Define what is meant by term pharmacokinetics
study of the time course of drug in body
"what body does to drug"
Define the term pharmacodynamics
The relationship between drug concentration and effect in body
"what drug does to body"
True or False:
Different isomers of the same drug may produce a different magnitude of response at the same receptor type
In the Emax pharmacodynamic model, define what Emax is
Emax is the maximum effect or response that can be achieved
How does a drug which is a partial agonist at a receptor differ from a drug which is a full agonist?
A partial agonist cannot produce a maximal response at the receptor. A full agonist can produce maximum response
What is an antagonist?
Drug that binds to receptor and does not activate receptor- can block action of agonist
Define tolerance to a drug
Effectiveness of drug decreased with continued use- need more drug present to produce same response
The acronym ADME is used in pharmacokinetics. What does each letter stand for?
How does serum differ from plasma?
With serum, when we collect the blood, we allow it to clot then centrifuge it. With plasma, the blood sample is placed in tube with heparin and does not clot.
True or False: It is only drug bound to plasma proteins that can pass through biological membranes
True or False:
It is only unbound (free) drug that can interact with receptors
Describe the processes that occur when we swallow a tablet
Tablet must disintegrate into small fragments
Drug must dissolve before it can be absorbed in gut
What is the main organ in the body where metabolism occurs?
True or False:
The properties of a drug can influence the rate and extent of absorption from the gut when administered orally
Which of the following routes of administration do NOT involve an absorption step?
What do we mean by transdermal drug delivery?
Drug is delivered via the skin to the systemic circulation
What is therapeutic drug monitoring involve?
Generally, it involves measuring drug concentration in a biological fluid (usually serum or plasma)
Therapeutic drug monitoring relies on good correlation between concentration and effect. What factors may lead to poor correlation between concentration and effect?
Chirality (different response from different isomers)
Active metabolites not measured
What is meant when a drug has a "Narrow Therapeutic Index"?
Only a very small change in drug concentration required to go from minimum effective concentration to toxicity (ratio of minimum concentration for toxicity to minimum effective concentration is very small)
How is a therapeutic range determined?
usually by studying plasma drug concentration and effect in a large population of patients and generating a cumulative plot of percent of patients experiencing a therapeutic response plotted versus concentration
True or False:
If we measure the plasma drug concentration in a patient and it is above the maximum safe concentration (or maximum tolerated concentration), the patient will always have signs of toxicity
False: The therapeutic range is a GUIDE, it is likely that patients above the MTC will experience adverse effects but this is not always the case
When we administer the same dose to a number of patients, what factors will contribute to the variability we see in achieved plasma drug concentrations?
variation in absorption
variation in drug distribution
variation in metabolism
What makes a drug a good candidate for therapeutic drug monitoring?
good correlation exists between pharmacological response and plasma drug concentration
wide inter subject variation in plasma drug concentration achieved for given dose
drug has narrow therapeutic index
drug's desired pharmacological effects cannot be assessed readily by other simple means
List some different assay techniques used in TDM
An assay is only as good as the performance of the assay technique. Discuss how selectivity of assay is important
Some assays use antibodies that can cross-react with metabolites of drug or endogenous compounds and the measured concentration may be artificially high due to lack of selectivity
With assay techniques, it is important to have good accuracy and precision.
What do we mean by accuracy and precision
Accuracy is how close the measured values are to the true values
Precision is how close the values are to each other when replicate assays of same sample are performed
Why is it important that the correct type of blood collection tube is used when the sample is taken from the patient?
Some drugs may adsorb to material in certain types of tubes - for example the silicon plug in a serum tube. This will lead to a loss of drug from sample and result being lower than the true value