Complete Set for NE481 PDF

Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 1. Biomaterial a material intended to interface with biological systems to evaluate, treat, augment, or replace any tissue, organ, or function of the body...

Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 1. Biomaterial a material intended to interface with biological systems to evaluate, treat, augment, or replace any tissue, organ, or function of the body 2. Types of bioma- - metals terials (4) - ceramics - polymers - hybrid materials 3. Metals - strong - adaptable to form different shapes - conduct electricity 4. Ceramics - resistance to degradation in biological environments 5. Polymers - versatile - wide range of physical and chemical properties 6. Advantages of - variety of polymers available polymers (6) - ease of fabrication into many different forms - flexibility for soft tissues - very low or non-toxicity - light weight / density - low cost 7. Natural polymers - Extracellular matrix protein-based materials - Fibrin, fibrinogen - Polysaccharides - Glycosaminoglycans - Hyaluronic acid-based materials 8. Extracellular ma- - Collection of extracellular molecules secreted by cells trix that provide structural and biochemical support surround- ing the cells 9. What does ECM - Fibrous proteins --> collagen, elastin, fibronectin, lamin- consist of? in - Glycoaminoglycans --> heparan sulfate, chondroitin sul- fate 1 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 10. How do cells ad- A) Initial contact between cell and surface here to biomate- B) Formation of bonds between cell surface receptor and rials adhesion ligands C) cytoskeletal reorganization with spreading of the cell on the substrate for attachment strength 11. Integrins - transmembrane proteins - help cell-cell and cell-extracellular matrix adhesion - they transmit signals between the ECM and cytoskeleton 12. Driving forces of - secondary bond formations such as electrostatic ionic protein adsorp- bonds and hydrogen bonds tion - hydrophobic interaction 13. Protein activity 1. Increases local concentration after adsorption 2. changes reactivity. access to cell binding site increas- onto biomaterial es/decreases 3. denaturation. decreases binding to cell adhesion recep- tors 14. Low fouling sur- - prevents nonspecific protein binding faces 15. Chain hydration - hydrophilic surfaces are electrically neutral and have hydrogen bond acceptors and donors - zwitterionic surfaces are electrically neutral to proteins but allow for ionic solvation 16. protein absorp- reversible process tion 17. Micro- and Used in biomedical applications like drug delivery, imag- nanoparticles ing, research 18. Materials used - natural metals for microparticle - synthetic polymers synthesis 19. Microparticle - single and double emulsion preparation - precipitation and coacervation 2 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 (emulsion based) 20. Emulsions Heterogenous system. At least one immiscible liquid droplet phase dispersed in a second phase 21. Emulsifying - Mostly surfactants agents - lipophilic tail and hydrophilic head 22. How do emulsify- - Reduce interfacial tension ing agents stabi- - Forming a rigid interfacial film - mechanical barrier to lize (3) coalescence - Forming an electric double layer - electric barrier to approach particles 23. Forces of emulsi- - hydration forces --> O/W fiers - steric forces --> W/O - electrostatic forces --> ionic surfactant - polymers --> steric forces - solid powders --> hydrophobic forces 24. HLB - hydrophilic-lipophilic balance - describes interaction between oil and surfactant - for nonionic surfactants - emulsion is stabilized by matching the HLB of surfactant with required HLB - HLB number increases with hydrophilicity 25. How to deter- To determine HLB, calculate MW of ethylene oxide, cal- mine HLB culate total MW, find % of EO, and divide by 5 26. Suspension - coarse dispersion where solid particles are dispersed in liquid medium - for drugs that are unstable in solution - development of liquid dosage with sufficient drug in small volume 27. Formulation cri- - Slow settling and readily dispersed when shaken teria for mak- - Constant particle size throughout long periods of stand- 3 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 ing suspension ing products (3) - Pours readily and easily or flows through a needle 28. Topical suspen- - Spreads over surface but doesn't run off sion formulation - Dry quickly, remain on skin, provide an elastic protective film containing the drug - Acceptable colour and odor 29. Oral suspension - Easier to swallow - Flexibility in dose range - Flavored and sweetened 30. Topical suspen- - dry on skin after application sions - to be shaken before use 31. Parameters af- - particle size fecting suspen- - rate of sedimentation sion stability - zeta potential - particle surface hydration - flocculation - structured vehicles 32. Tablets - Solid preparation containing a single dose of one or more active ingredients