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75 Cards in this Set
- Front
- Back
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Pharmacokinetics:
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amount of drug in the body fluids and tissues over time
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Single Compartment Pharmokinetic model
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A, M, E all directly proportional to [drug] in compartment the transfer is coming from
*does not take tissue specific info into account |
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Two-Compartment Pharmokinetic Model
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Looks at specific tissue blood supply, partition coefficient, capillary permeability to assess how drug will enter and leave central compartment
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Central compartment in 2-compartment model:
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Blood/plasma
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Peripheral compartment in 2 compartment model:
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Tissues
(Molecules can only enter and leave via central compartment) |
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Which drug, the active or the metabolite, is measured experimentally?
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Pharmacologically active
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How is the rate of reaction determined?
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By measuring the disappearance of the drug over time
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What is a zeroth order pharmokinetic reaction?
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The amount of drug is directly related to time
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What is the rate constant for a 0th order reaction?
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K (sub 0)
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What is the equation for a zeroth order pharmokinetic reaction?
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A (Amount of drug)= -k(sub zero)t + A(sub zero)
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For a zeroth order pharmokinetic equation, does the drug concentration per unit time depend on concentration?
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No
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What is true about the rate of elimination for a zeroth order reaction?
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It is constant
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What is a saturated rate of elimination?
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It means that the rate of elimination is at its maximum rate and cannot change when the concentration changes
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How is a drug eliminated in zeroth order reactions?
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A constant amount, NOT A FRACTION, of the drug in the body is eliminated in each equal interval of time
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What is a first order reaction?
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The amount of drug present is related to its concentration
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What is the equation for first order pharmokinetic equations?
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ln A= -kt + ln A(sub 0)
or A=A(sub 0)e^(-kt) |
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How is drug eliminated in 1st order kinetics?
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As a fraction of the drug concentration (not a constant amount) with each equal time interval
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What is mixed order kinetics?
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A drug can convert from 0th to 1st or 1st to 0th at clinically relavent concentrations
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When do non-linear or dose dependent kinetic drugs demonstrate mixed order kinetics?
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When the enzyme becomes saturable at concentrations approximating the range of therapeutic concentrations
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When do drugs following non-linear kinetics function in 1st order kinetics?
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At low doses the drugs will approximate 1st order and are concentration dependent
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When do drugs following non-linear kinetics function in 0-order kinetics?
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At high dosages in the therapeutic range the system becomes saturated and the elimination proceeds at a constant rate, regardless of drug concentration.
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What are examples of drugs that use mixed order kinetics?
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Phenytoin, Aspirin
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What is considered a compartment?
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A tissue or group of tissues that have similar blood flow and drug affinity
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Is compartment a real physiologic or anatomic region?
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NO
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What assumptions are made regarding drugs within a particular compartment?
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1. The drug distribution is uniform
2. Mixing within the compartment is rapid and homogenous, so there is an average concentration "well-stirred" 3. Rate constants are used to represent the overall rate processes of drug entry into and out of the compartment 4. The model is an open system because the drug can be eliminated 5. Based on linear assumptions using linear differential equations |
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What assumptions are made for the one compartment model?
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The body is a single, well-mixed container
1. The drug in the blood is in rapid equilibrium with the drug in the extravascular tissues 2. The drug is mixed instantaneously in the blood or plasma 3. Drug elimination follows first order kinetics |
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What is V(sub D)?
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Apparent volume of Distribution
The hypothetical volume that a drug is distributed into under equilibrium conditions |
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How are dosage and V(sub D) related?
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Dose= V(sub D)*C(sub P)
C(sub P)= drug [ ] in plasma |
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How is V(sub D) related to the amount of drug in the body?
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V(sub D)= (amount of drug in body)/[drug] in plasma]
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What factors influence the volume of distribution?
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1. Plasma protein binding (increase Cp=decrease Vd)
2. Lipid solubility (increase lipid solubility= increase Vd) 3. Tissue binding (greater tissue binding/plasma binding= increase Vd) |
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What is drug clearance?
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A measure of drug elimination from the body without identifying the mechanism
C= volume of plasma fluid cleared of the drug/time Fraction of drug removed / time |
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Does clearance tell us how a drug is being removed?
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No
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What are possible routes for clearance from the body?
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Kidney, liver, lung, x
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What are the units for clearance?
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ml/min
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What is the equation for total body clearance?
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Cl (total)= elimination rate/ plasma concentration
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How is drug elimination expressed for 0th order kinetics?
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mass/ unit time
mg/min or mg/hr Rate is constant this way |
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How is drug elimination expressed for 1st order kinetics?
