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160 Cards in this Set
- Front
- Back
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Pharmacology
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Study of the effect of chemicals on living tissue
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Pharmacokinetics
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Study of absorption, distribution, metabolism, and excretion of drugs.
"Effects of body on drug" |
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Pharmaceutics
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Formulation and preparation of drugs
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Pharmacoeconomics
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Study of economic impact of drugs
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Toxicology
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Study of harmful effects of chemicals
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Pharmacognosy
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Study of medicinal uses of naturally occurring compounds
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Pharmacy
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Study of preparation and dispensing of drugs
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Pharmacogenetics
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Study of genetic influences by and on drugs
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Pharmacodynamics
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Study of physiological and biochemical mechanisms of action of drugs.
"Effects of drug on body" |
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Januvia
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Sitagliptan
increase the insulin made in your pancreas and decrease the sugar made in your liver to lower blood sugar |
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Ligands are....
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Chemical substances that bind to a specific receptor
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When agonists bind to a receptor they....
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Stimulate the function of that receptor
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When antagonists bind to a receptor they.....
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Block the function of that receptor
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Competitive binding is
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Reversable
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Competitive binding means
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Different substances compete for the same receptor
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Noncompetitive binding is
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Non-reversible -
Example: ASA |
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ED50
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Effective dose if 50% of the population
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TD50
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Toxic dose in 50% of the population
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LD50
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Lethal dose in 50% of the population
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LD50/ED50
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Therapeutic index
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Therapeutic window (pharmaceutical window) is defined as...
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Index for estimation of drug dosage which can treat disease effectively while staying within the safety range
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What kind of chemical bonds can be used for drug binding?
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Covalent
Ionic Hydrogen Hydrophobic van der Waals |
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Strongest chemical bond is....
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covalent
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Weakest chemical bond is.....
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van der Waals
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What does dose response curve show?
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Affinity (potency)
Efficacy Variability Slope |
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Down - regulation happens when
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Effect of drug is diminished due to continuous stimulation of a cell with agonists
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Up-regulation happens with
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chronic administration of antagonists - number of receptors increase due to constant blockage
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Both up regulation and down regulation require increased/decreased dose?
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Increased
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Interaction
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Alteration in the therapeutic action of a drug by concurrent administration of other exogenous chemicals
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Addition
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Combined effect of two drugs acting via the same mechanism is equal to that expected by simple addition of their individual actions
1+1=2 :) |
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Synergism
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Combined effect of two drugs is greater than the algebraic sum of their individual effects
1+1=3 Versed and prop |
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Potentiation
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Enhancement of the action of one drug by a second drug that has no detectable action of its own
1+0=3 |
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Antagonism
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Action of one drug opposes the action of the other drug
1+1=0 MS and narcan |
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Sevoflurane MAC
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2
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Sevoflurane blood/gas partition
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0.6
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Sevoflurane oil/gas partition
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50
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What is MAC
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Minimum Alveolar Concentration
(dose of anesthetic) |
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What does blood/gas partition coefficient indicate?
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Speed of anesthetic
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What does oil/gas partition coefficient indicate?
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Potency - the higher the number the more potent the anesthetic
inc solub coeff=incr lipid solubility b/c the anesthetic must get to bbb=highly lipid and penetrate cell membranes (highly lipid) to produce it's action. b/g solub=how fast drug deliv to tissues; o/g solub=how effic it can access and effect the sites of axn. |
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Isoflurane MAC
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1.15
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Isoflurane blood/gas partition
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1.4
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Isoflurane oil/gas partition
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99
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N2O MAC
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105
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N2O blood/gas partition
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0.47
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N2O oil/gas partition
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1.4
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Desflurane MAC
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5.8
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Desflurane blood/gas partition
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0.42
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Desflurane oil/gas partition
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18.7
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For blood/gas partition coefficient - the lower the number the faster or slower the drug?
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Faster
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For oil/gas partition coefficent - the higher the number the higher or lower the potency?
