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61 Cards in this Set
- Front
- Back
What is pharmacokinetics?
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The study of the relationship between drug dose and concentration of drug at it's receptor.
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What is the equation for the volume of distribution?
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Vd = Amount of drug in body (mg)/ Concentration in plasma (mg/L)
units = mg / (mg/L) = L per kg body weight "The volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration." |
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What does a high Vd indicate?
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A high Vd indicates a greater distribution to the extravascular tissues than to the vascular compartment.
Example: The Vd for chloroquine in 13,000 L/70 kg |
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What does a low Vd indicate?
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A low Vd indicates a greater distribution to the vascular compartment
Example: The Vd of warfarin is 9.8 L/70kg |
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What is the approx volume of total water in a 70 kg individual?
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42L (0.6/kg)
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What is the approx volume of extracellular water in a 70 kg individual?
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14L (0.2 L/kg)
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What is the approx volume of blood in a 70 kg individual?
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5.6L (0.08 L/kg)
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Immediately following IV administration of 300mg of Drug X to a 70 kg man, plasma concentration of Drug X was measured to be 3.8 mg/L. What is the Vd of Drug X?
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Vd = Amount of drug in body / Concentration in plasma
Vd = 300/3.8 = 78.9 L |
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What is the definition of clearance?
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Clearance is a measure of the ability of the body to remove a drug.
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What are the three major types of clearance?
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1. First-order: Rate of elimination depends on the concentration of the drug. Plot will be hyperbolic.
2. Capacity limited (zero order): rate of elimination does not depend on the concentration of the drug. Plot is linear. 3. Flow dependent: rate of elimination depends on the rate of drug delivery to the organ of elimination. |
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What is the formula for first-order clearance?
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Rate of elimination = CL * [drug]
units = L/h * mg/L = mg/h/70kg y axis = Rate of elimination x axis = Plasma drug concentration |
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First order clearance: CL is ____over [drug] range.
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CL is CONSTANT over drug range.
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First order clearance: A constant _______ of drug is removed per unit time.
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A constant FRACTION of drug is removed per unit time.
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First order clearance can be estimated by calculating the ____ ___ ___ ___ ___ of the time-concentration profile after a drug dose.
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First-order clearance can be estimated by calculating the AREA UNDER THE CURVE (AUC) of the time-concentration profile after a drug dose.
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What are the units of first order clearance?
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L/h/70kg
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When do we see capacity limited clearance take place?
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When the drug dose exceeds clearance capacity (saturation).
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What drugs exhibit capacity clearance?
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aspirin
alcohol phenytoin |
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Capacity limited clearance: A constant _____ of drug is removed per unit time.
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A constant AMOUNT of drug is removed per unit time (i.e. the rate of elimination is constant).
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Capacity limited clearance: Clearance is ___ ______ but varies with ___ ______.
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Clearance is NOT CONSTANT but varies with DRUG CONCENTRATION.
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What is the formula for capacity limited clearance?
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Saturatable, non-linear, dose-dependent, Michaelis-Menten elimination
Rate of elimination = Vmax(C) / (Km + C) Vmax = maximum elimination capacity Km = drug concentration where rate of elimination is 1/2 Vmax C = concentration of drug |
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Flow-dependent clearance largely depends on what?
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The rate of drug delivery to the organ of elimination.
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What are some examples of drugs that exhibit flow-dependence?
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Morphine, propranolol.
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Flow-dependent clearance: most of the drug is cleared how/when?
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Cleared rapidly - most of the drug is cleared on the first pass through the organ of elimination.
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Drugs are eliminated by many routes (liver, kidney, lungs) thus clearance is ____?
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Additive.
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First order CL for drug X is 1.62 L/h/70kg. If plasma concentration of drug X is 3.8 mg/L immediately following oral administration of 300mg drug X to a 70 kg man, what is the rate of elimination?
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Rate of elimination = CL * [drug]
1.62 * 3.8 = 6.16 mg/h/70kg |
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What is the definition of half life?
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The half life is the time required to change the plasma concentration of a drug by one-half.
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Half-life is only relevant to drugs eliminated by ____ ____ kinetics.
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Half-life is only relevant to drugs eliminated by FIRST-ORDER kinetics.
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What does t1/2 indicate during dosing? During elimination?
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During dosing, t1/2 indicates the time required to attain 50% of steady-state.
During elimination, t1/2 indicates the time required to decay 50% from steady-state. |
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What is the equation for determining the half-life from the elimination constant?
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t1/2 = 0.693/k
k = - slope of log[drug] vs. time plot unit of k = /hr unti of t1/2 = hr |
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What is the equation that relates CL, k, and Vd?
So, by substitution, how does t1/2 relate to the above equation? |
CL = kVd
t1/2 = 0.693Vd/CL |
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What percentage of a drug is lost after two half-lives?
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75%
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What percentage of a drug is lost after four half-lives?
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100 --> 50 --> 25 --> 12.5 --> 6.25
0% -1-> 50% -2-> 75% -3-> 87.5% -4-> 93.75 |
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How much of a drug must you give before a maximum effect is achieved?