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volume/unit time
L/hr or mL/min It is constant if expressed in terms of volume/time because drug elimination for 1st order elimination is dependent on drug concentration |
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What does AUC stand for?
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Area under the curve
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What is drug half life?
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The time it takes for the plasma concentration of the drug to fall by 50% regardless of the initial value
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Is half-life meaningful for 0th or 1st order kinetics?
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Only for 1st order
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When referring to half-life, is the elimination phase being referred to or the distribution phase?
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Eliminatin phasse
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What is the elimination phase half-life of single compartment drugs?
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t (sub 1/2)
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What is the elimation phase half-life of a two compartment model?
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t (sub 1/2) beta
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What is the distribution phase half-life of a two compartment model?
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t (sub 1/2) alpha
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What are some factors that may affect half-life?
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Alteration in:
Distribution, metabolism, excretion (exp: plasma protein binding, liver metabolism, renal excretion) Age (may change capacity for elimination) |
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How will production of an alkaline urine influence the half-life of a drug that is a weak acid?
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It will decrease the half-life
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How is half-life related to volume of distribution and clearance?
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T (sub 1/2)= (0.693 * V(sub D))/Cl and Cl= k (sub elim) * V (sub D)
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What are factors that decrease half life?
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1. Decrease in volume of distribution
2. Increase in clearance |
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What are factors that increase half life?
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1. Increased volume of distribution
2. Reduced clearance |
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When does drug accumulation occur?
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If a drug is given at regular intervals that are too short to allow complete clearance of the drug
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When is a plateau or steady state level of drug accumulation reached?
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When drugs are eliminated according to 1st order kinetics
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What is a plateau or steady state level of drug accumulation?
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Rate of elimination of the drug = rate of drug entry into the body
Quantity cleared between doses = amount of the single dose |
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When does the plateau concentration remain constant?
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When the dose and frequency are constant
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What does drug entry depend on?
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Dose and interval between doses
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What does drug exit depend on?
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Total body clearance
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What happens to the plateau concentration if dose and interval are increased or decreased by the same factor?
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It is unchanged
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What is the accumulation ratio?
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mean steady state plasma concentration divided by the mean plasma concentration during the 1st dosing interval
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What does a large ratio of t (sub 1/2)/tau mean?
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There will be an accumulation of drug in the body because the dosage interval (tau) is being given faster than the body can remove it t(sub 1/2)
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When is the accumulation ratio exactly 2.0?
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When the drug is administered at intervals exactly equal to its half-life.
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What does an accumulation ration of 2.0 mean?
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the plateau plasma concentration will be twice that of the mean plasma concentration after the 1st dose
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What does the time required to reach steady state depend on?
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The half life
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Does the time required to reach steady state also depend on:
dose size, dosing interval (tau) or number of doses (n)? |
No. The time required to reach steady state is independent of dose size, dosing interval length and the number of doses
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What happens to the steady state level if the dose or dosage interval is altered?
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The time required to reach steady state remains the same, but the final steady state plasma level changes proportionately
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What is a huge factor in changes in the accumulation of drugs?
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Disease states that influence half life
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What are some examples of disease states that influence half life, how do they influence accumulation?
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1. Digoxin: Clearance reduced when pt has renal disease= half-life increases= steady state plasma conc. is acheived more slowly= final conc. is higher than in a pt with normal renal function
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How are accumulation and elimination related?
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Accumulation is the inverse of elimination
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For a drug with a short 1/2 life, what can we assume for time to achieve steady state and relative accumulation?
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Short 1/2 life= rapid attainment of steady-state concentration= small accumulation of the drug
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For a drug with a short 1/2 life, what can we assume for time to achieve steady state and relative accumulation?
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Long 1/2 life= slow attainment of steady state= much accumulation= potentially toxic
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What causes fluctuation?
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Changes in dose and dosing interval
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Would you find less fluctuation in a drug being taken with smaller doses at more frequent intervals or larger doses at less frequent intervals?
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Smaller doses at more frequent intervals
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Is there a steady-state plateau for drugs with 0th order kinetics?
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No.
A drug with 0-order kinetics, taken in intervals will continue to increase to potentially toxic levels. The amount in the body will continue to rise |
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When is a loading dose used?
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When a drug with a long half life needs to reach a certain steady-state plasma concentration quickly
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What is a loading dose?
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A larger dose that can be administered during the initial phase to rapidly bring the plasma concentration to a desired level
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What is the equation for a loading dose?
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Loading dose= Cp (ss) x V (sub D)
= desired plasma conc. at steady state x distribution in body |
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When is an example of when a loading dose is used?
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For antimalarial drug, Quinacrine
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