Term
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Definition
| the time-course of drugs in the tissues of the body; "drug deposition" and absorption, distribution, metabolism and elimination; what the body does to the drug |
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Definition
| drug concentration and pharmacologic response; what the drug does to the body |
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Definition
| established from studies in GROUPS of patients; "average" values; guide to therapy; some patients abive and some below but it is the range which most patients are going to respond |
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Definition
| absorption, distribution, metabolism and excretion |
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| factors that influence oral drug absorption |
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Definition
| molecular size, degree of ionization, and relative lipid solubility; if entry is indirect the drug formulation can influence the rate and extent of absorption |
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Term
| bioavailability; determined by |
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Definition
| quantify the rate and extent of drug absorption; is determined by absorption and degree of presystemic extraction |
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Definition
| comparing its rate and extent to that of another accepted orally administered standard. |
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Definition
| comparison is made to the same drug administered intravenously |
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Definition
| ratio of the bioavailability of an oral dosage to the IV dosage; percentage of unchanged drug that reaches the systemic circulation |
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| physical properties that effect distribution |
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Definition
| molecular weight, lipid solubility, pKa, and protein binding |
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Term
| which organs receive drugs first? |
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Definition
| highly perfused organs like the heart, liver, kidney and brain |
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Term
| what is the apparent volume of distribution |
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Definition
| extent of drug distribution; relates the total amount of drun in the body to the resulting plasma concentration; is an imaginary space; measured in liters and standardized to body weight (L/kg) |
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Term
| apparent volume of lipid soluble vs insoluble |
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Definition
| lipid soluble= distribution volumes that exceed body water and insoluble= smller |
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Term
| why would apparent volume of distribution correspond to plasma or blood volume? |
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Definition
| implies that tissue uptake and tissue storage is not extensive. |
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Term
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Definition
| albumin; ex: salicylate, phenytoina dn warfarin |
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Term
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Definition
| alpha1-aci glycoprotein; ex: lidocaine, many beta blockers, meperidine and methadone |
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Term
| activity of protein bound drug |
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Definition
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Term
| fractions of plasma concentrations |
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Definition
| amont of drug that exists bound to protien and the amount of drug that exists in the free (unbound) state |
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| how drug interactions occur |
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Definition
| drugs that compete for binding to a protein |
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Term
| if drug A is 40% bound and experiences a 20% reduction, the unboudn fraction increases by ____% up to _____% |
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Definition
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Definition
| any alteration of a drug by the body that results in the formation of a metabolite |
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Definition
| throguh the liver the first time and most, if not all, of the drug is megabolized; this reduces the bioavailability of the drug; doesn't take place with IV drugs |
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Term
| examples of first pass metabolism drugs |
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Definition
| lidocaine, propranolol, naloxone and hdralizine |
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Term
| what routes bypass the liver? |
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Definition
| IV, siblingual, 50% of rectal |
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Term
| extent of "first pass" metabolism is determined by |
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Definition
| amount of drug degradation in the GI as well as the amount of metabolism in the liver |
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Term
| functions of biotransformation |
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Definition
| to convert a lipid soluble drug into a more water-soluble compound to be extracted; to turn in inactive drug that is ingested into an active drug |
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Term
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Definition
| cortisone, prednisone azathioprine and fosphenytoin |
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Term
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Definition
| within the ER and expose a funcitonal group on the parent drug; becomes inactive or less active |
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Term
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Definition
| within the cytosol; conjugation reactions; involve covalent linkage of functional groups; may undergo phase I first or simply undergo phase II |
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Term
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Definition
| N and O-dealkylation, aliphatic and aromatic hydroxylation, N and S oxidation and deamination |
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Term
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Definition
| glucuronidation, sulfation and acetylation |
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Term
| describe hepatic enzyme induction |
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Definition
| de novo synthesis of cytochrome P450 enzyme; substances induce these enzymes to increase the metabolic degradation of other drugs; ex: phenobarbital, rifampin and carbamzepine |
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Term
| hepatic enzyme inhibition |
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Definition
| competition between two rugs for the same metabolic pathway; slows the rate of drug metabolism; ex: azole antifungals and macrolide antibiotics |
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Term
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Definition
| constant amount of drug is eliminated; clearance pathways have become saturation; arithemetic scale; "non-linear kinetic" ex: ethanol; independent of concentration of drug; half-life varies; clearance not constant |
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Term
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Definition
| constant fraction of drug is eliminated; proportional to the drug concentration; logarithmic scalse as a straight line "linear kinetics"; constant half-life |
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Term
| Michaelis-Menten elimination |
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Definition
| rate of drug elimination is dependent upon the concentration of drug present; upper portion curve decays in a convex fashion (zero order) and lower portion is a straight line (first order); ex: phenytoin; clearance is not constant; half life is not constant |
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Term
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Definition
| some drugs are secreted directly into the canaliculi via an energy-dependent and carrier-specific process; may undergo enzyme deconjugation and reabsorbed or may be excreted without further reabsorption |
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Term