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Higher
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Lung concentration of inhaled anesthetics equals
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Brain concentration
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Concentration effect means
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The more you give, the faster it works
AKA overpressuring - N2O gets in faster d/t higher dose. Also, high admin of drug at beginning (like loading dose). Better effx with slow (high solubility) drugs. (fast drugs not as effected by high initial admin) |
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Contra indications for N2O administration are:
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pneumothorax
bowel obstruction inner ear surgery neuro and eye surgeries with air injections air embolism or potential for |
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Do obese patients require more anesthetic?
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No. They take longer to wake up due to fat uptake of anesthetic gases
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During the second phase of anesthesia - does increased HR speed up onset of anesthesia?
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No, it slows it down.
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Therapeutic window is....
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An index for estimation of drug dosage which can treat disease effectively while staying within the safe range
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Two types of ligands are?
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Agonists and antagonists
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Drug receptor is?
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Macromolecular complex which acts as the site of action for a drug.
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Drug receptors can be....
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Proteins, enzymes, carrier molecules, ion channels, nucleic acids.
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Slope is indirect measure of?
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Dose and effect
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Quantal dose - response curve demonstrates....
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the average effect of a drug depending on it's concentration
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Pediatric diff with anesthesia
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faster uptake of anesthesia drugs w/child than adult d/t inc alveolar vent per weight. CO inc per weight, but more goes to vessel rich (intravasc fluid, heart, lungs, brain, liver & kidneys) d/t body proportions. Muscle mass lower in children=inc concentration of drug in vital organs---->inc uptake in brain. Also, anesthetics seem less blood soluble (work faster) in children than adults. MAC is higher in children and decreases with > age. (N. 96-97)
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Effx of bad lungs (V/Q mismatch) on inhal drugs
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hinders effx-->Rapid-acting (low b/g solub) agents > effx than slow acting (high b/g solub) drugs. Inc soluble<less soluble effx
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Second gas effect
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faster drug (N2O) can drag in slower drug for a more rapid uptake. slow drug>increase. fast drug<increase
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inc cardiac output effx on induction
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Inc CO=decr onset - - highly soluble (slow) drugs = more effect (slower) b/c inc CO removes more anesthetic from lungs = slows the rise in lung and brain [c].
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Stage 3 anesthesia
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from end of stage 2 to cessation of respiration. When:
lose airway reflexes lose corneals lose tracheal (airway) reflexes stage of anesthesia unconsciousness, regular respiration, decreasing eye mvmt |
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vessel poor grp
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peripheral compartment; composed of muscle fat and bone = 90% of adult body mass and gets 25% of CO
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affinity (AKA)
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aka potency; agonists that activate the same receptor and can all produce the same max response (efficacy) but at differing conc the most potent drug = requires lowest dose
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efficacy (aka)
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intrinsic activity; the drug's ability to produce the desired response expected by stimulation of a given receptor population. refers to the max possible effx that can be achieved with the drug.
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Phase II reactions (metab)
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synthetic reactions;
conjugation & synthesis - depends on least E required body synthesizes a new compound by donating a fxnal grp usually derived from and endogenous acid=new compound=the conjugate of the drug or the drug product of the phase 1 reaction with either a glucuronic acid, sulfuric acid, glycine, acetic acid, or a methyl grp - - almost always have little or no biological activity |
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Stage 1 of anesthesia
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'stage of analgesia' - depends on agent
Amnesia* Complete analgesia* unconsciousness end of stage 1* euphoria loss of pain sensation still responsive (loss of consciousness=end of stage 1) pupils normal corneal reflex intact & reactive to light normal muscle tone |
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gas phase=
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the fraction of the anesthetic agent that will leave the blood and quickly diffuse into tissues. (not the part that will be soluble with the blood components that's the blood phase)
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ventilation effect=
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the faster and more deeply a pt breathes or is ventilated, the faster the pt loses consciousness at the start of anesthesia and emerges at the end.
