Term
| Is the interior of the cell electrically negative or positive with respect to the extracellular fluid? |
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Definition
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Term
| The dominant factor in determining the permeability of a membrane to a substance is the electrostatic interaction of the solute with _____? |
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Definition
| Water, because intermolec forces are stronger between water than lipids |
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Term
| True or false: There is a direct relationship of the number of H-bonds a molecule has and its membrane solubility. |
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Definition
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Term
| What accounts for greater solute permeability in increasingly sized hydrocarbons? |
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Definition
| Hydrophobic bonding due to additional methylene groups |
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Term
| Why can you increase the rate of drug transport by simply changing non-essential substituent groups to a molecule? |
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Definition
| Because diffusion across the bilayer accounts for the greatest permeation of drugs in the body |
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Term
| There are two classes of aquaporins(AQPs) what are they and what do they do? |
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Definition
| Orthodox, water-selective with unique tissue distribution; multifunctional, allow for water, glycerol, urea, small molecs to pass thru. |
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Term
| The water permeability of a plasma membrane depends on what 2 things? |
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Definition
| Permeability of the lipid, and type/density of AQPs |
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Term
| How does Vasopressin work? |
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Definition
| Controls reabsorption of water in the kidneys by recruiting AQPs to cell membranes |
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Term
| What are the three functional groups of solute transporters or carriers? |
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Definition
| Uniporters/facilitated transporters move molecules down a gradient like glucose in blood brain barrier; Cotransporters/symport/antiporters/secondary active uses the energy of electrochem gradient of one molecule to move another, like symport Na/Glucose in intestinal lining or Cl/HCO3 in RBCs; exchangers/active transporters use ATP to move stuff up gradient like Na/K pump |
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Term
| Despite the potential for molecules to move across a membrane, what 3 things limit the actual transport rate? |
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Definition
| Substrate concentration, affinity for substrate to carrier, rates of conversion |
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Term
| What is the most prevalent active transport/antiport carrier? |
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Definition
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Term
| What is the most important cotransport/symport carrier? |
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Definition
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Term
| The most important aspect of the intestinal Na/glucose transporter is oral rehydration therapy, what is that? |
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Definition
| It is a solution of salts and glucose to have the body actively restore lost fluid due to the questions mechanism. |
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Term
| These three transporters are from what type of mechanism: Cl/HCO3 (red blood cell), Na/H (pH balance), Na/Ca (cardiac muscle)? |
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Definition
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Term
| What type of cells form a barrier between the body and the external world, ie skin, lungs, GI, renal tubule, blood brain barrier? |
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Definition
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Term
| In general epithelia tight junctions have variable resistances to molecules, so what 2 classifications of epithelia are there? |
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Definition
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Term
| What ion regulates tight junction adherence? |
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Definition
| Calcium, more makes it stronger bond and less leaky |
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Term
| The low resistances of ion flows in epithelia are mainly due to what? |
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Definition
| How strong tight junctions are. |
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Term
| The urinary bladder, stomach, and renal collecting tubule have low epithelial resistances and small gradients? |
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Definition
| No, high resistance/gradients |
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Term
| Name 3 organ epithelia that have ion flow reistance. |
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Definition
| Renal proximal tubule, intestine, gall bladder, choroids plexus |
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Term
| What is so unique about the distribution of membrane proteins in epithlia versus other cells? |
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Definition
| In epithelia, membrane proteins are sorted in the trans-golgi face and put in transport vesicles to the apical and basolateral surfaces. |
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Term
| What does this mean: epithelial cells are polarized? |
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Definition
| There is a difference in structure and function between the apical and basolateral membranes of epithelia |
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Term
| Water transport is directly proportional to what? |
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Definition
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Term
| What area of epithelia creates a local osmotic gradient driving water in? |
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Definition
| intracellular spaces have many ions driving water into the cells |
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Term
| True or False: the ion gradient and selective permeability alone can create a potential difference in the cell. |
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Definition
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Term
| Which of these ions have either high or low concentrations inside the cell: K, Cl, Na, Ca. |
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Definition
| K is higher inside cell, rest high outside cell |
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Term
| What type of molecules diffuse into the cell without assitance? |
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Definition
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Term
| What is equilibrium potential in a cell? |
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Definition
| The voltage at which the net flow of ions is zero. |
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Term
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Definition
| the interrelationships between the absorption, distribution, metabolism, excretion, and its concentration at the site of action. |
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Term
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Definition
| biochemical effects of drugs, metabolism, relation between drug concentrations and biological effects |
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Term
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Definition
| the fraction of the population that responds to a given dose, ie LD/ED/TD50 |
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Term
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Definition
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Term
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Definition
| range of doses that is sufficient to provide efficacy but not toxicity |
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Term
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Definition
| drugs that bind to receptors and mimic endogenous signaling compound |
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Term
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Definition
| maximal response achievable with drug; like full agonist or partial agonist |
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Term
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Definition
| effective dose that produces 50% of max efficacy |
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Term
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Definition
| drugs that bind to receptors but do not produce response, inhibitors |
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Term
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Definition
| drug binds to same site on receptor as natural signal compound |
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Term
| Noncompetitive antagonist |
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Definition
| drug binds to site other than that of natural signal compound |
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Term
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Definition
| drug that causes a conformational change in receptor that is irreversible |
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Term
| What is the dissacociation rate constant, Kd, refer to in pharmacology? |
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Definition
