomy, plasma adrenaline was reduced 89% in spontaneously hypertensive rats, but blood pressure was unaffected. Ten weeks after adrenal medullectomy in young stroke-prone rats, resting blood pressure was slightly higher (167 +/- 2 mmHg) than in control rats (157 +/- 2 mmHg), although adrenaline was reduced by 34% in plasma and 67% in adrenal glands. Nitroprusside was infused acutely to lower blood pressure and reflexly elevate plasma noradrenaline. Neither of these responses were affected by chronic adrenaline infusion or adrenal medullectomy. In both adrenaline-infused Wistar Kyoto and medullectomised stroke-prone rats, autonomic blockade reduced blood pressure to a similar extent as in controls, indicating that the degree of sympathetic vasoconstriction was not altered by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)