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stage 4 anesthesia
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medullary (paralysis) depression & death;
*stage of overdose *No BP or HR begins with respiratory arrest. Cardiac depression and arrest; no eye mvmt; extreme flaccidity. Reflexes absent; skin cold and gray; sphincters relaxed; eyes very widely dilated. absent corneal reflexes & pupillary reaxn to light. |
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Blood/gas solubility coeffic =
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higher=slower (inc amt in blood phase) i.e. iso=1.4:1=1.4 times as much stays in blood as a nonrlseable fraction for every molecule that enters the tissue and produces anesthesia. Des=0.42:1 = 0.42 molec stay in blood for every 1 molec that enters tissues & produces anesthesia (grtr than twice as much enters the brain than that which stays in blood)
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Phase I reactions (metab)
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oxidation reactions (oxidation, reduction & hydrolysis depends on least E req); Oxygen is introduced into the molecule or the oxidative state of a molecule is changed so that its relative oxygen content is inc. CYP450 rxn-->results in more polar compound that has greater kidney excret. Phase 1 reactions place hydroxy or carboxy grps on molec to allow phase II reactions to occur.
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Pre/Post Ganglionic signal/receptors for SNS and PNS
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SNS: Pregang = ACh; receptor = nicotinic(cholinergic); Postgang = NE; receptor --->tissue = (adrenergic) alpha, beta, dopaminergic
PNS: Pregang = Ach; receptor = nicotinic (cholinergic); Postgang = Ach; receptor ----> tissue = muscarinic (cholinergic) |
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blocks the SNS receptor=
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sympatholytic (beta-blocker)
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stimulates similar to Vagus nerve (muscarinic)
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parasympathomimetic (cholinergics)
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Inhibits muscarinic receptors
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Anticholinergic (parasympatholytic) - ?atropine (blocks the tissue PNS receptor)
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pharmacogenomics
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ident discrete genetic diff among indiv that play a critical role in drug response. Involves DNA sequencing and gene mapping to ident the genetic basis for variations in drug efficacy, metab, and transport. ENCOMPASSES THE GENOME (not just the genes suspected of effecting the response like pharmacogenetics). Evolving from pharmacogenetics research and involves the ident of drug response markers at the levle of disease, drug metab, or target.
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Stage II=
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'stage of excitement'
*HTN & tachycardia common excitement, delirium, combative behavior, involunt motor activity, elev pulse and bp, shivering respirations, nystagmus & dilated pupils; have corneals and reflex to light; motor activity and muscle tone incr |
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blood phase=
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the proportion of the anesthetic that will be soluble in the blood, 'bind' to blood components, and not readily enter the tissues, versus the fraction of the drug that leaves blood and quickly diffuses into the tissues=(gas phase)
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acid drug with pka 7.1 envir pH 6.0 =
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99% nonionized
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acid drug with pka 5 envir pH 7.4
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99% ionized
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base drug w pka 7.8 envir pH 7.4
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75% ionized; 25% nonionized
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base drug with pka 6.0 envir pH 3
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99% ionized
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acid drug w pka 6.0 envir ph 3
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99% nonionized
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1
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1
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1
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1
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1
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1
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allosteric
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change in the shape and activity of an enzyme that results from molecular binding with a regulatory substance @ a site other than the metabolically active one.
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Which bond is non competitive?
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Covalent Bonds
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Slope measures what?
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indirect measure of the margin of safety of a drug. Steep slopes indicate drugs with a narrow margin of safety.
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Is it desirable to have a low or high therapeutic index?
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High therapeutic index means that the LD50 is significantly higher than the ED50 giving a wide margin with which to dose.
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How is Quantal Dose Response Curves useful?
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Useful for predicting effects of drugs and toxic/lethal doses for a population base.
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What initiates the regulation of physiologic and biochemical function yet itself is also subject to regulatory and homeostatic controls
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Receptors
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Give an example of down-regulation
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Bronchodilators stimulating B-adrenergic receptors. Continued stimulation of receptors results in desensitization (refractoriness) and causes decrease in effect and the necessity to increase drug dose.
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Give an example of up-regulation.
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Chronic administration of an antagonist ie: b-blockers results in the body's intentional increase in receptors to accomplish its innate tasks.
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What is bioavailability?
