USMLE Step 1 Pharmacology Verified
Solutions
Michaelis-Menten Kinetics - ANS-[S] = Concentration of substrate
V = Velocity
Km is inversely related to the affinity of the enzyme for its substrate
Vmax = Directly proportion to the enzyme concentration
Most enzymatic reactions follow of hyperbolic curve [Michaelis-Menten] kinetics
Enzymatic reactions that exhibit a sigmoid curve [Hemoglobin] exhibit positive
cooperativity
Lineweaver-Burk - ANS-↑ y-intercept, ↓ Vmax
The further to the right, the x-intercept [Closer to zero], the greater the Km, and the
lower the affinity
Enzyme Inhibition - ANS-Reversible competitive inhibitors cross each other
competitively, whereas nonreversible inhibitors do not [parallel]
Reversible Competitive Inhibitiors - ANS-Resemble Substrate: Yes
Overcomed by ↑ [S]: Yes
Binds Active Site: Yes
Effect on Vmax: Unchanged
Effect on Km: ↑
Pharmacodynamics: ↓ Potency
Irreversible Competitive Inhibitors - ANS-Resemble Substrate: Yes
Overcomed by ↑ [S]: No
Binds Active Site: Yes
Effect on Vmax: ↓
Effect on Km: Unchanged
Pharmacodynamics: ↓ Efficacy
Noncompetitive Inhibitors - ANS-Resemble Substrate: No
Overcomed by ↑ [S]: No
Binds Active Site: No
,Effect on Vmax: ↓
Effect on Km: Unchanged
Pharmacodynamics: ↓ Efficacy
Bioavailability [F] - ANS-Fraction of administered drug reaching systemic circulation
unchanged
For an IV dose, F = 100%
Oral, F < 100%, due to incomplete absorption and first pass metabolism
Volume of distribution [Vd] - ANS-Theoretical volume occupied by total amount of drug
in the body relative to the plasma concentration
Apparent Vd of plasma protein-bound drugs can be altered by LIVER and KIDNEY
DISEASE [↓ protein binding, ↑ Vd]
Vd = [Amount of drug in body]/[Plasma drug concentration]
Low Vd - ANS-Compartment: Blood
Drug/Types: Large/charged molecules, plasma protein bound
Medium Vd - ANS-Compartment: ECF
Drugs/Types: Small hydrophilic molecules
High Vd - ANS-Compartment: All tissues including FAT
Drugs: Small, lipophilic molecules, especially if bound to tissue protein
Clearance [CL] - ANS-The volume of plasma cleared of drug per unit time
CLEARANCE MAY BE IMPAIRED w/ DEFECTS IN CARDIAC, HEPATIC, or RENAL
FUNCTION
CL = [Rate of elimination of drug]/[Plasma concentration of drug] = Vd x Kc [Elimination
constant]
Half-life [T1/2] - ANS-The time required to change the amount of drug in the body by 1/2
during elimination [or constant infusion]
PROPERTY OF FIRST ORDER ELIMINATION
A drug infused at a constant rate takes 4-5 half lives to reach steady state.
, It takes 3.3 half lives to reach 90% of the steady-state level
T1/2 = [0.693 x Vd]/CL
# of Half-lives/Percent Remaining
1. 1 [50%]
2. 2 [25%]
3. 3 [12.5%]
4. 4 [6.25%]
Dosage Calculations - ANS-Loading Dose = [Cp x Vd]/F
Maintenance Dose = [Cp x CL x T]/F
Cp = Target plasma concentration at steady state
T = Dosage interval [Time between doses], if not administered continuously
IN RENAL AND LIVER FAILURE, MAINTENANCE DOSE ↓ and LOADING DOSE IS
UNCHANGED
Time to steady state depends primarily on T 1/2 and is independent of dose and dosing
frequency
Zero-order elimination - ANS-The rate of elimination is CONSTANT regardless of Cp
[Constant amount of drug is eliminated per unit time]
Cp ↓ linearly w/ time
Example:
1. Phenytoin
2. Ethanol
3. Aspirin [At high or toxic concentrations]
CAPACITY LIMITED ELIMINATION
PEA = A pea is round, shaped like a zero
First order elimination - ANS-Rate of elimination is DIRECTLY PROPORTIONAL to the
drug concentration [Constant fraction of drug eliminated per unit time]
Cp ↓ exponentially w/ time