obtained by compressing uniform volumes of particles - most common administration 33. Tablet composi- - approx 250 mg tion (6) - active ingredient --> drug (5-10%) - excipients --> inactive substance used as a carrier of active ingredient - fillers (80%) - binders (2-10%) - disintegrates (1-5%) - antifriction agents - glidants (1-2%) - lubricants (1%) 34. Classification of tablets 4 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 - immediate release - delayed release - extended release 35. Tablet types (4) - Disintegrate (immediate release) - Chewable (immediate release) - Effervescent (immediate release) - sublingual and buccal (immediate release) 36. Disintegrate - most common type tablet (3) - disintegration and dissolution time depends on choice of excipients - dissolution rate is the rate limiting step for hydrophobic drugs 37. Effervescent - dissolution in water prior to administration tablets (4) - used to obtain rapid drug action, fast bioavailability - achieved by using bicarbonate - used for analgesic drugs 38. Sublingual and - Sublingual --> under the tongue buccal tablets (2) - Buccal --> side cheek - both regions have high density blood vessels - rapid plasma drug concentration achieved without first pass liver metabolism 39. Tablet manufac- - die filling turing stages (3) - tablet formation - tablet ejection 40. Granulation - powder particles adhere to form large, multi-particle granules - occurs after dry mixing of powdered formulations so that uniform distribution of ingredients is achieved 41. Reasons for 1. prevent segregation of constituents in powder mix. granulation segregation is caused by different size and density of ingredients. 2. improve flow properties of the mix 3. improve compaction characteristics 5 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 4. reduce hazards of toxic dust of powders 5. reduce cost of storage and shipment 42. Dry granulation - Adhesion between particles is a result of applied pres- sure - forms a compact sheet, followed by milling and sieving 43. Wet granulation - dry powders are mixed with liquid under mechanical agitation - particles adhere to each other within a liquid film - nucleation, transition, ball growth 44. Compaction packing all components into a designated space 45. Compression reduction in volume 46. Direct com- - powder mixing and compaction in a tablet press paction without - for soluble and potent drugs granulation 47. Direct com- Pro: paction without - minimize production time and cost granulation ad- - improve drug stability given lack of heat or wetting treat- vantages and ment disadvantages Con: - need extra care on mixing, particles are prone to segre- gation - requires large quantity of excipients for drugs with poor compactability - requires specially designed fillers and dry binders - requires a large amount of quality tests before produc- tion 48. Compactability - ability of granules to form a porous specimen of defined shape during compression - poor compactability are more likely to have capping or lamination 49. 6 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 Fundamentals of - held within a confined space to reduce in volume while granule com- loading pression - rearrangement of particles in die for less porosity and closer packing - reduction in space will prevent interparticle movements 50. Problems with - variation in weight and dose manufacturing - low mechanical strength - capping and lamination - materials sticking to punch tips - friction during tablet ejection 51. Evaluation of - characterizing ejected tablets such as pore structure compression and pore size and distribution - characterizing compression and decrompression events such as punch force vs time, volume vs punch force. 52. Evaluation of - tensile strength and tensile fracture strength tablet strength - capping and lamination weaken tablet strength 53. Creaming upward movement of dispersed droplets 54. Sedimentation downward movement of dispersed droplets 55. Flocculation aggregation of droplets into larger units without any change in primary droplet size 56. Ostwald ripening aggregation of the droplet with change in primary droplet size 57. Coalescence thinning of the liquid film between droplets, with the result that fusion of two or more droplets occur to form larger droplets 58. nonionic emulsi- less sensitive to changes in pH, less GI irritatiing, suitable fying agent for drug administration 59. types of vessels arteries - distributing arterioles capillaries - rapid exchange 7 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 venules veins - collecting 60. structure of the has four chambers (right and left atriums, right and left heart ventricles) 61. types of muscle - skeletal - well defined contractile structures, (sarcoplas- cells mic reticulum) intracellular calcium storage - smooth - well defined contractile structures, (sarcoplas- mic reticulum) intracellular calcium storage - cardiac - electrically coupled to each other by gap junc- tions 62. cross-bridge