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The percentage of drug that enters systemic circulation unchanged after administration. This concept includes the amount of drug as well as rate of entry.
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definition of pKa
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The pH @ which 50% of drug is ionized and 50% is unionized.
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pH-pKa= 0
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50% ratio of ionized to nonionized
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pH-pKa= 0.5 (absolute value)
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75%
/ 25% |
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pH-pKa=1 (absolute value)
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99%
/ 1% |
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Functional Tolerance
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pharmacodynamic tolerance,
body adapting to the drug, change in tissue sensitivity |
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Dispositional tolerance
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Kinetic difference,
adaptive change to the absorption, distribution, metabolism or elimination of drug. |
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full vs partial agonists
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full has the ability to bind (activate) all receptors vs partial which is not able to activate all receptors and is less powerful.
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antagonist
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has affinity for the receptor but no efficacy. It interferes with the receptors ability to bind with agonists. It is often more potent (higher affinity) than the agonist.
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Give 3 examples of antagonists.
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pharmacokinetic
chemical physiologic |
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partial agonists an block receptors from full agonists and can thus be termed
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agonist/antagonist
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spare receptor concept
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maximal or nearly maximal response can often be produced by activation of only a fraction of the receptors present
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What is Tachyphylaxis
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Very rapid development of tolerance, frequently with acute drug administration.
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What is a ligand?
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a molecule that is able to bind and form a complex with a receptor to produce a biologic response. Can be endogenous or exogenous.
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What is biotransformation?
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When fat soluble drugs are metabolized to water soluble metabolites and permit renal excretion.
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Where does Hepatic metabolism occur?
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In the smooth ER of the liver and some in the cytosol by enzymes called DME (drug metabolizing enzymes).
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What effect does lipid solubility have on elimination?
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Body reabsorbs it and it cannot be removed easily.
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What is conjugation?
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Coupling the drug molecule to an endogenous subtituent group so that the resulting product will have greater water solubility leading to enhanced renal or biliary elimination.
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What is enzyme induction and how does it effect metabolism?
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When drugs, environmental chemicals, air pollutants and components of cigarette smoke stimulate the synthesis of DME. This causes faster drug metabolism. "eat up the drug"
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What is enzyme inhibition and how does it effect metabolism?
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The converse of enzyme induction, Metabolism of a drug slows down because of the inhibited enzymes, leading to an increase in the drug's effect.
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What is first-pass metabolism?
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When a drug is ingested via the stomach, it enters the portal vein and therefore the liver more directly. It does not have a chance to be absorbed into the blood stream but is immediately metabolized in the liver and large portions of the drug are either eliminated or changed causing poor bioavailability.
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Where can DMEs be found?
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Liver
lung kidney GI tract placenta GI tract bacteria |
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How do drugs cross lipid membranes?
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by passive diffusion or by carrier mediated transport
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What factors determine rate of passive diffusional transfer across membranes.
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Lipid solubility
concentration gradient molecular weight, but less important |
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What is able to diffuse across lipid membranes?
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uncharged species of weak acids (protonated form) and weak bases (unprotonated form)
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what does pH partition refer to?
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Refers to the fact that weak acids tend to accumulate in compartments of relatively high pH, whereas weak bases tend to leave compartments of high pH.
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what is the value of carrier-mediated transport?
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it is important for some drugs that are chemically related to endogenous substances.
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Absorption from the gut depends on what factors?
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GI motility
GI pH Particle size physiochemical interaction with gut contents |
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Why may bioavailability be low?
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because absorption is incomplete or because the drug is metabolized in the gut wall or liver before reaching the systemic circulation (first pass effect).
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What is bio-equivalence?
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implies that if one formulation of a drug is substituted for another, there will be no untoward effects.
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How does protein binding influence how a drug is distributed?
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Protein bound drugs are unable to act on receptors.
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High protein binding results in high or low plasma concentration.
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High plasma concentration because high protein binding prevent the drug from leaving the blood to enter into tissue.
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How is the degree of protein binding for a drug proportional to its lipid solubility?
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The more lipid soluble an agent, the more highly protein bound it tends to be.
