Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although numerous NSAIDs are available for use in the management of rheumatic disease, most of the members of this large class of drugs possess very similar characteristics. The great majority are acidic compounds. The acidity of the drugs allow distribution not only into inflamed tissues but also the kidneys and gastric mucosa. It is likely that these compounds produce anti-inflammatory analgesia by inhibiting prostaglandin synthesis. As a result of these similarities, NSAIDs have in general relative similar efficacy and toxicity when used in appropriate dosages. Common adverse effects include dyspepsia, gastritis, mucosal ulcers, interstitial nephritis and acute renal failure. Most of the adverse effects associated with the clinical use of these drugs are related to their effect on prostaglandin production. In some susceptible individuals, the inhibition of prostaglandin synthesis may result in a potentially fatal bronchospastic episode. Most clinical trials fail to consistently distinguish between NSAIDs. Patients however often develop distinct preferences for certain NSAIDs. The reason for this is still obscure but may reflect subtle pharmacological differences between these drugs. NSAIDs with short half-lives are quite effective on an 8 or 12 hourly dosage regimen. Compounds with longer half-lives may be associated with accumulation in the elderly and hence a higher risk of toxicity. The use of NSAIDs in the management of rheumatic disease should therefore be highly individualised.
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PMID:NSAIDS--a consideration of their efficacy and toxicity. 265 71

The H2-receptor antagonist, cimetidine, was used instead of magnesium trisilicate BPC as routine antacid therapy before both elective and emergency obstetric anesthesia. Two trials of its efficacy in increasing intragastric pH and decreasing the volume of gastric contents in parturients are reported. In the first trial, 400 mg of cimetidine given orally to patients being delivered by elective cesarean section effectively decreased gastric acidity, providing induction of anesthesia occurred 90-150 min after its administration. Of 62 patients requiring emergency anesthesia during active labor and who had been treated with 200 mg of cimetidine orally at 2-h intervals, 80% had gastric contents with a pH higher than 2.5. Failure to decrease gastric acidity to this level was mainly due to anesthesia being required within 60 min of the loading dose, but it also was considered that inaccurate timing of repeat doses and possibly delay in uptake due to gastric stasis by narcotic analgesia played a part. In trial 2 the same cimetidine regimen plus a 15-ml oral dose of 0.3 M sodium citrate given 10 min before induction of anesthesia was studied. All 72 women delivered by elective cesarean section had a low volume of gastric contents with pH greater than 2.5. Only 4% of 135 patients requiring emergency anesthesia had gastric aspirates the pH of which was less than 2.5. The volume (97 +/- 8.4 ml) of gastric contents removed from the latter patients were considered to still pose a hazard at induction of general anesthesia. No maternal or infant side effects related to cimetidine therapy were noted.
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PMID:Use of cimetidine as an oral antacid in obstetric anesthesia. 634 54

Seventy-two healthy dogs required sedation and analgesia for a variety of procedures causing discomfort or pain. They were treated either with the alpha 2-agonist medetomidine at 40 micrograms/kg (15 intravenously and 17 intramuscularly), or 80 micrograms/kg (15 intravenously and 15 intramuscularly) or with xylazine plus l-methadone (1.0 mg)(10 intravenously). The levels of sedation, analgesia and safety were compared clinically and by measurements of the effects on the electrocardiogram (ECG) and blood gases, body temperature, haematology and clinical chemistry. Sedation was achieved reliably with both medetomidine and xylazine plus l-methadone but its onset, depth and duration were influenced by the dose and route of administration. In the medetomidine-treated dogs, intravenous administration resulted in more rapid sedation and the effects of the higher dose were deeper and longer lasting. The small dogs receiving 40 micrograms/kg may have been underdosed. The initial analgesic effects in response to a pin prick to the body surface were sufficient and similar for both drugs, except for the intramuscular dose of 40 micrograms/kg medetomidine. Analgesia for the clinical procedures was less reliable with medetomidine and was not always adequate even at the high dose, but xylazine plus l-methadone assured analgesia in almost every case. Medetomidine resulted in marked bradycardia, lasting as long as the sedation and the ECG revealed a sinus arrhythmia with sinoatrial and atrioventricular blocks grade I and II as a sign of interference with transduction. The bradycardia with xylazine plus l-methadone was less pronounced. A decrease in respiratory rate accompanying sedation had no influence on blood gases and blood acidity in the dogs treated with medetomidine but caused a respiratory acidosis with xylazine plus l-methadone. Body temperature decreased with all treatments for the duration of the period of sedation. Blood glucose concentration increased to a similar extent in all treatment groups, but all other haematological and clinicochemical variables remained unchanged. Treatment with the specific alpha 2 antagonist, atipamezole, reversed the sedation and cardiovascular and pulmonary effects due to medetomidine within minutes.
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PMID:Clinical comparison of medetomidine with xylazine/l-methadone in dogs. 865 Sep 15

