BBB, CNS, Anesthetic Gases Review Slides Exam 44 Questions with Verified Answers,100% CORRECT

BBB, CNS, Anesthetic Gases Review Slides Exam 44 Questions with Verified Answers Routes of transport across BBB (not on review slides, but on Kahoot) - CORRECT ANSWER Paracellular route -between cells -ions and hydrophillic subtances Transcellular route -through the cells -respiratory gases, water, lipophilic substances Active transport -movement of molecules by specific transporters or endocytosis Blood-CSF barrier - CORRECT ANSWER The choroid plexus forms CSF and regulates concentration of molecules in CSF Choroid plexus consists of highly vascularized masses of pia mater tissue that dip into pockets formed by ependymal cells Choroidal epithelial cells also form tight junctions that prevent macromolecules from effectively passing into the CSF from the blood Compared to BBB endothelial cells, CSF epithelial cells have less resistance Nociceptors - CORRECT ANSWER Sensory neurons that respond to pain Substance P - CORRECT ANSWER Key neurotransmitter in pain transmission Opioids inhibit the release of substance P by bonding to opioid receptors (e.g. morphine binds to Mu, Kappa, and perhaps Delta receptors) This blocks the message before it reaches the brain and is perceived as pain Intrathecal drug delivery - CORRECT ANSWER Places medication directly into the CSF that surrounds the spinal cord Morphine - CORRECT ANSWER Morphine delivered directly into the intrathecal space is particularly effective because it does not have to circulate systemically to reach the CSF and the dorsal horn of the spinal cord As a result, much smaller doses are needed (approx 1/300th), and frequency of SEs is reduced Intraspinal drug delivery - CORRECT ANSWER Provides agents directly into their site of action Intraspinal drug delivery via indwelling pump is an effective means of treating refractory pain Epidural drug administration - CORRECT ANSWER The term epidural is short for epidural anesthesia, a form of regional anesthesia involving injection of drugs through a catheter placed into the epidural space Anaesthesia - CORRECT ANSWER Loss of sensation Analgesia - CORRECT ANSWER Loss of pain Epidural space - CORRECT ANSWER (aka extradura space or peridural space) A part of the human spine inside the spinal canal separated from the spinal cord and its surrounding CSF by the dura mater Modalities for drug delivery across BBB - CORRECT ANSWER Disruption of the BBB by osmotic means The use of vasoactive substances such as bradykinin Use of vesicles such as liposomes, nanoparticles and microspheres Prodrugs Localized exposure to ultrasound Disruption of BBB by osmotic means - CORRECT ANSWER Intracarotid arterial administration of hypertonic solutions Intracarotid or intravertebral infusion of hyperosmotic saccharides (mannitol) leads consistently to a reversible opening of the barrier BBB and vasoactive substances - CORRECT ANSWER Administration of endogenous ligands or their analogs to increase BBB permeability Brain endothelial cells possess numerous neurotransmitter and peptide receptors on both their luminal and abluminal membrane surfaces Vasoactive substances - CORRECT ANSWER Histamine, serotonin, adenosine, arachidonic acid, bradykinin Bradykinin - CORRECT ANSWER An endogenous nonapeptide Cereport - CORRECT ANSWER API: Labradimil or RMP-7 B2 bradykinin receptor agonist Transiently increases permeability of BBB Nanocarriers - CORRECT ANSWER Active targeting is a non-invasive approach, which consists in transporting drugs to target organs using site-specific ligands Drug-loaded nanocarriers capable of recognizing brain capillary endothelial cells and cerebral tumor cells have shown promising potential in oncology Endogenous and chimeric ligands binding to carriers or receptors of the BBB have been directly or indirectly conjugated to nanocarriers Micelles and brain delivery - CORRECT ANSWER Polymeric micelles are formed from a spontaneous association of amphiphilic copolymers in aqueous phase Characterized by a diameter not exceeding 100 nm The attractive force leading to micellization is