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pharmacodynamic acetaminophen

Marianne J Chapman, Adam M Deane, Stephanie L O'Connor, Nam Q Nguyen, Robert J L Fraser, Duncan B Richards, Kimberley E Hacquoil, Lakshmi S Vasist Johnson, Matthew E Barton, George E Dukes
BACKGROUND: The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients. METHODS: A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]...
2016: Critical Care: the Official Journal of the Critical Care Forum
Shingo Tanaka, Satoko Hori, Hiroki Satoh, Yasufumi Sawada
AIM: Use of nonsteroidal antiinflammatory drugs (NSAIDs) during the final trimester of pregnancy can cause fetal toxicity, such as ductus arteriosus (DA) constriction. The aim of this study was to predict quantitatively the fetal DA-constrictive effects of NSAIDs after various routes of administration to the mother by means of harmacokinetic/pharmacodynamic (PK/PD) modeling. METHODS: We evaluated acetaminophen, which is a first-line analgesic/antipyretic for the third trimester of pregnancy, together with the following NSAIDs: indometacin, diclofenac, ibuprofen, flurbiprofen, ketoprofen, loxoprofen, felbinac, naproxen, and celecoxib...
October 2016: International Journal of Clinical Pharmacology and Therapeutics
Mellar P Davis
INTRODUCTION: Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid abuse, misuse; addiction and diversion. Guidelines have been published to guide management; neuromodulation, exercise, mindfulness-based stress reduction and cognitive behavior therapies among other non-pharmacological reduce the pain of CLBP with minimal toxicity. Pharmacological management includes acetaminophen, NSAIDs and antidepressants, mainly duloxetine...
July 2016: Expert Opinion on Drug Metabolism & Toxicology
Stanley Cohen, Megan Clowse, Patricia Pardo, Indranil Bhattacharya, Sandeep Menon, Ian Gourley, Annette Diehl
PURPOSE: SBI-087 is a Small Modular Immunopharmaceutical Protein™(SMIP™) drug that binds to CD20 and has been reported to deplete B cells in murine/primate studies. The safety, tolerability and pharmacokinetic/pharmacodynamic properties of SBI-087 were evaluated in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). METHODS: Single-dose SBI-087 was evaluated in 2 Phase I, open-label, escalating-dose studies in patients with RA or SLE...
June 2016: Clinical Therapeutics
Tingting Yan, Hong Wang, Min Zhao, Tomoki Yagai, Yingying Chai, Kristopher W Krausz, Cen Xie, Xuefang Cheng, Jun Zhang, Yuan Che, Feiyan Li, Yuzheng Wu, Chad N Brocker, Frank J Gonzalez, Guangji Wang, Haiping Hao
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice...
May 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
B KuKanich
The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4-23.1 mg/kg) and codeine phosphate at 90 mg (2.1-3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6-2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine-6-glucuronide were 7...
October 2016: Journal of Veterinary Pharmacology and Therapeutics
Terri L Morton, Krishna Devarakonda, Kenneth Kostenbader, Jeannie Montgomery, Thomas Barrett, Lynn Webster
OBJECTIVE: To correlate abuse-related pharmacodynamic measures and pharmacokinetic measures after administering immediate-release/extended-release and immediate-release oxycodone/acetaminophen fixed-dose combination analgesics DESIGN: Randomized, double-blind, active- and placebo-controlled, 7-way crossover study SETTING: Contract research organization SUBJECTS: Nondependent recreational users of prescription opioids. METHODS: Participants received single doses of intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 15/650 mg, intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, crushed immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, and placebo...
August 25, 2015: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
L Manchikanti, S Atluri, A M Kaye, A D Kaye
Hydrocodone bitartrate is the most commonly used drug for acute and chronic pain in the U.S. with over 135 million prescriptions in 2012. The U.S. is the primary consumer of hydrocodone, using 99% of the global supply for 4.4% of the global population. With its easy availability and abuse patterns, hydrocodone has been touted as a primary driver of opioid-related abuse and misuse. There are no clinical efficacy studies of hydrocodone in short-acting form in combination with acetaminophen or ibuprofen in chronic pain...
July 2015: Drugs of Today
Markus Gosch
Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults...
July 2015: Zeitschrift Für Gerontologie und Geriatrie
Nirav Shastri
Acetaminophen is a commonly used pediatric medication that has recently been approved for intravenous use in the United States. The purpose of this article was to review the pharmacodynamics, indications, contraindications, and precautions for the use of intravenous acetaminophen in pediatrics.
June 2015: Pediatric Emergency Care
Joseph V Pergolizzi, Robert Taylor, Robert B Raffa
Acute pain, prevalent as part of postoperative and traumatic pain, is often sub-optimally or inadequately treated. Fixed-dose combination analgesic products that combine a reduced amount of opioid with a nonopioid analgesic such as acetaminophen (paracetamol) in a single tablet offer potential pharmacodynamic and/or pharmacokinetic benefits, and may also result in an opioid-sparing effect. A new analgesic product (XARTEMIS™ XR, Mallinckrodt Brand Pharmaceuticals, Dublin, Ireland) combines oxycodone (7.5 mg) with acetaminophen (325 mg) in an immediate-release/extended-release (ER) formulation that is indicated for the treatment of acute pain...
