Lecture 2 1/24/24 Flashcards
Why are membrane barriers important to drug function?
drugs with different absorptions can pass through different barriers, allowing different drugs to be used to target different treatment sites
What are the potential mechanisms by which molecules cross a membrane barrier?
-transcellular passive transport
-paracellular passive transport
-transcellular facilitated transport
-transcellular active transport
-pinocytosis
What are the characteristics of transcellular passive transport?
-driven by concentration gradient
-molecules have high degree of lipid solubility and some water solubility
What are the characteristics of paracellular passive transport?
-intercellular gaps
-pore size varies
-driven by concentration gradient
What are the characteristics of transcellular facilitated transport?
-driven by concentration gradient
-accelerated rate
-not active/no energy involved
What are the characteristics of transcellular active transport?
-against a concentration gradient
-requires energy
What are the characteristics of pinocytosis?
-engulfing of extracellular material via membrane vesicles
-less common
-used for large molecules
Which factors impact the rate of diffusion?
-size, conformation, and water solubility
-membrane surface area
-lipid solubility
-membrane thickness
-concentration gradient
Which factors that impact the rate of diffusion are limiting factors?
-membrane thickness
-potentially concentration gradient
Which factors impact water and lipid solubility of a drug?
-polarity of drug
-degree of ionization/electrolytes
How does polarity impact drug solubility?
-non-polar drugs are more lipid soluble
-polar drugs are more water soluble
What is pKa?
the pH at which 50% of drug molecules are ionized and 50% are non-ionized
What is ion trapping?
-an acidic drug can be trapped by placing it in an environment with high pH
-a basic drug can be trapped by placing it in an environment with low pH
What is urine alkalinization?
trapping of an acidic drug in the urine by making the urine more basic, thus preventing the drug from reabsorbing
What are the general characteristics of passive diffusion?
-no external energy spent
-net transfer is zero at equilibrium
-non-selective and non-saturable
-rate is proportional to amount
What is a first order elimination pharmacokinetic system?
-constant proportion/percentage of drug is eliminated per unit time
-linear relationship when presented on a log scale
How does exposure relate to dose in first order pharmacokinetics?
exposure/peak concentration is proportional to the dose
What are the general characteristics of active transport?
-requires a carrier
-requires energy expenditure
-selective for specific drugs
-saturable
What is a zero order elimination pharmacokinetic system?
-constant amount of drug is eliminated per unit time
-curved relationship when presented on a log scale
What is a non-linear elimination pharmacokinetic system?
drug clearance mimics first-order kinetics at low concentration and zero-order kinetics at high concentration
How does exposure relate to dose in non-linear and zero order pharmacokinetics?
exposure is not proportional to dose