| The affinity of a drug for a receptor or concentration needed to occupy 50% of receptor pool |
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Term
| Elaborate on the 5 receptor regulation responses to drugs: desensitization/tachyphlaxis, tolerance, sensitization, down-regulation, up-regulation |
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Definition
| effect diminishes with continued exposure, gradual decrease in response, increase in responsiveness, decrease of receptor number, increase receptor number |
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Term
| List the 4 major types of drug-receptor complexes in order from slowest to fastest. |
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Definition
| Control of DNA transcription, direct control of effector enzyme, indirect G protein coupling via 2nd messengers, direct control of ion channel |
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Term
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Definition
| each process of absorption, distribution, metabolism, elimination is governed by defined factors |
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Term
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Definition
| movement of drug from site of administration to the plasma compartment |
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Term
| Differentiate the two routes of drug absorption. |
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Definition
| Parenteral - non-gi administration, enteral - gi, oral, rectal |
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Term
| Describe the 3 ways drugs cross membranes. |
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Definition
| Transmembrane protein recognizes substrate and moves it across (ATP dependent, regulated), pinocytosis, diffusion |
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Term
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Definition
| A higher buildup of a drug across a membrane due to the difference in pH across surfaces and pKa value of drug, non-ionized forms pass membrane more readily. Weak acids absorbed by acidic areas like stomach, weak bases taken by basic areas like small intestine |
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Term
| What is enterohepatic circulation? |
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Definition
| First pass of drug gets metabolized through liver before general circulation |
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Term
| What types of drugs pass the blood-brain barrier? |
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Definition
| Low polarity (carrier mediated) or neutral non-polar compounds |
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Term
| What happenes in a phase 1 and 2 drug metabolism? |
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Definition
| Phase 1 - a polar function is introduced to reaction (CYP oxidation), phase 2 - substrate (phase 1 metabolite)is coupled to endogen compound making it more polar (glucuronidation) |
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Term
| Why is it necessary to metabolize drugs and make them more polar? |
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Definition
| The greater the polarity, more water soluble, more easily excreted |
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Term
| Where is the most important metabolic enzyme, CYP450, located in the cell and highest concentration in body? |
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Definition
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Term
| What 3 things can affect drug enzyme availability? |
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Definition
| Age (old/young have less enzymes), genetics (natural variations in enzyme production), environment (chemicals induce or inhibit enzymes) |
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Term
| What is difference in metabolic enzyme induction and inhibition by drugs? |
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Definition
| Induction increases production of enzyme quantity and inhibition is created when there is competition for binding sites on enzyme |
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Term
| Is CYP a phase 1 or 2 enzyme? |
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Definition
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Term
| What is the consequence of induction or inhibition? |
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Definition
| More metabolism and less drug in system, less metabolism and more drug in system |
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Term
| As far as physicians are concerned, what is the importance of confidence intervals and p values? |
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Definition
| It simply describes a range of plausible values from sample size that apply to population that are not impacted by chance alone other than extremes (p-values). |
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Term
| What would does a 95% CI mean in real terms? |
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Definition
| If the study were conducted over and over again, 95% of results would have true values. |
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Term
| In observation studies, what does confounding refer to? |
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Definition
| The influence of factors associated with exposure being studied and outcome measured, ie study design, lack of complete info in retrospective studies |
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Term
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Definition
| The fraction of administered does that reaches circulation |
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Term
| Pharmaco: what is the area under the curve of a bioavailability curve? |
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Definition
| It is amount of bioavailability. |
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Term
| Pharmaco: what is volume of distribution? |
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Definition
| The apparent volume of fluid to contain the total amount of drug, i.e. its solubility in the body |
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Term
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Definition
| Two drugs that are similar in efficacy and safety in bioavailability |
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Term
| How does the volume of distribution affect blood concentration of drugs? |
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Definition
| Larger Vd, spreads farther through body, longer to eliminate, need more drug to maintain blood-drug levels |
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Term
| What are the 3 fundamental processes for renal excretion? |
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Definition
| Glomuler filtration, proximal tube excretion, passive reabsorption at distal tubule |
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Term
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Definition
| Elimination is based on drug concentration, same fraction is lost over interval of time |
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Term
| Zeroeth order elimination? |
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Definition
| Elimination is constant due to metabolic saturation, constant amount is lost over a given interval |
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|
Term
| What is a one-compartment model? |
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Definition
| A model based on a drug filling one compartment and it is eliminated linearly from that single area |
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Term
| What is a two-compartment model? |
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Definition
| A model based on a drug filling one area, and perfusing to a second compartment, so drug is initially lost linearly from the main compartment(blood, organs), then at a slower rate as the drug moves from the second compartment(peripheral tissues) to the first |
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Term
| What is the difference between alpha and beta phases in a two compartment model? |
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Definition
| Alpha is intial distribution and elimination in main compartment, beta is elimination from main compartment by diffusion from second compartment |
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Term
|
Definition
| The volume of drug cleared from plasma per unit of time |
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|
Term
| What is steady state drug concentration? |
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Definition
| The rate of infusion of drug is equal to rate of clearance |
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|
Term
| What is capacity limited elimination? |
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Definition
| A zero order kinetic elimination where there is a max of drug that can be eliminated per amount of time |
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Term
| Define these: dyspnea, purulent, bronchiectasis. |
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Definition
| Shortness of breath, puss-filled, localized dilation of bronchial tree |
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Term
| How many molecules of ATP are necessary to complete one cycle of a Na/K pump? |
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Definition
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|
Term
| What does the Nernst equation describe? |
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Definition
| The membrane potential regarding only one ionic species |
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|
Term
| What is the partition coefficient of a drug? |
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Definition
| The distribution between lipid and aqueous phases |
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