Therapeutic Drug Monitoring - NO L.O.s Flashcards
Define therapeutic drug monitoring.
The individualisation of dosage by maintaining plasma or blood drug concentrations within a target range (therapeutic range, therapeutic window).
What is the difference between pharmacokinetics and pharmacodynamics?
PHARMACODYNAMICS = “what the drug does to the body” PHARMACOKINETICS = “what the body does to the drug”
There are two major sources of variability between individual patients in drug response. What are they?
• Dose and plasma concentration (pharmacokinetic
variability)
• Drug concentration at the receptor and the response
(pharmacodynamic variability)
What does (CL) ADME stand for?
- Compliance
- Liberation
- Absorption
- Distribution
- Metabolism
- Elimination
How does time to be absorbed differ for the IV and PO routes?
IV seconds vs PO hours
Describe first pass metabolism.
Oral medication goes through intestinal tract –> portal vein to the liver –> hepatic vein through systemic circulation –> hepatic artery to liver
I.e. goes through the liver before reaching systemic circulation
What is a ‘prodrug’?
ACTIVE DRUG
What is an ‘active drug’?
inactive or active metabolite
Drugs pass into tissues after absorption. The amount varies from tissue-to-tissue. What does this depend on? (2)
Lipophilicity
Protein binding
What does the Volume of Distribution (Vd) describe?
Use low Vd and high Vd to explain.
This partitioning between blood and tissues, i.e. low Vd mainly in blood and high Vd mainly in tissues (“lipid loving”)
What factors influence Vd? (3)
- Body fat levels
- Tissue perfusion
- Plasma protein levels
What is phase I metabolism in terms of reactions? (5)
Oxidation, reduction, methylation, deamination,
hydroxylation
Includes metabolism by cytochrome P450 enzymes
What is phase II metabolism?
Conjugation
What is meant by pharmacogenomics?
Relates to the effect of genes on drug handling by the body, and drug response
Various genetic differences may account for changes in metabolism, for example genetic polymorphisms can effect drug concentration and effect, and predisposition to toxicity
Define a genetic polymorphism.
A variation in nucleotide sequence occurring at a frequency of greater than 1%
Use the example of isoniazid and genetic polymorphisms.
N-acetylation - can be fast or slow acetylators eg, slow acetylator will not metabolise isoniazid and thus risks isoniazid toxicity
What does elimination depend on? (4)
- Renal function
- Liver function
- Genetics
- Drug interactions
Define first order kinetics.
Rate of elimination proportional to amount of drug
Define zero order kinetics and give three drug examples.
Rate of elimination independent to the amount of drug (e.g. ethanol, phenytoin, salicylates) - a constant amount of drug is eliminated per unit time
Define capacity-limited kinetics.
Rate of elimination changes from first-order to zero-order as a result of saturation of elimination mechanisms
Which is better - TDM or monitoring response?
If the clinical effect can be readily measured (e.g. heart rate, blood pressure), it is obviously better to adjust the dose on the basis of response. This forms the majority of drugs.
What are the major sources of pharmacokinetic variability?
- Compliance
- Age – neonates, elderly
- Physiology – gender, pregnancy
- Disease – hepatic, renal
- Drug interactions
- Genetic polymorphisms of drug metabolism