based on the interaction between the hydrophobic and electrostatically neutral parts of copolymers Critical micelle concentration (CMC) - CORRECT ANSWER Copolymer threshold value at which self-assembly starts Polyvinylpyrrolidone (PVP) - CORRECT ANSWER Commonly used polymer in micelles Liposomes and brain delivery - CORRECT ANSWER Liposomes are spherical vesicles with a membrane composed of a phospholipid bilayer used to deliver drugs or genetic material into a cell Phospholipid molecules - CORRECT ANSWER 3 major parts: 1 head, 2 chains Head: hydrophilic choline, phosphate, glycerol Tail: hydrophobic fatty acid Stealth or pegylated liposomes - CORRECT ANSWER Liposomes stabilized by conjugation with polyethylene glycol (PEG) In addition, receptor-specific monoclonal antibodies (mAbs) can also be attached to liposomes Prodrugs - CORRECT ANSWER Usually used to improve some deficient physiocochemical property such as membrane permeability or solubility Esterification or amidation of hydroxy-, amino- or carboxylic acid-containing drugs may greatly enhance lipid solubility and hence entry into the brain Gel - CORRECT ANSWER Solid or semisolid system of at least two constituents consisting of a condensed mass enclosing and interpenetrated by a liquid Jelly - CORRECT ANSWER When the coherent matrix is rich in liquid Xerogel - CORRECT ANSWER When the liquid is removed and only the framework remains Hydrogels - CORRECT ANSWER Gels that are dispersible in water Nanogels - CORRECT ANSWER Small hydrogel particles that have been synthesized by cross-linking of polyethyleneimine (PEI) with nonionic polythyleleglycol (PEG) chains using an emulsification/solvent evaporation technique Glial cells - CORRECT ANSWER Commonly called neuroglia or glia, are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system Glia outnumber neurons by as much as 50:1 Gliadel wafer - CORRECT ANSWER API: carmustine Polymer: biodegradable polyanhydride copolymer Anesthetic gases - CORRECT ANSWER For more extensive surgical procedures, anesthesia frequently includes the use of preoperative benzodiazepines, IV thiopental or propofol and maintenance with inhaled and IV anesthetic drugs Nitrous oxide - CORRECT ANSWER An important anesthetic agent Other volatile liquids for inhalation are halothane, enflurane, isoflurane and sevoflurane Brain delivery of anesthetic gases - CORRECT ANSWER Depends on several factors including gas partial pressure, solubility of the anesthetic, concentration in the inspired air, pulmonary blood flow and ventilation rate The gas usually moves from alveolar air to the blood and then the brain Blood-gas partition coefficient - CORRECT ANSWER Good index of solubility and defines relative affinity of an anesthetic for the blood compared to air Partition coefficients for desflurane and nitrous oxide - CORRECT ANSWER Less than 0.5 Partition coefficient for halothane - CORRECT ANSWER Greater than 2 Blood solubility and partial pressure (tension) - CORRECT ANSWER Blood solubility is inversely related to partial pressure (tension), so nitrous oxide with low blood solubility reaches high arterial tension rapidly and equilibrates faster with the brain In other words, low blood-gas partition coefficient = faster onset of anesthesia Desflurane and servoflurane - CORRECT ANSWER Also have low blood-gas partition coefficients and thus cause rapid onset of anesthesia Halothane - CORRECT ANSWER Has a moderate solubility and thus a slow onset of action Ventilation - CORRECT ANSWER The rate of rise of anesthetic gases is also dependent on the rate and depth of ventilation Arterial tension of agents with moderate (halothane) to high solubility (methoxuflurane) increase with hyperventilation Pulmonary blood flow - CORRECT ANSWER An increase in pulmonary blood flow (increased cardiac output) slows down arterial tension (inverse relationship) since a larger volume of blood is exposed to the anesthetic Arteriovenous concentration gradient - CORRECT ANSWER Also affects brain delivery much in the same way it affects other diffusional processes i.e. the higher the gradient, the faster the brain delivery