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How can protein binding be overcome?
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By adding more agents.
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When a drug has been in chronic use and is at steady state, what will be the relationship between free and protein-bound drug?
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there will be equilibrium between the free and the protein-bound drug.
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Albumin binds....
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acidic drugs primarily
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b-globulin and alpha, acid glycoprotein binds...
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basic drugs
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How does the type of solution effect absorption
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Drugs given in aqueous solution are more rapidly absorbed than those in oily solution or solid form.
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What is elimination half life?
(t1/2) |
The time necessary for the plasma content of a drug to drop to half its prevailing concentration after a rapid bolus injection.
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When is a drug considered fully eliminated?
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when about 95% has been eliminated from the body (4 or 5 half lives)
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first order kinetics
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it is not dose dependent.
Drug leaving the body at a constant rate or percentage over time. It explains why half life is constant. |
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Zero order elimination
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A constant amount is eliminated over time (not a percent)
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Michaelis-menton model of elimination
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elimination which is dose dependent and follows zero order at high levels and 1st order after levels have fallen.
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Context sensitive half time
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defined as the time to halving of the blood concentration after termination of drug administration by an infusion designed to maintain a constant concentration.
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What determines the F1 in the FA/F1 ratio.
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F.G.F. rate
circuit volume circuit absorption |
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What determines the FA in the FA/F1 ratio
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uptake
ventilation concentration effect 2nd gas effect |
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What affects Fa
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ventilation/perfusion mismatching
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What are the 4 major factors involved in the uptake and distribution of inhalant anesthetics
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Machine
lungs blood tissue |
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How do V/Q problems effect uptake and distribution?
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by decreasing uptake and prolonging induction
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Discuss nitrous diffusion
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nitrous oxide occupies a larger volume than Nitrogen. When it enters closed spaces that cannot vent, the nitrous will expand and create pressure. Therein lies the problem
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What conditions would provide contraindication to the use of Nitrous.
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pneumothorax
air embolism bowel obstruction retinal surgery inner ear surgery neuro surgery done with air |
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What aspects of the blood component impact uptake and distribution?
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Vessel Rich Groups receive 70-75% of CO.
Changes in CO in the 1st 5 minutes effect uptake. Higher C.O.slows uptake and is more pronounced with slower drugs. |
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What are the components of tissue attributes that contribute to the uptake (distribution)?
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oil/gas solubility
metabolism diffusion hypoxia |
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How does metabolism effect uptake and distribution?
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Inhalants are designed NOT to be metabolized. Des, Iso, and Nitrous are only trace soluble whereas Sevo is the highest with 5-7% metabolized.
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How does the concept of diffusion hypoxia effect uptake and distribution of inhalants?
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It more deals with the effect it has on tissues when it is eliminated. Nitrous rushes out quickly and dilutes O2 in lungs causing hypoxia. Treat by giving 100% 02 while nitrous is turned off to counteract effect.
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How does diffusion hypoxia effect ventilation?
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It dilutes the 02 as well as the C02 causing hypoxia and hypocarbia which creates hypoventilation which would further compound hypoxia in spontaneously breathing pts.
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Why is nitrous faster (based on the alveolar concentration graph) despite Desflurane's lower Bld/gas Coefficient?
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Because of the concentration effect. Nitrous is administered at 50-70% whereas Desflurane is less than 10% (pg 49, binder)
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How does ventilation effect the different gases as a result of their solubility?
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The most soluble (slowest) anesthetics are more greatly effected by increased ventilation. (the higher the b/g solubility, the higher the effect of the increased ventilation)
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What effect do V/Q abnormalities have on induction times?
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Decreased ventilation/perfusion has a greater impact on the low solubility (faster drugs)
'If the bus breaks down, everyone walks' |
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What happens when cardiac output increases in the first 5 minutes of the case?
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Soluble drugs (slower drugs) will be more greatly effected.
Insoluble drugs (faster drugs) will be less effected. 'fast inhalants don't need the bus anyway' |
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Pharmacogenomics
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id's genetic differences among individuals that play a critical role in drug response
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