Pharmacokinetics Flashcards
(20 cards)
What is the difference between zero-order and first-order kinetics in terms of the elimination of a drug?
- For zero-order kinetics, the elimination rate of a drug is independent of its concentration in the blood
- For first-order kinetics, the elimination rate of a drug is dependent of its concentration in the bood. The higher the concentration, the more rapidly the drug is eliminated
How is the concentration of a drug at a certain time point calculated ?
C_t = C_0 * e^(-k*t)
C_t: Concentration of a certain time point
C_0: Initial concentration
k: Elimination constant
How is the half-life of a drug calculated ?
t_1/2 = ln(2/k)
t_1/2 = Half-life
k: Elimination constant
What is the “therapeutic window” ?
The concentration of a drug in the blood, which is
- high enough to have an effect
- low enough to avoid adverse effects and toxicity
What is c_max and t_max in concentration-time-curves ?
- c_max: The maximum concentration of a drug in the blood
- t_max: The time point of c_max
How are c_max and t-max changing, if the effect of a drug occurs early or delayed ?
- Early effect: Increase of c_max and decrease of t_max
- Delayed effect: Decrease of c_max and increase of t_max
What are the five phases of the pharmacokinetic process (LADME) ?
- Liberation
- Food intake and delayed release - Absorption
- Overcome of external membrane barriers - Distribution
- Transport from blood plasma into tissues - Metabolism
- Phase-1 oxidation and phase-2 conjugation - Excretion
- Elimination mainly through kidneys and liver
Which characteristics determine the passive transport across membranes ?
- Permeability of the surface
- Concentration gradient
Which characteristics of a molecule determine its ability to pass passively through membranes?
- size
- shape
- lipid solubility
- charge
- pH of molecule and medium
Which factors affect the absorption in the gastrointestinal (GI) tract ?
- Blood flow
- Motility and mixing in GI tract
- Chemical stability in gastric and intestinal fluids
- Presence and type of food
- Rate of gastric emptying
- Total adsoption area
Approximately how large is the total adsorption area of the intestine ?
Around 200 m^2
Why is the absorption through the lungs usually very fast ?
- large surface area
- thin barrier
- high blood flow
The distribution defines the transport of a drug after its absorption. What determines the initial and the later phases of distribution ?
- Initial phase is determined by the blood flow
- Later phases are determined by the tissue affinity
How is the volume into which a drug appears to distribute calculated ?
V_d = (Amount of drug in the body) / (Concentration in plasma)
What effect does a high hydrophilicity of a drug have on its elimination and excretion ?
The higher the hydrophilicity, the better the elimination and excretion of the drug.
Which effects can the metabolism have on a drug ?
- Toxification and Detoxification
- Metabolic activation of pre-drugs
Name four enzymes which catalyse oxidations in the phase-1 metabolism.
- Cytochrome P450 (CYP)
- Flavin dependent monooxygenases (FMO)
- Monoaminoxidases (MAO)
- Cyclooxygenases (COX)
What is the function of glutathion-S-transferases (GSTs) in the phase-2 metabolism ?
- Transfer of glutathiones on electrophilic centres of substrates
- This makes substrates more hydrophilic and easier to excrete
In phase-2 metabolism GSH-conjugates are created. Name three examples.
- Glucuronides
- Sulfates
- Amides
By what factor is the volume reduced during the conversion from primary urine to final urine ?
~ 100