June 2015: Advances in Therapy
Hartley C Atkinson, Amanda L Potts, Brian J Anderson
BACKGROUND: Increased bioavailability of phenylephrine is reported when combined with paracetamol in over-the-counter formulations for the symptomatic treatment of the common cold and influenza. Such formulations could increase phenylephrine-related cardiovascular adverse events particularly in susceptible individuals. Quantification of the effect of phenylephrine concentration on blood pressure allows simulation of potential adverse combination therapy effects. METHODS: MEDLINE and EMBASE databases were searched for papers discussing or describing any adverse effect, hypersensitivity or safety concerns related to phenylephrine alone or in combination with other drugs...
August 2015: European Journal of Clinical Pharmacology
Joseph V Pergolizzi, Gül Köknel Talu, Gianpetrio Zmponga, Serdar Erdine, Robert Taylor, Burak Ayan, Robert B Raffa
The modern approach to the management of pain involves optimizing all aspects of the process. This includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiology of the pain with the analgesic's mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfies all of the requirements for all patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are effective options for inflammatory pain and, as is acetaminophen, for mild pain...
2015: Aǧrı: Ağrı (Algoloji) Derneği'nin Yayın Organıdır, the Journal of the Turkish Society of Algology
Milena Mennecozzi, Brigitte Landesmann, Taina Palosaari, Georgina Harris, Maurice Whelan
There is increasing amount of evidence for sex variation in drug efficiency and toxicity profiles. Women are more susceptible than men to acute liver injury from xenobiotics. In general, this is attributed to sex differences at a physiological level as well as differences in pharmacokinetics and pharmacodynamics, but neither of these can give a sufficient explanation for the diverse responses to xenobiotics. Existing data are mainly based on animal models and limited data exist on in vitro sex differences relevant to humans...
2015: PloS One
Kay Brune, Paola Patrignani
Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2...
2015: Journal of Pain Research
Todd J Zurlinden, Brad Reisfeld
The principal aim of this study was to develop, validate, and demonstrate a physiologically based pharmacokinetic (PBPK) model to predict and characterize the absorption, distribution, metabolism, and excretion of acetaminophen (APAP) in humans. A PBPK model was created that included pharmacologically and toxicologically relevant tissue compartments and incorporated mechanistic descriptions of the absorption and metabolism of APAP, such as gastric emptying time, cofactor kinetics, and transporter-mediated movement of conjugated metabolites in the liver...
June 2016: European Journal of Drug Metabolism and Pharmacokinetics
A Raskovic, I Milanovic, N Pavlovic, B Milijasevic, M Ubavic, M Mikov
OBJECTIVE: The use of herbal medicinal products in the management of pain has been increasing steadily in recent years, often in combination with conventional analgesics, which can induce significant interactions. In traditional medicine, rosemary was used as mild analgesic, for relieving renal colic pain and dysmenorrhea. The aim of our study was to examine analgesic effects of rosemary essential oil and its pharmacodynamic interactions with codeine and paracetamol in mice. MATERIALS AND METHODS: The identification and quantification of chemical constituents of the essential oil isolated from air-dried aerial parts of rosemary were carried out by GC/FID and GC/MS...
January 2015: European Review for Medical and Pharmacological Sciences
C Mattia, A Ferrari
Acute pain of mild to moderate intensity is one of the problems most frequently encountered in primary care and emergency medicine and is a major reason of request for visit by patients. In recent years the focus has been more on the treatment of chronic pain, perhaps ignoring the negative impact of acute pain on quality of life and functional status of the patient, despite a growing number of evidence indicating the need to treat optimally also acute pain to avoid it prolongs in time. The remarkable progress achieved in the understanding of the physiological mechanisms of the nociceptive stimulus, as well as those common to biochemical inflammation and acute pain, highlighted the active and complex role of central nervous system in the genesis and maintenance of pain that from acute, if not promptly and adequately treated, can become chronic...
December 2014: Minerva Medica
Swagatika Sahoo, Hulda S Haraldsdóttir, Ronan M T Fleming, Ines Thiele
Metabolism contributes significantly to the pharmacokinetics and pharmacodynamics of a drug. In addition, diet and genetics have a profound effect on cellular metabolism with respect to both health and disease. In the present study, we assembled a comprehensive, literature-based drug metabolic reconstruction of the 18 most highly prescribed drug groups, including statins, anti-hypertensives, immunosuppressants and analgesics. This reconstruction captures in detail our current understanding of their absorption, intracellular distribution, metabolism and elimination...
January 2015: FEBS Journal
Uma A Bhosale, Rahul Khobragade, Chetana Naik, Radha Yegnanarayan, Jyoti Kale
BACKGROUND: The preclinical incision pain models and clinical studies in healthy volunteers have demonstrated the central serotonergic analgesic mechanism, paracetamol analgesia. This has been evidenced by raised serotonin concentrations in the brain following paracetamol administration in a few studies. The inhibition of paracetamol analgesia by 5-HT3 antagonists suggests that this analgesia is 5-HT3 mediated. However, in a few studies, 5-HT3 antagonists themselves exhibited an analgesic action...
May 2015: Journal of Basic and Clinical Physiology and Pharmacology
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