Term
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Definition
describes the time-course of drugs in the tissues of the body, it is based upon the idea of drug disposition, and addresses absorption, distribution, metabolism, and elimination
what the body does to the drug |
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Term
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Definition
describes the relationship between drug concentration and pharmacologic response
what the drug does to the body |
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Term
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Definition
| the concentration range of a drug at which patients are most likely to respond |
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Term
| absorption, distribution, metabolism, and excretion |
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Definition
| what does ADME stand for? |
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Term
1) IV (directly)
2) across membranes (indirectly) |
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Definition
| what are the 2 ways drugs enter the body? |
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Term
1) molecular size
2)degree of ionization
3)relative lipid solubility |
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Definition
| list the factors that influence oral drug absorption |
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Term
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Definition
| a term used to quantify the rate and extent of drug absorption |
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Term
| by comparing its rate of absorption(area under the curve) to that of another accepted orally administered standard |
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Definition
| how is the relative bioavailability of an oral drug determined? |
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Term
| when the oral drug is compared to the same drug administered intravenously ( IV route drugs are 100% available) |
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Definition
| how is the absolute bioavailability determined? |
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Term
F is the ratio of bioavailability of an oral doasage form to the IV dosage form
this value ranges from 1(completely available) to 0.
F aka the percent of unchanged drug that reaches the system circulation |
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Definition
| What is F, and what values does it include? |
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Term
1) absorption
2) degree of presystemic extraction |
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Definition
| what 2 factors determine bioavailability? |
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Term
1) molecular weight
2) lipid solubility
3) pKa
4) protein binding |
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Definition
| what factors affect the distribution of a drug? |
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Term
| the highly perfused ones: heart, liver, kidney, and brain |
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Definition
| what are the first organs to receive a drug? |
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Term
| apparent volume of distribution |
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Definition
| term that describes the extent of drug distribution |
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Term
apparent volume of distribution
-it is defined only by knowing the dose of the drug and the resulting plasma concentration sampled immediately after the drug administration is complete |
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Definition
| this term relates the total amount of drug in the body to the resulting plasma concentration, and does not correspond to an actual physiologic volume |
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Term
| liters, usually standardized to body weight (liters/kg) |
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Definition
| what are the units that volume of distribution is measured in? |
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Term
lipid soluble will exceed body water, lipid INsoluble have smaller apparent volumes of distribution
extensive tissue binding of the drug will also elevate the apparent volume of distribution |
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Definition
| if a drug is highly lipid soluble, will the distribution volume exceed body water or have a smaller apparent volume of distribution? |
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Term
| if the vol. of distribution corresponds in size to the plasma/blood volume or extracellular fluid |
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Definition
| what sort of apparent volume of distribution would imply that tissue uptake and tissue storage is not extensive? |
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Term
| inactive: only free drugs interact with receptors and is available for clearance from the body |
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Definition
| drug bound to protein is ____ |
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Term
acids: albumin ex: salicylate, phenytoin, warfarin
bases: alpha acid glycoprotein ex: lidocaine, beta blockers, merperidine, methadone |
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Definition
| drugs classified as weak acids typically bind to ___ while weak bases typically bind to ______ |
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Term
1) the amount of drug that exists bound to protein
2) the amount of drug that exists in the free state |
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Definition
| the total plasma drug concentration is usually reported as 2 fractions, what are they? |
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Term
low: depends on number of binding sites
high: depends on number binding sites AND drug concentration |
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Definition
| at low concentrations, the fraction of a drug bound to protein is a function of the ________, at high concentrations it is determined by ______ |
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Term
| metabolism/biotransformation |
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Definition
| any alteration of a drug by the body that results in the formation of metabolite (which may be active) with a different chemical structure from the parent compound |
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Term
the liver receives the drug after absorption from the GI tract via the portal vein and as it goes on its first pass through the liver, most of the drug is metabolized despite good oral absorption, reducing the bioavailabiltiy
ex: lidocaine, propanolol, naloxone, hydralzine |
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Definition
| what is " first pass metabolism?" |
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Term
| the oral dose is typically larger |
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Definition
| how does an oral dose of a drug compare to a parenteral dose if the drug has large first pass metabolism? |
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Term
| no, sublingual bypasses liver and 50% of a rectally absorbed drug bypasses the liver |
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Definition
| do IV drugs undergo first pass metabolism? |
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Term
1) the amount of drug degradation that occurs in the GI tract
2) the amount of metabolism that occurs in the liver |
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Definition
| what primarily determines the extent of first pass metabolism? |
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Term
| prodrugs ex: cortisone, prednisone, azathiopne, fosphenytoin |
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Definition
| drugs that are inactive when ingested and require metabolic activation to exert their action |
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Term
Phase 1: occur in the ER and introduce/expose a fxnl group on the parent drug
usually the parent compound becomes inactive or less active with metabolism
ex: N&O de-alkylation, aliphatic and aromatic hydroxylation, N&S oxidation, and de-amination |
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Definition
| describe phase 1 reactions that occur with drug metabolism |
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Term
Phase 2: occur in the cytosol, also referred to as conjugation reactions
involve: covalent linkage of fxnl groups such as glucuronic acid, sulfate, aa's etc. (glucuronidation, sulfation, acetylation)
note: a drug can undergo a phase 1 rxn, then a phase 2, or just a phase 2 |
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Definition
| describe phase 2 reactions that occur with drug metabolism |
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Term
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Definition
| what enzyme family is responsible for most enzymatic drug metabolism? |
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Term
de novo synthesis of cytochrome P450 enzyme resulting in an increase rate of drug biotransformation
-substances that induce these enzymes can increase the metabolic degradation of other hepatically metabolized drugs
ex: phenobarbital, rifampin, carbamzepine |
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Definition
| what does "hepatic enzyme induction" refer to? |
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Term
it typically refers to a competition between two drugs for the same metabolic pathway. This "competitive inhibition" slows the rate of drug metabolism, giving rise to a prolonged or slowed effect
ex: azole antifungals and macrolide antibiotics |
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Definition
| what does "hepatic enzyme inhibition" refer to? |
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Term
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Definition
| means that a constant AMOUNT of drug is eliminated per unit of time |
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Term
straight line(linear) decay on an arithmetic scale, but with the log scale on the Y axis it is a curve so it is referred to as a NON-LINEAR KINETIC
ex: ethanol |
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Definition
| how does zero order elimination plot on a graph? |
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Term
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Definition
| means that a constant FRACTION of drug is eliminated per unit of time |
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Term
| the rate the drug is removed is proportional to the concentration so on a log scale on the Y axis(concentration) vs X(time) the drug conc. decay curve plots as a straight line == LINEAR KINETICS |
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Definition
| describe the graph for a 1st order reaction |
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