Psychopharmacology EMIs
Michael Reilly, Bangaru Raju in Extended Matching Items for the MRCPsych Part 1, 2018
Active transport.Bioavailability.Bioequivalence.Blood–brain barrier.Elimination half-life.First-order kinetics.First-pass effect.Plasma protein binding.Volume of distribution.Zero-order kinetics.
Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Body water is distributed primarily into the following major body compartments while the total body water as a percentage of body weight varies from 50% to 70% in women and men, respectively. Extracellular fluid comprises the blood plasma and contains approximately 4.5% of the body weight, while interstitial fluid is ∼16% while lymph ∼1.2%. Interstitial fluid (30%–40%) is the sum of the fluid contents of all cells in the body. Transcellular fluid (∼2.5) includes cerebrospinal, intraocular, peritoneal, pleural, and synovial fluids as well as digestive secretions. Fat is ∼20% (Rang et al., 2016). Within each of the aqueous compartments, substances usually exist both in free solution and in bound form. Substances are transported via the circulatory system partially unbound and partly bound as noted previously. Proteins such as albumin chemically “lock” a substance which renders it pharmacologically inactive while the unbound portion of the substance is considered to be the free fraction and is the pharmacologically active portion of the substance. Plasma protein binding significantly influences both the distribution and the relationship between the pharmacological activity and the substance concentration in the plasma (Waterhouse and Farmery, 2012). As the number of available binding sites approaches saturation at higher substance concentration levels, other substances may be displaced. This displacement activity is a critical function in chemical interactions.
Adrenergic Antagonists
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
It is an adrenergic nonselective β adrenergic blocker which is hydrophilic in nature. The drug does not show ISA or membrane-stabilizing activity. Apart from its β blockade property it has activity on cardiac ion channels which helps in prolonging action potential and because of this it is used in the treatment of arrhythmia. Studies report a typical hemodynamic activity of sotalol; reduced cardiac output and the rate of the heart with not much change in the BP and the stroke volume, respectively. After an oral dose the drug has a bioavailability of 100% as the first-pass metabolism is not significant. It reaches the peak plasma concentration in about 2–3 h. The Vd is 1.3 L/kg. The drug shows negligible plasma protein binding. Excretion occurs renally with about 75% excretion occurring in 72 h. Half-life range is about 7–18 h (Antonaccio et al., 1990; Brunton et al., 2011; Taboulet et al., 1993).
Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Nawaf A. Alsaif, Mohammed S. Taghour, Mohammed M. Alanazi, Ahmad J. Obaidullah, Abdulrahman A. Al-Mehizia, Manal M. Alanazi, Saleh Aldawas, Alaa Elwan, Hazem Elkady
To investigate pharmacokinetics properties of the prepared compounds, computer aided ADME studies were accomplished using Accelrys Discovery Studio 4.0 software. Sorafenib was used as a reference molecule. These studies include the estimation of certain parameters. 1) Blood brain barrier penetration which measures the ability of molecule to diffuse through blood brain barrier. 2) Absorption level which determines human intestinal absorption (HIA) of a chemical after its oral administration. A well-absorbed compound is one that is absorbed at least 90% into the blood stream59,60. iii) Solubility level in which the solubility of a chemical in water was predicted at 25 °C. iv) CYP2D6 binding which analyzes cytochrome P450 2D6 enzyme inhibition61,62. v) Plasma protein binding which predicts the fraction of drug bound to plasma proteins in the blood63. The results were predicted and listed in Table 6.
In silico screening and identification of potential GSK3β inhibitors
Published in Journal of Receptors and Signal Transduction, 2018
Trinath Daggupati, Rishika Pamanji, Suneetha Yeguvapalli
We used preADMET online server (http://preadmet.bmdrc.org) to calculate ADME properties for the following parameters. (a) Percent human intestinal absorption (%HIA – Zhao et al. [30] reported that most of the absorption data found in the literature was based on bioavailability, excretion in urine, feces following oral administration or on the ratio of cumulative urinary excretion of drug-related material following oral and intravenous administration (b) in vitro Caco2 cell permeability, (c) in vitro Maden Darby Canine Kidney (MDCK) cell permeability (Caco-2 cell model and MDCK cell models are the reliable in vitro models for the prediction of oral drug absorption), (d) in vitro plasma protein binding (Plasma protein binding influences drug action, disposition and efficacy), and (e) Blood–Brain Barrier (BBB) penetration.
Disposition and metabolism of antibacterial agent, triclocarban, in rodents; a species and route comparison
Published in Xenobiotica, 2020
Suramya Waidyanatha, Sherry R. Black, Purvi R. Patel, Scott L. Watson, Rodney W. Snyder, Vicki Sutherland, Jason Stanko, Timothy R. Fennell
Clearance of triclocarban was investigated in male and female rat, mouse, and human hepatocytes. Concentration versus time plots are presented in Supplementary Figure S8. Half-life and clearance data are presented in Table 7. In rats, the clearance of triclocarban was slow with 4.3 and 5.1 mL/min*kg for male and female rats; corresponding half-lives were 843 and 742 min, in males and females, respectively. Clearance of triclocarban in mice and human hepatocytes were similar (8.1 to 10.2 mL/min*kg) and was ∼2-fold higher than in rat hepatocytes; half-lives were 359–398 min. There was no sex difference in clearance of triclocarban in any of the three species investigated. Plasma protein binding was investigated in rat, mouse, and human plasma. Triclocarban was highly bound to plasma protein with 99.9% bound in all three species. Metabolite identification in hepatocytes was also conducted with LC-MS analysis. Low levels of metabolites were detected and identified in human and mouse hepatocytes, but not in rat hepatocytes. These included hydroxy-triclocarban, triclocarban-O-sulfate, and triclocarban-O-glucuronide.
Related Knowledge Centers
- Globulin
- Intrinsic Activity
- Glycoprotein
- Cell Membrane
- Blood Plasma
- Serum Albumin
- Medication
- Blood Protein
- Drug
- Lipoprotein