cy- As the thick and thin filaments interact, the sarcomeres cling (sarcomere shorten, pulling the ends of the muscle fiber closer to- shortening) gether 1. myosin head attaches to actin in thin filament to form a cross bridge 2. Pi is released, initiating power stroke. myosin head pivots and bends as it pulls on thin filament. ADP is released 3. new ATP attaches to myosin head, link between myosin and actin weakens and detatches 4. ATP is split into ADP and Pi, myosin head is energized. cocked into high energy conformation 63. sarcomere contractile unit of a muscle fiber 64. excitation-con- - connection between muscle fiber stimulation and muscle traction contraction coupling - more calcium entry produces more contractile force characteristics - extracellular calcium concentration increases, intracellu- lar Ca2+ and force increase 65. excitation-con- surface membrane depolarization > calcium entry > in- traction coupling crease in intracellular free Ca2+ > calcium binding to troponin C > crossbridge cycling > force generation 66. electrical excita- - self-initiating action potential, no need for neural initia- tion of the heart tion 8 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 1. starts in the sinoatrial node (SAN) in the right atrium 2. spreads through atria 3. hits atrioventricular node (AVN) which delays the spread of excitation to ventricles so that the volume can fill in ventricles - synchronized ventricular contraction 67. electromechani- P - atrial depolarization cal events of the QRS - ventricular depolarization heart T - ventrical repolarization 68. cardiac output heart rate x stroke volume 69. blood vessel - transport oxygen and carbon dioxide function - transport nutrients - transport cells of immune systems - transport chemical messengers (hormones, clotting fac- tors) 70. hydraulic filter of - dampens impact of pulsatile pressure the heart - maintain steady flow in capillary networks 71. smooth muscle - slower than skeletal or cardiac muscle contraction - from increase in intracellular Ca2+ from electrochemical coupling or pharmacomechanical coupling 72. regulation of ar- - short term - peripheral resistance (neural mechanism, terial blood pres- chemical in blood) sure - long term - blood volume (renal mechanism) 73. baroreceptor - in aorta and carotid artery - stimulated by stretch in arterial wall and increased BP - rapid response to short term changes in BP 74. arterial pressure - arterial blood volume and arterial compliance affect arterial pressure - cardiac output and peripheral resistance affect arterial blood volume and arterial compliance 75. SA node 9 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 heart rate is normally deter- mined by the ac- tion potential fre- quency in the... 76. SA node sinoatrial node -- generates an electrical signal that caus- es the upper heart chambers (atria) to contract 77. AV node atrioventricular node -- signal travels from SA node to AV node. the lower heart chambers (ventricles), causing them to contract 78. maximum aortic systolic pressure pressure during cardiac cycle is called 79. systole Contraction of the heart 80. diastole Relaxation of the heart 81. P atrial depolarization 82. QRS ventricular depolarization 83. T ventrical repolarization 84. stroke volume = EDV (end-diastolic volume) - ESV (end-systolic volume) 85. ejection fraction SV/EDV 86. cardiac cycle P --> SA node generates electrical signal that contracts the atria chambers. depolarization of atria. pressure in- creases in atria. low blood flow. AV valves were already open and passive blood flow already occurred, so ven- tricles are mostly filled with blood. AV valve closes and creates first heart beat sound. beginning of systole QRS --> electrical signal generated from SA node travels to AV node and purkinje fibres that contracts the ventricle 10 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 chambers. depolarization of ventricles. pressure increas- es in ventricles. high blood flow to aorta. T --> ventricular repolarization. pressure falls. semilunar valves close and creates second heart beat sound. all valves are closed. ventricles relax. atria is filled with blood. atria pressure slightly increases and AV valves open for passive blood flow to ventricles. 