Bishop Chapter 30 Therapeutic Drug Monitoring Flashcards
What is therapeutic drug monitoring (TDM)?
Monitoring the circulating drug concentrations in serum, plasma, and whole blood specimens.
What are the main purposes for TDM?
(1) To ensure drug dosage is within a range that produces maximal therapeutic benefit.
(2) Identify when the drug is outside the therapeutic range, leading to drug inefficacy or toxicity.
Define standard dose.
The dose providing therapeutic benefits as statistically derived from observations in a healthy population.
The basis of TDM includes consideration of what?
The route of administration, rate of absorption, distribution of drug within the body, and rate of elimination.
Which route of administration offers the most direct and effective delivery to sites of action?
Intravenous (IV)
Define bioavailability.
The fraction of the administered dose that eventually reaches its site of action.
___ administration is the most common route of delivery as it is the least invasive for patients.
Oral
For orally administered drugs, the efficiency of absorption from the GI tract is dependent on what factors?
(1) Dissociation from its administered form
(2) Solubility in GI fluids
(3) Diffusion across GI membranes
Drugs are most commonly absorbed by which type of diffusion?
Passive diffusion
The volume of distribution index is used to describe what?
The distribution characteristics of a drug. Vol (L) = Dose (mg or g) / Concentration (mg/L or g/L).
What is first-pass metabolism?
The first pass effect is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation.
What is pharmacogenomics?
The study of variations in drug metabolism related to a patient’s genetics.
Most drugs are xenobiotics; what does that mean?
Exogenous substances that are capable of entering biochemical pathways intended for endogenous substances.
What is the basic function of the haptic mixed-function oxidase (MFO) system?
This system involves taking hydrophobic substances and, through a series of enzymatic reactions, converting them into water-soluble products. These products can then either be transported into the bile or released into general circulation for elimination by renal filtration.
Describe Phase I of the MFO system.
Reactions produce reactive intermediates.
Describe Phase II of the MFO system.
Conjugate functional groups (i.e. glutathione, glycine, phosphate, and sulfate) to reactive sites on the intermediates resulting in water-soluble products.
What occurs within the MFO system when there is excess drug (i.e. an overdose)?
The MFO system becomes overwhelmed and cannot effectively metabolize it to a safe, water-soluble end product for elimination. The conjugating group can become depleted and an accumulation of phase I products occur.
May lead to toxic effects.
Induction of the MFO system typically results in ___ clearance and a corresponding ___ drug half-life.
Induction of the MFO system typically results in accelerated clearance and a corresponding shorter drug half-life.
How would the drug half-life be effected for a patient with decreased glomerular filtration rate?
Increased drug half-life and elevated plasma concentration.
Independent of the clearance mechanism, decreases in the plasma drug concentration most often occur as what type of process?
First-order process
First-order processes indicate what type of loss?
Exponential rate of loss.
The elimination rate constant describes what?
The fraction of drug eliminated per unit of time or the rate at which plasma concentrations will decline during the elimination phase.
Hence why the rate constant is negative (decreasing value).
What are the two ways drugs are eliminated?
Hepatic metabolism, renal filtration, or a combination of the two.
Define pharmacokinetics.
The activity of a drug in the body as influenced by absorption, distribution, metabolism, and excretion.
Define peak drug concentration.
The maximum blood drug concentration.
