pharm (conceptual) High yield FA Flashcards
(147 cards)
what is Km and how does it relate to substrate affinity?
Km = [S] at 1/2 Vmax. Km is inversely related to affinity of the enzyme for its substrate (high Km = low affinity and vice versa)
How is Vmax of a reaction related to the enzyme concentration?
Vmax is directly proportional to the [enzyme] (as the enzyme increases, so does the Vmax)
if an enzymatic reaction follows Michaelis-Mentin kinetics (as most do), the graph of [s] vs Vmax is what shape? What shape is the graph for reactions that follow cooperative kinetics?
Michaelis-Menten = hyperbolic, cooperative = sigmoidal (think Hgb)
What is the X axis on a Line weaver burke plot? What is the Y axis? And what is the benefit of this graph?
X axis = 1/[substrate], y axis = 1/V. The benefit of this graph is you can see how inhibitors (competetive and non-comp) affect the graph
In a Lineweaver-Burke plot, what does the Slope represent? What is the X-intercept? The Y-intercept?
Lineweaver burke plot, X axis = 1/[substrate], y axis = 1/V. so the slope = Km/Vmax, x-intercept = 1/-km, y=1/Vmax
On a Lineweaver burke plot, a higher Km (and therefore a lower affinity) crosses the X axis…. whereas a lower Km (and therefore a higher affinity) crosses the X axis…
high Km = on the left of the y intercept, but as close to it as possible (small negative numbers), low Km = as far to the left of the y intercept as possible (big negative numbers)
On a Lineweaver burke plot, a higher Vmax crosses the Y axis…. whereas a lower Vmax (and therefore a higher affinity) crosses the Y axis…
A higher Vmax crosses the Y axis closer to the X-axis, a smaller Vmax crosses the Y axis in the positive quadrant as far away from the x-axis as possible
Do competitive inhibitors: 1) Resemble the substrate, 2) Overcome by increase [S], 3) Bind active site, 4) Effect Vmax, 5) Effect Km, 6) Effect Pharmacodynamics?
competitive inhibitors: 1) Resemble the substrate = yes, 2) Overcome by increase [S] = yes, 3) Bind active site = yes, 4) Effect Vmax = no, you can add more substrate and get to the same Vmax, 5) Effect Km = increased (affinity is decreased) be you need more substrate to get to 1/2 Vmax, 6) Effect Pharmacodynamics = it makes it less potent (you need more substrate to get the same effect)
Do noncompetitive inhibitors: 1) Resemble the substrate, 2) Overcome by increase [S], 3) Bind active site, 4) Effect Vmax, 5) Effect Km, 6) Effect Pharmacodynamics?
noncompetitive inhibitors: 1) Resemble the substrate = no, 2) Overcome by increase [S] = no, 3) Bind active site = no, 4) Effect Vmax = yes, Vmax is decreased bc Vmax is directly proportional to the amt of enx avb and now there are fewer enz avb, 5) Effect Km = no, Km is unchanged, 6) Effect Pharmacodynamics = decreased efficacy ( you decrease the maximal effect a drug can provide)
How does a Competitive inhibitor compare to the normal substrate on a lineweaver burke plot in terms of where it crosses on the X and Y axis?
the competitive inhibitor crosses the x-axis further to the right of the normal substrate (the Km increases, the affinity decreases), and at the same point of the y-axis (vmax is unchanged) – competitive inhibitors cross each other competitively, noncompetitive inhibitors do not
How does a noncompetitive inhibitor compare to the normal substrate on a lineweaver burke plot in terms of where it crosses on the X and Y axis?
the noncompetitive inhibitor crosses the x-axis at the same site of the normal substrate (the Km is unchanged), and a higher point of the y-axis (Vmax is less) – competitive inhibitors cross each other competitively, noncompetitive inhibitors do not
What is the bioavailability of a drug?
the fraction of the administered drug that reaches systemic circulation unchanged
What is the bioavailability of an IV drug? An oral drug?
IV = 100% (bc the bioavailability is the fraction of the drug administered that reaches the systemic circ. unchanged). Oral bioavailability is typically <100% due to incomplete absorption and first pass metabolism
What is the Volume of Distribution of a drug (Vd), both definition and equation
The theoretical fluid vlume required to maintain the total absorbed drug amount at the plasma concentration. volume of distribution = (amount of drug in the body)/(plasma drug concentration)
The Volume of distribution (Vd) can be affected by diseases in what two organ systems?
liver and kidney- decreased protein binding increases Volume of distribution
If the Volume of distribution (Vd) is low (4-8 L), where is the drug likely contained and what types of molecules are these?
It’s largely distributed in the blood, and it’s large/charged molecules that are plasma protein bound
If the Volume of distribution (Vd) is medium, where is the drug likely contained and what drug types/molecules are these?
It’s largely distributed in the ECF and it’s mainly small hydrophilic molecules
If the Volume of distribution (Vd) is high, where is the dug likely contained and what drug types/molecules are these?
It’s largely distributed in all tissues, and this is mainly small lipophilic molecules, especially i bound to tissue protein
If a drug has first-order elimination, how many half lives does it take to reach a steady state [ ] of the drug?
4-5 half lives
equation for a drug’s half life
t(1/2) = (0.7 x Volume of Distribution)/CL where CL = rate of elimination of drug plasma drug concentrations = Vd (volum of distribution) * Ke (elimination constant), sp t(1/2) = 0.7 x Vd/ Vd x Ke
What is Clearance
relates the rate of elimination of a drug to the plasma concentration = Vd (volume of distrbution) x Ke (the elimination constant)
Clearance can be impaired with defects in which three organ systems?
cardiac, hepatic and renal
How do you calculate the Loading Dose for a drug?
Loading Dose = Cp x (Vd/F) where Cp = target plasma conc., Vd = volume of distribution and F = bioavailability
How do you calculate Maintenance dose?
Maintenance dose = Cp x CL/F where Cp = target plasma conc, CL = clearance (Vd x Ke (the elimination constant) and F = bioavailability