87. Neurons Functional cell type in carrying chemical-electrical signals throughout the nervous system 88. Four functional 1. Input component (dendrite) regions of neu- 2. Trigger area (soma) rons 3. Conductive component (axon) 4. Output components (synapse) 89. Glial cells - supportive cells for neurons - support: assist and facilitate signal transmission in neu- rons - protect: produce myelin to insulate nerve cell axon - form lining around blood vessels: blood brain barrier 90. Central nervous The spinal cord, medulla, pons, cerebellum, midbrain, system (7) diencephalon, cerebral hemispheres: basal ganglia and cerebral cortex 91. Blood supply to circle of willis, internal carotid artery, vertebral artery the brain 92. Blood brain bar- - produced in the ventricles rier and cerebral - cushion and buffer spinal fluid - autoregulation of blood circulation 93. Peripheral nerve motor and sensory axons bundled into a defined trunk 94. Afferent division Sensory and special senses sensory and visceral stimuli > afferent division > CNS 95. Efferent division 11 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 Motor system CNS > efferent division > somatic nervous system and autonomic nervous system 96. action potential - rapid electrical excitation in the plasma membrane of a cell resulting from a series of potential changes - voltage-dependent ion channel in the plasma membrane - patterns encode information - all or nothing response 97. membrane po- - difference in electrical potential between intracellular tential and extracellular compartment - current flow: movement of positive charges 98. phases of action Phase 0: resting potential - activation gate closes the potential: Na+ channel channel Phase 1: depolarization - depolarizing stimulus arrives at the channel. with the activation gate open, NA+ enters the cell Phase 2: overshoot/peak - inactivation gate closes and Na+ entry stops Phase 3: repolarization - during repolarization caused by K+ leaving the cell, the two gates reset to their original position Phase 4: hyperpolarization - continued closure of Na+ and opening of K+ 99. myelination - insulation - decreases capacitance across cell membrane - increases conduction velocity 100. conduction us- - keeps current in axons and voltage doesn't decay much ing myelinated - action potentials are generated only in the nodes of axon Ranvier and appear to jump rapidly from node to node 101. glial cells in CNS CNS: astrocytes, oligodendrocytes, microglia, ependymal and PNS cells PNS: Schwann cells, satellite cells 102. 12 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 synaptic trans- the process of transferring information from one cell to mission another at a synapse 103. electrical trans- direct flow of ions from one neuron to another, hence mission direct influence of electric current from one to another 104. chemical trans- neurotransmitter substance released from presynaptic mission cell, diffuses across synaptic cleft, producing effect of postsynaptic neuron 105. neurotransmitter - substance that mediates chemical signaling between neurons - releases upon depolarization of the terminal 106. autonomic ner- - part of PNS that regulates visceral organs (smooth and vous system cardiac muscles) and mostly involuntary - maintains homeostasis (constant internal environment) - controlled through hypothalamus 107. organization of sympathetic, parasympathetic, visceral fiber, enteric ner- ANS vous system 108. sympathetic ner- fight or flight vous system 109. parasympathet- rest and digest ic nervous system 110. sympathetic vs - The sympathetic nervous system is distributed to more parasympathetic tissues than the parasympathetic nervous system - The sympathetic and parasympathetic divisions of the autonomic nervous system tend to have opposite effects of dually-innervated effector tissues 111. baroreceptor - short term regulator - baroreceptor reflexes regulate blood pressure ade- quately - stretch receptors in blood vessels - not useful for controlling pressure for more than days 13 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 112. depolarization of opening of sodium channels, delayed closing of sodium a neuron to channels, delayed opening of potassium channels. threshold stimu- lates 113. neurotransmit- axon terminals ters are released from 114. functions of kid- - regulate volume, osmolarity, mineral composition, acid- ney ity in extracellular fluid - remove metabolic waste from blood and excretion in urine - remove foreign chemicals from blood and excretion in urine - secrete hormones - gluconeogenesis 115. body fluid com- - Total body water (60% of body weight) partments - Intracellular fluid (2/3 TBW) - Extracellular fluid (1/3 TBW) - Interstitial fluid (75% ECF) - Plasma (25% ECF) 116. ECF and ICF os- - when osmolality differs, water will transport by osmosis molality until osmotic equilibrium is reached 117. osmotic pres- pressure that must be applied to prevent osmotic move- sure ment across a selectively permeable membrane 118. osmolarity measure of osmoles of solute per volume (L) 119. osmolality measure of osmoles of solute per mass of solvent (kg) 120. oncotic pressure osmotic pressure of plasma protein 121. nephron - functional unit of the kidney - consist of glomerular capsule, bowman capsule, and renal tubule 14 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 - function for blood plasma processing and urine forma- tion 122. excretion filtered - reabsorbed + secreted - glomerular filtration - tubular filtration - tubular secretion - excretion 123. glomerular flow - kidney function depends on filtration rate - filtration barrier is size and charge selective 124. renal clearance - measurement of glomerular filtration rate and renal blood flow - for