Intro to Pharmacokinetics Flashcards
Define pharmacology
The study of the effects of drugs on the function of living systems
Pharmacokinetics
What body does to drug
Pharmacodynamics
What the drug does to the body
What are the pharmacokinetic parameters that influence the amount of drug in the blood?
Absorption Distribution Metabolism Excretion
Define absorption
Drug is absorbed from site of administration into blood stream
Define distribution
Drug leaves bloodstream and distributes to interstitial and intracellular fluids
Define metabolism (in context of ADME)
Drug may be biotransformed by metabolism in liver and other tissues b/c body wants to break down compound for excretion once it enters body
Define excretion
Drug and metabolites are excreted from the body in urine, bile or feces
What is meant by volume of distribution?
That a high enough dose needs to be given to account for the fact that the drug will distribute through whole body not just end organ of interest
What is the onset of action?
Time it takes for drug to reach plasma following oral administration
What two things determine how fast a drug will work?
Pharmaceutic phase (formulation of drug, liquid, powder, etc.) Pharmacodynamic phase (ADME)
How is the volume of distribution calculated? (Vd)
Vd = Dose / initial concentration, Co
What does a lower Vd mean?
Lower initial concentration has what effect on Vd (if dose kept constant)?
The drug tends to stay in the plasma and not distrubute to other tissues
Lower Co = Higher Vd
What does it mean if the Vd exceeds the total body water amount for a person?
That the drug has distributed into the body’s tissues. Fat can act as a drug depot and store drug within its tissue. Drugs can also distrubtue into muscle.
Some drugs can bind to albumin (plasma protein in the blood). What effect does this have on ADME?
Proteins bound to plasma proteins have a predictable and restricted volume of distribution and the binding allows them to exert their effects over a longer period of time (increased half life) because they aren’t being metabolized by the body right away. When the concentration of the drug in the body decreases, this concentration gradient will drive more drug to dissociate from albumin and absorb into the body.
Imagine that drug A is administered to a person and is bound to albumin in the plasma. Now imagine that drug B is given to that person and drug B competes with drug A to bind to albumin. What effect will this have on the Vd of drug A?
If Drug B competes with Drug A for albumin binding, then the concentration of Drug A in the plasma will increase. An increase in concentration leads to a subsequent decrease in Vd for that drug. Thus, this drug will be more confined to the plasma.
What two bodily factors can contribute to changes in the pattern of drug distribution?
Accumulation of fat (drug depot for lipophilic drugs)
Accumulation of fluids (drug depot for water soluble drugs)
What is a Phase 2 reaction with respect to drug metabolism?
A reaction that makes drugs much more hydrophilic and often increases their molecular weight by attaching bulky hydrophilic groups.
Example: Glucuronidation
The half life of a reaction that follows first order kinetics is variable.
A) True
B) False
B) False - it is constant
The half life of a reaction that follows saturation kinetics is variable.
A) True
B) False
A) True - half life depends on starting plasma concentration
What is the equation for the elimination rate?
How does this equation simplify in clinical situations?
How would this equation simplify if the drug was given at a very high dose?
- Most drug dosages are administered at concentrations that are much smaller than the Km of the enzymes that eliminate the drugs. As such, the drug plasma concentration does not need to be considered in the denominator only.
- If given at a very high dose, the [C] drug in plasma is likely to be much higher than the Km, so the opposite would be true and the denominator would simplify simply [C]