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4 half-lives (>90% of a steady-state concentration must be achieved)
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What is the "Rule of 4?"
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A drug must be administered for four half-lives before a maximum effect is seen.
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What will happen if a drug's dosing interval is less than four half-lives?
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The drug will accumulate.
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What is the equation used to calculate the concentration of a drug at any time, t?
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Ct = C(0)(0.5)^t/(t1/2)
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How can bioavailability be measured?
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Bioavailability can be measured as the area under the curve in a plot of plasma concentration vs. time.
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What is the bioavailability of a drug given intravenously?
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1 (100%)
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What is the equation for bioavailability by any route?
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AUC of the route used / AUC of IV administration.
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What administration routes avoid the first-pass effect?
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IV, IM, SC, inhalation, sublingual, and transdermal routes (do not enter the portal circulation).
Rectum partial avoids the first-pass effect. |
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What is the equation for the extraction ratio?
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ER = CL in liver / Q
Q = hepatic blood flow 90L/h/70kg |
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What is the equation for systemic bioavailability?
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Systemic bioavailability (F) is defined as:
F = f * (1 - ER) f = extent of GI absorption |
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If hepative blood flow is 90L/h in a 70 kg person and hepatic clearance of morphine is 60 L/h/70kg, the first pass extraction ratio is...
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.ER = CL in liver / Q
ER = 60/90 = 0.67 |
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If hepatic flow is 90 L/h in a 70 kg person, hepatic clearance of midazolam is 25 L/h?70 kg, and GI absorption is 44%, the systemic bioavailability of midozolam is:
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F = f * (1 - ER)
F = 0.44 * (1 - 25/90) = 0.318 = 32% |
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What is the definition of bioavailability?
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Bioavailability is the fraction of unchanged drug that reaches the circulation.
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The decline in the intensity of pharmacologic effect with time following a single large dose has _ parts. Which of these parts behaves in a linear fashion?
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3 parts.
Part number 2 behaves linearly. |
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(extra credit)
Gentamicin shows more renal toxicity following _____ infusion rather than ______ dosing. |
Gentamicin shows more renal toxicity following CONSTANT infusion rather than INTERMITTENT dosing.
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At a steady state, the dosing rate must equal _______________.
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At a steady state, the dosing rate must equal THE RATE OF ELIMINATION.
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What is the equation for a steady-state maintenance dose?
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Steady-state maintenance dose = (CL * TC * Dosing interval) / F
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A TC plasma [erythromycin] of 1.5 mg/L is required to treat a bacterial infection. CL for erythromycin is 38.4 L/h/70kg. Calculate the dosing rate for erythromycin administered countinuously by IV.
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CL * TC = 38.4 * 1.5 = 57.6 mg/h/70kg
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A TC plasma [erythromycin] of 1.5 mg/L is required to treat a bacterial infection. CL for erythromycin is 38.4 L/h/70kg. Calculate the dosing rate for erythromycin administered countinuously by IV.
Calculate the maintenance dose for erythromycin given orally when dosing every 12h. F<oral> for erythromycin (enteric coated) is 0.80. |
CL * TC * Dosing interval/F = 38.4 * 1.5 * 12/0.8 = 864 mg/70kg
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What is the equation for a loading dose that is given by IV administration?
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Loading dose = Vd * TC
units = L * mg/L = mg |
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What is the equation for a loading dose that is given via a route other than IV?
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Loading dose for route other than IV (bioavailability, F must be considered)
Loading dose = Vd * TC/F |
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(extra credit)
The loading dose of a multicompartment drug should be given how? |
Slowly, because initial plasma concentration might be toxic.
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What kind of dose do you give if you want to acheive target concentration (TC) rapidly?
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You would give a loading dose.
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What is the most important parameter for adjusting drug dosing?
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Clearance.
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What is the equation for dose adjustment for clearance in a patient with altered renal function?
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Dose<corrected> = Dose<average> * Patient's Creatinine Clearance / 100mL/min
Note that if a problem were to say that drug X is "80% cleared" by the kidney, then the equation would be: Dose<corrected> = [Dose<average> * Percent cleared by that organ] * Patient's Creatinine Clearance / 100mL/min where 100mL/min is the normal creatinine clearance. |
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Pancuronium is 80% cleared bt the renal route. the normal dose of pancuronium is 2mg/mL. The corrected dose for a 70kg man with a creatinine clearance of 80mL/min is:
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Apply correction to the portion of the dose that is cleared by the kidney: 0.8 * 2 = 1.6 mg/mL
Dose<corrected> = 1.6 * 80/100 = 1.28 Add portion of dose not cleared by kidney: 1.28 + 0.4 = 1.68 mg/mL |
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What is the equation for a steady state dosing rate?
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Dosing rate<steady state> = CL * TC
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What is a formula for giving a maintenance dose?
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Maintenance dose = dosing rate * dosing interval
Maintenance dose = CL * Target Concentration * (dosing interval/bioavailability) |
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What is the equation for giving a loading dose?
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Loading dose = Vd * Target Concentration/Bioavailability
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