Pharmacology- Pharmacokinetics and Pharmacodynamics Flashcards
Michaelis-Menten kinetics
Km is inversely related to the affinity of the enzyme for its substrate.
Vmax is directly proportional to the enzyme concentration.
Most enzymatic reactions follow a hyperbolic curve;
however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (eg, hemoglobin).
Effects of enzyme inhibition
¨Pag 228
Lineweaver-Burk plot
The higher the y-intercept, the lower the Vmax.
The further to the right the x-intercept, the greater the Km and the lower the affinity.
Kompetitive inhibitors increase Km.
Bioavailability (F)
Fraction of administered drug reaching systemic circulation unchanged. For an IV dose, F = 100%.
Orally: F typically < 100%.
Volume of distribution (Vd)
Theoretical volume occupied by the total amount of drug in the body relative to its plasma concentration.
Vd = amount of drug in the body / plasma drug concentration
Low Vd: Intravascular
Medium Vd: ECF
High Vd: All tissues
Clearance (CL)
The volume of plasma cleared of drug per unit time.
CL = rate of elimination of drug / plasma drug concentration = Vd × Ke (elimination constant)
Half-life (t1/2)
The time required to change the amount of drug in the body by 1⁄2 during elimination.
In first-order kinetics, 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 = 0.7 × Vd / CL
*in first-order elimination
Loading dose =
Maintenance dose=
Cp × Vd / F
Cp × CL × τ / F
Cp = target plasma concentration at steady state
τ = dosage interval (time between doses), if not
administered continuously
Types of drug interactions
- Additive
- Permissive
Effect of substance A and B together is equal to the sum of their individual effects (Aspirin and acetaminophen).
Presence of substance A is required for the full effects of substance B (Cortisol on catecholamine responsiveness).
Types of drug interactions
- Synergistic
- Tachyphylactic
Effect of substance A and B together is greater than the sum of their individual effects (Clopidogrel with aspirin)
Acute decrease in response to a drug after initial/repeated administration (Nitrates, niacin, phenylephrine, LSD, MDMA)
Competitive antagonist (pag. 230)
Shifts curve right (Low potency), no change in efficacy. Can be overcome by increasing the concentration of agonist substrate.
Diazepam (agonist) + flumazenil (competitive antagonist) on GABA receptor.
Noncompetitive antagonist (pag. 230)
Shifts curve down (Low efficacy). Cannot be
overcome by Increasing agonist substrate concentration.
Norepinephrine (agonist) + phenoxybenzamine
(noncompetitive antagonist) on α-receptors.
Partial agonist (alone) (pag. 230)
Acts at same site as full agonist, but with lower maximal effect (Low efficacy). Potency is an independent variable.
Morphine (full agonist) vs buprenorphine (partial agonist) at opioid μ-receptors.
Zero-order elimination
Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp decrease linearly with time.
PEA: Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations). *Capacity-limited elimination
First-order elimination
directly proportional to the drug concentration (ie, constant Fraction of drug eliminated per unit time). Cp Decrease exponentially with time. Applies to most drugs.
*Flow-dependent elimination.
