Pharm - Pharmacokinetics/-dynamics (Enzyme kinetics, Pharmacokinetics, & Dosage calculations) Flashcards
Pg. 238-239 in First Aid 2014 Sections include: -Enzyme kinetics -Pharmacokinetics vs. pharmacodynamics -Pharmacokinetics -Dosage calculations
What are the axes of the Michaelis-Menten kinetics graph?
x-axis: [S] = concentration of substrate, y-axis: Velocity (V)
Draw the Michaelis-Menten kinetics graph, graph a reaction, including and labeling the following: (1) Km (2) Vmax (3) 1/2 Vmax (4) Saturation.
See p. 238 in First Aid 2014 for graph at top
How does Km relate to affinity of enzyme for its substrate?
Km is inversely related to the affinity of the enzyme for its susbstrate
How does Vmax relate to enzyme concentration?
Vmax is directly proportional to the enzyme concentration
What kind of curve do most enzymatic reactions exhibit? What does this mean?
Most enzymatic reactions follow a hyperbolic curve (follow Michaelis-Menten kinetics)
What causes an enzymatic reaction to exhibit a sigmoid curve? Give an example of such a reaction.
Enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (i.e.., hemoglobin)
What are the axes of the Lineweaver-Burk plot?
x-axis: 1/[S], y-axis: 1/V
Draw the Lineweaver-Burk plot, graph a reaction, including and labeling the following: (1) 1/-Km (2) 1/V max (3) slope = Km/Vmax.
See p. 238 in First Aid 2014 for middle graph
What is the slope of the Lineweaver-Burk plot?
slope = Km/Vmax
What happens to Vmax as the y-intercept of the Lineweaver-Burk plot is increased?
increase y-intercept, decrease Vmax
On the Lineweaver-Burk plot, what does it mean to move the x-intercept to the right (in terms of numerical value)? What effect does this have on Km and affinity?
The further to the right the x-intercept (i.e., closer to zero), the greater the Km and the lower the affinity
Graph the following lines on the Lineweaker-Burk plot: (1) Competitive inhibitor (2) Noncompetitive inhibitor (3) Uninhibited.
See p. 238 in First Aid 2014 for bottom graph
How do competitive versus noncompetitive inhibitors interact with their own kind?
Competitive inhibitors cross each other competitively, whereas noncompetitive inhibitors do not
Does each of the following resemble substrate: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Yes (2) Yes (2) No
Is each of the following overcome by increasing [S]: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Yes (2) No (3) No
Does each of the following bind the active site: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Yes (2) Yes (3) No
What effect does each of the following have on Vmax: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Unchanged (2) Decrease (3) Decrease
What effect does each of the following have on Km: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Increase (2) Unchanged (3) Unchanged
What effect does each of the following have on potency/efficacy: (1) Competitive inhibitors, reversible (2) Competitive inhibitors, irreversible (3) Noncompetitive inhibitors?
(1) Decrease potency (2) Decrease efficacy (3) Decrease efficacy
In general, what does pharmacokinetics study? Give 4 specific examples.
The effects of the body on the drug; (1) Absorption (2) Distribution (3) Metabolism (4) Excretion; Think: “ ADME”
In general, what does pharmacodynamics study? Give 4 specific examples of concepts.
The effects of the drug on the body; Includes concepts of (1) receptor binding (2) drug efficacy (3) drug potency (4) toxicity.
Define Bioavailability. What is its abbreviation?
Bioavailability (F): Fraction of administered drug that reaches systemic circulation unchanged
What is the bioavailability of an IV dose?
For an IV dose, F = 100%
What is the bioavailability of an oral dose, and why?
Orally: F typically < 100% due to incomplete absorption and first-pass metabolism
Define Volume of distribution (Vd)
Theoretical volume occupied by the total absorbed drug amount at the plasma concentration.
What alters the apparent Vd of plasma protein-bound drugs?
Apparent Vd of plasma-protein bound drugs can be altered by liver and kidney disease (decreased protein binding, increased Vd)
What is a minor but important consideration in calculating volume of distribution?
Drugs may distribute in more than one compartment
What is the equation for Vd?
Vd = amount of drug in the body / plasma drug concentration
Into what compartment do drugs with a low Vd distribute? What characterizes such drugs?
Blood (4-8 L); Large/charged molecules, Plasma protein bound
Into what compartment do drugs with a medium Vd distribute? What characterizes such drugs?
ECF; Small hydrophilic molecules
Into what compartment do drugs with a high Vd distribute? What characterizes such drugs?
All tissues including fat; Small lipophilic molecules, especially if bound to tissue protein
What defines half-life (t 1/2)?
The time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion)
Of what type of elimination is half-life a property?
Property of first-order elimination
What is the equation for half-life?
t 1/2 = (0.693 x Vd) / CL
At the following half-lives, what percentage of drug remains: (1) 1 (2) 2 (3) 3 (4) 4?
(1) 50% (2) 25% (3) 12.5% (4) 6.25%
Define Clearance (CL).
The volume of plasma cleared of drug per unit time
What are 3 factors/conditions that may impair clearance.
Clearance may be impaired with defects in cardiac, hepatic, or renal function.
What is the equation for Clearance (CL)?
CL = rate of elimination of drug / plasma drug concentration = Vd x Ke (elimination constant)
What is the equation for the loading dose?
Loading dose = (Cp x Vd) / F; Cp = target plasma concentration at steady state,
What is the equation for the maintenance dose?
Maintenance dose = (Cp x CL x tao) / F; Cp = target plasma concentration at steady state, tao = dosage interval (time between doses), if not administered continuously
What happens to maintenance versus loading doses in renal or liver disease?
In renal or liver disease, maintenance dose decreases and loading dose is usually unchanged
On what factor does time to steady state depend? Of what 2 factors is it independent?
Time to steady state depends primarily on t 1/2 and is independent of dose and dosing frequency
In Michaelis-Menten kinetics, what is Km?
Km is [S] at 1/2 V max