What is meant by the term "biodisposition"
This is just another word for pharmacokinetics
What is meant by the term "biotransformation"
This is just another word for metabolism of drugs
What are the two routes of administration that are subject to first-pass metabolism by the liver?
Oral and rectal
The fraction of the administered drug which reaches the systemic circulation. It is denoted by "F".
How can you measure bioavailability?
Draw the time-concentration graphs for both the IV drug and the oral or rectal drug. Get the areas under the curve. Divide the Oral/Rectal-AUC by the IV-AUC. Bioavailability: F = Oral-AUC / IV-AUC
If you give a drug orally, and you know its bioavailability, how can you figure out how much of it is absorbed?
Mass(absorbed) = Mass(administered) x Bioavailability. e.g. Penicillin G has an oral bioavailability of 25%. If 10mg is administered orally, then 2.5mg will reach the systemic circulation.
Why is rectal administration only partially subject to first-pass metabolism by the liver?
Because blood drainage from the inferior rectum goes straight to the IVC, bypassing the liver. However, blood drainage from the superior rectum goes via the portal circulation to the liver. Therefore, approximately 50% of the rectally administered dose is subject to first-pass metabolism.
What does Fick's law describe, in the context of pharmacokinetics?
Fick's law describes the tendency of a drug to be absorbed more quickly if there is better bloodflow to its site of administration.
For the purposes of calculating drug concentrations after a given dose administered, what can you assume is the volume of plasma in a normal 70kg person?
Of Total Body Mass, 60% is fluid. Of this Total Body Water, 1/3 is Extracellular. Of this ECF, 20% is Plasma. Thus, 70 x 0.6 x 1/3 x 0.2 = 2.8 Therfore a 70kg person has approximately 2.8L of plasma.
When calculating drug concentrations and distribution, it is important to know the plasma volume and interstitial fluid volume. How much bigger is the interstitial fluid volume than the plasma volume?
TBW = 60% body weight. ECF = 1/3 TBW. Plasma forms 20% of ECF, and Interstitial Fluid forms the remaining 80%. Therefore the interstitial fluid volume is about 4 times the size of the plasma volume. (Some sources say 3-4 times)
Give a few examples of drugs that undergo zero-order kinetics at clinically relevant doses?
Ethanol, Phenytoin, Salicylates, Lithium
Give a definition of first-order kinetics.
The drug's rate of elimination is proportional to the drug's plasma concentration. Metabolism and elimination is flow-dependent. A constant PROPORTION of drug is eliminated per unit of time.
In first-order kinetics, after how many half-lives has 95% of the drug been eliminated?
Approx 4.5 half-lives.
Give a definition for Clearance, and explain which units are used.
Clearance is the Volume of Plasma that is cleared of a drug per unit time. Units: mL/hr.
If a drug has hepatic excretion, how is the drug physically excreted from the body? And if the drug has renal excretion?
Hepatic excretion: in bile. Renal excretion: in urine.
If you are plotting a drug's elimination on a semi-log plot of time vs concentration, and the drug elicits first-order kinetics, what does the curve look like?
It is a straight line.
Give a definition for "steady state".
This is when the infusion rate (the rate in) is equal to the elimination rate (the rate out)
If you are giving an IV infusion, how long does it take to reach steady state? Does this depend on the rate of infusion?
It will always take about 4-5 half-lives, REGARDLESS of the infusion rate.
What is the purpose of giving a loading dose?
This allows you to reach steady state much more quickly. If you were giving an IV-infusion without a loading dose, it would take 4-5 half-lives to reach steady state.
What is a Quantal Dose-Effect Curve, and what is it used for? What is on the x-axis and y-axis?
A Quantal Dose-Effect Curve is used instead of a standard Dose-Response Curve. This is because it is used for a "quantal" pharmacological response, which is an all-or-nothing event such as prevention of seizures. The x-axis is the dose, and the y-axis is the percentage of individuals responding (exhibiting the specified quantal effect)
With regard to a quantal pharmacologic response, what is the ED50 ?
The ED50 is the dose at which 50% of the population will exhibit the specified quantal effect, e.g. prevention of arrhythmia. It is called the median effective dose.
With regard to a quantal pharmacologic response, what is the LD50 ?
The LD50 is the dose at which 50% of the population would be killed; i.e. the lethal dose. It is called the median lethal dose.
With regard to a quantal pharmacologic response, What is the TD50 ?
The TD50 is the dose at which 50% of the population would exhibit a specified toxic response, and it is called the median toxic dose.
How do you calculate the therapeutic index?
This is the ratio of the TD50 to the ED50. It is therefore calculated as TD50 divided by ED50 (for a given clinical toxic effect and a given therapeutic effect)
What is Phase I metabolism? What is Phase II metabolism?
Phase I - oxidation / reduction / hydrolysis. Phase II - conjugation (e.g. glucuronidation, acetylation, sulfation).
What is meant by the Volume of Distribution?
This is the measure of the apparent space in the body available to contain the drug, and does not represent an actual anatomical or physical volume. It is the volume required to distribute the drug homogenously at the same concentration found in the blood, plasma, or water.
What is the lowest possible Volume of Distribution?
This is equivalent to the volume of plasma. So it would be 2.8L/70kg, or 0.04L/kg.
What are some of the highest Volumes of Distribution?
If the unit is per 70kg, some drugs will have a Vd as high as 500, 1000, 4000. If the unit is per kg of body weight, some drugs will have a Vd as high as 7, 15, 60.