a substance that is freely filterable across glomerulus and bowman's capsule, but not secreted, reabsorbed, or metabolized, and has no effect on GFR, can be used in measuring GFR 125. gastrointestinal salivary gland, esophagus, stomach, pancreas, liver, bil- tract iary tract, small intestine, colon, rectum components 126. gastrointestinal - break down food into forms that can be reabsorbed tract functions - absorb nutrients and water 127. digestion mechanical: chewing and GI movement chemical: secretion and enzyme hydrolysis: addition of water molecules to break molecular bonds 128. carbohydrates polysaccharides > monosaccharides break into 129. lipids break into triglycerides > fatty acids 130. proteins break peptides > amino acids into 131. functions of liver 15 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 - blood enters liver from digestive tract by the hepatic portal system, it has the first choice of absorbed nutrients - produce proteins like albumin - detoxification and metabolic - homeostasis of carbohydrates (blood glucose) - homeostasis of lipids and production of cholesterol - storage of vitamins and minerals - produces bile 132. actions of GI 1. digestion tract 2. secretion (chemical digestion) (DSAM) 3. absorption 4. motility (mechanical digestion, propulsion, defecation) 133. tubular secretion selectively moves substances from blood to filtrate in renal tubules and collecting ducts 134. increase in re- increases water reabsorption absorption of solutes 135. primary active - against an electrochemical gradient transport - using ATP 136. similarity be- carrier is involved tween active transport and fa- cilitated trans- port 137. facilitated diffu- - with concentration gradient sion - does not require energy 138. blockage of bile interferes with the digestion of lipids only into duodenum 139. failure to secrete false amylase would make it impossi- 16 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 ble to digest any- thing 140. gastrin stimulates secretion of acid by the stomach 141. pharmacokinet- - what the body does to the drug ics - science of the kinetics, drug absorption, distribution, metabolism, and elimination (ADME) 142. pharmacodynam- - what the drug does to the body ics - relationship between drug and physiology that influence the interaction of drug with receptor 143. ADME absorption, distribution, metabolism, excretion 144. routes of admin- - oral (enteral) istration - inhalation - mucous membrane - injection (parenteral) - transdermal 145. oral drug admin- - safe istration advan- - economical tage (4) - convenient - practical 146. oral drug admin- - blood levels are difficult to predict due to factors that limit istration disad- absorption vantages (3) - some drugs destroyed by stomach acid - some drugs irritate GI 147. IV injection ad- - no absorption involved ministration ad- - rate of infusion can be controlled vantages (3) - more accurate prediction of dose 148. IV injection ad- - rapid onset of action can be dangerous ministration dis- - too rapid administration affects heart and respiratory advantages (4) function - cant use drugs insoluble in water - sterile technique needed 17 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 149. plasma level vs. drug concentration in plasma samples taken at various time curve time intervals after a drug is administered 150. peak plasma lev- time of maximum drug concentration in plasma el 151. area under curve amount of drug absorbed systemically 152. half life - time taken for the amount of drug in the plasma concen- tration to fall by half - longer is better 153. first pass clear- the extent to which a drug is removed by the liver during ance its first passage in the portal blood through the liver to the systemic circulation 154. Bioavailability - AUC oral/AUC IV equation - F = fg (drug absorbed by) x fh (drug escaped liver from first pass clearance) 155. bioavailability - fraction of the dose which reaches the systemic circula- tion as intact drug - depends on how well the drug is absorbed - depends on first pass clearance -- drug being removed by the liver before reaching systemic circulation 156. Absorption (oral the extent to which intact drug is absorbed from the gut administration) lumen into portal circulation 157. factors affecting - gastric emptying time drug absorption - effect of food (4) - gastrointestinal mobility - perfusion of GI tract 158. gastric emptying - slow gastric emptying time --> slow the rate and extent time on absorp- of drug absorption and prolong the drug onset time. tion - this is undesirable for a drug that is unstable in acid or irritates GI tract 18 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 159. Effect of food on - delay in gastric emptying absorption - change in pH of GI - more calories and fat affect GI bioavailability 160. elimination by liver metabolism 161. elimination by kidney excretion 162. metabolism - drugs and toxins are foreign to the body - drugs undergo metabolism in the lungs, blood and liver - body works to convert drug to less active form 163. glomerular filtra- - unbound drug in plasma are filtered in Bowman's cap- tion rate sule - drugs not bound to plasma, or secreted or absorbed, will head to renal clearance 164. prodrug inactive drug that is converted to an active state by the liver 165. hepatic clear- the ability of the liver to remove substances from the blood ance 166. hepatic clear- - hepatic blood flow - rate of delivery of drug to liver ance depends on - fraction of drug unbound in plasma (3) - activity of drug metabolizing enzyme 167. Cytochrome major drug metabolizing enzyme P450s 168. first pass metab- drug metabolism that occurs in the intestines and liver olism during oral absorption of drugs into the systemic circula- tion 169. drug distribution passage of a drug from the blood to the tissues, cell membranes, capillaries, blood brain barrier, placenta 170. 19 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 volume of distri- describes the relative strength of binding drugs to tissues. bution a large V is when the drug is tightly bound to tissue 171. volume of distri- Vd = (dose administered in body) / (plasma drug concen- bution equation tration) 172. most critical site small intestine for drug absorp- tion 173. drug clearance - efficiency of irreversible elimination of drug from sys- temic circulation - excretion of unchanged drug into urine, gut, air, sweat - metabolized drug 174. elimination rate clearance (L/hr) * drug plasma concentration (mg/L) formula 175. renal system 176. gi system 177. evidence that a large apparent volume of distribution drug is stored in tissue 178. renal clearance GFR of inulin is a mea- surement of 179. which tissue liver has the capacity to bio-transform drugs 180. renal excretion - extent of plasma protein binding of drugs factors (3) - glomerular filtration rate - active renal tubular absorption 181. 20 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 two mechanisms hepatic metabolism (liver) and renal excretion (kidney) for the termina- are important mechanisms involved tion of drug ac- tion 182. clearance rate volume of blood cleared of drug per time 183. initial loading D = VD (volume of distribution) * CSS (steady state con- dose centration) / F (bioavailability) 184. sustained re- release drugs for short periods of time (hours) and require leased drug repeated administration 185. controlled re- constant concentration within the therapeutic window for leased drug a desired amount of time 186. examples of con- 1. diffusion controlled --> reservoir, matrices trolled release 2. solvent controlled --> swelling, osmosis systems 3. chemically controlled --> biodegradable, pendant chain DECS 4. externally activated or modulated --> smart materials 187. Diffusion con- - aqueous solution of drug in polymer membrane trolled mem- - drug escapes through membrane at a controlled rate branes based on thickness and composition 188. Solid biodegrad- - use of biodegradable polymer as a matrix to achieve able matrices slow, controlled release of drug - drug escapes and controlled by polymer degradation rate 189. Water-soluble - water soluble polymers diffuse slowly though the tissues polymer-bound - not excreted rapidly as small molecules drugs 190. Reasons for inef- 1. rapid dilution of drug ficiency of con- 2. ease of excretion of small molecule drugs through ventional drug kidney therapy (2) 191. - stimuli like heat, ultrasound, magnetic energy, light 21 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 Stimuli respon- sive drug release 192. Targeted deliv- - drugs selectively delivered to site of action ery 193. Advantages of - lower dose required targeted delivery - control over toxicity and bioavailability - extended duration of release - controlled release directly to site - avoid systemic drug exposure 194. EPR effect enhanced permeability and retention 195. EPR effect and - tumors develop vessels that are abnormal; leaky vessels cancer therapy and defective lymphatic drainage - leads to abnormal molecular transport; EPR effect, and molecules accumulate at the tumor sites more than nor- mal tissue 196. Advantages of - enhanced local drug release stimuli respon- - respond to specific microenvironments, releasing thera- sive drug release peutics on demand - extrinsic stimuli can be controlled more precisely 197. Challenges of - complex chemistry stimuli respon- - lack of precise control for internal stimuli sive drug release - limited tissue penetration for external stimuli - poor control over localization 198. Glucose respon- - gel is dehydrated under normoglycemic conditions, and sive delivery sys- hydrates when glucose concentration increases tem - a decrease in glucose concentration forms a hydropho- bic barrier through surface dehydration, inhibiting drug diffusion 199. Intranasal drug pros: delivery pros and - higher bioavailability cons - direct transport into system circulation, CNS - lower risk of overdose 22 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 