CKD-732 [6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate] is a new fumagillin anticancer drug that belongs to an angiogenesis inhibitor. Its effect on the central nervous system (CNS), general behavior, cardiovascular-respiratory system and the other organ systems were studied. CKD-732 was intravenously administered with the dosages of 10, 30, 40 or 50 mg/kg and the highest dosage of 50 mg/kg prolonged the hexobarbital-induced sleep time. CKD-732 at the dosage of 50 mg/kg, also, caused the decrease of body temperature from 15 to 120 min after the administration, which was recovered at 240 min. In the study of the effects on gastric secretion, CKD-732 induced the increase of pH and decrease of total acidity. However, CKD-732 showed no effect on general behavior, spontaneous locomotor activity, motor coordination, analgesia, convulsion, mean arterial pressure, and cardiac functions except for heart rate of isolated rat heart, respiration, isolated smooth muscle, intestinal charcoal transport and renal function. Based on the results, we suggested that CKD-732 is safe general pharmacologically at clinical supposed dose (1.75 mg/kg) and demonstrated to have much better safety than other fumagillin derivatives.
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PMID:General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system. 1568 72

Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague-Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular-respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbital-induced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.
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PMID:Safety pharmacology of sibutramine mesylate, an anti-obesity drug. 1590 Oct 50

Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60-90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.
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PMID:Single-dose fentanyl sublingual spray for breakthrough cancer pain. 2390

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR) , and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial) . Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.
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PMID:General Pharmacology of Artesunate, a Commonly used Antimalarial Drug:Effects on Central Nervous, Cardiovascular, and Respiratory System. 2427 28

To prevent perioperative aspiration pneumonitis, it is necessary to reduce the volume and acidity of gastric content. The guideline for preoperative fasting published by Japanese Society of Anesthesiologists recommends fasting from intake of clear fluids, breast milk and nonhuman milk at least 2h, 4h and 6h, respectively, before elective procedures requiring general anesthesia, regional anesthesia or sedation/analgesia. Gastrointestinal stimulants, histamine-2 receptor antagonists, proton pump inhibitors, antacids, antiemetics, anticholinergics are effective for reduction of the volume or acidity of gastric content. However, the routine preoperative use of these drugs to reduce the risk of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended.
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PMID:[Prevention of Perioperative Aspiration Pneumonitis]. 2700 83

Local anesthetics have been extensively employed to treat postoperative pain, but they generally suffer from short acting duration and potential neurotoxicity under high local concentrations, which require the controlled and sustained releasing patterns of treatment drugs. In this work, it is reported, for the first time, the construction of hollow mesoporous organosilica nanoparticles (HMONs)-based nanoplatforms for localized delivery and controlled/sustained release of loaded ropivacaine for local anesthetics, which can be repeatedly triggered by either external ultrasound irradiation or acidity triggering to release the payload, causing on-demand and long-lasting analgesia. Based on the in vivo mouse model of incision pain, the controlled and sustained release of ropivacaine achieves more than six hours of continuous analgesia, which is almost three times longer as compared to single free ropivacaine injection. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle-enabled analgesia are also demonstrated both in vitro and in vivo. This designed/constructed HMONs-based nanoplatform provides a potential methodology for clinical pain management via on-demand and long-lasting pain relief.
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PMID:Ultrasound/Acidity-Triggered and Nanoparticle-Enabled Analgesia. 3090 Nov 64