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Distribution, Metabolism and Excretion

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allelipraise's version from 2017-10-25 13:10

Section 1

Question Answer
Distributiontransfer of the drug from the plasma to the interstitium
Distributionmechanism of drug removal from the blood
Distributionmay result to drug accumulation if distribution occurs to deeper sites where the drug may remain for some time
Membrane permeability Blood perfusionRate of distribution
Lipid solubility pH-pKa Plasma protein binding Intracellular bindingExtent of distribution
Vascular system/Body water/One or more tissues that may or may not be the site of action/CombinationDistribution Patterns
Vascular systemplasma substitutes and drugs bound to plasma protein
Body watersome low MW water soluble compounds
One or more tissues that may or may not be the site of actionhighly lipid soluble compounds that distribute into fat tissue
Combination determined by membrane permeability and lipid/water solubility highest concentrations in the kidney, liver, and intestine
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Section 2

Question Answer
LiverMajor organ for metabolism
hepatic microsomes in the smooth endoplasmic reticulummajor substructure for Metabolism
kidneys, lungs, skin, gut wall, eye, and bloodOther sites of metabolism
First pass effectPresystemic Metabolism
Enzymes and normal oral floraMouthPresystemic Metabolism
Acidic pHStomach :Presystemic Metabolism
Enzymes and intestinal floraSmall IntestinePresystemic Metabolism
EnzymesGut wall and blood leading to the liver :Presystemic Metabolism
Phase I and Phase II metabolismLiverPresystemic Metabolism
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Section 3

Question Answer
Phase I Reactionsconvert lipophilic molecules into more polar molecules
Phase I Reactionsintroducing or unmasking a polar functional group such as – OH or –NH2
Phase I Reactionscan be excreted by the kidneys
Phase I Reactionsfrequently catalyzed by the cytochrome P450 system (microsomal mixed function oxidase)
Oxidationaddition of oxygen and/or the removal of hydrogen
OxidationMostly occurs in the endoplasmic reticulum
Reductionaddition of hydrogen or the removal of oxygen
Hydrolysisaddition of water with the breakdown of the molecule
HydrolysisMostly occurs in blood plasma (esterases) and liver
Phase II ReactionsConjugation reactions with endogenous substrates that result to polar, more water-soluble compounds
Phase II Reactionsoccur when the metabolites from Phase I are too lipophilic to be retained in the kidney tubules
Phase II Reactionsmost often therapeutically inactive metabolites
Phase II ReactionsGlucuronidation
Phase II Reactionsmain conjugation reaction
Phase II Reactionsoccurs in the liver with bilirubin and thyroxine
Phase II ReactionsAcetylation Glycine addition Sulfate addition
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Section 4

Question Answer
Pharmacogeneticsstudy of the effects that genetic differences have on the metabolism of certain drugs
Fast and Slow AcetylatorsPharmacogenetics Examples
Excretionirreversible transfer of drug from the blood to the urine or other excretory compartments
kidneymajor organ or site of excretion
nephronfunctional unit of excretion
skin, saliva, bile, lungs, tears and milkOther sites of excretion
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Section 5

Question Answer
Filtration (glomerulus)/ Secretion (proximal tubule)Major Excretion Processes
Filtrationglomerulus ?
Secretionproximal tubule ?
Filtrationlow MW molecules
100-130 mL/minnormal GFR ?
Filtrationmeasured by the renal clearance of inulin
active secretion of some weak electrolyte especially weak acids and reabsorption of waterSecretion
requires a carrier and energy supplySecretion
reabsorptiondistal tubule ?
Secretion passive excretion and reabsorption of lipid soluble drugs
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