cons: - affected by cold, allergies - irritation of nasal mucosa - volume limitation - defence mechanisms like mucocillary clearance and ciliary beating affects drug permeability 200. Inhalation drug pros: delivery pros and - avoid first pass metabolism cons - suitable for drugs that get degraded in the gut - can target to lungs cons: - irritate respiratory tract - bioavailability depends on inhalation technique 201. Transdermal pros: drug delivery - steady permeation of drug across skin - controlled and sustained release - minimum risk of side effect or toxic effect - convenient and easy cons: - local irritation - allergic reaction - low permeability on skin - only potent drugs suitable - variation depending on site of skin - maintain contact between device and skin 202. Cardiovascular angioplasty stent has medication coated to reduce local delivery chance of reocclusion 203. Ocular local de- - drug loaded soft contact lens increases residence time livery of drug and bioavailability - microneedle to treat eye disorders 204. Cancer therapy - active delivery is the binding of the agent to the moiety local delivery - can be directly attached to the drug or to the nanosize carrier loaded with therapeutic drug 23 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 205. Sterility the complete destruction of all living organisms and their spores 206. bioburden the number of viable micro-organisms on the implant prior to sterilization 207. goal to achieve a sterility assurance level (SAL) of 10e-6. prob- ability of no more than 1 in 1 million that an implant is non-sterile 208. process determine initial bioburden, then assess possible steril- ization procedures for efficacy and influence on polymer properties 209. kinetics of cell in- death rate follows first order kinetics. guaranteed sterility activation would require infinite time 210. sterilization tech- steam, radiation, gas niques 211. steam steriliza- pros: tion - no toxic residues cons: - deformation due to water 212. radiation steril- pros: ization - high penetration, low chemical reactivity, quick cons: - instability and deterioration, breaking polymer chains 213. gas sterilization pros: - low temp range cons: - lengthy process, residues are toxic 214. drug - agent used to diagnose, mitigate, treat, cure, or prevent a disease - recognized as safe and effective under recommended conditions. 24 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 215. approval path for - preclinical testing a new drug - investigational new drug application (IND) approval - clinical trials (3 phases) - new drug application (NDA) - FDA approval 216. Pre-clinical test- - test new drug on animal for toxicity, multiple species ing and IND used for safety and efficacy - submits an IND that include drug composition, manufac- turing and plan for testing on humans - FDA verifies that humans will not be placed under risk of harm 217. Clinical trials Phase 1: emphasize safety. studies what the frequent side effects are and how it is metabolized and excreted. Phase 2: emphasize effectiveness. studies whether drug works on people who have a certain disease or condition. compared against placebo or different drug. short term side effects studied. Phase 3: more info on safety and effectiveness. studies different populations and different dosages, and combi- nation with other drugs. 218. safety determines highest tolerable dose or optimal dose to achieved clinical benefit and adverse effect in that range. 219. efficacy determines if drug has a positive clinical benefit over placebo or other intervention. tests in ideal, strictly con- trolled conditions. 220. effectiveness determines drugs clinical benefit in real world situation. if drug administration guidelines are not strictly followed, other conditions, other medications 221. Phase 1 patients patients: 20-100 and duration duration: several months 222. Phase 2 patients patients: 100s and duration duration: months to 2 years 25 / 26  Complete Set for NE481 Study online at https://quizlet.com/_g8ikc9 223. Phase 3 patients patients: 1000s and duration duration: 1 to 4 years 224. Phase 1 - tolerability and safety of drug - healthy volunteers - initial dose is low and builds up until evidence of drug action - studies metabolism and drug action 225. Phase 2 - efficacy of drug and side effects - patients suffering from disease volunteers and close observation 226. Phase 3 - safety and efficacy of drug - private practitioners brought in - practitioners report to principal investigator who relays information and evaluation to FDA and HPFB 227. NDA submission - formally asks FDA to approve drug for marketing by submitting NDA. - all animal and human data and analyses of data, infor- mation on how drug behaves in body and manufactured - FDA has 60 days to file it, then a review team evaluates research - FDA reviews labelling and ensures info is communicated to consumers and health care - FDA inspects manufacturing sites - FDA approves or issue a response letter 26 / 26