FLOW-DEPENDENT ELIMINATION
Solutions
Michaelis-Menten Kinetics - ANS-[S] = Concentration of substrate
V = Velocity
Km is inversely related to the affinity of the enzyme for its substrate
Vmax = Directly proportion to the enzyme concentration
Most enzymatic reactions follow of hyperbolic curve [Michaelis-Menten] kinetics
Enzymatic reactions that exhibit a sigmoid curve [Hemoglobin] exhibit positive
cooperativity
Lineweaver-Burk - ANS-↑ y-intercept, ↓ Vmax
The further to the right, the x-intercept [Closer to zero], the greater the Km, and the
lower the affinity
Enzyme Inhibition - ANS-Reversible competitive inhibitors cross each other
competitively, whereas nonreversible inhibitors do not [parallel]
Reversible Competitive Inhibitiors - ANS-Resemble Substrate: Yes
Overcomed by ↑ [S]: Yes
Binds Active Site: Yes
Effect on Vmax: Unchanged
Effect on Km: ↑
Pharmacodynamics: ↓ Potency
Irreversible Competitive Inhibitors - ANS-Resemble Substrate: Yes
Overcomed by ↑ [S]: No
Binds Active Site: Yes
Effect on Vmax: ↓
Effect on Km: Unchanged
Pharmacodynamics: ↓ Efficacy
Noncompetitive Inhibitors - ANS-Resemble Substrate: No
Overcomed by ↑ [S]: No
Binds Active Site: No
,Effect on Vmax: ↓
Effect on Km: Unchanged
Pharmacodynamics: ↓ Efficacy
Bioavailability [F] - ANS-Fraction of administered drug reaching systemic circulation
unchanged
For an IV dose, F = 100%
Oral, F < 100%, due to incomplete absorption and first pass metabolism
Volume of distribution [Vd] - ANS-Theoretical volume occupied by total amount of drug
in the body relative to the plasma concentration
Apparent Vd of plasma protein-bound drugs can be altered by LIVER and KIDNEY
DISEASE [↓ protein binding, ↑ Vd]
Vd = [Amount of drug in body]/[Plasma drug concentration]
Low Vd - ANS-Compartment: Blood
Drug/Types: Large/charged molecules, plasma protein bound
Medium Vd - ANS-Compartment: ECF
Drugs/Types: Small hydrophilic molecules
High Vd - ANS-Compartment: All tissues including FAT
Drugs: Small, lipophilic molecules, especially if bound to tissue protein
Clearance [CL] - ANS-The volume of plasma cleared of drug per unit time
CLEARANCE MAY BE IMPAIRED w/ DEFECTS IN CARDIAC, HEPATIC, or RENAL
FUNCTION
CL = [Rate of elimination of drug]/[Plasma concentration of drug] = Vd x Kc [Elimination
constant]
Half-life [T1/2] - ANS-The time required to change the amount of drug in the body by 1/2
during elimination [or constant infusion]
PROPERTY OF FIRST ORDER ELIMINATION
A drug infused at a constant rate takes 4-5 half lives to reach steady state.
, It takes 3.3 half lives to reach 90% of the steady-state level
T1/2 = [0.693 x Vd]/CL
# of Half-lives/Percent Remaining
1. 1 [50%]
2. 2 [25%]
3. 3 [12.5%]
4. 4 [6.25%]
Dosage Calculations - ANS-Loading Dose = [Cp x Vd]/F
Maintenance Dose = [Cp x CL x T]/F
Cp = Target plasma concentration at steady state
T = Dosage interval [Time between doses], if not administered continuously
IN RENAL AND LIVER FAILURE, MAINTENANCE DOSE ↓ and LOADING DOSE IS
UNCHANGED
Time to steady state depends primarily on T 1/2 and is independent of dose and dosing
frequency
Zero-order elimination - ANS-The rate of elimination is CONSTANT regardless of Cp
[Constant amount of drug is eliminated per unit time]
Cp ↓ linearly w/ time
Example:
1. Phenytoin
2. Ethanol
3. Aspirin [At high or toxic concentrations]
CAPACITY LIMITED ELIMINATION
PEA = A pea is round, shaped like a zero
First order elimination - ANS-Rate of elimination is DIRECTLY PROPORTIONAL to the
drug concentration [Constant fraction of drug eliminated per unit time]
Cp ↓ exponentially w/ time
FLOW-DEPENDENT ELIMINATION