| drugs that are excreted by biliary clearance as intact drug or metabolite |
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Definition
| digoxin, estradiol, lovastatin fluvastatin spironalactone testosterone doxorubicin and vincristine |
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Term
| drugs excreted by clearance and subsequently reabsorbed |
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Definition
| digitoxin, impipramine indomethacin, morphine, and pregnenolone |
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Term
| three pathways in the kidney of drugs |
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Definition
| glomerular filtration, active tubular secretion and passive tubular reabsorption |
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Term
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Definition
| passively filtered across (protein bound is not filtered); creatinine clearance is used as an indicator and as the basis for determining the need for dosage adjustments |
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Term
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Definition
| distinct nonselective active secretion exist in the proximal tubule; acidic= furosemide, penicillis, salicylates; basic= amiloride, morphine, quinidine and amphetamine |
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Term
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Definition
| passive reabsorption of filtered and/or secreted drugs dictated by lipid solubility, degree of ionization adn drug concentration gradients; this reduces the amount of drug excreted |
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Term
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Definition
| the elmination of drug from the body from liver, kidney and others; rate at which drug is elminated from its unique volume of distribution and its units are volume per unit time |
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Term
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Definition
| (0.693 x volume of distribution) / half-life |
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Term
| clearance for first order elimination |
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Definition
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Term
| clearance for zero-order elimination |
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Definition
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Term
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Definition
| the amount of time that is required for the concentration of drug in the plasma to fall by 50%; influences the frequency with which you administer drugs |
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Definition
| rate of drug entering the systemic circulation equals the rate of drug elimination so the amount of drug in the body remains constant |
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Term
| steady state for first-orer elimination |
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Definition
| steady state conditions are achieved after approximately 5 half lives; and have life is the ONLY factor whch influences when steady state is achieved; |
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Term
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Definition
| administered to rapidly achieve concentrations that approximate those which will eventually exist at steady state |
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Term
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Definition
| when a drug is administered repeatedly, drug accumulation occurs unless the time exceeds the half-life; rising serum concentrations |
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Term
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Definition
| average serum concentration at steady sate divided by the average drug concentration after the first dose. |
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Term
| accumulation ratio when the time interval equals its half life |
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Definition
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Term
| accumulation ratio when the time interval is less than the half-life |
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Definition
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Term
| accumulation ratio when the time interval is greater than the half-life |
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Definition
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Term
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Definition
| IV bolus; rapid IV infusion of a drug within seconds; Cmax is reached rapidly; drug concentration is proportional to the total amount of drug administered; drug concentration has vanished after 4-5 half lives |
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Term
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Definition
| multiple IV bolus; drug accumulation depicted as rising drug oncentrations with each succeeding dose becuase the previous dose has not been eliminated; concentration peads after 4-5 half lives raching a "steady state"; fluctuates between max (CPss max) and min (CPss min) |
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Term
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Definition
| constant IV infusion; CPss average is reached at the same rate as multiple IV bolus profile' CPss average is related to the ratio of infusion rate to clearanc; 50% raise in drug during the infusion and is identical to the half-life defining the 50% decrease in concentration after te infusion is stopped; CPss is almost completely ttained after 4-5 half lifes; CPss averagei is independent of the infusion rate and is only related to the half life |
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Term
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Definition
| bolus X constant infusion; the observed drug concentration is the sum of each concentration profile contributed by the IV bolus and the infusion; the declining concentration profile from the bolus is offset by the rising concentration profile form the infusion, resulting in maintenance of a constant concentration at CPss max; the half-life applies to the drug concentration disappearance curve following the cessation of the infusion |
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Term
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Definition
| single oral dose; Cmax is reached rapidly or slowly depending upon fraction absorbed, dose, volume of distribution and clearance |
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Term
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Definition
| multiple oral dose; quasi-steady state reached avter 4-5 half lives; average steady-state drug concentration occurs only for an instant during each dosing interval and its value lies midway between the max and min; CPss is related to bioavailability, dose dosing interval and clearance |
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Term
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Definition
| loading dose and multiple oral dose; equivalent to the IV bolus + constant infusion; drug concentration fluctuates between CPss mx and CPss min; average concentration is attained only for an instant during each dosing interval |
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Term
| equation for loading dose |
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Definition
LD = (deltaC x Vd) / (F x S)
-F is the fraction of the drug dose systemically available; F=1 for IV administered drugs
-C is the targe oncentration, if drug already present then deltaC
-Vd is a constant for each drug
-S is the fraction of active drug present within the salt, for drugs not administered as salts S=1 |
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Term
| equation for peak concentration |
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Definition
| delta Cp = (F X S X loading dose) / Vd |
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Term
| equation for maintenance dose |
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Definition
| MD = (Cpss x clearance) / (F X S) |
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Term
| equation for average steady state concentration |
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Definition
| CPss = (F x S x dose) / clearance |
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Term
| equation for time to reach steady state |
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Definition
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Term
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Definition
| half-life = (0.693 x Vd) / clearance |
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